JP5893607B2 - 空間コード化生物学的アッセイ - Google Patents
空間コード化生物学的アッセイ Download PDFInfo
- Publication number
- JP5893607B2 JP5893607B2 JP2013503861A JP2013503861A JP5893607B2 JP 5893607 B2 JP5893607 B2 JP 5893607B2 JP 2013503861 A JP2013503861 A JP 2013503861A JP 2013503861 A JP2013503861 A JP 2013503861A JP 5893607 B2 JP5893607 B2 JP 5893607B2
- Authority
- JP
- Japan
- Prior art keywords
- probe
- encoded
- target
- sample
- biological
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6804—Nucleic acid analysis using immunogens
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
- C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6841—In situ hybridisation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B30/00—Methods of screening libraries
- C40B30/04—Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/04—Integrated apparatus specially adapted for both screening libraries and identifying library members
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
- G01N2458/10—Oligonucleotides as tagging agents for labelling antibodies
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Dispersion Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
- Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
Description
、150超、500超、750超、1,000超、5,000超、10,000超、25,000超、50,000超、100,000超、500,000超、もしくは1,000,000超、またはそれ以上である。他の態様では、少なくとも5万個のコード化プローブの配列が並列方式で決定され、他の態様では、少なくとも10万個のコード化プローブ配列が並列方式で決定され、いくつかの態様では、少なくとも50万個のコード化プローブの配列が並列方式で決定され、いくつかの態様では、少なくとも100万個、1000万個、1億個、10億個、100億個、1000億個、またはそれ以上のコード化プローブの配列が並列方式で決定される。
達する工程であって、各コード化プローブは、生物学的標的と相互作用しうるプローブ領域と、コード化プローブが送達された部位の位置の特定および生物学的標的の特定を行うコードタグとを含む工程と、コード化プローブを生物学的標的と相互作用させる工程と、コード化プローブの配列の全部または一部を決定する工程と、複数の生物学的標的の存在量もしくは活性またはその両方をサンプル中の部位の位置に関連付ける工程とを行う。
本明細書で用いられる用語は、当業者により理解される明白な通常の意味を有するものとする。以下の定義は、読者が本発明を理解するのに役立てることを意図したものであり、とくに指定がないかぎり、そのような用語の意味を変更したり、さもなければ限定したりすることを意図したものではない。
「相補的」または「実質的に相補的」とは、ヌクレオチド間または核酸間におけるハイブリダイゼーション、塩基対形成、または二重鎖形成を意味する。ヌクレオチド間または核酸間としては、たとえば、二本鎖DNA分子の2つの鎖間、またはオリゴヌクレオチドプライマーと一本鎖核酸上のプライマー結合部位との間などがある。相補的ヌクレオチドは、一般的には、AとT(もしくはAとU)、またはCとGである。2つの一本鎖のRNA分子またはDNA分子は、一方の鎖のヌクレオチドが、最適なアライメントおよび比較ならびに適切なヌクレオチド挿入または欠失を行って、他方の鎖の少なくとも約80%、通常は少なくとも約90%〜約95%、さらには約98%〜約100%と対合する場合、実質的に相補的であると言われる。
、ゲノム全体にわたり見いだされ、個体間の遺伝的変異の多くは、SNP遺伝子座での変異に起因し、多くの場合、この遺伝的変異は、個体間の表現型変異をもたらす。本発明で使用するためのSNPおよびそのそれぞれの対立遺伝子は、公共のデータベース(U.C.サンタクルーズ・ヒトゲノム・ブラウザ・ゲートウェイ(U.C.Santa Cruz Human Genome Browser Gateway)(http://genome.ucsc.edu/cgi−bin/hgGateway)またはNCBI
dbSNPウェブサイト(http://www.ncbi.nlm.nih.gov/SNP/)などの多くの情報源に由来しうるか、または米国特許第6,969,589号明細書および「ヒトゲノム多型」という名称の米国特許出願公開第2006/0188875号明細書に記載されるように実験的に決定しうる。SNPの使用は、本明細書に提示された実施形態のいくつかで説明されているが、他の両対立遺伝子マーカーまたは複対立遺伝子マーカーも使用しうることは理解されよう。両対立遺伝子マーカーは、2つの多型体または対立遺伝子を有するマーカーである。上述したように、形質に関連する両対立遺伝子マーカーでは、対照群と比較して症例群の遺伝的組成物中に豊富に存在する対立遺伝子は、「関連対立遺伝子」と称され、他の対立遺伝子は「非関連対立遺伝子」と呼ばれうる。したがって、所与の形質(たとえば、疾患または薬剤応答)に関連する両対立遺伝子多型では、対応する関連対立遺伝子が存在する。本明細書に提示された方法で使用しうる他の両対立遺伝子多型としては、多重ヌクレオチド変化、挿入、欠失、および転座が挙げられるが、これらに限定されるものではない。さらに、本明細書でのDNAへの言及は、ゲノムDNA、ミトコンドリアDNA、エピソームDNA、および/またはDNAの誘導体、たとえば、アンプリコン、RNA転写物、cDNA、DNA類似体などを包含しうることも理解される。関連解析(association study)でスクリーニングされる多型遺伝子座は、二倍体または一倍体の状態で存在可能であり、理論上、ゲノム全体にわたる部位に由来する。
umina,Inc.),サンディエゴ,カリフォルニア州(San Diego,CA)により製品化されているもの、HeliScope(商標)であって、ヘリコスバイオサイエンス社(Helicos Biosciences Corporation),ケンブリッジ,マサチューセッツ州(Cambridge,MA)により製品化されているもの、およびPacBio RSであって、パシフィックバイオサイエンス・カリフォルニア社(Pacific Biosciences of California,Inc.),メンロパーク,カリフォルニア州(Menlo Park,CA)により製品化されているもの)、イオン検出技術によるシークエンシング(イオントレント社(Ion Torrent,Inc.),サウスサンフランシスコ,カリフォルニア州(South San Francisco,CA))、DNAナノボールのシークエンシング(コンプリートゲノミクス社(Complete Genomics,Inc.),マウンテンビュー,カリフォルニア州(Mountain View,CA))、ナノ細孔に基づくシークエンシング技術(たとえば、オックスフォードナノポアテクノロジーズ社(Oxford Nanopore Technologies,LTD),オックスフォード,英国(Oxford,UK))により開発されたもの)、および高度並列シークエンシング法などが挙げられるが、これらに限定されるものではない。
Analysis):実験マニュアルシリーズ(Vol.I−IV)(1999);ワイナー(Weiner),ガブリエル(Gabriel),ステフェンス(Stephens)編,遺伝的変異(Genetic Variation):実験マニュアル(2007);ディーフェンバハ(Dieffenbach),ドベクスラー(Dveksler)編,PCRプライマー(PCR Primer):実験マニュアル(2003);ボウテル(Bowtell)およびサムブルック(Sambrook),DNAマイクロアレイ(DNA Microarrays):モレキュラークローニングマニュアル(2003);マウント(Mount),バイオインフォマティクス(Bioinformatics):シークエンスおよびゲノム解析(2004);サムブルック(Sambrook)およびラッセル(Russell),モレキュラー・クローニング プロトコル要約集(Condensed Protocols from Molecular Cloning):実験マニュアル(2006);サムブルック(Sambrook)およびラ
ッセル(Russell),モレキュラー・クローニング:実験マニュアル(2002)(すべて、コールド・スプリング・ハーバー・ラボラトリー出版社(Cold Spring Harbor Laboratory Press)刊);ストライヤー(Stryer),生化学(Biochemistry)第4版(1995);W.H.フリーマン(W.H.Freeman),ニューヨーク,ニューヨーク州;ゲイト(Gait),「オリゴヌクレオチド合成(Oligonucleotide Synthesis)」:実用手法(2002),IFLプレス(IRL Press),ロンドン、ネルソン(Nelson);コックス(Cox),レーニンジャーの新生化学(2000)第3版,W.H.フリーマン出版社,ニューヨーク,ニューヨーク州;ならびにバーグ(Berg)ら,生化学(2002)第5版,W.H.フリーマン出版社,ニューヨーク,ニューヨーク州(それらはすべて、それらの全体があらゆる目的で参照により本明細書に組み入れられるものとする)などの標準的実験マニュアルに見いだしうる。
本発明に係るアッセイ系は、1)効率的な空間コード化スキームを用いて高レベルの多重化が可能なアッセイと、2)空間パターンに従って試薬を送達しうる機器と、3)本質的にデジタル読取情報により決定されるデコード化とを含む、空間コード化多重化アッセイを提供する。本発明に係るアッセイ系では、生物学的標的の存在もしくは不在および相対量または生物学的標的の指標となる生物学的活性、さらには生物学的サンプル(たとえば、顕微鏡用スライドや培養ディッシュなどの担体上に配置された組織切片または他の生物学的構造物)中の生物学的標的の位置または活性を検出する。
わめて革新的なアッセイ系の主要要素を提供し、遺伝子発現およびペプチド局在化を含めて、意味のある空間環境中の多数の生物学的標的または活性の測定を可能する。このアッセイ系で使用されるコード化スキームでは、多重化アッセイの生成物を生物学的サンプルから取り出して分析に供すべくプールした後、生物学的サンプル中の生物学的標的または活性(またはその欠如)の位置を決定することが可能である。コード化スキームのデコード化は、たとえば、低コストで数百万〜数兆のデータ点を容易に提供する次世代シークエンシングにより、実施可能である。次いで、生物学的標的の量または活性などのアッセイ結果を生物学的サンプル中の特定の位置に対しマッピングすることが可能である。アッセイ系は、生物学的サンプル中の細胞機能および調節の複雑な空間パターンを知る新しい解析の機会を与える。
ーブをサンプルから洗浄除去することにより、達成可能である。同様に、アプタマー、小分子、およびタンパク質のプローブを使用するアッセイを含めて、アフィニティー結合に基づく他のアッセイでは、親和性の低い結合剤を、洗浄工程を用いて除去することが可能である。プローブが標的との相互作用を介して変換される場合(たとえば、ペプチドの場合、たとえば、プロテアーゼによる切断またはキナーゼによるリン酸化を介して)、すべてのコード化プローブ、すなわち、生物学的標的と相互作用して変換されたコード化プローブおよび変換されなかったコード化プローブの両方を捕集することが便利である。捕集後またはプール後、抗体または他の親和性捕獲剤を用いて、一部分(たとえば、リン酸基)の付加により変換されたプローブを捕獲することが可能である。プローブが切断を介して変換された場合、たとえば、変換(たとえば、切断による)時に変換されたプローブから除去されるタグを介して変換されなかったプローブを捕獲することにより、または切断の部位に新しいタグを付加することにより、変換されたプローブを分離することが可能である。
を明らかにする。本発明をよりよく説明するために、この実施形態は特定の順序での個々の工程を示しているが、工程の厳密な順序は変更することが可能である。たとえば、工程220と250とを組み合わせることが可能であって、プローブとコード化オリゴヌクレオチドとの混合物を、選択された空間パターンに従って送達するようにすることができる。次いで、組み合わされた工程220および250の直後にまたはそれらと同時に、結合工程260を行うことが可能である。次いで、この場合、工程260の後、工程240が行われる。したがって、この一連の工程の2つの主要な結果(すなわち、プローブ分子の位置特異的コード化、および対応する標的分子と相互作用するその能力に基づくプローブ分子の分離)は、特定の工程の実行時、いくらかの柔軟性をもたせて達成可能であることを認識しうる。同様に、コード化スキームのデザインにもかなりの柔軟性が存在する。以下で述べるように、本発明に係るアッセイは、コンビナトリアル法にとくに適合する。
本発明に係るアッセイ系のアッセイ部分は、次の一般的工程、すなわち、コード化剤(いくつかの実施形態では、プローブにあらかじめ結合されている)が既知の空間パターンに従ってサンプルに送達されるようにプローブおよびコード化剤を送達する工程と、プローブをサンプル中の生物学的標的と相互作用または反応させる工程と、プローブおよびコード化剤があらかじめ結合されていない場合、コード化剤をプローブに結合させる工程とを含む。
ある。例示的な生物学的サンプルは、組織切片(たとえば、全動物切除切片および組織生検試料を含む)、スライド上または培養ディッシュ上の細胞集団などを含む。本発明に係るアッセイ系は、新しいサンプル(一次組織切片など)および保存したサンプル(限定されるものではないが、凍結サンプル、パラホルマリン固定サンプル、パラフィン包埋(FFPE)サンプル)を含めて、多数の生物学的サンプルタイプに適合可能であるという点でとくに有利である。本発明に係るアッセイ系の重要な態様は、生物学的サンプルが個別の独立して測定可能な領域を有する基材表面上に固定されることである。
第2のアダプター329を含む最終構築物は、この時点で、デジタルハイスループットシークエンシングプロセスに投入可能な状態にある。
Symp.Quant.Biol.,68:69−78(2003);(イルミナ社(Illumina,Inc.),サンディエゴ,カリフォルニア州(San Diego,CA)参照)などの場合、追加のオリゴヌクレオチドを利用するアッセイを利用しうる。
コード化の効率を最大化するために、コード化オリゴヌクレオチドでコードタグ対を使用するコンビナトリアル手法を使用することが可能である。標的特異的情報とコードタグとを切り離すことにより、所要のオリゴヌクレオチドの数は、劇的に低減され、それに付随してコストが削減される。
プライミング部位に会合するコードタグ406、またはシークエンシング技術を用いてコード識別子の同定を可能にするアダプター410を含む。
特異的オリゴヌクレオチド1および2で配列読取情報が得られた。a1b4、a2b4、またはa3b4(陰影無しで示された位置)ではいずれの標的特異的オリゴヌクレオチドでも配列読取情報が得られなかった。したがって、アッセイが行われた生物学的サンプルにおいて、第1の標的核酸は、生物学的サンプルの左側の大部分および下側で検出され、第2の標的核酸は、生物学的サンプルの左上部分でのみ検出され、いずれの標的核酸も、生物学的サンプルの右上部分では検出されなかった。この時点で、2つの標的核酸の示差発現を生物学的サンプルに戻して生物学的サンプル中のこれらの位置の生物学的構造または細胞型に対しマッピングすることが可能である。
本発明に係る試薬送達系は、生物学的サンプルの離散部分への試薬の送達およびコード化スキームの空間パターンの整合性の維持を可能にする機器を含む。本発明に係るアッセイ系の試薬送達系は、任意選択のイメージング手段と試薬送達ハードウェアと制御ソフトウェアとを含む。試薬送達は、いくつかの異なる方法で達成可能である。試薬送達は、一
度に多くの異なる生物学的サンプルに対して行われることに留意されたい。単一の組織切片を本明細書に例示してきたが、複数の生物学的サンプルを固定して同時に分析することが可能である。たとえば、組織サンプルの連続切片を並列方式で解析し、データを合わせて3Dマップを構築することが可能である。
ンプは、いくつかある手段の中でとくに、流体および/もしくは流体移送構造体に正圧または負圧を機械的に加えることにより、電気的に電界の適切な印加を行うことにより、またはその両方により、駆動することが可能である。例示的な機械式ポンプは、シリンジポンプ、蠕動ポンプ、ロータリーポンプ、加圧ガス、ピペッターなどを含みうる。機械式ポンプは、微細加工されたり、成型されたりすることが可能である。例示的な電気式ポンプは、電極を含みうる。また、電気泳動、電気浸透、電気毛管現象、誘電泳動(進行波形態を含む)などにより駆動しうる。
ッセイ系の他の特徴と統合された画像処理(たとえば、免疫組織化学または他の染色化学により識別された細胞型の画像)を用いて、生物学的サンプルのサンプル領域を特定することが可能である。いくつかの態様では、ソフトウェアを用いて、画像情報を試薬送達パターンに自動変換する。したがって、試薬送達のために生物学的サンプルを非常に正確に位置合せし整合させる機構は、本発明に係るアッセイ系の重要な要素である。スライド上での基準マーカーの使用および/または他の非常に正確な物理的位置決めシステムなどの機構は、この目的に適合しうる。
本発明に係るアッセイ系のコード化プローブ中のコードタグおよびプローブ配列を同定するために、多くの方法を使用することが可能である。質量分析(たとえば、Maldi−Tof,LC−MS/MS)、核磁気共鳴イメージング、または好ましくは核酸シークエンシングなどの技術を用いてコードタグを検出することが可能である。本発明に係るコードタグをデコード化するための技術の例は、たとえば、米国特許出願公開第20080220434号明細書(引用により本明細書に組み入れられるものとする)に見いだしうる。たとえば、コードタグは、オリゴヌクレオチド質量タグ(OMTまたはmassTag)でありうる。そのようなタグは、たとえば、米国特許出願公開第20090305237号明細書(その全体が引用により組み入れられるものとする)に記載されている。さらに他の選択肢では、コード化プローブを増幅してマイクロアレイにハイブリダイズさせることが可能である。このためには、コード特異的プライマーの使用により達成される個別の増幅反応を行う必要がある。この場合、各増幅は、特定の空間コードまたはコードのサブセットに特有なものである。各増幅はまた、異なる解像可能標識(たとえば、発蛍光団)を含む。ハイブリダイゼーションに続いて、サンプル中の異なる空間位置にマッピングされた特定の標的の相対量を、解像可能標識の相対存在量により決定することが可能である。
ゼーションに基づく方法、たとえば、ドルマナック(Drmanac)の米国特許第6,864,052号明細書、同第6,309,824号明細書、および同第6,401,267号明細書、ならびにドルマナック(Drmanac)らの米国特許出願公開第2005/0191656号明細書に開示されるもの、シークエンシング・バイ・シンセシス方法、たとえば、米国特許第6,210,891号明細書、同第6,828,100号明細書、同第6,969,488号明細書、同第6,897,023号明細書、同第6,833,246号明細書、同第6,911,345号明細書、同第6,787,308号明細書、同第7,297,518号明細書、同第7,462,449号明細書、および同第7,501,245号明細書、米国特許出願公開第20110059436号明細書、同第20040106110号明細書、同第20030064398号明細書、および同第20030022207号明細書、ロナギ(Ronaghi)ら,Science,281:363−365(1998)、およびリー(Li)ら,Proc.Natl.Acad.Sci.,100:414−419(2003)、ライゲーションに基づく方法、たとえば、米国特許第5,912,148号明細書および同第6,130,073号明細書、および米国特許出願第20100105052号明細書、同第20070207482号明細書、および同第20090018024号明細書、ナノ細孔シークエンシング、たとえば、米国特許出願第20070036511号明細書、同第20080032301号明細書、同第20080128627号明細書、同第20090082212号明細書、およびソニ(Soni)およびメラー(Meller),Clin Chem 53:1996−2001(2007)、さらには他の方法、たとえば、米国特許出願第20110033854号明細書、同第20090264299号明細書、同第20090155781号明細書、および同第20090005252号明細書が挙げられるが、これらに限定されるものではない。また、マッカーナン(McKernan)ら,Genome Res.,19:1527−41(2009)、およびベントレー(Bentley)ら,Nature 456:53−59(2008)をも参照されたい。それらはすべて、それらの全体があらゆる目的で本明細書に組み入れられるものとする。
