公开(公告)号：US11788124B2

公开(公告)日：2023-10-17

申请号：US17046228

申请日：2019-04-08

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Yuling Luo ,  Xiao-Jun Ma ,  Steve Chen ,  Nan Su ,  Emerald Doolittle ,  Bingqing Zhang ,  Xiaoming Wang ,  Xingyong Wu ,  Xiao Yan Pimentel ,  Helen Jarnagin

IPC: C07H21/02 ,  C12Q1/6841 ,  C12Q1/682 ,  C12Q1/6876

CPC classification number: C12Q1/6841 ,  C12Q1/682 ,  C12Q1/6876 ,  C12Q2543/10

Abstract: The present invention relates to detection of nucleic acids and provides a composition comprising a Signal Generating Complex, wherein the composition comprises: (A) a pair of target probes (TPs), wherein a first TP of the pair of TPs comprises a nucleic acid sequence comprising two segments; (B) a pair of base PPAs comprising the first and second base PPAs, wherein the first base PPA comprises a nucleic acid sequence comprising three segments; (C) a set of extension PPAs comprising the first and second extension PPAs, wherein the first extension PPA comprises a nucleic acid sequence comprising two segments; (D) a plurality of pre-amplifiers (PAs), wherein the PAs comprise a nucleic acid sequence comprising three segments; (E) a plurality of amplifiers (AMPs), wherein the AMPs comprise a nucleic acid sequence comprising two segments; and (F) a plurality of label probes (LPs), wherein the LPs comprise a nucleic acid sequence comprising two segments.

公开(公告)号：US20230295698A1

公开(公告)日：2023-09-21

申请号：US18042278

申请日：2021-08-19

Applicant: Advanced Cell Diagnostics, Inc.

Inventor： Xiao-Jun Ma ,  Wei Wei ,  Brenda Nguyen ,  Niyati Jhaveri ,  Alisa Baker ,  Robert Monroe ,  Bingqing Zhang

IPC: C12Q1/6841

CPC classification number: C12Q1/6841

Abstract: The present disclosure provides compositions and methods related to the detection of mRNA variants. In particular, the present disclosure provides compositions and methods for detecting alternatively spliced mRNA variants using RNA in situ hybridization technology, which can be used to evaluate a disease state (e.g., malignancy) in a subject.

公开(公告)号：US20230175048A1

公开(公告)日：2023-06-08

申请号：US17998113

申请日：2021-05-06

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Xiao-Jun Ma ,  Bingqing Zhang ,  Courtney Todorov ,  Lydia Hernandez

IPC: C12Q1/6841 ,  C12Q1/6806 ,  G01N33/58

CPC classification number: C12Q1/6841 ,  C12Q1/6806 ,  G01N33/582 ,  G01N2474/20

Abstract: A method of simultaneously detecting target nucleic acids and target proteins in a biological sample, comprising treating the biological sample with a crosslinking agent, that is after incubating it with a primary antibody that detects the target proteins and prior to detecting the target nucleic acids by in situ hybridization.

公开(公告)号：US20230151415A1

公开(公告)日：2023-05-18

申请号：US17995561

申请日：2021-04-05

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Miguel Angel Mata ,  Aparna Sahajan ,  Xiao-Jun Ma ,  Bingqing Zhang ,  Li Wang ,  Li-Chong Wang

IPC: C12Q1/6841

CPC classification number: C12Q1/6841 ,  C12Q1/6806

Abstract: A method of detecting target nucleic acids, including small non-coding RNAs (sncRNAs), microRNAs (miRNAs), small interfering RNAs (siRNAs), PIWI-interacting RNA (piRNA), or antisense oligonucleotides (ASO) molecules, in a cell, comprising a post-fixation step using an aldehyde-containing fixative after the initial fixation step prior to in situ hybridization.

公开(公告)号：US20230151413A1

公开(公告)日：2023-05-18

申请号：US18046770

申请日：2022-10-14

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Yuling Luo ,  Shiping Chen

IPC: C12Q1/6837 ,  C12Q1/682 ,  C12Q1/6841

CPC classification number: C12Q1/6837 ,  C12Q1/682 ,  C12Q1/6841

Abstract: Methods of detecting multiple nucleic acid targets in single cells through indirect capture of labels to nucleic acid are provided. Methods of assaying the relative levels of nucleic acid targets through normalization to levels of reference nucleic acids are also provided. Methods of detecting individual cells, particularly rare cells from large heterogeneous cell populations through detection of nucleic acids are described. Related compositions, systems, and kits are also provided.

公开(公告)号：US20220154262A1

公开(公告)日：2022-05-19

申请号：US17430463

申请日：2020-02-14

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Xiao-Jun MA ,  Bingqing ZHANG ,  Li-chong WANG ,  Han LU ,  Li WANG ,  Hailing ZONG

IPC: C12Q1/6841 ,  C12Q1/682 ,  C12Q1/6876 ,  C12Q1/6818

Abstract: The invention relates to methods of multiplex detection of a plurality of target nucleic acids by contacting a sample comprising a cell with target probe sets that specifically hybridize to target nucleic acids, with pre-amplifiers or pre-pre-amplifiers specific for each target probe set, with amplifiers specific for the pre-amplifiers, and with label probes specific for the amplifiers, resulting in specific labeling of multiple target nucleic acids. The invention also relates to samples, slides and kits relating to detection of multiple target nucleic acids.

