Abstract: Disclosed herein are methods of amplifying an analyte in a biological sample using a bridging oligonucleotide that hybridizes to a captured analyte. The methods disclosed herein include steps of (a) contacting a biological sample with a substrate having capture probes comprising a capture domain and a spatial barcode; (b) hybridizing the analyte to the capture domain; and (c) contacting the analyte to a bridging oligonucleotide comprising (i) a capture-probe-binding sequence, and (ii) an analyte-binding sequence; (d) extending the bridging oligonucleotide; and (e) determining (i) all or a part of the sequence of the analyte, or a complement thereof, and (ii) the spatial barcode, or a complement thereof, and using the determined sequence of (i) and (ii) to determine the location of the analyte in the biological sample.

Abstract: Presented are methods and compositions for spatial detection and analysis of nucleic acids in a tissue sample. The methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue.

Abstract: A method is presented that enables the spatial mapping of nucleic acids of tissue samples with high resolution and without sacrificing the degree of multiplexing that is available from next-generation sequencing. The method is based on the application of patterns of barcoded oligonucleotides probes onto predefined locations in a region of interest in a tissue sample. Every nucleic acid analyzed can be allocated to a certain position inside the sample based on the barcode. Various printing technologies can be used and different ways of patterning can be employed, like a regular array with a certain pitch or alternatively an object-based patterning with defined regions of interest without shape constraints.

Abstract: The present disclosure provides methods and assay systems for use in spatially encoded biological assays, including assays to determine a spatial pattern of abundance, expression, and/or activity of one or more biological targets across multiple sites in a sample. In particular, the biological targets comprise proteins, and the methods and assay systems do not depend on imaging techniques for the spatial information of the targets. The present disclosure provides methods and assay systems capable of high levels of multiplexing where reagents are provided to a biological sample in order to address tag the sites to which reagents are delivered; instrumentation capable of controlled delivery of reagents; and a decoding scheme providing a readout that is digital in nature.

Abstract: The present disclosure provides fully integrated microfluidic systems to perform nucleic acid analysis. These processes include sample collection, nucleic acid extraction and purification, amplification, sequencing, and separation and detection. The present disclosure also provides optical detection systems and methods for separation and detection of biological molecules. In particular, the various aspects of the invention enable the simultaneous separation and detection of a plurality of biological molecules, typically fluorescent dye-labeled nucleic acids, within one or a plurality of microfluidic chambers or channels. The nucleic acids can be labeled with at least 6 dyes, each having a unique peak emission wavelength. The present systems and methods are particularly useful for DNA fragment sizing applications such as human identification by genetic fingerprinting and DNA sequencing applications such as clinical diagnostics.

Abstract: The invention generally relates to a molecular classification of disease predisposition and particularly to molecular markers for cancer predisposition and methods of use thereof.

Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Abstract: The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.

Abstract: In a first location of a mass spectrometer, a plurality of ionized molecules of an ion source are selected that have mass-to-charge ratios within a mass-to-charge ratio window width. The plurality of selected ionized molecules are transmitted from a first to a second location. Reagent ions are transmitted to the second location to reduce a charge state of one or more of the plurality of selected ionized molecules. A mass analyzer is used to analyze the plurality of reduced ionized molecules and produce a mass spectrum. A compound is identified from a peak of the spectrum that has a mass-to-charge ratio less than or equal to the highest mass-to-charge ratio in the window width if the noise is multiply charged and greater than the highest mass-to-charge ratio in the window width if the noise is singly charged.

Abstract: Apparatus, systems, and methods for detecting, screening and sampling of cells are disclosed.

Abstract: The invention provides a bio-sensing nanodevice comprising: a stabilized G-protein coupled receptor on a support, a real time receptor-ligand binding detection method, a test composition delivery system and a test composition recognition program. The G-protein coupled receptor can be stabilized using surfactant peptide. The nanodevice provides a greater surface area for better precision and sensitivity to odorant detection. The invention further provides a microfluidic chip containing a stabilized G-protein coupled receptor immobilized on a support, and arranged in at least two dimensional microarray system. The invention also provides a method of delivering odorant comprising the step of manipulating the bubbles in complex microfluidic networks wherein the bubbles travel in a microfluidic channel carrying a variety of gas samples to a precise location on a chip. The invention further provides method of fabricating hOR17-4 olfactory receptor.