生物学的サンプル中の生物学的標的の量および空間位置を同時に測定可能なハイスループット多重化アッセイ系が有益と思われる生物学的研究、診断法、および薬剤開発の重要な領域が多数存在することは、本開示を読めば当業者には明らかである。たとえば、さまざまなRNA転写物(trancripts)の相対存在量を推定する能力と、組織中の多くの位置(個別細胞程度の大きさであってもよいし、さらにはそれよりも小さくてもよい)にわたり存在量の空間パターンの画像を再構築する能力とを組み合わせることにより、多種多様な領域の基礎研究が可能になる。以下のものは、例示的な使用であり、なんら範囲を限定するものでないない。
初期概念実証として、実用的単一アッセイを実証すべくマイクロアレイを用いてモデル系を開発する。より複雑な生物学的サンプルの解析に関する問題に対処する前に、基本デザインによりアッセイの概念を検証し、実用的アッセイを確立する。この概念実証のための読取として従来のシークエンシングを使用する。
イドは、単一のオリゴヌクレオチド鋳型配列を有し、行われるアッセイは、ライゲーション、または伸長およびそれに続くライゲーション(これは特定の多型の決定に有用でありうるため)のいずれかを利用しうる。
ハイスループット試験で使用するためのアッセイの拡張性を確証するために、アッセイ系の複雑度を増大させる。マイクロアレイモデル系を用いて24プレックス(plex)×24部位アッセイを行うことにより、空間コード化およびアッセイ系の両方の拡張性を実証する。
する。
ゲノムDNAがRNAアッセイの概念実証としてアッセイされる。これは、単一コピーの参照シグナルを確証する方法を提供するためである。FFPEサンプル用に実用的アッセイを開発した後、それをRNAアッセイに適合化する。この目的のために、高多重化で適合性を確保すべくアッセイオリゴヌクレオチド濃度をアッセイする。細胞直径が10ミクロンの細胞直径であって、各細胞に対して直径10ミクロンの試薬小滴を送達すると仮定すると、小滴の容積は、500μl以下であり、1μΜの濃度で3×1011個以下の分子を含有しうる。10,000個の細胞で1,000個の標的配列をアッセイするためには、一小滴中に2,000個以下のターゲティングオリゴヌクレオチドが必要とされる。したがって、各小滴は、各アッセイオリゴの1.6億以下のコピー数(細胞内の数千個の標的配列よりもはるかに過剰)を含有しうる。
人為的系を形成するために対照RNA鋳型を固体担体に固定する。DNA/RNAハイブリッド中のニックを修復可能なT4 DNAリガーゼを用いてアッセイを行う。対応付けられたスライド上または同一のスライドの異なる部分上でアッセイを行い、一方ではgDNAをアッセイし、他方ではRNAをアッセイする。gDNAをアッセイする場合、スライドをRNアーゼで前処理することが可能であり、RNAをアッセイする場合、スライドをDNアーゼで前処理する。gDNAまたはRNAを抽出してそれぞれqPCRまたはRT−qPCRで相対量を定量することにより、アッセイの結果を確認する。
Claims (23)
- サンプル中の複数の部位における複数の生物学的標的の存在量もしくは活性またはその両方を決定する方法であって、
担体に固定されたサンプルを提供する工程と、
複数の生物学的標的に対するコード化プローブを前記サンプル中の前記複数の部位に送達する工程であって、各コード化プローブは、(1)生物学的標的と相互作用するプローブ領域と、(2)前記コード化プローブが送達された部位の位置を特定するオリゴヌクレオチドを含むコードタグとを含む、送達工程と、
前記コード化プローブを前記生物学的標的と相互作用させる工程と、
前記生物学的標的と相互作用するコード化プローブを前記生物学的標的と相互作用しないコード化プローブから分離する分離工程と、
前記生物学的標的と相互作用するコード化プローブを配列決定のためにプールする工程と、
前記生物学的標的と相互作用するコード化プローブの配列を決定する決定工程であって、各配列は、前記コードタグのオリゴヌクレオチドの配列の全部または一部を含み、前記コードタグのオリゴヌクレオチドの前記配列は、コード化プローブが送達される前記部位の位置を特定する、決定工程と、
前記複数の生物学的標的の存在量もしくは活性またはその両方を、前記サンプル中の前記部位の位置に関連付ける関連付け工程と、
を含む、方法。 - サンプル中の複数の部位における複数の生物学的標的の存在量もしくは活性またはその両方を決定する方法であって、
担体に固定されたサンプルを提供する工程と、
複数の生物学的標的に対するプローブを前記サンプル中の前記複数の部位に送達する送達工程と、
前記プローブを前記生物学的標的と結合させる工程と、
結合していないプローブを前記サンプルから分離する分離工程と、
コード化剤を前記サンプル中の前記複数の部位の位置に送達する工程であって、各コード化剤が、該コード化剤が送達される前記部位の位置を特定するオリゴヌクレオチドを含
む、送達工程と、
前記コード化剤と、前記生物学的標的に結合する前記プローブとを結合させてコード化プローブを形成する結合工程と、
前記生物学的標的に結合したコード化プローブを配列決定のためにプールする工程と、
前記コード化プローブの配列を決定する決定工程であって、各配列は、前記コード化剤のオリゴヌクレオチドの配列の全部または一部を含み、前記コード化剤のオリゴヌクレオチドの前記配列は、前記コード化剤が送達された前記部位の位置を特定する、決定工程と、
前記複数の生物学的標的の存在量もしくは活性またはその両方を前記サンプル中の前記複数の部位の位置に関連付ける関連付け工程と、
を含む、方法。 - 前記生物学的標的が核酸であり、かつ前記コード化プローブがオリゴヌクレオチドである、
請求項1または2に記載の方法。 - 前記複数の核酸の標的のそれぞれに対して2つのコード化プローブが存在する、
請求項3に記載の方法。 - 前記複数の生物学的標的がタンパク質であり、前記コード化プローブのプローブ領域がタンパク質またはアプタマーを含み、かつ前記コードタグまたは前記コード化剤がオリゴヌクレオチドを含む、
請求項1または2に記載の方法。 - 前記複数の生物学的標的が酵素を含む、
請求項5に記載の方法。 - 前記コード化プローブの配列の増幅を行う工程をさらに含む、
請求項1および3〜6のいずれか一項に記載の方法。 - 前記決定工程が、核酸シークエンシング、ハイスループットシークエンシング、またはデジタルシークエンシングにより行われる、
請求項1〜7のいずれか一項に記載の方法。 - 前記コード化プローブまたは前記コード化剤は、既知の空間パターンに従い、前記サンプル中の複数の部位に送達される、
請求項1〜8のいずれか一項に記載の方法。 - ソフトウェアのプログラムされたハードウェアが、前記送達工程、前記分離工程、前記決定工程、および前記関連付け工程のうちの少なくとも2つの工程を行う、
請求項1〜9のいずれか一項に記載の方法。 - 前記コード化プローブのプローブ領域がタンパク質であり、かつ前記分離工程が、前記生物学的標的と相互作用する前記コード化プローブを捕獲する親和性捕獲剤を用いることにより達成される、
請求項1または2に記載の方法。 - 前記コード化プローブのプローブ領域が核酸であり、かつ前記分離工程が前記サンプルの洗浄により達成される、
請求項1または2に記載の方法。 - サンプル中の複数の部位における複数の核酸標的の存在量もしくは活性またはその両方を決定する方法であって、
担体に固定されたサンプルを提供する工程と、
複数の核酸標的に対するオリゴヌクレオチドプローブを前記サンプル中の前記複数の部位に送達する工程と、
前記オリゴヌクレオチドプローブを前記核酸標的にハイブリダイズさせる工程と、
ハイブリダイズされていないオリゴヌクレオチドプローブを前記サンプルから洗浄除去する工程と、
コード化剤を前記サンプル中の前記複数の部位の位置に送達する工程であって、各コード化剤が、該コード化剤が送達される前記部位の位置を特定するオリゴヌクレオチドを含んでいる、工程と、
前記コード化剤と、前記核酸標的にハイブリダイズする前記オリゴヌクレオチドプローブとを結合させてコード化プローブを形成する結合工程と、
前記核酸標的にハイブリダイズしたコード化プローブを配列決定のためにプールする工程と、
前記核酸標的にハイブリダイズしたコード化プローブの配列を決定する決定工程であって、各配列は、前記コード化剤のオリゴヌクレオチドの配列の全部または一部を含み、前記コード化剤のオリゴヌクレオチドの前記配列は、前記コード化剤が送達される前記部位の位置を特定する、決定工程と、
前記複数の核酸標的の存在量もしくは活性またはその両方を前記サンプル中の前記複数の部位の位置に関連付ける関連付け工程と、
を含む、方法。 - 前記複数の核酸標的のそれぞれに対して2つのオリゴヌクレオチドプローブが送達される、
請求項13に記載の方法。 - 前記結合工程がライゲーションにより行われるか、伸長およびそれに続くライゲーションにより行われる、
請求項13または14に記載の方法。 - 前記結合工程と前記決定工程との間に増幅を行う工程をさらに含む、
請求項13〜15のいずれか一項に記載の方法。 - サンプル中の複数の部位における複数のタンパク質標的の存在量もしくは活性またはその両方を決定する方法であって、
担体に固定されたサンプルを提供する工程と、
複数のタンパク質標的に対するコード化プローブを前記サンプル中の前記複数の部位に送達する工程であって、各コード化プローブは、(1)タンパク質標的と相互作用するタンパク質プローブ領域と、(2)コードタグとを含み、該コードタグは、前記コード化プローブが送達された前記部位の位置を特定するか、該コードタグがその一部をなす前記コード化プローブの前記タンパク質プローブ領域を特定するか、またはそれら両方の特定を行うオリゴヌクレオチドを含む、工程と、
前記コード化プローブを前記タンパク質標的と相互作用させる工程と、
前記タンパク質標的と相互作用するコード化プローブを前記タンパク質標的と相互作用しないコード化プローブから分離する分離工程と、
前記タンパク質標的と相互作用するコード化プローブを配列決定のためにプールする工程と、
前記タンパク質標的と相互作用するコード化プローブの配列を決定する決定工程であっ
て、各配列は、前記コードタグのオリゴヌクレオチドの配列の全部または一部を含み、前記コードタグのオリゴヌクレオチドの前記配列は、前記コード化プローブが送達される前記部位の位置を特定する、決定工程と、
前記複数のタンパク質標的の存在量もしくは活性またはその両方を前記サンプル中の前記複数の部位の位置に関連付ける関連付け工程と、
を含む、方法。 - 前記コード化プローブの配列の増幅を行う工程をさらに含む、
請求項17に記載の方法。 - 前記タンパク質標的が酵素であり、かつ前記コード化プローブの前記タンパク質プローブ領域が、前記酵素に対する基質である、
請求項17または18に記載の方法。 - 前記コード化プローブのプローブ領域が親和性捕獲剤、抗体、またはアプタマーである、
請求項17〜19のいずれか一項に記載の方法。 - 前記タンパク質標的と相互作用するコード化プローブを前記タンパク質標的と相互作用しないコード化プローブから分離することは、前記タンパク質標的と相互作用するコード化プローブと、前記タンパク質標的と相互作用しないコード化プローブとを識別する親和性捕獲剤により達成される、
請求項17〜20のいずれか一項に記載の方法。 - 前記コードタグがオリゴヌクレオチドである、
請求項17〜21のいずれか一項に記載の方法。 - サンプル中の複数の部位における複数の生物学的標的の存在量もしくは活性またはその両方を決定する方法であって、
担体に固定されたサンプルを提供する工程と、
複数の生物学的標的に対するコード化プローブを前記サンプル中の前記複数の部位に送達する工程であって、各コード化プローブは、(1)生物学的標的と相互作用するプローブ領域と、(2)コードタグとを含み、該コードタグは、前記コード化プローブが送達された前記部位の位置の特定、または前記生物学的標的の特定、またはそれら両方の特定を行うオリゴヌクレオチドを含む、工程と、
前記コード化プローブを前記生物学的標的と相互作用させる工程と、
前記生物学的標的と相互作用したコード化プローブを配列決定のためにプールする工程と、
前記生物学的標的と相互作用するコード化プローブの配列を決定する工程であって、各配列は、前記コードタグのオリゴヌクレオチドの配列の全部または一部を含み、前記コードタグのオリゴヌクレオチドの前記配列は、前記コード化プローブが送達される前記部位の位置を特定する、工程と、
前記複数の生物学的標的の存在量もしくは活性またはその両方を前記サンプル中の前記部位の位置に関連付ける工程と、
を含む、方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32112410P | 2010-04-05 | 2010-04-05 | |
US61/321,124 | 2010-04-05 | ||
PCT/US2011/031308 WO2011127099A1 (en) | 2010-04-05 | 2011-04-05 | Spatially encoded biological assays |
US13/080,616 US9371598B2 (en) | 2010-04-05 | 2011-04-05 | Spatially encoded biological assays |
US13/080,616 | 2011-04-05 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013523151A JP2013523151A (ja) | 2013-06-17 |
JP2013523151A5 JP2013523151A5 (ja) | 2014-05-22 |
JP5893607B2 true JP5893607B2 (ja) | 2016-03-23 |
Family
ID=44710331
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013503861A Expired - Fee Related JP5893607B2 (ja) | 2010-04-05 | 2011-04-05 | 空間コード化生物学的アッセイ |
Country Status (18)
Country | Link |
---|---|
US (21) | US9371598B2 (ja) |
EP (1) | EP2556171B1 (ja) |
JP (1) | JP5893607B2 (ja) |
KR (1) | KR101866401B1 (ja) |
CN (2) | CN102834526B (ja) |
AU (1) | AU2011237729B2 (ja) |
CA (1) | CA2794522C (ja) |
DK (1) | DK2556171T3 (ja) |
ES (1) | ES2555106T3 (ja) |
HK (2) | HK1182143A1 (ja) |
HR (1) | HRP20151294T1 (ja) |
HU (1) | HUE026666T2 (ja) |
PL (1) | PL2556171T3 (ja) |
PT (1) | PT2556171E (ja) |
RS (1) | RS54482B1 (ja) |
SI (1) | SI2556171T1 (ja) |
SM (1) | SMT201500301B (ja) |
WO (1) | WO2011127099A1 (ja) |
Families Citing this family (215)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9085798B2 (en) | 2009-04-30 | 2015-07-21 | Prognosys Biosciences, Inc. | Nucleic acid constructs and methods of use |
US8835358B2 (en) | 2009-12-15 | 2014-09-16 | Cellular Research, Inc. | Digital counting of individual molecules by stochastic attachment of diverse labels |
CN102834526B (zh) | 2010-04-05 | 2015-12-02 | 普罗格诺西斯生物科学公司 | 空间编码的生物学测定 |
US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
EP3150750B1 (en) | 2011-04-08 | 2018-12-26 | Prognosys Biosciences, Inc. | Peptide constructs and assay systems |
GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
CA2850509C (en) | 2011-10-14 | 2023-08-01 | President And Fellows Of Harvard College | Sequencing by structure assembly |
ES2952728T3 (es) | 2011-12-22 | 2023-11-03 | Harvard College | Métodos para la detección de analitos |
WO2014163886A1 (en) | 2013-03-12 | 2014-10-09 | President And Fellows Of Harvard College | Method of generating a three-dimensional nucleic acid containing matrix |
US11021737B2 (en) | 2011-12-22 | 2021-06-01 | President And Fellows Of Harvard College | Compositions and methods for analyte detection |
SG11201405274WA (en) | 2012-02-27 | 2014-10-30 | Cellular Res Inc | Compositions and kits for molecular counting |
US9914967B2 (en) | 2012-06-05 | 2018-03-13 | President And Fellows Of Harvard College | Spatial sequencing of nucleic acids using DNA origami probes |
US10323279B2 (en) | 2012-08-14 | 2019-06-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US9701998B2 (en) | 2012-12-14 | 2017-07-11 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10584381B2 (en) | 2012-08-14 | 2020-03-10 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10533221B2 (en) | 2012-12-14 | 2020-01-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
WO2014145047A1 (en) | 2013-03-15 | 2014-09-18 | Prognosys Biosciences, Inc. | Methods for detecting peptide/mhc/tcr binding |
WO2014188941A1 (ja) | 2013-05-22 | 2014-11-27 | オリンパス株式会社 | 核酸分析キットおよび核酸分析方法 |
