公开(公告)号：US20250146068A1

公开(公告)日：2025-05-08

申请号：US18919127

申请日：2024-10-17

Applicant: Element Biosciences, Inc.

Inventor： Tsung-Li LIU ,  Sinan ARSLAN ,  Michael PREVITE ,  Tuval BEN-YEHEZKEL ,  Connor THOMPSON ,  Matthew KELLINGER ,  Hui Zhen MAH ,  Molly HE ,  Andrew PRICE

IPC: C12Q1/6874 ,  C12N15/10 ,  C12Q1/6804 ,  C12Q1/6841 ,  C12Q1/6844 ,  G01N33/58

Abstract: The present disclosure provides methods for conducting in situ multiplex and multi-omics detection and identification using coded padlocks probes. The methods comprise simultaneous use of RNA-specific padlock probes and polypeptide-specific padlock probes to detect both RNA and polypeptides in a cellular sample. Both types of probes include a barcode that unique identifies the RNA or polypeptide that that padlock probe detects. Both types of probes also include a batch-specific sequencing primer binding site to enable sequencing a desired subset of concatemer template molecules. Use of the batch-specific sequencing primers reduces overcrowding signals and images, to produces optical images that are intense and resolvable. By conducting multiple rounds of sequencing on the same cellular sample using different batch-specific sequencing primers enables multiplex and multi-omics sequencing to reveal numerous target RNAs and their encoded polypeptides.

公开(公告)号：US12241891B2

公开(公告)日：2025-03-04

申请号：US17675154

申请日：2022-02-18

Applicant: Element Biosciences, Inc.

Inventor： Michael Previte ,  Molly He ,  Junhua Zhao ,  Hui Zhen Mah ,  Chunhong Zhou ,  Sinan Arslan ,  Matthew Kellinger ,  Lorenzo Berti ,  Steve Xiangling Chen

IPC: G01N33/53 ,  C12Q1/68 ,  C12Q1/6874 ,  G01N33/58

Abstract: Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.

公开(公告)号：US20250034628A1

公开(公告)日：2025-01-30

申请号：US18426101

申请日：2024-01-29

Applicant: Element Biosciences, Inc.

Inventor： Sinan ARSLAN ,  Molly HE ,  Michael PREVITE

IPC: C12Q1/6834 ,  B01J19/00 ,  C12Q1/6806 ,  C12Q1/6832

Abstract: Nucleic acid hybridization buffer formulations and uses thereof are described that yield improvements in hybridization specificity, rate, and efficiency. The buffer formulation composition includes a target nucleic acid; at least one organic solvent having a dielectric constant in the range of no greater than 115; and a pH buffer system, wherein the target nucleic acid is attached to the surface via hybridization to a surface bound nucleic acid tethered to the surface, and wherein the hybridization of the target nucleic acid and surface bound nucleic acid has a high stringency and annealing rate.

公开(公告)号：US12163163B2

公开(公告)日：2024-12-10

申请号：US18160952

申请日：2023-01-27

Applicant: Element Biosciences, Inc.

Inventor： Jendrik Boothby-Hentschel ,  Tyler Lopez ,  Michael Klein ,  Virginia Saade ,  Matthew Kellinger ,  Mark Ambroso

IPC: C12N9/12 ,  C12Q1/6869

Abstract: Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.

公开(公告)号：US12134766B2

公开(公告)日：2024-11-05

申请号：US18153268

申请日：2023-01-11

Applicant: Element Biosciences, Inc.

Inventor： Matthew Kellinger ,  Sinan Arslan ,  Michael Previte ,  Junhua Zhao

IPC: C12N15/10 ,  C12N9/12 ,  C12Q1/6869

Abstract: Provided herein are methods for generating circular nucleic acid molecules and circular nucleic acid libraries. The methods can be used to generate clonal populations of target nucleic acid molecules for downstream applications such as sequencing.

公开(公告)号：US20240201088A1

公开(公告)日：2024-06-20

申请号：US18417995

申请日：2024-01-19

Applicant: Element Biosciences, Inc.

Inventor： Arash GHORBANI ,  Russell HUDYMA ,  John BAILEY ,  Michael PREVITE

IPC: G01N21/64 ,  C12Q1/6869

CPC classification number: G01N21/6428 ,  C12Q1/6869 ,  G01N21/6458 ,  G01N2021/6439

Abstract: Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.

公开(公告)号：US20240191278A1

公开(公告)日：2024-06-13

申请号：US18510487

申请日：2023-11-15

Applicant: Element Biosciences, Inc.

Inventor： Sinan ARSLAN ,  Junhua ZHAO ,  Molly HE ,  Samantha SNOW ,  William LIGHT ,  Matthew KELLINGER ,  Michael PREVITE ,  Michael KIM ,  Hua YU ,  Yu-Hsien HWANG-FU ,  Marco TJIOE ,  Andrew BODDICKER ,  Mark AMBROSO ,  Tyler LOPEZ ,  Michael KLEIN ,  Virginia SAADE

IPC: C12Q1/6806 ,  C12Q1/6834 ,  C12Q1/6853 ,  C12Q1/6874 ,  G01N21/64

CPC classification number: C12Q1/6806 ,  C12Q1/6834 ,  C12Q1/6853 ,  C12Q1/6874 ,  G01N21/6428 ,  G01N21/6458 ,  C12Q2600/158

Abstract: The present disclosure provides compositions and methods that employ the compositions for conducting pairwise sequencing and for generating concatemer template molecules for pairwise sequencing. The concatemers can be generated using a rolling circle amplification reaction which is conducted either on-support, or conducted in-solution and then distributed onto a support. The rolling circle amplification reaction generates concatemers containing tandem copies of a sequence of interest and at least one universal adaptor sequence. An increase in the number of tandem copies in a given concatemer increases the number of sites along the concatemer for hybridizing to multiple sequencing primers which serve as multiple initiation sites for polymerase-catalyzed sequencing reactions. When the sequencing reaction employs detectably labeled nucleotides and/or detectably labeled multivalent molecules (e.g., having nucleotide units), the signals emitted by the nucleotides or nucleotide units that participate in the parallel sequencing reactions along the concatemer yields an increased signal intensity for each concatemer.

公开(公告)号：US20240011022A1

公开(公告)日：2024-01-11

申请号：US18347440

申请日：2023-07-05

Applicant: Element Biosciences, Inc.

Inventor： Junhua ZHAO ,  Xiaodong QI ,  Shawn LEVY

IPC: C12N15/10

CPC classification number: C12N15/1065

Abstract: The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors, e.g., PCR-free workflows. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence and/or an index sequence.

公开(公告)号：US20230326065A1

公开(公告)日：2023-10-12

申请号：US18078820

申请日：2022-12-09

Applicant: Element Biosciences, Inc.

Inventor： Connor THOMPSON ,  Tsung-li LIU ,  Semyon KRUGLYAK ,  Minghao GUO

IPC: G06T7/66 ,  G06T7/30 ,  G06V10/75 ,  G06V20/69 ,  G06F18/232 ,  G06V10/762

CPC classification number: G06T7/66 ,  G06T7/30 ,  G06V10/751 ,  G06V20/693 ,  G06V20/695 ,  G06F18/232 ,  G06V10/763 ,  G06V20/69 ,  G06V2201/04

Abstract: Image data analysis, and particularly identifying cluster or polony locations for performing base-calling in a digital image of a flow cell during DNA sequencing is described. A method may include generating a first plurality of flow cell images of a cellular sample immobilized on a support by conducting one or more cycles of sequencing reactions. The cellular sample may include a plurality of concatemer molecules therewithin. For the first plurality of flow cell image, pixel intensities, and a respective color purity of each of the pixel intensities may be determined. A base calling template may include base calling locations based on the pixel intensities and the respective color purity of the pixel intensities. The base calling template may be for registering a second plurality of flow cell images of the support in one or more subsequent cycles of the one or more cycles.

公开(公告)号：US11781185B2

公开(公告)日：2023-10-10

申请号：US17947984

申请日：2022-09-19

Applicant: Element Biosciences, Inc.

Inventor： Sinan Arslan ,  Molly He ,  Michael Previte ,  Ramreddy Tippana ,  Hua Yu ,  William Light ,  Junhua Zhao

IPC: C12Q1/68 ,  C12Q1/6874 ,  C12Q1/6806

CPC classification number: C12Q1/6874 ,  C12Q1/6806

Abstract: Provided herein are fluorescently-labeled nucleotide conjugates for nucleic acid analysis. Also provided are reagents used for forming binding complexes between a fluorescently-labeled nucleotide conjugate and a target nucleic acid sequence in the presence of one or more reagents disclosed herein. Binding complexes can be detected in the presence of the one or more reagents. For example, the one or more reagents may contain a photobleaching reducing agent configured to reduce photobleaching resulting from use of the fluorescently-labeled nucleotide conjugate to form the binding complex in a nucleic acid analysis. Such nucleic acid analysis may be used to identify sites of nucleobase binding or incorporation between the target nucleic acid sequence and one or more nucleotide moieties of the fluorescently-labeled nucleotide conjugate in a nucleic acid sequence reaction.