Abstract: The present technology relates to methods and systems for detection of pyrophosphate. As such, disclosed herein are methods and systems that permit improved pyrophosphate detection. Also disclosed herein are methods and systems which utilize improved pyrophosphate detection for nucleotide sequencing.

Abstract: Multiplexed assays are disclosed for detection of duster differentiation 4 (CD4) glycoprotein expressed on the cell surface of I-helper cells, monocytes, macrophages, and dendritic cells; cluster differentiation 25 (CD25), a type transmembrane protein present on activated T-cells, activated B-cells, thymocytes, myeloid precursors, and oligodendrocytes; and Forkhead box P3 (FOXP3), an intracellular protein involved in immune system responses in cell cultures, tissues samples, humans, and biological samples. The multiplexed assays can be used to detect 1r-cells, activated I-cells, and other similar cell types (e.g. natural T regulatory cells, adaptive/induced T regulatory T cells). The multiplexed assays employ quantum dots of various shapes, types, compositions, coatings, sizes, ligands and other such characteristics.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

Abstract: A nanoarray or microarray of antibodies includes a planar surface having an ultraflat surface, which has a planar substrate functionalized with a first monolayer of linking molecules, preferably APTES molecules, and a second monolayer of small peptides of the general formula (I) capable of binding the Fc region of antibodies. The nanoarray or microarray includes capture antibodies immobilized on the planar support, preferably in the form of a matrix of spots, and is suitable to be used for detecting antigens in a biological sample by AFM imaging.

Abstract: Disclosed is a method of producing a two dimensional microarray using a three dimensional or structured microarray. The invention involves forming defined functionalized areas by layering an inert material over the surface structures of the three dimensional microarray. Sufficient of the inert material and of the top of the surface structures are then removed to expose defined areas of the surface structures within the inert material.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: The present invention relates to a multisensor array for detection of analytes in the gas phase or in the liquid phase, comprising at least two different chemo-selective compounds represented by the general formula (I) wherein the hetero atoms X1-X4 and the substituents R1-R4 are defined in the specification and the dashed bonds represent independently of each other either a single bond or a double bond. Said chemo-selective compounds are capable of individually changing physicochemical properties when exposed to analytes or analyte mixtures and these changes can be detected by a transducer or an array of transducers. The present invention does also relate to the use of at least two different chemo-selective compounds in a sensor array, a method for preparation of such sensor arrays and the use of said sensor arrays. Furthermore the present invention relates to methods for detecting and identifying analytes or mixtures thereof in the gas phase or in the liquid phase.

Abstract: A slotted pin tool, a delivery system containing the pin tool, a substrate for use in the system and methods using the pin tool and system are provided. The slotted pin tool contains a plurality of pins having slotted ends designed to fit around each loci of material deposited on a surface, such as a microarray, without contacting any of the deposited material. Sample is delivered by contacting the pin tool with the surface; the amount delivered is proportional to the velocity of the pin tool as it contacts the surface or the velocity of the liquid when movement of the pin is halted.

Abstract: A microfluidic test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing configured for hand-held portability, the outer casing having an inlet for receiving the fluid containing the target nucleic acid sequences, a hybridization chamber mounted in the casing, the hybridization chamber containing electrochemiluminescent (ECL) probes for detecting the target nucleic acid sequences, each of the ECL probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, and electrodes for receiving an electrical pulse to excite the ECL luminophores, wherein, the hybridization chamber has a volume less than 900,000 cubic microns.

Abstract: A test module for excitation of electrochemiluminescent probes configured to detect target nucleic acid sequences, the test module having an outer casing having a receptacle for receiving a fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, electrodes for receiving an electrical pulse to excite the ECL luminophores, a detection photosensor for exposure to the photons emitted by the ECL luminophores, control circuitry providing the electrical pulse to the electrodes, and, a universal serial bus (USB) connection such that the outer casing is configured as a USB drive for transmitting data regarding detection of the targets in the fluid to an external device, wherein during use, the ECL probes that have detected one of the target nucleic acid sequences reconfigure such that the functional moiety do

Abstract: We describe assay modules (e.g., assay plates, cartridges, multi-well assay plates, reaction vessels, etc.), processes for their preparation, and method of their use for conducting assays. Reagents may be present in free form or supported on solid phases including the surfaces of compartments (e.g., chambers, channels, flow cells, wells, etc.) in the assay modules or the surface of colloids, beads, or other particulate supports. In particular, dry reagents can be incorporated into the compartments of these assay modules and reconstituted prior to their use in accordance with the assay methods. A desiccant material may be used to maintain and stabilize these reagents in a dry state.