Abstract: A sensor system is formed from a micro machined resonant structure with multiple resonant elements, a tracking resonator control electronics, and signal processing algorithms. The moving elements of the resonator are coated with chemically active materials that change mass when exposed to the target chemical resulting in a change in frequency or period of oscillation. The changes in frequency or period are processed by multi-sensor chemical detection algorithms to identify chemical types and concentrations. In essence, the resonator and drive electronics form a closed loop oscillator operating at the resonator's natural frequency. The resonators are formed from silicon using photolithographic processes. The resonator design includes in-plane resonant motion combined with dynamic balance to operate with a high Q even in the presence of atmospheric pressure.

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Abstract: This disclosure provides methods, devices and systems for using a stamp to enhance selectivity between surface layers of a substrate, and to facilitate functionalizing selected layers. An array of flat stamps may be used to concurrently stamp multiple regions of a substrate to transfer one or more substances to the topmost layer or layers of the substrate. If desired, the affected regions of the substrate may be isolated from each other through the use of a reactor plate that, when clamped to the substrate's surface, forms reaction wells in the area of stamping. The stamp area can, if desired, be configured for stamping the substrate after the reactor plate has been fitted, with the individual stamps sized and arranged in a manner that permits stamping within each reaction well.

Abstract: Systems and methods for the detection of biomarkers. In at least one embodiment of a microarray system of the present disclosure, the microarray system comprises a microarray product comprising at least 100 diagnostic markers/cm2, a microarray identifier, and a stabilizing agent, a control microarray product comprising a first specific binding pair member that binds to a first detectable label, and a processor for providing information regarding the identification and concentration of markers on the microarray based on the identity of the array provided by the microarray identifier.

Abstract: An integrated instrument for oligonucleotide synthesis and PCR, and a system and method thereof are disclosed. The integrated instrument is basically composed of two independent modules. The first module is a unit for chemical de novo synthesis of oligonucleotides such as oligonucleotide primers and/or oligonucleotide hybridization probes. The second module is a unit for performing an analytical polymerase chain reaction amplification in real time, i.e. a qPCR. The two modules are operatively linked to each other in such a way that a user can load a nucleic sample to be analyzed into the integrated instrument and perform a PCR reaction by programming the instrument without a previous external synthesis of oligonucleotide amplification primers.

Abstract: There is provided a portable measuring system having a biophotonic sensor. The portable measuring system also includes a tunable light source, an output intensity detector and an output wavelength detector, which are mounted therein. The portable measuring system can precisely measure a variation in the reflectivity spectrum and/or the transmittance spectrum of the biophotonic sensor before and after an antigen-antibody reaction by varying the wavelength of the tunable light source. Thus, the concentration of the antigen is precisely measured.

Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: An arrangement is provided in at least one embodiment, having a magazine for supplying a plurality of microfluidic devices. The microfluidic devices each contain at least one element/device for binding at least one biological molecule, wherein the at least one element/device for binding the at least one biological molecule can be moved relative to the microfluidic device. A sample presumably containing biological molecules to be examined is introduced into the microfluidic device. The biological molecule to be examined is bound by the at least one element/device for binding the biological molecule. In at least one embodiment, the at least one element/device for binding the at least one biological molecule, or the substrate-molecule complex, can then be moved in the microfluidic device, e.g. in accordance with a predetermined reaction sequence, for example by means of a magnetic field. The microfluidic device is transported through the arrangement.

Abstract: The present invention provides a system for analyzing and screening disease related genes from microarray database. After normalizing the collected microarray datasets and related experiment data by using pre-processing unit, the relative important feature vector can be systematically extracted by the feature selection unit. The maximal likelihood discriminate rule of classification unit calculates probability statistics of the classification and diagonal quadratic discriminant analysis module is used to decide classification and set up disease prediction module. Also, the generalized rule induction information statistics calculation module of rule extraction unit is used to obtain organized information statistics and information theoretic rule induction algorithm module is employed to generate best relationship rule and associate rule module can be set up.