CA3176690A1 (en) | 2013-06-04 | 2014-12-11 | President And Fellows Of Harvard College | Rna-guided transcriptional regulation |
CN105849275B (zh) * | 2013-06-25 | 2020-03-17 | 普罗格诺西斯生物科学公司 | 检测样品中生物靶标的空间分布的方法和系统 |
KR102182834B1 (ko) | 2013-08-28 | 2020-11-27 | 벡톤 디킨슨 앤드 컴퍼니 | 대량의 동시 단일 세포 분석 |
US10288608B2 (en) | 2013-11-08 | 2019-05-14 | Prognosys Biosciences, Inc. | Polynucleotide conjugates and methods for analyte detection |
US9834814B2 (en) * | 2013-11-22 | 2017-12-05 | Agilent Technologies, Inc. | Spatial molecular barcoding of in situ nucleic acids |
US9824068B2 (en) | 2013-12-16 | 2017-11-21 | 10X Genomics, Inc. | Methods and apparatus for sorting data |
JP6838969B2 (ja) | 2014-06-26 | 2021-03-03 | 10エックス ジェノミクス, インコーポレイテッド | 個々の細胞または細胞集団由来の核酸の分析方法 |
WO2016007839A1 (en) | 2014-07-11 | 2016-01-14 | President And Fellows Of Harvard College | Methods for high-throughput labelling and detection of biological features in situ using microscopy |
EP3174993B1 (en) | 2014-07-30 | 2023-12-06 | President and Fellows of Harvard College | Probe library construction |
EP2983297A1 (en) * | 2014-08-08 | 2016-02-10 | Thomson Licensing | Code generation method, code generating apparatus and computer readable storage medium |
US10584366B2 (en) | 2014-12-03 | 2020-03-10 | IsoPlexis Corporation | Analysis and screening of cell secretion profiles |
WO2016114970A1 (en) | 2015-01-12 | 2016-07-21 | 10X Genomics, Inc. | Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same |
ES2836802T3 (es) | 2015-02-27 | 2021-06-28 | Becton Dickinson Co | Códigos de barras moleculares espacialmente direccionables |
ES2934982T3 (es) | 2015-03-30 | 2023-02-28 | Becton Dickinson Co | Métodos para la codificación con códigos de barras combinatorios |
EP4119677B1 (en) | 2015-04-10 | 2023-06-28 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
US10724078B2 (en) * | 2015-04-14 | 2020-07-28 | Koninklijke Philips N.V. | Spatial mapping of molecular profiles of biological tissue samples |
US11390914B2 (en) | 2015-04-23 | 2022-07-19 | Becton, Dickinson And Company | Methods and compositions for whole transcriptome amplification |
SG10202107055SA (en) | 2015-07-17 | 2021-08-30 | Nanostring Technologies Inc | Simultaneous quantification of a plurality of proteins in a user-defined region of a cross-sectioned tissue |
EP3325650B1 (en) | 2015-07-17 | 2024-01-03 | Nanostring Technologies, Inc. | Simultaneous quantification of gene expression in a user-defined region of a cross-sectioned tissue |
CA2993463A1 (en) * | 2015-07-27 | 2017-02-02 | Illumina, Inc. | Spatial mapping of nucleic acid sequence information |
US10619186B2 (en) | 2015-09-11 | 2020-04-14 | Cellular Research, Inc. | Methods and compositions for library normalization |
WO2017075293A1 (en) | 2015-10-28 | 2017-05-04 | Silicon Valley Scientific, Inc. | Method and apparatus for encoding cellular spatial position information |
CN108474022A (zh) | 2015-11-03 | 2018-08-31 | 哈佛学院董事及会员团体 | 用于包含三维核酸的基质容积成像的设备和方法 |
US11371094B2 (en) | 2015-11-19 | 2022-06-28 | 10X Genomics, Inc. | Systems and methods for nucleic acid processing using degenerate nucleotides |
US10774370B2 (en) | 2015-12-04 | 2020-09-15 | 10X Genomics, Inc. | Methods and compositions for nucleic acid analysis |
CA3210120C (en) | 2016-04-25 | 2024-04-09 | President And Fellows Of Harvard College | Hybridization chain reaction methods for in situ molecular detection |
AU2017259794B2 (en) * | 2016-05-02 | 2023-04-13 | Encodia, Inc. | Macromolecule analysis employing nucleic acid encoding |
US10301677B2 (en) | 2016-05-25 | 2019-05-28 | Cellular Research, Inc. | Normalization of nucleic acid libraries |
US10640763B2 (en) | 2016-05-31 | 2020-05-05 | Cellular Research, Inc. | Molecular indexing of internal sequences |
US10202641B2 (en) | 2016-05-31 | 2019-02-12 | Cellular Research, Inc. | Error correction in amplification of samples |
EP4050112A1 (en) | 2016-06-21 | 2022-08-31 | 10X Genomics, Inc. | Nucleic acid sequencing |
CN109923216A (zh) | 2016-08-31 | 2019-06-21 | 哈佛学院董事及会员团体 | 将生物分子的检测组合到使用荧光原位测序的单个试验的方法 |
WO2018045181A1 (en) | 2016-08-31 | 2018-03-08 | President And Fellows Of Harvard College | Methods of generating libraries of nucleic acid sequences for detection via fluorescent in situ sequencing |
IL265478B1 (en) | 2016-09-26 | 2024-06-01 | Becton Dickinson Co | Measurement of protein expression using reagents with barcoded oligonucleotide sequences |
EP4036578A1 (en) | 2016-11-11 | 2022-08-03 | Isoplexis Corporation | Compositions and methods for the simultaneous genomic, transcriptomic and proteomic analysis of single cells |
EP3545284A4 (en) | 2016-11-22 | 2020-07-01 | Isoplexis Corporation | SYSTEMS, DEVICES AND METHODS FOR CAPTURING CELLS AND MANUFACTURING METHODS THEREOF |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10815525B2 (en) | 2016-12-22 | 2020-10-27 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP4029939B1 (en) | 2017-01-30 | 2023-06-28 | 10X Genomics, Inc. | Methods and systems for droplet-based single cell barcoding |
CN110382708A (zh) | 2017-02-01 | 2019-10-25 | 赛卢拉研究公司 | 使用阻断性寡核苷酸进行选择性扩增 |
KR20190140906A (ko) | 2017-04-14 | 2019-12-20 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 세포-유래 마이크로필라멘트 네트워크의 생성 방법 |
US11788123B2 (en) | 2017-05-26 | 2023-10-17 | President And Fellows Of Harvard College | Systems and methods for high-throughput image-based screening |
EP3635135A1 (en) | 2017-06-05 | 2020-04-15 | Becton, Dickinson and Company | Sample indexing for single cells |
US10837047B2 (en) | 2017-10-04 | 2020-11-17 | 10X Genomics, Inc. | Compositions, methods, and systems for bead formation using improved polymers |
WO2019068880A1 (en) | 2017-10-06 | 2019-04-11 | Cartana Ab | RNA MATRIX LIGATION |
CN114525273A (zh) | 2017-10-27 | 2022-05-24 | 10X基因组学有限公司 | 用于样品制备和分析的方法和系统 |
US11513126B2 (en) | 2017-10-31 | 2022-11-29 | Encodia, Inc. | Kits for analysis using nucleic acid encoding and/or label |
WO2019099751A1 (en) | 2017-11-15 | 2019-05-23 | 10X Genomics, Inc. | Functionalized gel beads |
CN112005115A (zh) | 2018-02-12 | 2020-11-27 | 10X基因组学有限公司 | 表征来自单个细胞或细胞群体的多种分析物的方法 |
US20190249248A1 (en) | 2018-02-12 | 2019-08-15 | Nanostring Technologies, Inc. | Biomolecular probes and methods of detecting gene and protein expression |
US11639928B2 (en) | 2018-02-22 | 2023-05-02 | 10X Genomics, Inc. | Methods and systems for characterizing analytes from individual cells or cell populations |
ES2945191T3 (es) | 2018-05-03 | 2023-06-29 | Becton Dickinson Co | Análisis de muestras multiómicas de alto rendimiento |
CN112243461A (zh) | 2018-05-03 | 2021-01-19 | 贝克顿迪金森公司 | 在相对的转录物末端进行分子条形码化 |
US11932899B2 (en) | 2018-06-07 | 2024-03-19 | 10X Genomics, Inc. | Methods and systems for characterizing nucleic acid molecules |
US11703427B2 (en) | 2018-06-25 | 2023-07-18 | 10X Genomics, Inc. | Methods and systems for cell and bead processing |
US20200032335A1 (en) | 2018-07-27 | 2020-01-30 | 10X Genomics, Inc. | Systems and methods for metabolome analysis |
SG11202101934SA (en) | 2018-07-30 | 2021-03-30 | Readcoor Llc | Methods and systems for sample processing or analysis |
US20200071691A1 (en) * | 2018-08-28 | 2020-03-05 | Cellular Research, Inc. | Sample multiplexing using carbohydrate-binding and membrane-permeable reagents |
WO2020047004A2 (en) | 2018-08-28 | 2020-03-05 | 10X Genomics, Inc. | Methods of generating an array |
US20210317524A1 (en) | 2018-08-28 | 2021-10-14 | 10X Genomics, Inc. | Resolving spatial arrays |
US11519033B2 (en) | 2018-08-28 | 2022-12-06 | 10X Genomics, Inc. | Method for transposase-mediated spatial tagging and analyzing genomic DNA in a biological sample |
CN112805389A (zh) | 2018-10-01 | 2021-05-14 | 贝克顿迪金森公司 | 确定5’转录物序列 |
EP3877520A1 (en) | 2018-11-08 | 2021-09-15 | Becton Dickinson and Company | Whole transcriptome analysis of single cells using random priming |
US11208648B2 (en) | 2018-11-16 | 2021-12-28 | International Business Machines Corporation | Determining position and transcriptomes of biological cells |
EP3891299A1 (en) * | 2018-12-04 | 2021-10-13 | F. Hoffmann-La Roche AG | Spatially oriented quantum barcoding of cellular targets |
WO2020123309A1 (en) | 2018-12-10 | 2020-06-18 | 10X Genomics, Inc. | Resolving spatial arrays by proximity-based deconvolution |
US11492660B2 (en) | 2018-12-13 | 2022-11-08 | Becton, Dickinson And Company | Selective extension in single cell whole transcriptome analysis |
US11649485B2 (en) | 2019-01-06 | 2023-05-16 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11926867B2 (en) | 2019-01-06 | 2024-03-12 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11845983B1 (en) | 2019-01-09 | 2023-12-19 | 10X Genomics, Inc. | Methods and systems for multiplexing of droplet based assays |
ES2945227T3 (es) | 2019-01-23 | 2023-06-29 | Becton Dickinson Co | Oligonucleótidos asociados con anticuerpos |
US11467153B2 (en) | 2019-02-12 | 2022-10-11 | 10X Genomics, Inc. | Methods for processing nucleic acid molecules |
US11851683B1 (en) | 2019-02-12 | 2023-12-26 | 10X Genomics, Inc. | Methods and systems for selective analysis of cellular samples |
SG11202108788TA (en) | 2019-02-12 | 2021-09-29 | 10X Genomics Inc | Methods for processing nucleic acid molecules |
US11655499B1 (en) | 2019-02-25 | 2023-05-23 | 10X Genomics, Inc. | Detection of sequence elements in nucleic acid molecules |
WO2020176788A1 (en) | 2019-02-28 | 2020-09-03 | 10X Genomics, Inc. | Profiling of biological analytes with spatially barcoded oligonucleotide arrays |
