The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

Aniosotropic Ratchet Conveyor (“ARC”)-based biomolecule processing devices and related methods are described. The ARC-based biomolecule processing devices include (i) a substrate having an ARC track defined on or within the substrate and including a biomolecule receiving area, which is designed to receive biomolecule, and a reconstituting area, which is designed to contain dry reagents and is designed to receive a transport solution such that at the reconstituting area, dry reagents are reconstituted with transport solution; and (ii) a microheater area disposed at or near the biomolecule receiving area, fitted with a microheater, which is designed to heat biomolecule that is received through the biomolecule receiving area and designed to process heated biomolecule and dry reagents reconstituted with transport solution. The ARC track includes an arrangement of a plurality of hydrophilic rungs disposed on a hydrophobic region such that between consecutive hydrophobic rungs, a portion of the hydrophobic region is exposed.

Aniosotropic Ratchet Conveyor (“ARC”)-based biomolecule processing devices and related methods are described. The ARC-based biomolecule processing devices include (i) a substrate having an ARC track defined on or within the substrate and including a biomolecule receiving area, which is designed to receive biomolecule, and a reconstituting area, which is designed to contain dry reagents and is designed to receive a transport solution such that at the reconstituting area, dry reagents are reconstituted with transport solution; and (ii) a microheater area disposed at or near the biomolecule receiving area, fitted with a microheater, which is designed to heat biomolecule that is received through the biomolecule receiving area and designed to process heated biomolecule and dry reagents reconstituted with transport solution. The ARC track includes an arrangement of a plurality of hydrophilic rungs disposed on a hydrophobic region such that between consecutive hydrophobic rungs, a portion of the hydrophobic region is exposed.

The present invention relates to a kit and a method of linear amplification of a least one nucleic acid target in a sample, said method comprising: (a) contacting each target in the sample with a nucleic acid polymerase and a primer comprising a component preventing copying of the primer by the nucleic acid polymerase; and at least one nuclease blocking nucleotide; (b) generating a primer extension product; (c) preventing priming by the 3′-end of the primer extension product, and (d) repeating steps b) and c) at least once.

The present invention relates to a kit and a method of linear amplification of a least one nucleic acid target in a sample, said method comprising: (a) contacting each target in the sample with a nucleic acid polymerase and a primer comprising a component preventing copying of the primer by the nucleic acid polymerase; and at least one nuclease blocking nucleotide; (b) generating a primer extension product; (c) preventing priming by the 3′-end of the primer extension product, and (d) repeating steps b) and c) at least once.

Provided is a PCR primer pair, comprising: a first primer and a second primer, wherein the first primer comprises a first specific sequence and a first random sequence; the first specific sequence is located on 3′ end of the first primer, and the first random sequence is located on 5′ end of the first primer; the second primer comprises a second specific sequence and a second random sequence, the second specific sequence is located on 3′ end of the second primer, and the second random sequence is located on 5′ end of the second primer; moreover, the first specific sequence and the second specific sequence are an upstream primer and a downstream primer directed to a target sequence respectively, and the first random sequence and the second random sequence are inverse complementary.

Provided is a PCR primer pair, comprising: a first primer and a second primer, wherein the first primer comprises a first specific sequence and a first random sequence; the first specific sequence is located on 3′ end of the first primer, and the first random sequence is located on 5′ end of the first primer; the second primer comprises a second specific sequence and a second random sequence, the second specific sequence is located on 3′ end of the second primer, and the second random sequence is located on 5′ end of the second primer; moreover, the first specific sequence and the second specific sequence are an upstream primer and a downstream primer directed to a target sequence respectively, and the first random sequence and the second random sequence are inverse complementary.

The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.