Abstract: The present invention relates to solution microarrays. In particular, the present invention relates to an aqueous 2-phase system for solution microarrays and uses thereof. Additional embodiments are described herein.

Abstract: A microfluidic test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing having an inlet for receiving the fluid containing the target nucleic acid sequences, electrode pairs for receiving an electrical pulse, electrochemiluminescent (ECL) probe spots in contact with each of the electrode pairs respectively, the ECL probe spots containing ECL probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, such that the electrical pulse to the electrode pair excites the ECL luminophores, wherein, the mass of the ECL probes in each of the probe spots is less than 270 picograms.

Abstract: A portable test module for excitation of electrochemiluminescent probes configured to detect target nucleic acid sequences, the test module having an outer casing configured for hand-held portability, the outer casing having a receptacle for receiving a fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, and, electrodes for receiving an electrical pulse to excite the ECL luminophores, wherein during use, the ECL probes that have detected one of the target nucleic acid sequences reconfigure such that the functional moiety does not quench the photon emission from the ECL luminophore when excited by the electrodes.

Abstract: A combined detector capable of simultaneously detecting both a value indicating a physical/chemical phenomenon such as a pH value and the intensity of an energy beam such as light. The combined detector comprises a physical/chemical phenomenon detecting system (10) and an energy beam detecting system. The physical/chemical phenomenon detecting system (10) has a sensing section (21) whose potential varies with a physical/chemical phenomenon, a charge supply section (22) for supplying first charge to the sensing section, a charge supply control section (23) provided between the sensing section (21) and the charge supply section (22), a first charge storage section (26) for storing the first charge transferred from the sensing section (21), and a charge transfer control section (27) provided between the sensing section (21) and the first charge storage section (26).

Abstract: Disclosed is a technique for binding microparticles to patterned bonding pads of a metal (e.g., gold) formed on a support. The microparticles each carry a nucleic acid synthetase or DNA probe immobilized thereon for capturing a nucleic acid sample fragment. The technique involves forming, on a support surface, a film having a thickness equivalent to that of the bonding pads; controlling the size of microparticles with respect to the size of bonding pads; and thereby immobilizing microparticles each bearing a single nucleic acid sample fragment to the bonding pads in a one-to-one manner in a grid form. This allows high-density regular alignment and immobilization of many types of nucleic acid fragment samples on a support and enables high-throughput analysis of nucleic acid samples. Typically, immobilization of microparticles at 1-micrometer intervals easily provides a high density of 106 nucleic acid fragments per square millimeter.

Abstract: A device is provided for the controlled sampling of fluid into a well formed within an upper surface, in which the well may be filled under dynamic wetting conditions by contacting a droplet on the upper surface with the top of the well. Wetting is supported by the increased hydrophilicity of the upper surface relative to that of the well side wall. The relative difference in hydrophilicity may be achieved by providing an upper surface with greater roughness than the side wall, effectively amplifying the hydrophilicity of the upper surface relative to that of the side wall. Wells are preferably formed in an unpolished surface of a siliconwafer, and can achieve a stable film with micron depth and an aspect ratio in excess of 100.

Abstract: A method for providing an integrated circuit such that first and second sensing electrodes respectively have at their surfaces first and second receptor molecules for selectively binding to first and second analytes of interest; exposing the integrated circuit to a sample potentially comprising at least one of the first and second analytes, providing a first bead having a first electrical signature attached to a first molecule having a conformation/affinity for binding to the first sensing electrode dependent on the presence of the first analyte; providing a second bead having a second electrical signature attached to a second molecule having a conformation/affinity for binding to the second sensing electrode dependent on the presence of the second analyte; and determining the presence of the electrical signature of the first and/or second bead(s) on the first and second sensing electrodes respectively. An IC for implementing this method.

Abstract: The invention provides a combinatorial library, a method for preparation of that combinatorial library, a method for sequence identification, a method for sequencing the elements of combinatorial libraries of oligonucleotides and/or oligonucleotide analogues, the use of a linker to generate combinatorial libraries and a sequence identification set. More precisely, the objective of the invention is the ability to “read” sequences of selected elements of combinatorial libraries of freely modified synthetic oligonucleotides. The solution may be used both for researching for leading compounds in the pharmaceutical industry, and as a tool for studying the properties of oligonucleotides in the aspect of their potential use in experimental antisense or antigen therapy. The invention develops an appropriate strategy for determining the structure of isolated library elements, as usefulness of the combinatorial library depends on the ability to recognize the structure of its elements.