US11920183B2 (en) | 2019-03-11 | 2024-03-05 | 10X Genomics, Inc. | Systems and methods for processing optically tagged beads |
EP3938538A1 (en) | 2019-03-15 | 2022-01-19 | 10X Genomics, Inc. | Methods for using spatial arrays for single cell sequencing |
EP3887542A1 (en) | 2019-03-22 | 2021-10-06 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
CA3138367A1 (en) | 2019-04-30 | 2020-11-05 | Encodia, Inc. | Methods for preparing analytes and related kits |
WO2020227543A2 (en) * | 2019-05-07 | 2020-11-12 | Fluidigm Corporation | Sequence based imaging |
JP2022540744A (ja) * | 2019-05-15 | 2022-09-20 | ビージーアイ シェンチェン | 核酸の空間情報を検出するためのアレイ及び方法 |
EP3976820A1 (en) | 2019-05-30 | 2022-04-06 | 10X Genomics, Inc. | Methods of detecting spatial heterogeneity of a biological sample |
WO2020240025A1 (en) | 2019-05-31 | 2020-12-03 | Cartana Ab | Method of detecting target nucleic acid molecules |
CN114051534A (zh) | 2019-07-22 | 2022-02-15 | 贝克顿迪金森公司 | 单细胞染色质免疫沉淀测序测定 |
US11514575B2 (en) | 2019-10-01 | 2022-11-29 | 10X Genomics, Inc. | Systems and methods for identifying morphological patterns in tissue samples |
US20210130881A1 (en) | 2019-11-06 | 2021-05-06 | 10X Genomics, Inc. | Imaging system hardware |
EP4055185A1 (en) | 2019-11-08 | 2022-09-14 | 10X Genomics, Inc. | Spatially-tagged analyte capture agents for analyte multiplexing |
EP4025711A2 (en) | 2019-11-08 | 2022-07-13 | 10X Genomics, Inc. | Enhancing specificity of analyte binding |
US11773436B2 (en) | 2019-11-08 | 2023-10-03 | Becton, Dickinson And Company | Using random priming to obtain full-length V(D)J information for immune repertoire sequencing |
EP4058598A1 (en) | 2019-11-13 | 2022-09-21 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
CA3158603A1 (en) | 2019-11-18 | 2021-05-27 | Neil Ira WEISENFELD | Systems and methods for tissue classification |
US20210155982A1 (en) | 2019-11-21 | 2021-05-27 | 10X Genomics, Inc. | Pipeline for spatial analysis of analytes |
CN117746422A (zh) | 2019-11-22 | 2024-03-22 | 10X基因组学有限公司 | 使用基准对齐对分析物进行空间分析的系统和方法 |
EP4073241A2 (en) | 2019-12-11 | 2022-10-19 | 10X Genomics, Inc. | Reverse transcriptase variants |
WO2021133849A1 (en) | 2019-12-23 | 2021-07-01 | 10X Genomics, Inc. | Methods for spatial analysis using rna-templated ligation |
EP4339299A3 (en) | 2020-01-10 | 2024-05-15 | 10X Genomics, Inc. | Methods for determining a location of a target nucleic acid in a biological sample |
EP4090763A1 (en) | 2020-01-13 | 2022-11-23 | Becton Dickinson and Company | Methods and compositions for quantitation of proteins and rna |
US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
US11821035B1 (en) | 2020-01-29 | 2023-11-21 | 10X Genomics, Inc. | Compositions and methods of making gene expression libraries |
US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
US20230047782A1 (en) | 2020-02-07 | 2023-02-16 | 10X Genomics, Inc. | Quantitative and automated permeabilization performance evaluation for spatial transcriptomics |
US11835462B2 (en) | 2020-02-11 | 2023-12-05 | 10X Genomics, Inc. | Methods and compositions for partitioning a biological sample |
WO2021168278A1 (en) | 2020-02-20 | 2021-08-26 | 10X Genomics, Inc. | METHODS TO COMBINE FIRST AND SECOND STRAND cDNA SYNTHESIS FOR SPATIAL ANALYSIS |
EP4107282A1 (en) | 2020-02-21 | 2022-12-28 | 10X Genomics, Inc. | Capturing genetic targets using a hybridization approach |
WO2021168287A1 (en) | 2020-02-21 | 2021-08-26 | 10X Genomics, Inc. | Methods and compositions for integrated in situ spatial assay |
US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
US11926863B1 (en) | 2020-02-27 | 2024-03-12 | 10X Genomics, Inc. | Solid state single cell method for analyzing fixed biological cells |
US11768175B1 (en) | 2020-03-04 | 2023-09-26 | 10X Genomics, Inc. | Electrophoretic methods for spatial analysis |
EP4242325A3 (en) | 2020-04-22 | 2023-10-04 | 10X Genomics, Inc. | Methods for spatial analysis using targeted rna depletion |
EP4146819A1 (en) | 2020-05-04 | 2023-03-15 | 10X Genomics, Inc. | Spatial transcriptomic transfer modes |
US11851700B1 (en) | 2020-05-13 | 2023-12-26 | 10X Genomics, Inc. | Methods, kits, and compositions for processing extracellular molecules |
US11661625B2 (en) | 2020-05-14 | 2023-05-30 | Becton, Dickinson And Company | Primers for immune repertoire profiling |
CN116134308A (zh) | 2020-05-19 | 2023-05-16 | 10X基因组学有限公司 | 电泳盒和仪器 |
AU2021275906A1 (en) | 2020-05-22 | 2022-12-22 | 10X Genomics, Inc. | Spatial analysis to detect sequence variants |
WO2021237056A1 (en) | 2020-05-22 | 2021-11-25 | 10X Genomics, Inc. | Rna integrity analysis in a biological sample |
WO2021236929A1 (en) | 2020-05-22 | 2021-11-25 | 10X Genomics, Inc. | Simultaneous spatio-temporal measurement of gene expression and cellular activity |
WO2021242834A1 (en) | 2020-05-26 | 2021-12-02 | 10X Genomics, Inc. | Method for resetting an array |
AU2021283174A1 (en) | 2020-06-02 | 2023-01-05 | 10X Genomics, Inc. | Nucleic acid library methods |
AU2021283184A1 (en) | 2020-06-02 | 2023-01-05 | 10X Genomics, Inc. | Spatial transcriptomics for antigen-receptors |
EP4162074B1 (en) | 2020-06-08 | 2024-04-24 | 10X Genomics, Inc. | Methods of determining a surgical margin and methods of use thereof |
WO2021252576A1 (en) | 2020-06-10 | 2021-12-16 | 10X Genomics, Inc. | Methods for spatial analysis using blocker oligonucleotides |
WO2021252591A1 (en) | 2020-06-10 | 2021-12-16 | 10X Genomics, Inc. | Methods for determining a location of an analyte in a biological sample |
CN116034166A (zh) | 2020-06-25 | 2023-04-28 | 10X基因组学有限公司 | Dna甲基化的空间分析 |
US11761038B1 (en) | 2020-07-06 | 2023-09-19 | 10X Genomics, Inc. | Methods for identifying a location of an RNA in a biological sample |
US11981960B1 (en) | 2020-07-06 | 2024-05-14 | 10X Genomics, Inc. | Spatial analysis utilizing degradable hydrogels |
US11932901B2 (en) | 2020-07-13 | 2024-03-19 | Becton, Dickinson And Company | Target enrichment using nucleic acid probes for scRNAseq |
CN116323968A (zh) | 2020-07-31 | 2023-06-23 | 10X基因组学有限公司 | 用于空间分析的去交联化合物和使用方法 |
WO2022032194A1 (en) | 2020-08-06 | 2022-02-10 | Singular Genomics Systems, Inc. | Methods for in situ transcriptomics and proteomics |
US11434525B2 (en) | 2020-08-06 | 2022-09-06 | Singular Genomics Systems, Inc. | Spatial sequencing |
US11981958B1 (en) | 2020-08-20 | 2024-05-14 | 10X Genomics, Inc. | Methods for spatial analysis using DNA capture |
WO2022060798A1 (en) | 2020-09-15 | 2022-03-24 | 10X Genomics, Inc. | Methods of releasing an extended capture probe from a substrate and uses of the same |
CN116507739A (zh) | 2020-09-16 | 2023-07-28 | 10X基因组学有限公司 | 使用多个孔确定生物样品中分析物位置的方法 |
CN116194590A (zh) | 2020-09-18 | 2023-05-30 | 10X基因组学有限公司 | 样品处理设备和图像配准方法 |
WO2022061152A2 (en) | 2020-09-18 | 2022-03-24 | 10X Genomics, Inc. | Sample handling apparatus and fluid delivery methods |
US11926822B1 (en) | 2020-09-23 | 2024-03-12 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
WO2022081643A2 (en) | 2020-10-13 | 2022-04-21 | 10X Genomics, Inc. | Compositions and methods for generating recombinant antigen binding molecules from single cells |
US20240018572A1 (en) | 2020-10-22 | 2024-01-18 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification |
AU2021376399A1 (en) | 2020-11-06 | 2023-06-15 | 10X Genomics, Inc. | Compositions and methods for binding an analyte to a capture probe |
US20230407404A1 (en) | 2020-11-18 | 2023-12-21 | 10X Genomics, Inc. | Methods and compositions for analyzing immune infiltration in cancer stroma to predict clinical outcome |
US11827935B1 (en) | 2020-11-19 | 2023-11-28 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification and detection probes |
WO2022109343A1 (en) | 2020-11-20 | 2022-05-27 | Becton, Dickinson And Company | Profiling of highly expressed and lowly expressed proteins |
EP4012046A1 (en) | 2020-12-11 | 2022-06-15 | 10X Genomics, Inc. | Methods and compositions for multimodal in situ analysis |
EP4121555A1 (en) | 2020-12-21 | 2023-01-25 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
WO2022147296A1 (en) | 2020-12-30 | 2022-07-07 | 10X Genomics, Inc. | Cleavage of capture probes for spatial analysis |
US20240068017A1 (en) | 2020-12-30 | 2024-02-29 | 10X Genomics, Inc. | Methods for analyte capture determination |
WO2022164615A1 (en) | 2021-01-29 | 2022-08-04 | 10X Genomics, Inc. | Method for transposase mediated spatial tagging and analyzing genomic dna in a biological sample |
WO2022182682A1 (en) | 2021-02-23 | 2022-09-01 | 10X Genomics, Inc. | Probe-based analysis of nucleic acids and proteins |
AU2022238446A1 (en) | 2021-03-18 | 2023-09-07 | 10X Genomics, Inc. | Multiplex capture of gene and protein expression from a biological sample |
WO2022216688A1 (en) | 2021-04-05 | 2022-10-13 | 10X Genomics, Inc. | Recombinant ligase composition and uses thereof |
EP4305196A1 (en) | 2021-04-14 | 2024-01-17 | 10X Genomics, Inc. | Methods of measuring mislocalization of an analyte |
WO2022226057A1 (en) | 2021-04-20 | 2022-10-27 | 10X Genomics, Inc. | Methods for assessing sample quality prior to spatial analysis using templated ligation |
WO2022232571A1 (en) | 2021-04-30 | 2022-11-03 | 10X Genomics, Inc. | Fusion rt variants for improved performance |
WO2022236054A1 (en) | 2021-05-06 | 2022-11-10 | 10X Genomics, Inc. | Methods for increasing resolution of spatial analysis |
