Abstract: Methods and kits for sequencing a nucleic acid molecule are provided, which include utilizing four different compounds that are respectively derivatives of nucleotides A, (T/U), C and G, wherein the hydroxyl at the 3?-position of sugar of each of the four compounds is protected by a reversible protecting group. Each of the four compounds comprises a first linker, a second linker, and a terminal molecular label binding to or reactive to a receptor in a detectable group comprising a luminescence-activating molecule and the receptor, the luminescence-activating molecule capable of causing emission of fluorescence in the presence of a suitable substrate. The second linkers in the four compounds are different, and can be cleaved at different conditions.

Abstract: This disclosure provides an improved filtering techniques that can provide higher sequencing accuracy for processing high-throughput sequencing data. The filtering structure uses a hierarchical network structure comprising one or more network blocks for obtaining high quality sequences. Each network block comprises a base network module (or simply a base network) and a sequence filter. The base network generates one or more sequencing quality indicators. The sequencing quality indicators can represent qualities of accuracy of the basecalling of individual bases in a sequence, the quality of one or more sequences individually, or the quality of a group of sequences as a whole. The sequence filter generates the filtered results based on the various filtering strategies based on the one or more sequencing quality indicators.

Abstract: Methods and systems for determining a plurality of sequences of nucleic acid (e.g., DNA) molecules in a sequencing-by-synthesis process are provided. In one embodiment, the method comprises obtaining images of fluorescent signals obtained in a plurality of synthesis cycles. The images of fluorescent signals are associated with a plurality of different fluorescence channels. The method further comprises preprocessing the images of fluorescent signals to obtain processed images. Based on a set of the processed images, the method further comprises detecting center positions of clusters of the fluorescent signals using a trained convolutional neural network (CNN) and extracting, based on the center positions of the clusters of fluorescent signals, features from the set of the processed images to generate feature embedding vectors. The method further comprises determining, in parallel, the plurality of sequences of DNA molecules using the extracted features based on a trained attention-based neural network.

Abstract: The present disclosure describes a throughput-scalable image sensing system for analyzing biological or chemical samples is provided. The system includes a plurality of image sensors configured to detect at least a portion of light emitted as a result of analyzing the biological or chemical samples. The plurality of image sensors is arranged on a plurality of wafer-level packaged semiconductor dies of a single semiconductor wafer. Each image sensor of the plurality of image sensors is disposed on a separate packaged semiconductor die of the plurality of packaged semiconductor dies. Neighboring packaged semiconductor dies are separated by a dicing street; and the plurality of packaged semiconductor dies and a plurality of dicing streets are arranged such that the plurality of packaged semiconductor dies can be diced from the single semiconductor wafer as a group.

Abstract: A biosensor for detecting light signals emitted by a biological material is provided. The biosensor includes a light signal detector which comprises an array of light sensor pixels. The biosensor further includes a light signal filter layer disposed on a surface of the light sensor pixel array, a metal nanometer light focusing unit array layer, a grating array layer which comprises micro-gratings, and a biological material sample bearing area which comprises a plurality of sample gathering units. Each sample gathering unit aligns with one micro-grating and one metal nanometer light focusing unit in the vertical direction, and at least one of the light sensor pixels.

Abstract: A method for fabricating a throughput-scalable sensing system is disclosed. The method includes receiving a first semiconductor wafer and a second semiconductor wafer. The first semiconductor wafer includes a semiconductor substrate and a plurality of sensors disposed in the semiconductor substrate. Each sensor of the plurality of sensors is disposed in a separate semiconductor die of the first semiconductor wafer. The method further includes bonding the first semiconductor wafer to the second semiconductor wafer and preparing the bonded first semiconductor wafer and the second semiconductor wafer for conductive path redistribution. The method further includes forming one or more redistribution paths and dicing an array of semiconductor dies as a group from the plurality of semiconductor dies. The array of semiconductor dies includes a group of sensors associated with the throughput-scalable sensing system.

Abstract: The present disclosure describes a throughput-scalable photon sensing system. The system includes a plurality of semiconductor dies sharing a common semiconductor substrate and a plurality of photon detection sensors configured to perform a single molecule analysis of biological or chemical samples. Two immediately neighboring photon detection sensors are arranged on respective two semiconductor dies separated by a dicing street. Each photon detection sensor is arranged on a separate semiconductor die. The system further includes a first optical waveguide, a plurality of second optical waveguides disposed above the first optical waveguide, one or more wells disposed in the plurality of second optical waveguides, and one or more light guiding channels.