Abstract: This invention comprises a method for generating functional neural networks using neural progenitor cells on microelectrode arrays (MEAs). The method involves dissociating neural progenitor cells from an embryo, propagating the neural progenitor cells, passaging the neural progenitor cells and seeding the neural progenitor cells on MEAs to produce a functional neural network. The neural progenitor cells may be continuously passaged to propagate an endless supply of neural progenitor cells. The resultant passaged progenitor cell derived neural network MEA may be used to detect and/or quantify various biological or chemical toxins.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. A composition is provided that comprises an array of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. The inventive arrays are generated by: providing a solid support functionalized with a selected chemical moiety capable of interacting with a chemical compound to form an attachment and delivering compounds to the solid support having a density of at least 1000 spots per cm2. The present invention also provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

Abstract: T cells are profiled with respect to their expression of antigen receptor. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused MHC-antigen complexes. The cells may further be characterized with respect to their ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like.

Abstract: The present invention discloses systems and methods for minimizing or eliminating steps in immunosorbent assays for single and multiple analytes by eliminating both the need to attach target molecules to the test well and the need to remove unbound antibodies through rinsing. The immunosorbent assay (ISA) is utilized for a single analyte or target and includes the step of mixing the immunologic molecules with the sample and detection. The present invention further discloses an immunosorbent assay for multiple analytes (ISAMA) for testing a plurality of analytes or targets in a single well using a modified ISA test wherein different tags are attached to different antibody pairs. Alternate embodiments use multiple types of scavenger antigens with corresponding elimination of the need for scavenger antibodies. The present invention discloses various types of test wells for the rapid and simultaneous testing of fluids for a plurality of components and a methodology for a continuous immunosorbent assay.

Abstract: A device, method and system for ensuring proper orientation and installation of trays for processing biological sensors in an automated and flexible system are provided. The system comprises an instrument handling robot that transfers a plurality of arrays mounted on pegs on a strip to liquid reaction stations. In particular, the method comprises a first orientation marking on a tray and a second orientation marking on a deck, indicating the proper station in which the tray is placed for a specific process.

Abstract: The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying the optimum probe attachment site. Biosensors are provided having environmentally sensitive dyes that can locate specific biomolecules within living cells and detect chemical and physiological changes in those biomolecules as the living cell is moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, the environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound.

Abstract: Temperature control devices and methods are described. The described temperature control devices and methods comprise optical emission and detection assemblies and can be used in PCR and qPCR applications.

Abstract: Methods for sequencing nucleic acids are presented. Sequencing is accomplished through the detection of a redox active species that is indicative of nucleotide incorporation. In embodiments of the invention, an electrochemical signal indicative of nucleotide incorporation is amplified through cycling before it is detected. Arrays are provided that are capable of massively parallel nucleic acid sequence determination.

Abstract: The invention relates to a device for containing, reacting and measuring, and a method of containing, reacting and measuring, and provides a device for containing, reacting and measuring, and a method of containing, reacting and measuring which is also able to effectively and quickly perform the reaction processing, measuring and identification.

Abstract: A method for computer-based processing of biological data, comprising the steps of: selecting a gene as lead gene to be patented; searching homologues for the selected lead gene; creating a patent pool on the basis of the selected lead gene; generating and outputting a pool report for the planned patent application.

Abstract: Structural models for a rhomboid protease alone and bound to inhibitors and peptide substrates and compositions and methods for preparing rhomboid protease binding compounds and methods for using such rhomboid protease binding compounds for modulation of these proteases catalytic activity are disclosed herein.

Abstract: Aspects of the invention include methods of systems of pairwise filtering candidate probe nucleic acid sequences. Aspects of the invention further include methods and systems of selecting candidate probe nucleic acid sequences from plurality thereof, which methods and systems employ a pairwise elimination ranked record of a plurality of candidate probe nucleic acids for a genomic region of interest.

Abstract: The invention relates to a substrate material for analyzing fluids which has first areas with a high porosity and second areas with a lower porosity.

Abstract: The invention concerns a method for analyzing nucleic acids using a small-size probe array comprising deoxylnostines (dl) instead of deoxyguanogines (dG). The invention also concerns such probe arrays and their use in methods for detecting and/or quantifying target oilgonucleotides present in DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) molecules in a sample, in particular mRNA editing rate of the serotonin 5-HT2c receptor (5-HT2c-R). The invention further concerns a biochip or a reactor in liquid medium comprising such probe arrays as well as their uses, in particular for detecting and/or identifying genetic polymorphisms or for determining an mRNA editing rate, whether it is that of a 5-HT2c-R mRNA or any other RNA capable of being edited.