Abstract: A method for manufacturing an optical sensor is provided. The operations of the method for manufacturing the optical sensor includes providing a semiconductive layer having an electrical circuit area and an optical sensing area; forming a first electrical contact directly over the electrical circuit area; forming a first light guiding part directly over the optical sensing area simultaneously with forming the first electrical contact; forming a first metal layer directly over the first electrical contact; forming a second light guiding part directly over the first light guiding part simultaneously with forming a second electrical contact directly over the first electrical contact; forming a thick metal layer over the electrical circuit area and an optical sensing area; and forming an aperture in the thick metal layer, wherein the aperture aligning with the optical sensing area.

Abstract: An oriented loading system is provided. The oriented loading system includes a substrate, a plurality of wells formed in the substrate, each well having a bottom and sidewalls, a plurality of particles loaded in the wells, wherein the particle comprises a core structure and an inner layer comprising magnetic material partially covering the core structure such that a part of the core structure uncovered by the inner layer is exposed, and a metal layer comprising magnetic material deposited partially in the sidewalls of the wells, wherein the inner layer is attracted by the metal layer such that the exposed core structure is oriented towards the bottom of the well or the inner layer is oriented towards the bottom of the well.

Abstract: A composition comprising a recombinant DNA polymerase and 3?-esterified nucleotide analogues is provided. The recombinant DNA polymerase includes an amino acid sequence that is at least 90% homology with 9° N DNA polymerase (SEQ ID NO: 1), and the recombinant DNA polymerase includes at least two mutations at the positions corresponding to amino acid residues 141 and 143 of the 9° N DNA polymerase. A recombinant DNA polymerase is further provided. The recombinant DNA polymerase includes an amino acid sequence that is at least 90% homology with 9° N-III DNA polymerase (SEQ ID NO: 3), and the recombinant DNA polymerase includes one or two mutations at the positions corresponding to amino acid residue 480 and 486 of the 9° N-III DNA polymerase. A method of performing a polymerization reaction is also provided.

Abstract: A method of constructing a circular template includes preparing a partially double stranded linear DNA molecule, and incubating the partially double stranded linear DNA molecule with a ligase capable of intra-molecular ligation of single stranded DNA molecules to generate a partially double stranded circular DNA molecule. A method of detecting DNA molecules includes the following steps. Target DNA molecules are isolated with probes to form partially double stranded linear DNA molecules. The partially double stranded linear DNA molecules are incubated with ligases capable of intra-molecular ligation of single stranded DNA molecules to generate partially double stranded circular DNA molecules. A circular sequencing of the partially double stranded circular DNA molecules is conducted by using the probes as primers.

Abstract: Some embodiments of the present disclosure provide an optical sensor. The optical sensor includes a semiconductive substrate; a light sensing region on the semiconductive substrate; a waveguide region configured to guide light from a wave insert portion through a waveguide portion and to a sample holding portion; and an interconnect region below the waveguide region, and the interconnect region being disposed above the light sensing region. The waveguide portion includes a first dielectric layer comprising a first refractive index and at least one second dielectric layer comprising a second refractive index, wherein the second refractive index is smaller than the first refractive index.

Abstract: Some embodiments of the present disclosure provide an optical sensor. The optical sensor includes a semiconductive block having a front side and a back side, a wave guide region, and a light sensing region. The wave guide region is positioned over the back side of the semiconductive block and having a core layer. The wave guide region is configured to guide an incident light. The light sensing region is positioned in the semiconductive block, having a multi-junction photodiode. The light sensing region is configured to sense emission lights from the wave guide region.

Abstract: A multi junction photodiode for molecular detection and discrimination and fabrication methods thereof. The multi junction photodiode includes a substrate having first conductive type dopants, an epitaxial layer having the first conductive type dopants, a deep well having second conductive type dopants, a first well having the first conductive type dopants, a second well having the second conductive type dopants, a third well having the first conductive type dopants, and a first doped region having the second conductive type dopants. The epitaxial layer is disposed on the substrate. The deep well is disposed in the epitaxial layer. The first well having three sides connected to the epitaxial layer is disposed in the deep well. The second well is disposed in the first well. The third well having three sides connected to the epitaxial layer is disposed in the second well. The first doped region is disposed in the third well.

Abstract: This invention is to describe nucleotide analogs used in a method for the determination of a nucleic acid sequence. The method involves an enzyme, an enzyme complex or plural number of enzymes with more than one enzymatic activity and a set of nucleotide analogs, to achieve high signal readout accuracy in nucleic acid sequencing by making each signal to have a long signaling time span which allows a higher signal clarity.

Abstract: An optical sensing module is configured to detect a characteristic of a sample. The optical sensing module includes a light source, a light guide plate, a first cladding layer, a light converging layer, a filter layer, and a plurality of sensors. The light source is configured to provide an exciting beam. Positions of the sensors correspond to positions of the holes. After the exciting beam enters the light guide plate, at least one portion of the exciting beam is transmitted to the sample through a portion of the surface of the light guide plate exposed by the holes, the sample is excited by the exciting beam to emit a signal beam, and the signal beam passes through the light converging layer and the filter layer in an order and travels to the sensors. Another optical sensing module is also provided.

Abstract: A sensing module including a sample loading layer, a sensing layer and an optical resonance layer locating between the sample loading layer and the sensing layer is provided. The sample loading layer includes at least a sample loading depression, and the sample loading depression exposes part of the optical resonance layer, and the sample loading depression is adapted to load sample. A surface of the optical resonance layer has optical resonance structures, and the optical resonance structures are located beside bottom of the sample loading depression or below the bottom of the sample loading depression. The sensing layer is configured to receive light and turn it into electrical signals. A sensing method is also provided.