Abstract: The present disclosure describes a throughput-scalable sensing system. The system includes a plurality of semiconductor dies sharing a common semiconductor substrate and a plurality of transmembrane pore based sensors configured to detect a change of current flow as a result of analyzing biological or chemical samples. Two immediately neighboring transmembrane pore based sensors are arranged on respective two semiconductor dies separated by a dicing street. Each transmembrane pore based sensor is arranged on a separate semiconductor die of the plurality of semiconductor dies. At least one transmembrane pore based sensor includes one or more detection electrodes disposed above the common semiconductor substrate and a lipid bilayer disposed above the one or more detection electrodes.

Abstract: A method for fabricating a throughput-scalable sensing system is disclosed. The method includes receiving a first semiconductor wafer and a second semiconductor wafer. The first semiconductor wafer includes a semiconductor substrate and a plurality of sensors disposed in the semiconductor substrate. Each sensor of the plurality of sensors is disposed in a separate semiconductor die of the first semiconductor wafer. The method further includes bonding the first semiconductor wafer to the second semiconductor wafer and preparing the bonded first semiconductor wafer and the second semiconductor wafer for conductive path redistribution. The method further includes forming one or more redistribution paths and dicing an array of semiconductor dies as a group from the plurality of semiconductor dies. The array of semiconductor dies includes a group of sensors associated with the throughput-scalable sensing system.

Abstract: A waveguide filter sensing unit is provided. The waveguide sensing unit includes an input waveguide for receiving an optical signal and an interference waveguide region for filtering the optical signal to remove noise therein. The waveguide sensing unit further includes a cladding layer wrapping around the input waveguide and the interference waveguide region; and an optical signal detector converting the filtered optical signal into an electrical signal. The width of the input waveguide is smaller than that of the interference waveguide region, and the refractive index of the cladding layer is smaller than that of the input waveguide and the interference waveguide region.

Abstract: The present disclosure describes a throughput-scalable photon sensing system. The system includes a plurality of semiconductor dies sharing a common semiconductor substrate and comprising one or more through-silicon vias. The system further includes a plurality of photon detection sensors configured to perform a single molecule or cluster sequencing analysis of biological or chemical samples. The system further includes a plurality of dicing streets separating the plurality of semiconductor dies from one another. Two immediately neighboring photon detection sensors of the plurality of photon detection sensors are arranged on respective two semiconductor dies separated by a dicing street of the plurality of dicing streets. A photon detection sensor comprises a plurality of sub-diffraction limit (SDL) photosensitive elements. Each SDL photosensitive element is sensitive to a single photoelectron.

Abstract: The present disclosure describes a throughput-scalable image sensing system for analyzing biological or chemical samples is provided. The system includes a plurality of image sensors configured to detect at least a portion of light emitted as a result of analyzing the biological or chemical samples. The plurality of image sensors is arranged on a plurality of wafer-level packaged semiconductor dies of a single semiconductor wafer. Each image sensor of the plurality of image sensors is disposed on a separate packaged semiconductor die of the plurality of packaged semiconductor dies. Neighboring packaged semiconductor dies are separated by a dicing street; and the plurality of packaged semiconductor dies and a plurality of dicing streets are arranged such that the plurality of packaged semiconductor dies can be diced from the single semiconductor wafer as a group.

Abstract: Combination products comprising an antisense oligonucleotide against the gene encoding a mammalian ribonucleotide reductase R2 protein and one or more immunotherapeutic agents, such as cytokines, non-cytokine adjuvants, monoclonal antibodies and cancer vaccines. The combinations can further comprise one or more chemotherapeutic agents. Methods of treating cancer in a mammal using the combinations are also provided.

Abstract: The invention relates to oligonucleotides from the untranslated regions of housekeeping genes, and methods and compositions for modulating cell growth using same. Specifically it relates to the use of the untranslated regions (UTR) from housekeeping genes specifically the R1 and R2 components of ribonucleotide reductase UTR, for inhibiting tumor cell growth.

Abstract: This invention relates to oligonucleotides complementary to the neuropilin genes which modulate tumor cell growth and angiogenesis in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells and angiogenesis in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.

Abstract: This invention relates to antisense oligonucleotides which modulate the expression of the ribonucleotide reductase or the secA genes in microorganisms. This invention is also related to methods of using such oligonucleotides in inhibiting the growth of microorganisms. These antisense oligonucleotides are particularly useful in treating pathological conditions in mammals which are mediated by the growth of microorganisms.

Abstract: Compounds and methods for modulating cell proliferation, preferably inhibiting the proliferation of tumor cells are described. Compounds that may be used to modulate cell proliferation include antisense oligonucleotides complementary to regions of the mammalian ribonucleotide reductase genes.

Abstract: This invention relates to oligonucleotides complementary to the thioredoxin and thioredoxin reductase genes which modulate tumor cell growth in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.

Abstract: The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.

Abstract: This invention relates to oligonucleotides complementary to the IGF-II genes which modulate tumor cell growth in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.