WO2022256503A1 (en) | 2021-06-03 | 2022-12-08 | 10X Genomics, Inc. | Methods, compositions, kits, and systems for enhancing analyte capture for spatial analysis |
WO2022265965A1 (en) | 2021-06-14 | 2022-12-22 | 10X Genomics, Inc. | Reverse transcriptase variants for improved performance |
WO2022271820A1 (en) | 2021-06-22 | 2022-12-29 | 10X Genomics, Inc. | Spatial detection of sars-cov-2 using templated ligation |
EP4108783B1 (en) * | 2021-06-24 | 2024-02-21 | Miltenyi Biotec B.V. & Co. KG | Spatial sequencing with mictag |
WO2023288225A1 (en) | 2021-07-13 | 2023-01-19 | 10X Genomics, Inc. | Methods for preparing polymerized matrix with controllable thickness |
WO2023287765A1 (en) | 2021-07-13 | 2023-01-19 | 10X Genomics, Inc. | Methods for spatial analysis using targeted probe silencing |
EP4370675A1 (en) | 2021-08-12 | 2024-05-22 | 10X Genomics, Inc. | Methods, compositions and systems for identifying antigen-binding molecules |
EP4196605A1 (en) | 2021-09-01 | 2023-06-21 | 10X Genomics, Inc. | Methods, compositions, and kits for blocking a capture probe on a spatial array |
WO2023044071A1 (en) | 2021-09-17 | 2023-03-23 | 10X Genomics, Inc. | Systems and methods for image registration or alignment |
WO2023076345A1 (en) | 2021-10-26 | 2023-05-04 | 10X Genomics, Inc. | Methods for spatial analysis using targeted rna capture |
WO2023086880A1 (en) | 2021-11-10 | 2023-05-19 | 10X Genomics, Inc. | Methods, compositions, and kits for determining the location of an analyte in a biological sample |
WO2023086824A1 (en) | 2021-11-10 | 2023-05-19 | 10X Genomics, Inc. | Methods for identification of antigen-binding molecules |
WO2023102313A1 (en) | 2021-11-30 | 2023-06-08 | 10X Genomics, Inc. | Systems and methods for identifying regions of aneuploidy in a tissue |
EP4305195A2 (en) | 2021-12-01 | 2024-01-17 | 10X Genomics, Inc. | Methods, compositions, and systems for improved in situ detection of analytes and spatial analysis |
WO2023114473A2 (en) | 2021-12-16 | 2023-06-22 | 10X Genomics, Inc. | Recombinant reverse transcriptase variants for improved performance |
WO2023122033A1 (en) | 2021-12-20 | 2023-06-29 | 10X Genomics, Inc. | Self-test for pathology/histology slide imaging device |
WO2023150163A1 (en) | 2022-02-01 | 2023-08-10 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing analytes from lymphatic tissue |
WO2023150098A1 (en) | 2022-02-01 | 2023-08-10 | 10X Genomics, Inc. | Methods, kits, compositions, and systems for spatial analysis |
WO2023150171A1 (en) | 2022-02-01 | 2023-08-10 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing analytes from glioblastoma samples |
WO2023159028A1 (en) | 2022-02-15 | 2023-08-24 | 10X Genomics, Inc. | Systems and methods for spatial analysis of analytes using fiducial alignment |
WO2023172670A2 (en) | 2022-03-11 | 2023-09-14 | 10X Genomics, Inc. | Sample handling apparatus and fluid delivery methods |
WO2023201235A2 (en) | 2022-04-12 | 2023-10-19 | 10X Genomics, Inc. | Compositions and methods for generating and characterizing recombinant antigen binding molecules |
US20240026427A1 (en) | 2022-05-06 | 2024-01-25 | 10X Genomics, Inc. | Methods and compositions for in situ analysis of v(d)j sequences |
WO2023215552A1 (en) | 2022-05-06 | 2023-11-09 | 10X Genomics, Inc. | Molecular barcode readers for analyte detection |
US20240002902A1 (en) | 2022-05-06 | 2024-01-04 | 10X Genomics, Inc. | Analysis of antigen and antigen receptor interactions |
WO2023225519A1 (en) | 2022-05-17 | 2023-11-23 | 10X Genomics, Inc. | Modified transposons, compositions and uses thereof |
WO2023229988A1 (en) | 2022-05-23 | 2023-11-30 | 10X Genomics, Inc. | Tissue sample mold |
WO2023229982A2 (en) | 2022-05-24 | 2023-11-30 | 10X Genomics, Inc. | Porous structure confinement for convection suppression |
WO2023250077A1 (en) | 2022-06-22 | 2023-12-28 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
WO2024015862A1 (en) | 2022-07-13 | 2024-01-18 | 10X Genomics, Inc. | Methods for characterization of antigen-binding molecules from biological samples |
WO2024015578A1 (en) | 2022-07-15 | 2024-01-18 | 10X Genomics, Inc. | Methods for determining a location of a target nucleic acid in a biological sample |
WO2024031068A1 (en) | 2022-08-05 | 2024-02-08 | 10X Genomics, Inc. | Systems and methods for immunofluorescence quantification |
WO2024036191A1 (en) | 2022-08-10 | 2024-02-15 | 10X Genomics, Inc. | Systems and methods for colocalization |
WO2024035844A1 (en) | 2022-08-12 | 2024-02-15 | 10X Genomics, Inc. | Methods for reducing capture of analytes |
WO2024044703A1 (en) | 2022-08-24 | 2024-02-29 | 10X Genomics, Inc. | Compositions and methods for antigenic epitope mapping in biological samples |
WO2024081212A1 (en) | 2022-10-10 | 2024-04-18 | 10X Genomics, Inc. | In vitro transcription of spatially captured nucleic acids |
WO2024081869A1 (en) | 2022-10-14 | 2024-04-18 | 10X Genomics, Inc. | Methods for analysis of biological samples |
WO2024086167A2 (en) | 2022-10-17 | 2024-04-25 | 10X Genomics, Inc. | Methods, compositions, and kits for determining the location of an analyte in a biological sample |
WO2024102809A1 (en) | 2022-11-09 | 2024-05-16 | 10X Genomics, Inc. | Methods, compositions, and kits for determining the location of multiple analytes in a biological sample |
Family Cites Families (557)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4883867A (en) | 1985-11-01 | 1989-11-28 | Becton, Dickinson And Company | Detection of reticulocytes, RNA or DNA |
US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
US5589173A (en) | 1986-11-04 | 1996-12-31 | Genentech, Inc. | Method and therapeutic compositions for the treatment of myocardial infarction |
GB8810400D0 (en) | 1988-05-03 | 1988-06-08 | Southern E | Analysing polynucleotide sequences |
US5130238A (en) | 1988-06-24 | 1992-07-14 | Cangene Corporation | Enhanced nucleic acid amplification process |
AU2684488A (en) | 1988-06-27 | 1990-01-04 | Carter-Wallace, Inc. | Test device and method for colored particle immunoassay |
US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
US5002882A (en) | 1989-04-27 | 1991-03-26 | New England Biolabs, Inc. | Method for producing the XmaI restriction endonuclease and methylase |
RU2145635C1 (ru) | 1989-05-18 | 2000-02-20 | Чирон Корпорейшн | Олигомер (варианты), способ обнаружения последовательности hcv (варианты), набор для обнаружения, способ получения крови |
CA2044616A1 (en) | 1989-10-26 | 1991-04-27 | Roger Y. Tsien | Dna sequencing |
US5494810A (en) | 1990-05-03 | 1996-02-27 | Cornell Research Foundation, Inc. | Thermostable ligase-mediated DNA amplifications system for the detection of genetic disease |
US5559032A (en) | 1990-06-29 | 1996-09-24 | Pomeroy; Patrick C. | Method and apparatus for post-transfer assaying of material on solid support |
US5455166A (en) | 1991-01-31 | 1995-10-03 | Becton, Dickinson And Company | Strand displacement amplification |
US5183053A (en) | 1991-04-12 | 1993-02-02 | Acuderm, Inc. | Elliptical biopsy punch |
US5474796A (en) | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
ATE152831T1 (de) | 1991-09-16 | 1997-05-15 | Molecular Probes Inc | Dimere unsymmetrische cyaninfarbstoffe |
US5321130A (en) | 1992-02-10 | 1994-06-14 | Molecular Probes, Inc. | Unsymmetrical cyanine dyes with a cationic side chain |
US5308751A (en) | 1992-03-23 | 1994-05-03 | General Atomics | Method for sequencing double-stranded DNA |
US5503980A (en) | 1992-11-06 | 1996-04-02 | Trustees Of Boston University | Positional sequencing by hybridization |
US5472881A (en) | 1992-11-12 | 1995-12-05 | University Of Utah Research Foundation | Thiol labeling of DNA for attachment to gold surfaces |
US5410030A (en) | 1993-04-05 | 1995-04-25 | Molecular Probes, Inc. | Dimers of unsymmetrical cyanine dyes containing pyridinium moieties |
US5658751A (en) | 1993-04-13 | 1997-08-19 | Molecular Probes, Inc. | Substituted unsymmetrical cyanine dyes with selected permeability |
US5436134A (en) | 1993-04-13 | 1995-07-25 | Molecular Probes, Inc. | Cyclic-substituted unsymmetrical cyanine dyes |
US5837832A (en) | 1993-06-25 | 1998-11-17 | Affymetrix, Inc. | Arrays of nucleic acid probes on biological chips |
EP0711303B2 (en) | 1993-07-30 | 2009-06-10 | Affymax, Inc. | Biotinylation of proteins |
US6401267B1 (en) | 1993-09-27 | 2002-06-11 | Radoje Drmanac | Methods and compositions for efficient nucleic acid sequencing |
US5610287A (en) | 1993-12-06 | 1997-03-11 | Molecular Tool, Inc. | Method for immobilizing nucleic acid molecules |
SE9400522D0 (sv) | 1994-02-16 | 1994-02-16 | Ulf Landegren | Method and reagent for detecting specific nucleotide sequences |
US5512462A (en) | 1994-02-25 | 1996-04-30 | Hoffmann-La Roche Inc. | Methods and reagents for the polymerase chain reaction amplification of long DNA sequences |
US5677170A (en) | 1994-03-02 | 1997-10-14 | The Johns Hopkins University | In vitro transposition of artificial transposons |
CA2185239C (en) | 1994-03-16 | 2002-12-17 | Nanibhushan Dattagupta | Isothermal strand displacement nucleic acid amplification |
US6015880A (en) | 1994-03-16 | 2000-01-18 | California Institute Of Technology | Method and substrate for performing multiple sequential reactions on a matrix |
US5552278A (en) | 1994-04-04 | 1996-09-03 | Spectragen, Inc. | DNA sequencing by stepwise ligation and cleavage |
US5807522A (en) | 1994-06-17 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for fabricating microarrays of biological samples |