Abstract: A test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing having a receptacle for receiving the fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, electrodes for receiving an electrical pulse to excite the ECL luminophores, and, a detection photosensor for exposure to the photons emitted by the ECL luminophores.

Abstract: To provide a sensing device using a piezoelectric sensor having an oscillation area for detection and an oscillation area for reference and capable of achieving a high measurement sensitivity by improving shapes of excitation electrodes. On a quartz-crystal piece 20a, there are provided strip-shaped left side area and right side area which are formed symmetrically to be separated from each other into left and right with respect to a center of a circle 53 being a contour of a planar shape of a reaction channel 52 and extend in a longitudinal direction in a parallel manner.

Abstract: A multi-pillar structure for molecular analysis is provided. The structure comprises at least two nanopoles, each nanopole attached at one end to a substrate and freely movable along its length. The opposite ends of the at least two nanopoles are each capable of movement toward each other to trap at least one analyte molecule at their opposite ends. Each nanopole is coated with a metal coating. An array of such multi-pillar structures is also provided. A method for preparing the multi-pillar structure is further provided.

Abstract: The disclosure relates to a method of forming a pattern having pattern elements with a plurality of sizes on a substrate surface with a tilted pen array that includes choosing a tilt geometry for a pen array with respect to a substrate, inducing the tilt geometry between the pen array and the substrate surface, and forming a pattern having pattern elements on the substrate surface with the titled pen array, whereby the size of the formed pattern elements varies across the substrate surface along the tilted axis or axes. For example, the tilt geometry is in reference to the substrate surface and comprises a first angle with respect to a first axis of the substrate and a second angle with respect to a second axis of the substrate, the second axis being perpendicular to the first axis, and at least one of the first and second angles being non-zero.

Abstract: The invention relates to a method of detecting a structural change in a molecule, said molecule being attached to a surface, said surface being electrically conductive, wherein the phase of the electrochemical impedance at said surface is monitored, and wherein a change in the phase in the electrochemical impedance at said surface indicates a change in the structure of said molecule. The invention further relates to methods for making arrays having molecules such as, polypeptides attached to electrically conductive surfaces such as electrodes, and to arrays.

Abstract: A method and compositions for sulfurizing at least one phosphite or thiophosphite linkage in an oligonucleotide. The addition of N-alkyl imidazole to the acetyldisulfide sulfurization solution enables the use of industrially preferred solvents or solvents that are derived from renewable resources.

Abstract: Compositions and methods are provided for detecting genomic DNA gain and loss. Embodiments of inventive compositions and methods include composite nucleic acid probes which specifically hybridize to two or more genomic loci in a genomic region of a reference genome for detection of genomic gain and/or loss in a subject genome. In some embodiments, a substrate-attached composite nucleic acid probe is provided which includes a mixture of separate populations of beads having attached DNA probes wherein all of the beads are identically encoded and wherein each individual bead has exclusively DNA derived from one source, such as a particular large insert vector containing chromosomal DNA, or amplicons generated by amplification of DNA derived from a large insert vector containing chromosomal DNA.

Abstract: A test module for concentrating pathogens in a biological sample, the test module having an outer casing with a receptacle for receiving the sample, a dialysis device in fluid communication with the receptacle and configured to separate the pathogens from other constituents in the sample, and, a lab-on-a-chip (LOC) device being in fluid communication with the dialysis device and configured to analyze the pathogens.

Abstract: The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the CFTR gene.

Abstract: Methods and devices relate to the isolation of nucleic acids of interest from within a population of nucleic acids such as libraries of nucleic acid sequences.

Abstract: The invention provides methods for making antibody conjugates for use in antibody screening assays and antibody conjugates produced by the claimed methods.

Abstract: Cell co-culturing methods and arrays providing versatility and high resolution. A method comprising: providing at least one substrate; providing at least one first tip with at least one first cell-adhesion material disposed thereon, and at least one second tip with at least one second cell-adhesion material disposed thereon, wherein the first cell-adhesion material is different from the second cell-adhesion material; depositing the first cell-adhesion material from the first tip to the substrate to form at least one first deposit, and depositing the second cell-adhesion material from the second tip to the substrate to form at least one second deposit; and wherein the first and second deposits are capable of providing selective binding to at least one first cell so that the first cell selectively binds to the first deposit, and wherein the second deposit is capable of binding to at least one second cell.

