Systems and methods of analyzing nucleic acid polymers and related components

A method of determining the sequence of a nucleic acid polymer, comprising

• synthesizing the nucleic acid polymer and/or its complementary strand using labeled ribonucleotide and/or deoxyribonucleotide tripho sphates, and
• identifying labeled ribonucleotides and/or deoxyribonucleotides in the nucleic acid polymer and/or its complementary strand using a particle beam,
• wherein the labeled ribonucleotides and/or deoxyribonucleotides, when incorporated in the nucleic acid polymer and/or its complementary strand are identifiable using the particle beam, and
• wherein the nucleic acid polymer and/or the complementary strand of the nucleic acid polymer is DNA or RNA,
• wherein the nucleic acid polymer and/or its complementary strand is synthesized by a nucleic acid polymerase enzyme or using polymerase chain reaction (PCR).

A method of determining the sequence of a nucleic acid polymer, comprising

• synthesizing the nucleic acid polymer and/or its complementary strand using labeled ribonucleotide and/or deoxyribonucleotide triphosphates, and
• identifying labeled ribonucleotides and/or deoxyribonucleotides in the nucleic acid polymer and/or its complementary strand using a particle beam,
• wherein the labeled ribonucleotides and/or deoxyribonucleotides, when incorporated in the nucleic acid polymer and/or its complementary strand are identifiable using the particle beam, and
• wherein the nucleic acid polymer and/or the complementary strand of the nucleic acid polymer is DNA or RNA, wherein the labels are specific for each type of nucleotide, and
• wherein the labels comprise one or more atoms.

A method of determining the sequence of a nucleic acid polymer, comprising

• synthesizing the nucleic acid polymer and/or its complementary strand using labeled ribonucleotide and/or deoxyribonucleotide triphosphates, and
• identifying labeled ribonucleotides and/or deoxyribonucleotides in the nucleic acid polymer and/or its complementary strand using a particle beam,
• wherein the labeled ribonucleotides and/or deoxyribonucleotides, when incorporated in the nucleic acid polymer and/or its complementary strand are identifiable using the particle beam, and
• wherein the nucleic acid polymer and/or the complementary strand of the nucleic acid polymer is DNA or RNA, wherein the nucleic acid polymer and/or the complementary strand are affixed to a substrate, and
• wherein prior to the step of identification the ribonucleotides and/or deoxyribonucleotides of the nucleic acid polymer and/or its complementary strand are substantially removed from the substrate, leaving the labels of the labeled ribonucleotides and/or deoxyribonucleotides affixed to the substrate;
• or wherein the nucleic acid polymer and/or the complementary strand are affixed to a substrate at both ends of the nucleic acid polymer and/or the complementary strand;
• or wherein the nucleic acid polymer and/or the complementary strand are affixed to a substrate at a plurality of locations along the length of the nucleic acid polymer and/or the complementary strand.

A method of determining the sequence of a nucleic acid polymer, comprising

• synthesizing the nucleic acid polymer and/or its complementary strand using labeled ribonucleotide and/or deoxyribonucleotide triphosphates, and
• identifying labeled ribonucleotides and/or deoxyribonucleotides in the nucleic acid polymer and/or its complementary strand using a particle beam,
• wherein the labeled ribonucleotides and/or deoxyribonucleotides, when incorporated in the nucleic acid polymer and/or its complementary strand are identifiable using the particle beam, and
• wherein the nucleic acid polymer and/or the complementary strand of the nucleic acid polymer is DNA or RNA, wherein the nucleic acid polymer and/or the complementary strand are affixed to a substrate, wherein the nucleic acid polymer and/or the complementary strand are substantially straightened prior to identifying the labeled ribonucleotides and/or deoxyribonucleotides, wherein the nucleic acid polymer and/or the complementary strand are straightened by fluid flow, and
• wherein the fluid flow comprises molecular combing, and/or wherein the fluid comprises one or more liquids, gases, phases or a combination thereof and/or wherein the nucleic acid polymer and/or the complementary strand are attached to a substrate and straightened by hybridization in a fluid flow to oligonucleotides that are attached to the substrate.

A method of determining the sequence of a nucleic acid polymer, comprising

• synthesizing the nucleic acid polymer and/or its complementary strand using labeled ribonucleotide and/or deoxyribonucleotide triphosphates, and
• identifying labeled ribonucleotides and/or deoxyribonucleotides in the nucleic acid polymer and/or its complementary strand using a particle beam,
• wherein the labeled ribonucleotides and/or deoxyribonucleotides, when incorporated in the nucleic acid polymer and/or its complementary strand are identifiable using the particle beam, and
• wherein the nucleic acid polymer and/or the complementary strand of the nucleic acid polymer is DNA or RNA,
• further comprising attaching the complementary strand and/or the nucleic acid polymer to a substrate,
• wherein the attachment is by nucleic acid sequence-specific molecules;
• or wherein the substrate is derivatized to provide attachment points that are sequence non-specific;
• or wherein the complementary strand and optionally the nucleic acid polymer are attached to the substrate in a grid pattern;
• or wherein the step of identifying labeled ribonucleotide and/or deoxyribonucleotide phosphates comprises performing a plurality of scans of the nucleic acid polymer and/or the complementary strand using the particle beam.