US5641658A (en) | 1994-08-03 | 1997-06-24 | Mosaic Technologies, Inc. | Method for performing amplification of nucleic acid with two primers bound to a single solid support |
EP0777749B1 (en) | 1994-08-19 | 2002-10-30 | PE Corporation (NY) | Coupled amplification and ligation method |
US5846719A (en) | 1994-10-13 | 1998-12-08 | Lynx Therapeutics, Inc. | Oligonucleotide tags for sorting and identification |
KR960022566A (ko) | 1994-12-30 | 1996-07-18 | 김충환 | 신규한 아미노올리고당 유도체 및 그의 제조방법 |
US5736351A (en) | 1995-01-09 | 1998-04-07 | New Horizons Diagnostics Corporation | Method for detection of contaminants |
US5959098A (en) | 1996-04-17 | 1999-09-28 | Affymetrix, Inc. | Substrate preparation process |
US5750341A (en) | 1995-04-17 | 1998-05-12 | Lynx Therapeutics, Inc. | DNA sequencing by parallel oligonucleotide extensions |
US5648245A (en) | 1995-05-09 | 1997-07-15 | Carnegie Institution Of Washington | Method for constructing an oligonucleotide concatamer library by rolling circle replication |
US5928928A (en) | 1995-06-07 | 1999-07-27 | Universiteit Van Amsterdam | Human chitinase, its recombinant production, its use for decomposing chitin, its use in therapy or prophylaxis against infection diseases |
SE504798C2 (sv) | 1995-06-16 | 1997-04-28 | Ulf Landegren | Immunanalys och testkit med två reagens som kan tvärbindas om de adsorberats till analyten |
JP4709333B2 (ja) | 1995-10-13 | 2011-06-22 | プレジデント・アンド・フエローズ・オブ・ハーバード・カレツジ | ホスホパンテテイニルトランスフェラーゼおよびその使用 |
US5716825A (en) | 1995-11-01 | 1998-02-10 | Hewlett Packard Company | Integrated nucleic acid analysis system for MALDI-TOF MS |
US5763175A (en) | 1995-11-17 | 1998-06-09 | Lynx Therapeutics, Inc. | Simultaneous sequencing of tagged polynucleotides |
US5854033A (en) | 1995-11-21 | 1998-12-29 | Yale University | Rolling circle replication reporter systems |
US6300063B1 (en) | 1995-11-29 | 2001-10-09 | Affymetrix, Inc. | Polymorphism detection |
EP0880598A4 (en) * | 1996-01-23 | 2005-02-23 | Affymetrix Inc | RAPID EVALUATION OF NUCLEIC ACID ABUNDANCE DIFFERENCE, WITH A HIGH-DENSITY OLIGONUCLEOTIDE SYSTEM |
EP2368897B1 (en) | 1996-02-09 | 2016-10-19 | Cornell Research Foundation, Inc. | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
US6852487B1 (en) | 1996-02-09 | 2005-02-08 | Cornell Research Foundation, Inc. | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
US6013440A (en) | 1996-03-11 | 2000-01-11 | Affymetrix, Inc. | Nucleic acid affinity columns |
JP4468488B2 (ja) | 1996-05-29 | 2010-05-26 | コーネル・リサーチ・ファンデーション・インコーポレイテッド | 組み合せたリガーゼ検出およびポリメラーゼ連鎖反応を用いる核酸配列相違の検出 |
US20050003431A1 (en) | 1996-08-16 | 2005-01-06 | Wucherpfennig Kai W. | Monovalent, multivalent, and multimeric MHC binding domain fusion proteins and conjugates, and uses therefor |
US5925545A (en) | 1996-09-09 | 1999-07-20 | Wisconsin Alumni Research Foundation | System for in vitro transposition |
US5965443A (en) | 1996-09-09 | 1999-10-12 | Wisconsin Alumni Research Foundation | System for in vitro transposition |
GB9620209D0 (en) | 1996-09-27 | 1996-11-13 | Cemu Bioteknik Ab | Method of sequencing DNA |
DE19639673A1 (de) | 1996-09-27 | 1998-04-09 | Daimler Benz Ag | In einem Kraftfahrzeug im Bereich der Frontscheibe angeordnetes Display |
US6083761A (en) | 1996-12-02 | 2000-07-04 | Glaxo Wellcome Inc. | Method and apparatus for transferring and combining reagents |
US6060240A (en) | 1996-12-13 | 2000-05-09 | Arcaris, Inc. | Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom |
US5837466A (en) | 1996-12-16 | 1998-11-17 | Vysis, Inc. | Devices and methods for detecting nucleic acid analytes in samples |
GB9626815D0 (en) | 1996-12-23 | 1997-02-12 | Cemu Bioteknik Ab | Method of sequencing DNA |
EP0968223B1 (en) | 1997-01-08 | 2016-12-21 | Sigma-Aldrich Co. LLC | Bioconjugation of macromolecules |
US6309824B1 (en) | 1997-01-16 | 2001-10-30 | Hyseq, Inc. | Methods for analyzing a target nucleic acid using immobilized heterogeneous mixtures of oligonucleotide probes |
US8207093B2 (en) | 1997-01-21 | 2012-06-26 | The General Hospital Corporation | Selection of proteins using RNA-protein fusions |
US6261804B1 (en) | 1997-01-21 | 2001-07-17 | The General Hospital Corporation | Selection of proteins using RNA-protein fusions |
ATE529509T1 (de) | 1997-01-21 | 2011-11-15 | Gen Hospital Corp | Selektion von proteinen unter verwendung von rna- protein-fusionen |
US5837860A (en) | 1997-03-05 | 1998-11-17 | Molecular Tool, Inc. | Covalent attachment of nucleic acid molecules onto solid-phases via disulfide bonds |
US6327410B1 (en) | 1997-03-14 | 2001-12-04 | The Trustees Of Tufts College | Target analyte sensors utilizing Microspheres |
US6023540A (en) | 1997-03-14 | 2000-02-08 | Trustees Of Tufts College | Fiber optic sensor with encoded microspheres |
US7622294B2 (en) * | 1997-03-14 | 2009-11-24 | Trustees Of Tufts College | Methods for detecting target analytes and enzymatic reactions |
JP2002503954A (ja) | 1997-04-01 | 2002-02-05 | グラクソ、グループ、リミテッド | 核酸増幅法 |
EP0975802B1 (en) | 1997-04-01 | 2004-06-23 | Manteia S.A. | Method of nucleic acid sequencing |
US6143496A (en) | 1997-04-17 | 2000-11-07 | Cytonix Corporation | Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly |
US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
US5919626A (en) | 1997-06-06 | 1999-07-06 | Orchid Bio Computer, Inc. | Attachment of unmodified nucleic acids to silanized solid phase surfaces |
WO1999005295A1 (en) | 1997-07-25 | 1999-02-04 | Thomas Jefferson University | Composition and method for targeted integration into cells |
GB9718455D0 (en) | 1997-09-02 | 1997-11-05 | Mcgregor Duncan P | Chimeric binding peptide library screening method |
JP2001519538A (ja) | 1997-10-10 | 2001-10-23 | プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ | 核酸アレイのレプリカ増幅 |
US6242246B1 (en) | 1997-12-15 | 2001-06-05 | Somalogic, Inc. | Nucleic acid ligand diagnostic Biochip |
ATE506449T1 (de) | 1997-12-22 | 2011-05-15 | Hitachi Chemical Co Ltd | Direkte rt-pcr auf oligonukleotid-immobilisierten pcr-mikroplatten |
US6844158B1 (en) | 1997-12-22 | 2005-01-18 | Hitachi Chemical Co., Ltd. | Direct RT-PCR on oligonucleotide-immobilized PCR microplates |
US7427678B2 (en) | 1998-01-08 | 2008-09-23 | Sigma-Aldrich Co. | Method for immobilizing oligonucleotides employing the cycloaddition bioconjugation method |
ES2656439T3 (es) | 1998-02-23 | 2018-02-27 | Wisconsin Alumni Research Foundation | Aparato para síntesis de matrices de sondas de ADN |
US6699710B1 (en) | 1998-02-25 | 2004-03-02 | The United States Of America As Represented By The Department Of Health And Human Services | Tumor tissue microarrays for rapid molecular profiling |
WO1999053102A1 (en) | 1998-04-16 | 1999-10-21 | Packard Bioscience Company | Analysis of polynucleotide sequence |
US6358475B1 (en) | 1998-05-27 | 2002-03-19 | Becton, Dickinson And Company | Device for preparing thin liquid for microscopic analysis |
WO1999063385A1 (en) | 1998-06-04 | 1999-12-09 | Board Of Regents, The University Of Texas System | Digital optical chemistry micromirror imager |
JP3662850B2 (ja) | 1998-06-24 | 2005-06-22 | イルミナ インコーポレイテッド | 微小球を有するアレイセンサーのデコード |
CA2321821A1 (en) | 1998-06-26 | 2000-01-06 | Visible Genetics Inc. | Method for sequencing nucleic acids with reduced errors |
US20040106110A1 (en) | 1998-07-30 | 2004-06-03 | Solexa, Ltd. | Preparation of polynucleotide arrays |
US20030022207A1 (en) | 1998-10-16 | 2003-01-30 | Solexa, Ltd. | Arrayed polynucleotides and their use in genome analysis |
US6787308B2 (en) | 1998-07-30 | 2004-09-07 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
US6159736A (en) | 1998-09-23 | 2000-12-12 | Wisconsin Alumni Research Foundation | Method for making insertional mutations using a Tn5 synaptic complex |
AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
US6573043B1 (en) | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
WO2000024940A1 (en) | 1998-10-28 | 2000-05-04 | Vysis, Inc. | Cellular arrays and methods of detecting and using genetic disorder markers |
US6391937B1 (en) | 1998-11-25 | 2002-05-21 | Motorola, Inc. | Polyacrylamide hydrogels and hydrogel arrays made from polyacrylamide reactive prepolymers |
NZ511699A (en) | 1998-12-02 | 2003-02-28 | Phylos Inc | DNA-protein fusions and uses thereof |
US6818418B1 (en) | 1998-12-10 | 2004-11-16 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
US6232075B1 (en) | 1998-12-14 | 2001-05-15 | Li-Cor, Inc. | Heterogeneous assay for pyrophosphate detection |
DE60042775D1 (de) | 1999-01-06 | 2009-10-01 | Callida Genomics Inc | Verbesserte sequenzierung mittels hybridisierung durch verwendung von sondengemischen |
GB9901475D0 (en) | 1999-01-22 | 1999-03-17 | Pyrosequencing Ab | A method of DNA sequencing |
US6565727B1 (en) | 1999-01-25 | 2003-05-20 | Nanolytics, Inc. | Actuators for microfluidics without moving parts |
US20020150909A1 (en) | 1999-02-09 | 2002-10-17 | Stuelpnagel John R. | Automated information processing in randomly ordered arrays |
US6294063B1 (en) | 1999-02-12 | 2001-09-25 | Board Of Regents, The University Of Texas System | Method and apparatus for programmable fluidic processing |
US6153389A (en) | 1999-02-22 | 2000-11-28 | Haarer; Brian K. | DNA additives as a mechanism for unambiguously marking biological samples |
EP1923471B1 (en) | 1999-04-20 | 2012-12-19 | Illumina, Inc. | Detection of nucleic acid reactions on bead arrays |
