Abstract: Disclosed are a method and an algorithm for genetic cross-matching based on the comparison of recipient and donor genotypes—and the underlying combinations of alleles and haplotypes. The method of the invention, rather than focusing on phenotype prediction, instead relies on a comparison of genetic variants identified in the recipient and available donors, whose information preferably will be compiled in a widely available donor registry, to maximize molecular compatibility. The genotypes can be matched based on the weighted clinical significance of a genotypic difference between donor and recipient, such that certain mismatches are more acceptable than others.

Abstract: Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including: methods of probe and target “engineering”, as well as methods of assay signal analysis relating to the modulation of the probe-target affinity constant, K by a variety of factors including the elastic properties of target strands and layers of immobilized (“grafted”) probes; and assay methodologies relating to: the tuning of assay signal intensities including dynamic range compression and on-chip signal amplification; the combination of hybridization-mediated and elongation-mediated detection for the quantitative determination of abundance of messages displaying a high degree of sequence similarity, including, for example, the simultaneous determination of the relative expression levels, and identification of the specific class of, untranslated AU-rich subsequences located near the 3? terminus of mRNA; and a new method of subtractive differential gene expression analysis which requires only a single color label.

Abstract: This invention provides compositions and methods for genetic testing of an organism and for correlating the results of the genetic testing with a unique marker that unambiguously identifies the organism. The markers may be internal markers, such as for example single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), or other sites within a genomic locus. Alternatively, the markers may be external, such that they are separately added to the genetic sample before testing.

Abstract: A dynamically configurable electrode includes a first planar electrode and a planar array of pixels in a different plane, wherein a polarizable liquid medium (including electrolyte solutions) is to reside in the gap between electrodes. The pixels are individually addressable by a time-varying voltage, and adjacent pixels receive, at any instant in time, either the same voltage waveform or a different voltage waveform. Adjacent pixels receiving different voltage waveforms generate corresponding movement of dipolar entities, including dipolar particles, ions, or dipolar molecules in the polarizable liquid medium between the electrodes, which can in turn generate fluid flow and movement of particles suspended in the fluid along the planar array surface.

Abstract: Disclosed is a method of iteratively optimizing two (or more) interrelated sets of probes for the multi-step analysis of sets of designated sequences, each such sequence requiring, for conversion, at least one conversion probe (“primer”), and each converted sequence requiring, for detection, at least one capture probe. The iterative method disclosed herein for the concurrent optimization of primer and probe selection invokes fast logical string matching functions to perform a complete cross-correlation of probe sequences and target sequences. The score function assigns to each probe-target alignment a “degree of matching” score on the basis of position-weighted Hamming distance functions introduced herein. Pairs of probes in the final selection may differ in several positions, while other pairs of probes may differ in only a single position. Not all such positions are of equal importance, and a score function is introduced, reflecting the position of the mismatch within the probe sequence.

Abstract: Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including: methods of probe and target “engineering”, as well as methods of assay signal analysis relating to the modulation of the probe-target affinity constant, K by a variety of factors including the elastic properties of target strands and layers of immobilized (“grafted”) probes; and assay methodologies relating to: the tuning of assay signal intensities including dynamic range compression and on-chip signal amplification; the combination of hybridization-mediated and elongation-mediated detection for the quantitative determination of abundance of messages displaying a high degree of sequence similarity, including, for example, the simultaneous determination of the relative expression levels, and identification of the specific class of, untranslated AU-rich subsequences located near the 3? terminus of mRNA; and a new method of subtractive differential gene expression analysis which requires only a single color label.

Abstract: Systems and methods are provided the autocentering, autofocusing, acquiring, decoding, aligning, analyzing and exchanging among various parties, images, where the images are of arrays of signals associated with ligand-receptor interactions, and more particularly, ligand-receptor interactions where a multitude of receptors are associated with microparticles or microbeads. The beads are encoded to indicate the identity of the receptor attached, and therefore, an assay image and a decoding image are aligned to effect the decoding. The images or data extracted from such images can be exchanged between de-centralized assay locations and a centralized location where the data are analyzed to indicate assay results. Access to data can be restricted to authorized parties in possession of certain coding information, so as to preserve confidentiality.

Abstract: Described are methods of assay design and assay image correction, useful for multiplexed genetic screening for mutations and polymorphisms, including CF-related mutants and polymorphs, using an array of probe pairs (in one aspect, where one member is complementary to a particular mutant or polymorphic allele and the other member is complementary to a corresponding wild type allele), with probes bound to encoded particles (e.g., beads) wherein the encoding allows identification of the attached probe. The methods relate to avoiding cross-hybridization by selection of probes and amplicons, as well as separation of reactions of certain probes and amplicons where a homology threshold is exceeded. Methods of correcting a fluorescent image using a background map, where the particles also contain an optical encoding system, are also disclosed.

