A processive enzyme molecular sensor for use in a DNA data storage system is disclosed that can extract digital information suitably encoded into a synthetic DNA molecule. In various aspects, such sensors are provided in a high-density chip-based format that can provide the high throughput, low-cost and fast data extraction capability required for large scale DNA data storage systems. The sensor for reading the digital data stored in DNA molecules processes individual encoded DNA molecules directly, eliminating the need for complicated sample preparation such as making copies of DNA or clonal populations of such molecules.

Disclosed herein are highly accurate approaches for single molecule electronic nanopore-based SBS.

Disclosed herein are highly accurate approaches for single molecule electronic nanopore-based SBS.

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.

A method for determining the type of a nucleotide on a nucleic acid sequence to be analyzed, and a nucleic acid sequencing method. In the method, at least one modified nucleotide for nucleic acid synthesis is separated from a nucleic acid sequence to be analyzed and other components on both sides of a membrane; when the modified nucleotide is transferred to the other side of the membrane under the action of an electric field by means of a nanopore embedded on the membrane, a synthesis reaction is conducted; moreover, the type of a base of the nucleotide is determined according to the change of the electrical properties of the nanopore in the process of the modified nucleotide is transferred by the nanopore, so as to implement sequencing.

A method for determining the type of a nucleotide on a nucleic acid sequence to be analyzed, and a nucleic acid sequencing method. In the method, at least one modified nucleotide for nucleic acid synthesis is separated from a nucleic acid sequence to be analyzed and other components on both sides of a membrane; when the modified nucleotide is transferred to the other side of the membrane under the action of an electric field by means of a nanopore embedded on the membrane, a synthesis reaction is conducted; moreover, the type of a base of the nucleotide is determined according to the change of the electrical properties of the nanopore in the process of the modified nucleotide is transferred by the nanopore, so as to implement sequencing.

Disclosed herein, inter alia, are phase protective reagent flow orders and methods useful for improving sequencing efficiency.

Disclosed herein, inter alia, are phase protective reagent flow orders and methods useful for improving sequencing efficiency.

Provided herein, among other things, is a conjugate comprising a polymerase and a nucleoside triphosphate, where the polymerase and the nucleoside triphosphate are covalently linked via a linker that comprises a cleavable linkage. A set of such conjugates, where the conjugates correspond to G, A, T (or U) and C is also provided. Methods for synthesizing a nucleic acid of a defined sequence are also provided. The conjugates can also be used for sequencing applications.