US20060275782A1 (en) | 1999-04-20 | 2006-12-07 | Illumina, Inc. | Detection of nucleic acid reactions on bead arrays |
US6673620B1 (en) | 1999-04-20 | 2004-01-06 | Cytologix Corporation | Fluid exchange in a chamber on a microscope slide |
US20050191698A1 (en) | 1999-04-20 | 2005-09-01 | Illumina, Inc. | Nucleic acid sequencing using microsphere arrays |
US6355431B1 (en) | 1999-04-20 | 2002-03-12 | Illumina, Inc. | Detection of nucleic acid amplification reactions using bead arrays |
US7276336B1 (en) | 1999-07-22 | 2007-10-02 | Agilent Technologies, Inc. | Methods of fabricating an addressable array of biopolymer probes |
US20010055764A1 (en) | 1999-05-07 | 2001-12-27 | Empedocles Stephen A. | Microarray methods utilizing semiconductor nanocrystals |
US6544732B1 (en) * | 1999-05-20 | 2003-04-08 | Illumina, Inc. | Encoding and decoding of array sensors utilizing nanocrystals |
CA2374390A1 (en) * | 1999-05-20 | 2000-12-14 | Illumina, Inc. | Combinatorial decoding of random nucleic acid arrays |
US7501245B2 (en) | 1999-06-28 | 2009-03-10 | Helicos Biosciences Corp. | Methods and apparatuses for analyzing polynucleotide sequences |
US6818395B1 (en) | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
US6465183B2 (en) * | 1999-07-01 | 2002-10-15 | Agilent Technologies, Inc. | Multidentate arrays |
ATE328277T1 (de) | 1999-07-26 | 2006-06-15 | Us Gov Health & Human Serv | Schichtvorrichtung mit einfangbereichen zur zellulären analyse |
EP1198583A1 (en) | 1999-08-02 | 2002-04-24 | Wisconsin Alumni Research Foundation | Mutant tn5 transposase enzymes and method for their use |
EP1206577B1 (en) | 1999-08-13 | 2006-03-01 | Yale University | Binary encoded sequence tags |
EP1218545B1 (en) | 1999-08-18 | 2012-01-25 | Illumina, Inc. | Methods for preparing oligonucleotide solutions |
WO2001018524A2 (en) | 1999-08-30 | 2001-03-15 | Illumina, Inc. | Methods for improving signal detection from an array |
US7244559B2 (en) | 1999-09-16 | 2007-07-17 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US6274320B1 (en) | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
AU7537200A (en) | 1999-09-29 | 2001-04-30 | Solexa Ltd. | Polynucleotide sequencing |
US6291180B1 (en) | 1999-09-29 | 2001-09-18 | American Registry Of Pathology | Ultrasound-mediated high-speed biological reaction and tissue processing |
EP1235932A2 (en) | 1999-10-08 | 2002-09-04 | Protogene Laboratories, Inc. | Method and apparatus for performing large numbers of reactions using array assembly |
US7585632B2 (en) | 1999-10-29 | 2009-09-08 | Hologic, Inc. | Compositions and methods for the detection of a nucleic acid using a cleavage reaction |
US6569674B1 (en) | 1999-12-15 | 2003-05-27 | Amersham Biosciences Ab | Method and apparatus for performing biological reactions on a substrate surface |
EP1238286A1 (en) | 1999-12-13 | 2002-09-11 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | High-throughput tissue microarray technology and applications |
US6485926B2 (en) | 1999-12-22 | 2002-11-26 | Fuji Photo Film Co., Ltd. | Method for measuring protease activity |
GB0002389D0 (en) | 2000-02-02 | 2000-03-22 | Solexa Ltd | Molecular arrays |
US8076063B2 (en) | 2000-02-07 | 2011-12-13 | Illumina, Inc. | Multiplexed methylation detection methods |
US7582420B2 (en) | 2001-07-12 | 2009-09-01 | Illumina, Inc. | Multiplex nucleic acid reactions |
EP1255865B1 (en) | 2000-02-07 | 2007-04-18 | Illumina, Inc. | Nucleic acid detection method using universal priming |
US7361488B2 (en) | 2000-02-07 | 2008-04-22 | Illumina, Inc. | Nucleic acid detection methods using universal priming |
US7955794B2 (en) | 2000-09-21 | 2011-06-07 | Illumina, Inc. | Multiplex nucleic acid reactions |
DE60143723D1 (de) | 2000-02-07 | 2011-02-03 | Illumina Inc | Nukleinsäuredetektionsverfahren mit universellem Priming |
US7611869B2 (en) | 2000-02-07 | 2009-11-03 | Illumina, Inc. | Multiplexed methylation detection methods |
US6770441B2 (en) | 2000-02-10 | 2004-08-03 | Illumina, Inc. | Array compositions and methods of making same |
WO2001061044A1 (en) | 2000-02-15 | 2001-08-23 | Lynx Therapeutics, Inc. | Data analysis and display system for ligation-based dna sequencing |
US7306904B2 (en) | 2000-02-18 | 2007-12-11 | Olink Ab | Methods and kits for proximity probing |
CA2403296A1 (en) | 2000-04-10 | 2001-10-18 | Benjamin F. Cravatt | Proteomic analysis using activity-based probe libraries |
US6368801B1 (en) | 2000-04-12 | 2002-04-09 | Molecular Staging, Inc. | Detection and amplification of RNA using target-mediated ligation of DNA by RNA ligase |
US7001792B2 (en) | 2000-04-24 | 2006-02-21 | Eagle Research & Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
US6828098B2 (en) | 2000-05-20 | 2004-12-07 | The Regents Of The University Of Michigan | Method of producing a DNA library using positional amplification based on the use of adaptors and nick translation |
EP1311839B1 (en) | 2000-06-21 | 2006-03-01 | Bioarray Solutions Ltd | Multianalyte molecular analysis using application-specific random particle arrays |
DE60131194T2 (de) | 2000-07-07 | 2008-08-07 | Visigen Biotechnologies, Inc., Bellaire | Sequenzbestimmung in echtzeit |
GB0018120D0 (en) | 2000-07-24 | 2000-09-13 | Fermentas Ab | Nuclease |
AU2001280796A1 (en) | 2000-07-25 | 2002-02-05 | The Regents Of The University Of California | Electrowetting-driven micropumping |
US7613571B2 (en) | 2000-07-28 | 2009-11-03 | Doyle Michael D | Method and system for the multidimensional morphological reconstruction of genome expression activity |
WO2002014860A1 (en) | 2000-08-15 | 2002-02-21 | Discerna Limited | Functional protein arrays |
CA2420949C (en) | 2000-08-21 | 2012-01-03 | Apitope Technology (Bristol) Limited | Peptide selection method |
US6713257B2 (en) | 2000-08-25 | 2004-03-30 | Rosetta Inpharmatics Llc | Gene discovery using microarrays |
US6773566B2 (en) | 2000-08-31 | 2004-08-10 | Nanolytics, Inc. | Electrostatic actuators for microfluidics and methods for using same |
US20020168639A1 (en) | 2000-09-22 | 2002-11-14 | Muraca Patrick J. | Profile array substrates |
US6897023B2 (en) | 2000-09-27 | 2005-05-24 | The Molecular Sciences Institute, Inc. | Method for determining relative abundance of nucleic acid sequences |
AT411066B (de) | 2000-10-24 | 2003-09-25 | Steiner Georg E | Verfahren und anordnung zur untersuchung von zellen |
US20020164611A1 (en) * | 2000-11-15 | 2002-11-07 | Bamdad R. Shoshana | Oligonucleotide identifiers |
AU2002227156A1 (en) | 2000-12-01 | 2002-06-11 | Visigen Biotechnologies, Inc. | Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity |
AR031640A1 (es) | 2000-12-08 | 2003-09-24 | Applied Research Systems | Amplificacion isotermica de acidos nucleicos en un soporte solido |
US20030215936A1 (en) | 2000-12-13 | 2003-11-20 | Olli Kallioniemi | High-throughput tissue microarray technology and applications |
US20030017451A1 (en) | 2000-12-21 | 2003-01-23 | Hui Wang | Methods for detecting transcripts |
JP4061043B2 (ja) | 2000-12-28 | 2008-03-12 | 株式会社ポストゲノム研究所 | invitro転写/翻訳系によるペプチド等の製造方法 |
ATE538380T1 (de) | 2001-01-23 | 2012-01-15 | Harvard College | Nukleinsäure-programmierbare protein-arrays |
US20030087232A1 (en) | 2001-01-25 | 2003-05-08 | Fred Christians | Methods for screening polypeptides |
US7645868B2 (en) | 2001-01-25 | 2010-01-12 | Luminex Molecular Diagnostics, Inc. | Families of non-cross-hybridizing polynucleotides for use as tags and tag complements, manufacture and use thereof |
KR20020063359A (ko) | 2001-01-27 | 2002-08-03 | 일렉트론 바이오 (주) | 핵산 및 올리거뉴클레오티드의 상보적 이중결합의 특정서열에 특이적으로 반응하는 절단기법을 이용한 핵산 혼성분석 방법 및 장치 |
EP1379549A2 (fr) | 2001-02-07 | 2004-01-14 | Institut Pasteur | Sequence du genome de photorhabdus luminescens souche tto1 et utilisations |
US6573051B2 (en) | 2001-03-09 | 2003-06-03 | Molecular Staging, Inc. | Open circle probes with intramolecular stem structures |
JP2004523243A (ja) | 2001-03-12 | 2004-08-05 | カリフォルニア インスティチュート オブ テクノロジー | 非同期性塩基伸長によってポリヌクレオチド配列を分析するための方法および装置 |
AU785425B2 (en) | 2001-03-30 | 2007-05-17 | Genetic Technologies Limited | Methods of genomic analysis |
AU2002305300B2 (en) | 2001-04-30 | 2006-06-01 | Ventana Medical Systems, Inc. | Reagents and methods for automated in situ or microarray hybridization |
WO2003002979A2 (en) | 2001-06-28 | 2003-01-09 | Illumina, Inc. | Multiplex decoding of array sensors with microspheres |
US7473767B2 (en) | 2001-07-03 | 2009-01-06 | The Institute For Systems Biology | Methods for detection and quantification of analytes in complex mixtures |
US20040241688A1 (en) | 2001-07-19 | 2004-12-02 | Cuneyt Bukusoglu | Human tissue specific drug screening procedure |
GB0118031D0 (en) | 2001-07-24 | 2001-09-19 | Oxford Glycosciences Uk Ltd | Self assembled protein nucleic acid complexes and self assembled protein arrays |
US7297778B2 (en) | 2001-07-25 | 2007-11-20 | Affymetrix, Inc. | Complexity management of genomic DNA |
DE60210014T2 (de) | 2001-07-31 | 2006-09-21 | Pfizer Products Inc., Groton | Auf Zellen gegründetes Phosphodiesterase-10A-Assay und Sequenzen |
US6696271B2 (en) | 2001-08-23 | 2004-02-24 | The Regents Of The University Of California | Frozen tissue microarray technology for analysis of RNA, DNA, and proteins |
AU2002333526B2 (en) | 2001-09-10 | 2008-01-17 | Meso Scale Technologies, Llc. | Methods and apparatus for conducting multiple measurements on a sample |
US20060188875A1 (en) | 2001-09-18 | 2006-08-24 | Perlegen Sciences, Inc. | Human genomic polymorphisms |