Abstract: Fluid analyte sensors include a photoelectrocatalytic element that is configured to be exposed to the fluid, if present, and to respond to photoelectrocatalysis of at least one analyte in the fluid that occurs in response to impingement of optical radiation upon the photoelectrocatalytic element. A semiconductor light emitting source is also provided that is configured to impinge the optical radiation upon the photoelectrocatalytic element. Related solid state devices and sensing methods are also described.

Abstract: Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.

Abstract: Embodiments of the invention include a wireless sensor, such as an RFID tag, that includes a substrate, an antenna disposed on the substrate, and an environmentally sensitive sensor material disposed over at least a portion of said substrate. Other embodiments an RFID tag and at least one antibody coupled to the RFID tag. The RFID tag includes a substrate, circuitry disposed on the substrate, and an antenna coupled to the substrate. The at least one antibody is capable of affecting the signals emanating from the RFID tag. Further embodiments include a detection system that includes a reader. Yet other embodiments include a method for detecting specific analytes. The method includes providing an RFID tag which emanates a first signal having a first frequency, and enabling the REID tag to emanate a second signal having a second frequency upon attraction of a specific analyte to the RFID tag.

Abstract: An apparatus for forming a surface reservoir to hold a sample for a desirable period of time is described. The apparatus contains a platform, a solid surface disposed onto the platform, and an assembly of a bottomless vessel mounted on the solid surface. Also described is an apparatus that forms an array of surface reservoirs on a solid surface when multiple bottomless vessels are used, which can be used for high throughput applications. The apparatus can be used in applications on a solid surface, such as immunohistochemistry (IHC), oligo synthesis, peptide synthesis, ELISA, DNA array, peptide array, protein array, antibody array, tissue array, cell culturing, etc.

Abstract: A heterobifunctional linker that comprises (a) a moiety capable of reversibly coupling the linker to a selected epitope of a target molecule; and (b) a moiety or moieties capable of irreversibly coupling the linker to the target, and optionally a moiety or moieties capable of irreversibly coupling the linker to a solid surface. Also described is a method of orienting molecules, such as proteins, with respect to a surface and to each other, employing such a linker, and an array of such oriented molecules, which may be the same or different.

Abstract: A method for fabricating a universal substrate for attaching biomolecules, including sequencing features and the resulting substrate. A method of direct detection of analytes utilizes a Complementary Metal Oxide Semiconductor (CMOS) sensor with the substrate.

Abstract: The present invention relates to a probe compound that can comprise any substrate or metabolite of an enzymatic reaction in addition to an indicator component, such as, for example, a fluorescence dye, or the like. Moreover, the present invention relates to means for detecting enzymes in form of an array, which comprises any number of probe compounds of the invention which each comprise a different metabolite of interconnected metabolites representing the central pathways in all forms of life. Moreover, the present invention relates to a method for detecting enzymes involving the application of cell extracts or the like to the array of the invention which leads to reproducible enzymatic reactions with the substrates. These specific enzymatic reactions trigger the indicator (e.g. a fluorescence signal) and bind the enzymes to the respective cognate substrates. Moreover, the invention relates to means for isolating enzymes in form of nanoparticles coated with the probe compound of the invention.

Abstract: In one embodiment the present invention provides a blood analyte meter that is user-friendly and easy to use. In accordance with an embodiment of the present invention an analyte measurement device, for use with a test strip for determining the amount of an analyte in a sample, displays a hierarchy of information or options to a user. The hierarchy of information or options may include, among other information or options, subroutines that are performable by the processor of the device, stored data related to past tests performed by the user, and alarm features of the device. A user scrolls through and selects individual options or pieces of information by rotating and translating a rotatable user interface around and along an axis of rotation.

Abstract: Methods and devices are provided for manipulating droplets on a support using surface tension properties, moving the droplets along a predetermined path and merging two droplets together enabling a number of chemical reactions. Disclosed are methods for controlling the droplets volumes. Disclosed are methods and devices for synthesizing at least one oligonucleotide having a predefined sequence. Disclosed are methods and devices for synthesizing and/or assembling at least one polynucleotide product having a predefined sequence from a plurality of different oligonucleotides having a predefined sequence.