Abstract: A method of constructing a circular template includes preparing a partially double stranded linear DNA molecule, and incubating the partially double stranded linear DNA molecule with a ligase capable of intra-molecular ligation of single stranded DNA molecules to generate a partially double stranded circular DNA molecule. A method of detecting DNA molecules includes the following steps. Target DNA molecules are isolated with probes to form partially double stranded linear DNA molecules. The partially double stranded linear DNA molecules are incubated with ligases capable of intra-molecular ligation of single stranded DNA molecules to generate partially double stranded circular DNA molecules. A circular sequencing of the partially double stranded circular DNA molecules is conducted by using the probes as primers.

Abstract: An optical sensing module is configured to detect a characteristic of a sample. The optical sensing module includes a light source, a light guide plate, a first cladding layer, a light converging layer, a filter layer, and a plurality of sensors. The light source is configured to provide an exciting beam. Positions of the sensors correspond to positions of the holes. After the exciting beam enters the light guide plate, at least one portion of the exciting beam is transmitted to the sample through a portion of the surface of the light guide plate exposed by the holes, the sample is excited by the exciting beam to emit a signal beam, and the signal beam passes through the light converging layer and the filter layer in an order and travels to the sensors. Another optical sensing module is also provided.

Abstract: Some embodiments of the present disclosure provide an optical sensor. The optical sensor includes a semiconductive substrate. A light sensing region is on the semiconductive substrate. A waveguide region is configured to guide light from a wave insert portion through a waveguide portion and to a sample holding portion. The waveguide portion includes a first dielectric layer including a first refractive index. A second dielectric layer includes a second refractive index. The second refractive index is smaller than the first refractive index. A first interconnect portion is positioned in the waveguide portion, configured to transmit electrical signal from the light sensing region to an external circuit. The sample holding portion is over the light sensing region.

Abstract: An optical sensing module is configured to detect a characteristic of a sample. The optical sensing module includes a light source, a light guide plate, a first cladding layer, a light converging layer, a filter layer, and a plurality of sensors. The light source is configured to provide an exciting beam. Positions of the sensors correspond to positions of the holes. After the exciting beam enters the light guide plate, at least one portion of the exciting beam is transmitted to the sample through a portion of the surface of the light guide plate exposed by the holes, the sample is excited by the exciting beam to emit a signal beam, and the signal beam passes through the light converging layer and the filter layer in an order and travels to the sensors. Another optical sensing module is also provided.

Abstract: This invention is to describe nucleotide analogs used in a method for the determination of a nucleic acid sequence. The method involves an enzyme, an enzyme complex or plural number of enzymes with more than one enzymatic activity and a set of nucleotide analogs, to achieve high signal readout accuracy in nucleic acid sequencing by making each signal to have a long signaling time span which allows a higher signal clarity.

Abstract: A sensing module including a sample loading layer, a sensing layer and an optical resonance layer locating between the sample loading layer and the sensing layer is provided. The sample loading layer includes at least a sample loading depression, and the sample loading depression exposes part of the optical resonance layer, and the sample loading depression is adapted to load sample. A surface of the optical resonance layer has optical resonance structures, and the optical resonance structures are located beside bottom of the sample loading depression or below the bottom of the sample loading depression. The sensing layer is configured to receive light and turn it into electrical signals. A sensing method is also provided.

Abstract: This invention is to describe a method for the determination of a nucleic acid sequence, in which it involves an enzyme, an enzyme complex or plural number of enzymes with more than one enzymatic activity and a set of nucleotide analogs, to achieve high signal readout accuracy in nucleic acid sequencing by making each signal to have a long signaling time span which allows a higher signal clarity.

Abstract: An oriented loading system is provided. The oriented loading system includes a substrate, a plurality of wells formed in the substrate, each well having a bottom and sidewalls, a plurality of particles loaded in the wells, wherein the particle comprises a core structure and an inner layer comprising magnetic material partially covering the core structure such that a part of the core structure uncovered by the inner layer is exposed, and a metal layer comprising magnetic material deposited partially in the sidewalls of the wells, wherein the inner layer is attracted by the metal layer such that the exposed core structure is oriented towards the bottom of the well or the inner layer is oriented towards the bottom of the well.

Abstract: A multi-junction photodiode for molecular detection and discrimination and fabrication methods thereof. The multi junction photodiode includes a substrate having first conductive type dopants, an epitaxial layer having the first conductive type dopants, a deep well having second conductive type dopants, a first well having the first conductive type dopants, a second well having the second conductive type dopants, a third well having the first conductive type dopants, and a first doped region having the second conductive type dopants. The epitaxial layer is disposed on the substrate. The deep well is disposed in the epitaxial layer. The first well having three sides connected to the epitaxial layer is disposed in the deep well. The second well is disposed in the first well. The third well having three sides connected to the epitaxial layer is disposed in the second well. The first doped region is disposed in the third well.

Abstract: The present disclosure provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles typically comprise steps of extension, ligation, and cleavage. In certain embodiments, the methods make use of extension probes containing phosphorothiolate linkages and agents capable of cleaving such linkages. Methods of determining information about a sequence using at least two distinguishably labeled probe families are provided, as are methods of performing multiple sequencing reactions on a single template. Automated sequencing systems, flow cells, image processing methods, and computer-readable media that store computer-executable instructions and/or sequence information that can be used in accordance with such methods are also provided. In certain embodiments, blocking oligonucleotides are provided to facilitate sequencing using disclosed methods.