Abstract: Solute-loaded polymer microparticles are obtained by immersing microparticles in a bath comprising a selected solute dissolved in a ternary solvent system. A first solvent of the ternary system is a strong solvent for both the solute and the polymer from which the microparticle was formed. A second solvent is a weak solvent or non-solvent for the solute and the polymer (tuning solvent). A third solvent is a weak solvent or non-solvent for the solute and polymer, but serves as a co-solvent with respect to the first and second solvents in that it is miscible with both the first and second solvents. The amount of solute incorporated into the microparticles is controlled by adjusting the ratio of solute with respect to the microparticle polymer, and by adjusting the composition of the ternary solvent system, principally the amount of tuning solvent.

Abstract: Disclosed are a method and an algorithm for genetic cross-matching based on the comparison of recipient and donor genotypes—and the underlying combinations of alleles and haplotypes. The method of the invention, rather than focusing on phenotype prediction, instead relies on a comparison of genetic variants identified in the recipient and available donors, whose information preferably will be compiled in a widely available donor registry, to maximize molecular compatibility. The genotypes can be matched based on the weighted clinical significance of a genotypic difference between donor and recipient, such that certain mismatches are more acceptable than others.

Abstract: Disclosed is a method for the physico-chemical encoding of a collection of beaded resin (“beads”) allowing determination of the chemical identity of bead-anchored compounds, following identification of beads bearing compounds of interest in an assay, by in-situ interrogation of individual beads, which does not require isolation of the beads of interest. These methods can be used to implement color-coding strategies in applications and including the ultrahigh-throughput screening of bead-based combinatorial compounds libraries as well as multiplexed diagnostic and environmental testing and other biochemical assays.

Abstract: Solute-loaded polymer microparticles are obtained by immersing microparticles in a bath comprising a selected solute dissolved in a ternary solvent system. A first solvent of the ternary system is a strong solvent for both the solute and the polymer from which the microparticle was formed. A second solvent is a weak solvent or non-solvent for the solute and the polymer (tuning solvent). A third solvent is a weak solvent or non-solvent for the solute and polymer, but serves as a co-solvent with respect to the first and second solvents in that it is miscible with both the first and second solvents. The amount of solute incorporated into the microparticles is controlled by adjusting the ratio of solute with respect to the microparticle polymer, and by adjusting the composition of the ternary solvent system, principally the amount of tuning solvent.

Abstract: Disclosed are a method and an algorithm for genetic cross-matching based on the comparison of recipient and donor genotypes—and the underlying combinations of alleles and haplotypes. The method of the invention, rather than focusing on phenotype prediction, instead relies on a comparison of genetic variants identified in the recipient and available donors, whose information preferably will be compiled in a widely available donor registry, to maximize molecular compatibility. The genotypes can be matched based on the weighted clinical significance of a genotypic difference between donor and recipient, such that certain mismatches are more acceptable than others.

Abstract: The present invention provides methods and apparatus for the application of a particle array in bioassay format to perform qualitative and/or quantitative molecular interaction analysis between two classes of molecules (an analyte and a binding agent). The methods and apparatus disclosed herein permit the determination of the presence or absence of association, the strength of association, and/or the rate of association and dissociation governing the binding interactions between the binding agents and the analyte molecules. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interactions of a number of analyte molecules in a sample.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relics on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The preset invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: This invention provides compositions and methods for genetic testing of an organism and for correlating the results of the genetic testing with a unique marker that unambiguously identifies the organism. The markers may be internal markers, such as for example single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), or other sites within a genomic locus. Alternatively, the markers may be external, such that they are separately added to the genetic sample before testing.

Abstract: An apparatus providing programmable illumination pattern generation for the manipulation of colloidal particulates and biomolecules in suspension between electrodes, is disclosed. The apparatus implements LEAPS (Light-controlled electrokinetic assembly of particles near surfaces), which relies on: AC electric field-induced assembly of particles: the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The apparatus generates patterns of illumination and projects them onto planar surfaces. i.e., a LEAPS electrode.

Abstract: The invention provides methods and processes for the identification of polymorphisms at one or more designated sites, without interference from non-designated sites located within proximity of such designated sites. Probes are provided capable of interrogation of such designated sites in order to determine the composition of each such designated site. By the methods of this invention, one or more mutations within the CFTR gene and the HLA gene complex can be can be identified.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: Disclosed is a registry system, including member institutions, in which transfusion donors and recipients are registered following genotyping, which would typically take place in a member institution, or a member institution would have access to the genotyping information, if performed outside. The registry database can be accessed and searched by members seeking samples of particular type(s). Systems are disclosed for maintaining economic viability of genotyping in connection with transfusions, by maximizing the number of units placed with the minimal number of candidate donors typed. Genotyping of potential donors, and product supply, is matched to forecasted demand. Genotyping can also be limited to the more clinically relevant markers. The registry system can also be integrated with one format of assay which generates an image for analysis, whereby the imaged results can be analyzed and redacted by experts in a central location, and then transmitted back to the patient or their representative.