US20040019005A1 (en) | 2001-10-01 | 2004-01-29 | Jeffrey Van Ness | Methods for parallel measurement of genetic variations |
AU2002360272A1 (en) | 2001-10-10 | 2003-04-22 | Superarray Bioscience Corporation | Detecting targets by unique identifier nucleotide tags |
US6942972B2 (en) | 2001-10-24 | 2005-09-13 | Beckman Coulter, Inc. | Efficient synthesis of protein-oligonucleotide conjugates |
US20030175947A1 (en) | 2001-11-05 | 2003-09-18 | Liu Robin Hui | Enhanced mixing in microfluidic devices |
WO2003056298A2 (en) | 2001-11-06 | 2003-07-10 | Agilix Corporation | Sensitive coded detection systems |
AU2002359436A1 (en) | 2001-11-13 | 2003-06-23 | Rubicon Genomics Inc. | Dna amplification and sequencing using dna molecules generated by random fragmentation |
GB0127564D0 (en) | 2001-11-16 | 2002-01-09 | Medical Res Council | Emulsion compositions |
AU2002359508A1 (en) | 2001-11-26 | 2003-06-10 | Keck Graduate Institute | Method, apparatus and article for microfluidic control via electrowetting, for chemical, biochemical and biological assays and the like |
US7057026B2 (en) | 2001-12-04 | 2006-06-06 | Solexa Limited | Labelled nucleotides |
US7098041B2 (en) | 2001-12-11 | 2006-08-29 | Kimberly-Clark Worldwide, Inc. | Methods to view and analyze the results from diffraction-based diagnostics |
WO2003070294A2 (en) | 2002-01-16 | 2003-08-28 | Mayo Foundation For Medical Education And Research | Method and apparatus for image-guided therapy |
US20040002090A1 (en) | 2002-03-05 | 2004-01-01 | Pascal Mayer | Methods for detecting genome-wide sequence variations associated with a phenotype |
US20030170637A1 (en) | 2002-03-06 | 2003-09-11 | Pirrung Michael C. | Method of analyzing mRNA splice variants |
US7223371B2 (en) | 2002-03-14 | 2007-05-29 | Micronics, Inc. | Microfluidic channel network device |
JP2005538695A (ja) | 2002-04-15 | 2005-12-22 | ザ リージェント オブ ザ ユニバーシティ オブ カリフォルニア | 概日リズム障害を治療するためのスクリーニング法および治療法 |
AU2003225085A1 (en) | 2002-04-19 | 2003-11-03 | California Institute Of Technology | Unnatural amino acid containing display libraries |
DK2151250T3 (da) | 2002-05-06 | 2013-12-16 | Endocyte Inc | Vitamin-targetede billeddannelsesmidler |
CA2487424C (en) | 2002-05-30 | 2011-01-04 | The Scripps Research Institute | Copper-catalysed ligation of azides and acetylenes |
US7108976B2 (en) | 2002-06-17 | 2006-09-19 | Affymetrix, Inc. | Complexity management of genomic DNA by locus specific amplification |
CN1675538A (zh) | 2002-06-18 | 2005-09-28 | 茵维特罗根公司 | 用于预先铸造可水合分离介质的低阻电泳的方法和设备 |
FR2841063B1 (fr) | 2002-06-18 | 2004-09-17 | Commissariat Energie Atomique | Dispositif de deplacement de petits volumes de liquide le long d'un micro-catenaire par des forces electrostatiques |
US20050019776A1 (en) | 2002-06-28 | 2005-01-27 | Callow Matthew James | Universal selective genome amplification and universal genotyping system |
US7205128B2 (en) | 2002-08-16 | 2007-04-17 | Agilent Technologies, Inc. | Method for synthesis of the second strand of cDNA |
SI3363809T1 (sl) | 2002-08-23 | 2020-08-31 | Illumina Cambridge Limited | Modificirani nukleotidi za polinukleotidno sekvenciranje |
US20040038385A1 (en) | 2002-08-26 | 2004-02-26 | Langlois Richard G. | System for autonomous monitoring of bioagents |
US20070166725A1 (en) | 2006-01-18 | 2007-07-19 | The Regents Of The University Of California | Multiplexed diagnostic platform for point-of care pathogen detection |
AU2003267111A1 (en) | 2002-09-11 | 2004-04-30 | Temple University - Of The Commonwealth System Of Higher Education | Automated system for high-throughput electrophoretic separations |
US7595883B1 (en) | 2002-09-16 | 2009-09-29 | The Board Of Trustees Of The Leland Stanford Junior University | Biological analysis arrangement and approach therefor |
CA2498764C (en) | 2002-09-20 | 2015-11-10 | New England Biolabs, Inc. | Helicase dependent amplification of nucleic acids |
US6911132B2 (en) | 2002-09-24 | 2005-06-28 | Duke University | Apparatus for manipulating droplets by electrowetting-based techniques |
JP2006501056A (ja) | 2002-09-25 | 2006-01-12 | カリフォルニア インスティテュート オブ テクノロジー | ミクロ流体大規模集積 |
US20060079453A1 (en) | 2002-10-03 | 2006-04-13 | John Sidney | Hla binding peptides and their uses |
US20040259105A1 (en) | 2002-10-03 | 2004-12-23 | Jian-Bing Fan | Multiplex nucleic acid analysis using archived or fixed samples |
US20040067492A1 (en) | 2002-10-04 | 2004-04-08 | Allan Peng | Reverse transcription on microarrays |
CA2502580C (en) | 2002-10-31 | 2013-09-10 | University Of Massachusetts | Rapid cell block embedding method and apparatus |
WO2004055159A2 (en) | 2002-12-12 | 2004-07-01 | Chiron Corporation | Identification of oligonucleotides for the capture, detection and quantitation of west nile virus |
AU2003301061A1 (en) | 2002-12-18 | 2004-07-22 | West Virginia University Research Corporation | Apparatus and method for edman degradation using a microfluidic system |
KR20040062847A (ko) | 2003-01-03 | 2004-07-09 | 삼성전자주식회사 | 핵산 어레이의 복제방법 |
US7547380B2 (en) | 2003-01-13 | 2009-06-16 | North Carolina State University | Droplet transportation devices and methods having a fluid surface |
GB0302058D0 (en) | 2003-01-29 | 2003-02-26 | Univ Cranfield | Replication of nucleic acid arrays |
DE602004026033D1 (de) | 2003-01-29 | 2010-04-29 | 454 Corp | Zweiendige sequenzierung |
FR2852317B1 (fr) | 2003-03-13 | 2006-08-04 | Biopuces a sondes et leurs methodes d'utilisation | |
US7083980B2 (en) | 2003-04-17 | 2006-08-01 | Wisconsin Alumni Research Foundation | Tn5 transposase mutants and the use thereof |
US7267994B2 (en) | 2003-04-28 | 2007-09-11 | Regents Of The University Of California | Element-coded affinity tags |
CA2526579A1 (en) | 2003-05-23 | 2004-12-02 | Epfl-Ecole Polytechnique Federale De Lausanne | Methods for protein labeling based on acyl carrier protein |
US20050026188A1 (en) | 2003-05-30 | 2005-02-03 | Van Kessel Andrew G. | Methods of identifying, characterizing and comparing organism communities |
WO2004108268A1 (en) | 2003-05-30 | 2004-12-16 | Applera Corporation | Apparatus and method for hybridization and spr detection |
US7255994B2 (en) | 2003-06-10 | 2007-08-14 | Applera Corporation | Ligation assay |
US20060216775A1 (en) | 2003-06-17 | 2006-09-28 | The Regents Of The University Of Califoenia | Compositions and methods for analysis and manipulation of enzymes in biosynthetic proteomes |
JP2007525963A (ja) | 2003-06-20 | 2007-09-13 | イルミナ インコーポレイテッド | 全ゲノム増幅および遺伝型決定のための方法および組成物 |
US20070128656A1 (en) | 2003-06-26 | 2007-06-07 | University Of South Florida | Direct Fluorescent Label Incorporation Via 1st Strand cDNA Synthesis |
CN1816636A (zh) | 2003-07-03 | 2006-08-09 | 加利福尼亚大学董事会 | 功能性dna元件和细胞蛋白的基因组作图 |
EP2918595B1 (en) | 2003-07-05 | 2019-12-11 | The Johns-Hopkins University | Method and compositions for detection and enumeration of genetic variations |
WO2005010494A2 (en) | 2003-07-21 | 2005-02-03 | Jie Wu | Multiplexed analyte detection |
US20050031176A1 (en) | 2003-08-08 | 2005-02-10 | Hertel Sarah R. | Method and apparatus of multi-modality image fusion |
CA2535332A1 (en) | 2003-08-08 | 2005-02-24 | Thomas Jefferson University | Method for rapid identification of alternative splicing |
US20050037362A1 (en) | 2003-08-11 | 2005-02-17 | Eppendorf Array Technologies, S.A. | Detection and quantification of siRNA on microarrays |
WO2005021794A2 (en) | 2003-09-02 | 2005-03-10 | Keygene N.V. | Ola-based methods for the detection of target nucleic acid sequences |
JP5171037B2 (ja) | 2003-09-10 | 2013-03-27 | アルセア・ディーエックス,インク. | マイクロアレイを用いた発現プロファイリング |
GB0321306D0 (en) | 2003-09-11 | 2003-10-15 | Solexa Ltd | Modified polymerases for improved incorporation of nucleotide analogues |
US11118215B2 (en) | 2003-09-18 | 2021-09-14 | Nuevolution A/S | Method for obtaining structural information concerning an encoded molecule and method for selecting compounds |
US7541166B2 (en) | 2003-09-19 | 2009-06-02 | Microfluidic Systems, Inc. | Sonication to selectively lyse different cell types |
US20050064435A1 (en) | 2003-09-24 | 2005-03-24 | Xing Su | Programmable molecular barcodes |
ATE434131T1 (de) | 2003-11-17 | 2009-07-15 | Koninkl Philips Electronics Nv | System zur handhabung einer fluidmenge |
WO2005051984A2 (en) | 2003-11-21 | 2005-06-09 | Arena Pharmaceuticals, Inc. | Methods for producing olfactory gpcrs |
CN101208437B (zh) | 2003-12-12 | 2012-07-04 | 圣路易斯大学 | 检测大分子和其它分析物的生物传感器 |
US7259258B2 (en) | 2003-12-17 | 2007-08-21 | Illumina, Inc. | Methods of attaching biological compounds to solid supports using triazine |
US20050132463A1 (en) | 2003-12-19 | 2005-06-23 | Kimberly-Clark Worldwide, Inc. | Surgical gown having adhesive tabs and methods of use |
US20050136414A1 (en) | 2003-12-23 | 2005-06-23 | Kevin Gunderson | Methods and compositions for making locus-specific arrays |
EP1732598A4 (en) | 2003-12-31 | 2009-08-26 | Pharmexa Inc | INDUCING CELLULAR IMMUNE RESPONSES TO HUMAN PAPILLOMAVIRUS USING PEPTIDE COMPOSITIONS AND NUCLEIC ACIDS |
EP3673986A1 (en) | 2004-01-07 | 2020-07-01 | Illumina Cambridge Limited | Improvements in or relating to molecular arrays |
WO2005067648A2 (en) | 2004-01-08 | 2005-07-28 | Vanderbilt University | Multiplex spatial profiling of gene expression |
US7569392B2 (en) | 2004-01-08 | 2009-08-04 | Vanderbilt University | Multiplex spatial profiling of gene expression |
US20080261204A1 (en) | 2004-01-23 | 2008-10-23 | