Abstract: A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.

Abstract: A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.

Abstract: The present invention provides methods for non-invasive determination of sex in a fetus or of Y chromosomal frequency abnormalities—indicative of aneuploidy or sex mosaicisms in a fetus—by detecting and determining the relative contribution genetic sequences from the Y chromosome in view of the percent fetal contribution in a maternal mixed sample.

Abstract: A scanning apparatus that can include (a) a scan actuator including a linear actuator and a mount for a removeable vessel, wherein the mount has a mechanical fastener that is configured to engage a complementary mechanical fastener on the removeable vessel, and wherein the linear actuator is configured to translate the mount while the mechanical fastener engages the complementary mechanical fastener on the removeable vessel; (b) a reference surface; and (c) a preload configured to urge the vessel to contact the reference surface, wherein the linear actuator is configured to slide the vessel along the reference surface while the preload urges the vessel to contact the reference surface.

Abstract: A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.

Abstract: The present invention provides assay systems and methods for determining the percent fetal contribution of cell-free DNA in a maternal sample from a pregnant female with an egg donor pregnancy. Further provided, are assay systems and methods for determining a statistical likelihood of the presence or absence of a fetal aneuploidy in a maternal sample using a determined percent fetal cell-free DNA in the sample.

Abstract: A flow cell that includes (a) a gasket interposed between a first substrate and a second substrate, wherein the gasket, the first substrate and the second substrate are impermeable to aqueous liquid and liquid adhesive, wherein the gasket has a footprint on the first substrate that delineates a channel for containing the aqueous liquid; (b) a via in the gasket, the via containing a solidified liquid adhesive that bonds the first substrate to the second substrate, wherein the solidified liquid adhesive in the via is separated from the channel by the gasket; and (c) a channel port connecting the channel to the exterior of the flow cell, wherein the channel port is permeable to the aqueous liquid.

Abstract: The present invention provides assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual.

Abstract: A method for identifying a nucleotide in a primed template nucleic acid, including the steps of (a) providing a vessel having a primed template nucleic acid, polymerase and a nucleotide cognate of a first base type; (b) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the first base type bound at a base position of the primed template nucleic acid; (c) delivering a nucleotide cognate of a second base type to the vessel, whereby the vessel retains the primed template nucleic acid and the polymerase from step (b); (d) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the second base type bound at the base position of the primed template nucleic acid; and (e) identifying the type of nucleotide at the base position of the primed template nucleic acid.

Abstract: A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.

Abstract: Methods, compositions, kits and apparatuses that include a fluid, the fluid containing a ternary complex and Li+, wherein the ternary complex includes a primed template nucleic acid, a polymerase, and a nucleotide cognate for the next correct base for the primed template nucleic acid molecule. As an alternative or addition to Li+, the fluid can contain betaine or a metal ion that inhibits polymerase catalysis such as Ca2+. In addition to Li+, the fluid can contain polyethylenimine (PEI) with or without betaine.

Abstract: The present invention provides assay systems and methods for determining the percent fetal contribution of cell-free DNA in a maternal sample from a pregnant female with an egg donor pregnancy. Further provided, are assay systems and methods for determining a statistical likelihood of the presence or absence of a fetal aneuploidy in a maternal sample using a determined percent fetal cell-free DNA in the sample.

Abstract: A method for identifying a nucleotide in a primed template nucleic acid, including the steps of (a) providing a vessel having a primed template nucleic acid, polymerase and a nucleotide cognate of a first base type; (b) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the first base type bound at a base position of the primed template nucleic acid; (c) delivering a nucleotide cognate of a second base type to the vessel, whereby the vessel retains the primed template nucleic acid and the polymerase from step (b); (d) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the second base type bound at the base position of the primed template nucleic acid; and (e) identifying the type of nucleotide at the base position of the primed template nucleic acid.

Abstract: Nucleic acid compositions having nucleotide sequences that do not occur in nature are provided. Also provided are populations of different nucleic acids having universal adapters or universal primer binding sites. Methods of capturing, copying or amplifying nucleic acids of interest using universal adapters, universal primer binding sites and/or universal primers are also provided.

Abstract: The present invention provides methods for non-invasive determination of X and/or Y chromosomal abnormalities indicative of aneuploidy or sex mosaicisms in a maternal sample by detecting and determining the relative contribution of genetic sequences from the X chromosome and/or the Y chromosome in the maternal sample.

Abstract: A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.

Abstract: The present invention provides assays systems and methods for detection of chromosomal abnormalities and status of single loci associated with monogenic or polygenic traits in a sample containing nucleic acids from a maternal and a fetal source.

Abstract: The present invention provides detection systems and methods for detection of loci and genomic regions in a sample, including mixed samples, using hybridization to an array.

Abstract: The present invention provides assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual.

Abstract: The present invention provides detection systems and methods for detection of loci and genomic regions in a sample, including mixed samples, using hybridization to an array.