Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

The present disclosure provides, inter alia, specially designed DNA adaptors and methods of preparing the same. Methods and kits for carrying out and detecting marker-free precision genome editing and genetic variation using such adaptors are also provided.

The present disclosure provides, inter alia, specially designed DNA adaptors and methods of preparing the same. Methods and kits for carrying out and detecting marker-free precision genome editing and genetic variation using such adaptors are also provided.

Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

A system includes a synthesizer unit having a fluid input to receive fluids and a communication input to receive commands to synthesize data-encoded DNA sequences and cleave the DNA. A first flexible chemistry reaction chamber module may be fluidically coupled to the synthesizer unit to receive the data-encoded DNA sequences and amplify the sequences. A deposition unit may be fluidically coupled to the first flexible chemistry reaction chamber module to receive the amplified DNA sequences and encapsulate the amplified DNA sequences into one or more wells in a storage plate for storage and retrieval to and from a plate storage unit. Retrieved DNA may be processed and read by further units.

A system for DNA gene assembly that utilizes a DNA symbol library and a DNA linker library. The symbol library has a number of DNA symbols each having a first overhanging end and a second overhanging end different than and non-complimentary to the first end, the first and second ends being the same nucleotides for each DNA symbol. The linker library has pairs of DNA linkers, a first linker of a pair having a first end and a second end and a second linker of the pair having a first end and a second end, the first end of the first linker being the same nucleotides for each first linker and the second end of the second linker being the same nucleotides for each second linker, wherein the second end of the first linker and the first end of the second linker have complementary nucleotides. The first linker joins to the first end of a DNA symbol and the second linker joins to the second end of another DNA symbol.

A system for DNA gene assembly that utilizes a DNA symbol library and a DNA linker library. The symbol library has a number of DNA symbols each having a first overhanging end and a second overhanging end different than and non-complimentary to the first end, the first and second ends being the same nucleotides for each DNA symbol. The linker library has pairs of DNA linkers, a first linker of a pair having a first end and a second end and a second linker of the pair having a first end and a second end, the first end of the first linker being the same nucleotides for each first linker and the second end of the second linker being the same nucleotides for each second linker, wherein the second end of the first linker and the first end of the second linker have complementary nucleotides. The first linker joins to the first end of a DNA symbol and the second linker joins to the second end of another DNA symbol.

Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

The present disclosure provides an apparatus for synthesizing a biopolymer, a method for preparing an apparatus for synthesizing a biopolymer, and a method of synthesizing a biopolymer. The apparatus comprises (a) a substrate comprising a top surface and a plurality of wells, wherein each of the plurality of wells comprises a first electrode disposed on the bottom of the well and a linker attached to the sides of the well; and (b) a fluidic chamber system disposed on the top surface of the substrate.

A method of synthesis of a nucleotide chain, the nucleotide chain including an ordered plurality of nucleotides, the method including: identifying a first nucleotide of the ordered plurality of nucleotides; controlling a polymerase enzyme to assemble the first nucleotide onto the nucleotide chain by electrically modulating an electrode; identifying a subsequent nucleotide in the ordered plurality of nucleotides as a current nucleotide; and controlling the polymerase enzyme to assemble the current nucleotide onto an end of the nucleotide chain by electrically modulating the electrode.