Abstract: The present invention relates to novel iminecalixarene derivatives, method of preparation thereof, and self-assembled monolayer prepared by the method, fixing method of oligo-DNA by using the self-assembled monolayer, and oligo-DNA chip prepared by the method. Also, the present invention relates to novel aminocalixarene derivatives, method of preparation thereof, and self-assembled monolayer prepared by the method, fixing method of oligo-DNA wherein the oligo-DNA is voluntarily fixed by molecular recognition on said self-assembled monolayer in a liquid phase, and oligo-DNA chip prepared by the method.

Abstract: A microarray assembly for detection of a target molecule is disclosed. The microarray assemblies comprise an array chamber having a microarray located therein and features that facilitate liquid movement within the array chamber. Also disclosed are methods for making the microarray assembly using rollable films and methods for detecting microarray spots using an internal control fluorophore in the array spot.

Abstract: The disclosure relates to the field of molecular recognition or detection of discontinuous or conformational binding sites or epitopes corresponding to a binding molecule, in particular, in relation to protein-protein, protein-nucleic acid, nucleic acid-nucleic acid or biomolecule-ligand interactions. Provided is a synthetic molecular library allowing testing for, identification, characterization, or detection of a discontinuous binding site able to interact with a binding molecule, the library having been provided with a plurality of test entities, each test entity comprising at least one first segment spotted next to a second segment, each segment having the capacity of being a potential single part of a discontinuous binding site.

Abstract: The present invention is directed to systems and method for predicting risk of AMD or a susceptibility to AMD in a patient by detecting elevated serum or plasma levels of C3, CFB or CFH and other complement factor polypeptides, wherein devated levels certain complement factors, genetic risk factors, medical risk factors, behavioral and environmental risk factors are associated with are indicative of susceptibility for or an increased risk of developing AMD, or an increased risk of progression of AMD in the patient.

Abstract: A system for classifying thyroid nodule tissue as malignant or benign is provided that is based on the identification of sets of gene transcripts, which are characterized in that changes in expression of each gene transcript within a set of gene transcripts can be correlated to with either malignant or benign thyroid nodule disease. The thyroid classification system provides for sets of “thyroid classifying” target sequences and further provides for combinations of polynucleotide probes and primers derived there from. These combinations of polynucleotide probes can be provided in solution or as an array. The combination of probes and the arrays can be used for diagnosis. The invention further provides further methods of classifying thyroid nodule tissue.

Abstract: Specialized microfluidic networks are utilized to deposit substances on sensor surfaces. In particular, a flow-based microfluidic printhead is used as an interface to deliver multiple analytes to a sensor for simultaneous analysis. Furthermore, internal referencing is incorporated into sensor regions for improved sensitivity.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

Abstract: Invention methods employ the use of acoustic waves to transfer small amounts of fluid in a non-contact manner. In invention methods, acoustic waves are propagated through a separated pool of a source fluid in such a manner that causes the ejection of a single micro-droplet from the surface of the pool. The droplet is ejected towards a target with sufficient force to provide for contact of the droplet with the target. Because the fluid is not contacted by any fluid transfer device such as a pipette, the opportunities for contamination are minimized. Invention methods may be employed to transfer fluids from an array of source sites to an array of target sites, thereby enabling the precision automation of a wide variety of procedures including screening, and synthesis procedures commonly used in biotechnology.

Abstract: The invention provides nucleic acid hybridization methods for detecting target nucleic acid sequences wherein complexes comprising nanoparticles non-covalently associated with single-stranded tartlet nucleic acid molecules are incubated with immobilized probe nucleic acid molecules. Because the nanoparticles function as competitors in the hybridization reaction between the target nucleic acid molecules and the probe nucleic acid molecules. The methods provide a high degree of discrimination between a perfectly matched target sequence and a sequence having at least a single-base-pair mismatch, even when the hybridization reaction is performed at room temperature. The invention also provides microarray methods and apparatus which incorporate the nanoparticle-assisted hybridization methods.

Abstract: Apparatus and methods are described for split synthesis combinatorial chemistry that provides candidate libraries where an even distribution of theoretical products is obtainable through even mixing during the pooling step, followed by controlled redistribution of the mixed pooled products from the prior addition step into separate synthesis columns, one for each different specie of subunit to be added.