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 is a registry for candidate transfusion donors, which invokes an inventory management policy to create and actively manage lists of candidate donors in order to minimize imbalances between demand and supply across multiple regions and across multiple categories of donors and recipients. Together with a genotyping laboratory, the registry does targeted recruitment of prospective donors who are typed for a set of genetic markers relating to clinically relevant antigens including mutations of Human Erythrocyte Antigens (HEA), genetic variants of Rh, and possibly additional antigens such as HLA and HPA. The registry monitors incoming demand for transfusion antigen genotypes, preferably stratify the demand into a set of categories representing stable subpopulations, and will apply strategies, disclosed herein, to tune the composition of candidate donor lists to match the demand, thereby avoiding excess, and unnecessary, typing of candidate donors.
Abstract:
Disclosed are methods of for constructing a bead-displayed library of oligonucleotide probes (or sequence-modified capture moieties such as protein-nucleic acid conjugates) by ligation of a capture probe, having an analyte-specific sequence, to an anchor probe that is attached, at its 5′-end, (or possibly at the 3′ end) to an encoded carrier such as a color-coded microparticle (“bead”). Such a library can also be constructed by elongation of an anchor probe, using a second probe as the elongation template, wherein the second probe has an anchor-specific subsequence and an analyte-specific subsequence.
Abstract:
The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. 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:
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:
A method and apparatus for the manipulation of colloidal particles 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. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.
Abstract:
A method and apparatus for the physico-chemical encoding of a collection of beaded resin (“beads”) to determine the chemical identity of bead-anchored compounds by in-situ interrogation of individual beads. The present invention provides method and apparatus 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:
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 on to planar surfaces. i.e., a LEAPS electrode. This enables the creation of patterns using graphical design or drawing software on a personal computer and the projection of said patterns, or sequences of patterns (“time-varying patterns”), onto the interface using a liquid crystal display (LCD) panel and an optical design which images the LCD panel onto the surface of interest, to provide for arrangements and assembly of particles in such patterns.
Abstract:
The present invention relates to a systematic process for the creation of functionally organized, spatially patterned assemblies polymer-microparticle composites including the AC electric field-mediated assembly of patterned, self supporting organic (polymeric) films and organic (polymeric)-microparticle composite films of tailored composition and morphology; the present invention further relates to the incorporation of said assemblies into other structures. The present invention. also relates to the application of such functional assemblies in materials science and biology. Additional areas of application include sensors, catalysts, membranes, micro-reactors, smart materials. Miniaturized format for generation of multifunctional thin films. Provides a simple set-up to synthesize thin films of tailored composition and morphology.
Abstract:
Disclosed are methods and algorithms (and their implementation) supporting the automated analysis and interactive review and refinement (“redaction”) of the analysis within an integrated software environment, for automated allele assignments. The implementation, preferably with a software system and a program referred to as the Automated Allele Assignment (“AAA”) program, provides a multiplicity of functionalities including: data management by way of an integrated interface to a portable database to permit visualizing, importing, exporting and creating customizable summary reports; system configuration (“Set-up”) including user authorization, training set analysis and probe masking; Pattern Analysis including string matching and probe flipping; and Interactive Redaction combining real-time database computations and “cut-and-paste” editing, generating “warning” statements and supporting annotation. It also includes a thresholding function, a method of setting thresholds, a method of refining thresholds by matching an experimental binary string (“reaction pattern”) setting for that probe, probe masking of signals produced by probes which do not contribute significantly to discriminating among alleles.