Bioarray Solutions Ltd.

Chiu Wo Chau

Michael Seul

Sukanta Banerjee

Jiacheng Yang

Xiongwu Xia

Ye Hong

Scott Determan

Hui Huang

Enqing Tan

Yi Zhang

Kairali Podual

Alice Xiang Li

This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

Arrays of microparticles and methods of preparation thereof

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 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 encoding information, so as to preserve confidentiality.

Analysis, secure access to, and transmission of array images

Disclosed herein are methods for array assembly and detection. The methods can use an incubation chamber containing a suspension of nucleic acid targets, polymerase and a set of oligonucleotide probes bound to magnetic beads in a randomly dispersed state. Each probe can have a target binding domain that is complementary to a target nucleic acid, a closing domain with a sequence that is complementary to the sequence of the target binding domain, and a joining region between the binding domain and the closing domain, which is not complementary to the target nucleic acid. Method steps can include providing the incubation chamber, placing the incubation chamber in a magnetic trap, generating a magnetic field that induces the magnetic beads to migrate towards a substrate and, once in proximity to the substrate, to interact with each other repulsively and reorganize into arrays, and imaging the array.

Methods for array assembly and detection involving elongation of self-complementary looped probes

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.

The present application 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.

Programmable illumination pattern for transporting microparticles

In a multiplexed assay method carried out in solution, wherein the solution contains nucleic acid targets and, wherein several different types of oligonucleotide probes, each type having a different sequence in a region designated as a target binding domain, are used to detect the nucleic acid targets, said assay method including a method for increasing the effective concentration of the nucleic acid targets at the surface of a bead to which the oligonucleotide probes are bound, by one or more of the following steps: adjusting assay conditions so as to increase the effective concentration of the targets available for binding to the probes, by one or more of the following: (i) selecting a particular probe density on the surface of the bead; (ii) selecting a solution having an ionic strength greater than a threshold; (ii) selecting a target domain of a size less than a threshold; or (iii) selecting target domains within a specified proximity to a terminal end of the targets.

Probe density self-considerations and elongation of complementary looped probes where probes are attached to a solid phase

Disclosed is number coding of pairs ('doublets') or small sets ('multiplets') of solid phase carriers which provides distinguishable subtypes of a given type of such carriers, where each carrier type is distinguishable on the bases of a different code. Such number coding is useful for augmenting a coding system, such as a color code, and thereby effectively multiplying the number of &#x201c;colors&#x201d; (distinguishable sub-types). It can be applied, for example, to determine whether a sample is homozygous or heterozygous at a number of different sites for one of two different alleles, where the same color code is applied for each of the two alleles, and the alleles with the same color code are distinguished by knowing how many carriers are associated with molecules which detect each different allele.

Number coding for identification of subtypes of coded types of solid phase carriers

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, patterning of an electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process, and real-time control of assembly via external illumination. The apparatus generates patterns of illumination and projects them onto planar surfaces, i.e., LEAPS electrodes. 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 that images the LCD panel onto the surface of interest to provide for the assembly of particles within such patterns.

Disclosed is number coding of pairs ('doublets') or small sets ('multiplets') of solid phase carriers which provides distinguishable subtypes of a given type of such carriers, where each carrier type is distinguishable on the basis of a different code. Such number coding is useful for augmenting a coding system, such as a color code, and thereby effectively multiplying the number of &#x201c;colors&#x201d; (distinguishable sub-types). It can be applied, for example, to determine whether a sample is homozygous or heterozygous at a number of different sites for one of two different alleles, where the same color code is applied for each of the two alleles, and the alleles with the same color code are distinguished by knowing how many carriers are associated with molecules which detect each different allele.

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.

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Edison, NJ, United States of America

Chiu Wo Chau