公开(公告)号：US20170101672A1

公开(公告)日：2017-04-13

申请号：US15291054

申请日：2016-10-11

Applicant: Advanced Cell Diagnostics, Inc.

Inventor： Yuling Luo ,  Xingyong Wu ,  Liuliu Pan ,  Xiaoming Wang ,  Xiao-Jun Ma ,  Nan Su ,  Steve Chen

IPC: C12Q1/68

CPC classification number: C12Q1/6841 ,  C12Q1/682 ,  C12Q1/6827 ,  C12Q2565/102 ,  C12Q2525/313

Abstract: The invention relates to methods of in situ detection of a nucleic acid variation of a target nucleic acid in a sample, including single nucleotide variations, multi-nucleotide variations or splice sites. The method can comprise the steps of contacting the sample with a probe that detects the nucleic acid variation or splice site and a neighbor probe; contacting the sample with pre-amplifiers that bind to the nucleic acid variation probe or splice site probe and neighbor probe, respectively; contacting the sample with a collaboration amplifier that binds to the pre-amplifiers; and contacting the sample with a label probe system, wherein hybridization of the components forms a signal generating complex (SGC) comprising a target nucleic acid with the nucleic acid variation or splice site, the probes and amplifiers; and detecting in situ signal from the SGC on the sample. The invention also provides samples, tissue slides, and kits relating to detection of nucleic acid variations, including single nucleotide variations, multi-nucleotide variations or splice sites, of a target nucleic acid.

公开(公告)号：US20240425908A1

公开(公告)日：2024-12-26

申请号：US18830213

申请日：2024-09-10

Applicant: Advanced Cell Diagnostics, Inc.

Inventor： Yuling LUO ,  John James FLANAGAN ,  Nan SU ,  Huei-Yu Fay WANG

IPC: C12Q1/6841

Abstract: The invention relates to methods of detecting nucleic acids, including methods of detecting one or more target nucleic acid sequences in multiplex branched-chain DNA assays, are provided. Nucleic acids captured on a solid support or suspending cells are detected, for example, through cooperative hybridization events that result in specific association of a label with the nucleic acids. The invention further relates to methods to improve probe hybridization specificity and their application in genotyping. The invention also relates to in situ detection of mis-joined nucleic acid sequences. The invention relates to reducing false positive signals and improve signal-to-background ratio in hybridization-based nucleic acid detection assay. The invention further relates to method to improve specificity in hybridization based nucleic acid using co-location probes. Compositions, tissue slides, sample of suspended cells, kits, and systems related to the methods are also described.

公开(公告)号：US20230313171A1

公开(公告)日：2023-10-05

申请号：US18245660

申请日：2021-09-17

Applicant: ADVANCED CELL DIAGNOSTICS, INC.

Inventor： Farzaneh Tondnevis ,  Li-Chong Wang ,  Bingqing Zhang ,  Xiao-Jun Ma

IPC: C12N15/10 ,  C12Q1/6841

CPC classification number: C12N15/1003 ,  C12Q1/6841

Abstract: The present disclosure provides compositions and methods related to the removal of RNA from a sample, and the preparation of samples for detection of DNA. Such methods are particularly useful to prepare samples for a DNA in situ hybridization assay.

公开(公告)号：US11078528B2

公开(公告)日：2021-08-03

申请号：US15291054

申请日：2016-10-11

Applicant: Advanced Cell Diagnostics, Inc.

Inventor： Yuling Luo ,  Xingyong Wu ,  Liuliu Pan ,  Xiaoming Wang ,  Xiao-Jun Ma ,  Nan Su ,  Steve Chen

IPC: C12Q1/68 ,  C12Q1/6841 ,  C12Q1/682 ,  C12Q1/6827

Abstract: The invention relates to methods of in situ detection of a nucleic acid variation of a target nucleic acid in a sample, including single nucleotide variations, multi-nucleotide variations or splice sites. The method can comprise the steps of contacting the sample with a probe that detects the nucleic acid variation or splice site and a neighbor probe; contacting the sample with pre-amplifiers that bind to the nucleic acid variation probe or splice site probe and neighbor probe, respectively; contacting the sample with a collaboration amplifier that binds to the pre-amplifiers; and contacting the sample with a label probe system, wherein hybridization of the components forms a signal generating complex (SGC) comprising a target nucleic acid with the nucleic acid variation or splice site, the probes and amplifiers; and detecting in situ signal from the SGC on the sample. The invention also provides samples, tissue slides, and kits relating to detection of nucleic acid variations, including single nucleotide variations, multi-nucleotide variations or splice sites, of a target nucleic acid.