公开(公告)号：US20240408564A1

公开(公告)日：2024-12-12

申请号：US18813890

申请日：2024-08-23

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Bichlien Hoang NGUYEN ,  Karin STRAUSS ,  Hsing-Yeh PARKER

IPC: B01J19/00 ,  C07K1/04 ,  C25D5/16 ,  C25D5/48 ,  C25D17/10

Abstract: High surface area coatings are applied to solid substrates to increase the surface area available for solid-phase synthesis of polymers. The high surface area coatings use three-dimensional space to provide more area for functional groups to bind polymers than an untreated solid substrate. The polymers may be oligonucleotides, polypeptides, or another type of polymer. The solid substrate is a rigid supportive layer made from a material such as glass, a silicon material, a metal material, and plastic. The coating may be thin films, hydrogels, microparticles. The coating may be made from a metal oxide, a high-κ dielectric, a low-κ dielectric, an etched metal, a carbon material, or an organic polymer. The functional groups may be hydroxyl groups, amine groups, thiolate groups, alkenes, n-alkenes, alkalines, N-Hydroxysuccinimide (NHS)-activated esters, polyaniline, aminosilane groups, silanized oxides, oligothiophenes, and diazonium compounds. Techniques for applying coatings to solid substrates and attaching functional groups are also disclosed.

公开(公告)号：US20240084349A1

公开(公告)日：2024-03-14

申请号：US18306653

申请日：2023-04-25

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Bichlien NGUYEN ,  Jake SMITH ,  Karin STRAUSS

IPC: C12P19/34 ,  B01J19/00

CPC classification number: C12P19/34 ,  B01J19/0046 ,  B01J2219/00596 ,  B01J2219/00722

Abstract: De novo polynucleotide synthesis is performed with a substrate-bound polymerase. The polymerase is attached to a solid substrate such as a microelectrode array. The polymerase adds nucleotides to growing polynucleotides strands that are also attached to the solid substrate. Spatial control of polymerase activity is achieved by changing the rate of nucleotide polymerization at selected locations on the surface of the solid substrate. The rate of polymerization is changed by inhibiting or promoting activity of the polymerase. In some implementations, activation of electrodes in the microelectrode array changes the rate of nucleotide polymerization. Nucleotides are added to the growing polynucleotide strands at areas where the polymerase is active. By varying the locations where the substrate-bound polymerase is active and the species of nucleotide added, a population of polynucleotides with different, arbitrary sequences is synthesized on the surface of the solid substrate.

公开(公告)号：US20220347645A1

公开(公告)日：2022-11-03

申请号：US17863033

申请日：2022-07-12

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Bichlien H. NGUYEN ,  Douglas P. KELLEY ,  Karin STRAUSS ,  Robert CARLSON ,  Hsing-Yeh PARKER ,  John MULLIGAN ,  Luis H. CEZE ,  Yuan-Jyue CHEN ,  Douglas CARMEAN

IPC: B01J19/00

Abstract: A system includes a synthesizer unit having a fluid input to receive fluids and a communication input to receive commands to synthesize data-encoded DNA sequences and cleave the DNA. A first flexible chemistry reaction chamber module may be fluidically coupled to the synthesizer unit to receive the data-encoded DNA sequences and amplify the sequences. A deposition unit may be fluidically coupled to the first flexible chemistry reaction chamber module to receive the amplified DNA sequences and encapsulate the amplified DNA sequences into one or more wells in a storage plate for storage and retrieval to and from a plate storage unit. Retrieved DNA may be processed and read by further units.

公开(公告)号：US20210155923A1

公开(公告)日：2021-05-27

申请号：US16698860

申请日：2019-11-27

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Yuan-Jyue CHEN ,  Bichlien NGUYEN ,  Jake SMITH ,  Karin STRAUSS

IPC: C12N15/10 ,  B01L3/00 ,  C12Q1/6874

Abstract: Electrically controlled hybridization is used to selectively assemble oligonucleotides on the surface of a microelectrode array. Controlled activation of individual electrodes in the microelectrode array attracts oligonucleotides in solution to specific regions of the array where they hybridize to other oligonucleotides anchored on the array. The oligonucleotides that hybridize may provide locations for subsequent oligonucleotides to hybridize. The active electrodes and the oligonucleotides in solution may be varied during each round of synthesis. This allows for multiple oligonucleotides each with different and specific sequences to be created in parallel. This is accomplished without the use of phosphoramidite chemical synthesis or template-independent DNA polymerase enzymatic synthesis. Oligonucleotides created with these techniques may be used to encode digital data. Fully assembled oligonucleotides may be separated from the array and sequenced, stored, or otherwise processed.

公开(公告)号：US20250075259A1

公开(公告)日：2025-03-06

申请号：US18950630

申请日：2024-11-18

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Karin STRAUSS ,  Bichlien Hoang NGUYEN

IPC: C12Q1/6834 ,  C07H21/04 ,  C07H99/00 ,  C07K1/04 ,  C07K1/10 ,  C07K14/00 ,  C07K17/00 ,  C07K17/02 ,  C07K17/08 ,  C07K19/00

Abstract: Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

公开(公告)号：US20240371470A1

公开(公告)日：2024-11-07

申请号：US18655208

申请日：2024-05-03

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Luis CEZE ,  Sergey YEKHANIN ,  Siena Dumas ANG ,  Karin STRAUSS ,  Cyrus RASHTCHIAN ,  Ravindran KANNAN ,  Konstantin MAKARYCHEV

IPC: G16B30/10 ,  G06F16/28 ,  G16B30/20 ,  G16B40/00

Abstract: A technique for clustering DNA reads from polynucleotide sequencing is described. DNA reads with a level of difference that is likely caused by errors in sequencing are grouped together in the same cluster. DNA reads that represent reads of different DNA molecules are placed in different clusters. The clusters are based on edit distance, which is the number of changes necessary to convert a given DNA read into another. The process of forming clusters may be performed iteratively and may use other types of distance that serve as an approximation for edit distance. Well clustered DNA reads provide a starting point for further analysis.

公开(公告)号：US20230395198A1

公开(公告)日：2023-12-07

申请号：US18236916

申请日：2023-08-22

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Karin STRAUSS ,  Yuan-Jyue CHEN

IPC: G16B50/30 ,  G16B50/00 ,  C12Q1/6806 ,  C12Q1/6869

CPC classification number: G16B50/30 ,  G16B50/00 ,  C12Q1/6806 ,  C12Q1/6869

Abstract: Techniques for random access of particular DNA strands from a mixture of DNA strands are described. DNA strands that encode pieces of the same digital file are labeled with the same identification sequence. The identification sequence is used to selectively separate DNA strands that contain portions of the same digital file from other DNA strands. A DNA staple positions DNA strands with the identification sequence adjacent to sequencing adaptors. DNA ligase joins the molecules to create a longer molecule with the region encoding the digital file flanked by sequencing adaptors. DNA strands that include sequencing adaptors are sequenced and the sequence data is available for further analysis. DNA strands without the identification sequence are not joined to sequencing adaptors, and thus, are not sequenced. As a result, the sequencing data produced by the DNA sequencer comes from those DNA strands that included the identification sequence.

公开(公告)号：US20230348945A1

公开(公告)日：2023-11-02

申请号：US18219079

申请日：2023-07-06

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Bichlien NGUYEN ,  Jake SMITH ,  Robert CARLSON ,  Karin STRAUSS

IPC: C12P19/34 ,  C12N15/10 ,  C12Q1/68 ,  C12Q1/6834

CPC classification number: C12P19/34 ,  C12N15/10 ,  C12Q1/68 ,  C12Q1/6834 ,  C12Q2521/101 ,  C12Q2521/131 ,  C12Q2525/186 ,  C12Q2525/101 ,  C12Q2533/101

Abstract: A universal template strand built with universal base analogs is used as a template for polynucleotide synthesis. The universal template strand can hybridize to any sequence of nucleotides. A new polynucleotide is synthesized by using a polymerase to extend a primer hybridized to the universal template strand. Unlike primer extension in polymerase chain reactions, base pairing with nucleotides in the template strand does not specify the sequence of the new polynucleotide. Instead, the sequence of the new polynucleotide is specified by the order of addition of protected nucleotides. After addition of a single species of protected nucleotide, the blocking group is removed and another protected nucleotide is added. The order of nucleotide addition can be varied to create any sequence. After synthesis, the polynucleotide can be dehybridized from the universal template strand. The universal template strand may then be reused to synthesize a different polynucleotide.

公开(公告)号：US20230101409A1

公开(公告)日：2023-03-30

申请号：US17490615

申请日：2021-09-30

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Yuan-Jyue CHEN ,  Bichlien Hoang NGUYEN ,  Jake Allen SMITH ,  Karin STRAUSS

IPC: G16B30/10 ,  C12Q1/6876 ,  G06K7/10

Abstract: Large numbers of polynucleotides with random sequences are used collectively as a molecular anti-counterfeiting tag. The polynucleotides are sequenced, placed on an item, and the sequences stored in an electronic record. Authenticity is determined by collecting the polynucleotides from a labeled item, sequencing those polynucleotides, and comparing the sequence to that stored in the electronic record. The number of polynucleotides used as the tag may be adjusted by aliquoting the original batch of randomly synthesized polynucleotides. Complexity of the polynucleotide tags may be increased by assembling individual polynucleotides from multiple dilutions to create longer assembled polynucleotides. Even if the sequences of the polynucleotides are known, the complexity of the tag can make the forgery of the tag itself technically difficult and prohibitively expensive.

公开(公告)号：US20220031619A1

公开(公告)日：2022-02-03

申请号：US17504822

申请日：2021-10-19

Applicant: MICROSOFT TECHNOLOGY LICENSING, LLC

Inventor： Karin STRAUSS ,  Bichlien Hoang NGUYEN

IPC: A61K9/127 ,  A61K47/69 ,  A61K47/62 ,  A61K31/7088 ,  A61K47/14 ,  A61K47/18 ,  A61K47/26 ,  A61K47/36

Abstract: Polynucleotides such as DNA are stored inside vesicles formed from self-assembling membranes. The vesicles may be protocells, liposomes, micelles, colloidosomes, proteinosomes, or coacervates. The vesicles may include surface functionalization to improve polynucleotide encapsulation and/or to bind polynucleotides having specific sequences. Encapsulation in vesicles provides protection for the polynucleotides. Additional protection is provided by addition of one or more stabilizers. The stabilizer may be nucleic-acid stabilizers that stabilize the polynucleotides or may be a protective structural layer around the vesicles such as a layer of silica. A process for stably storing polynucleotides in vesicles and a process for recovering stored polynucleotides from vesicles are both disclosed. The polynucleotides may be used for storage of digital information.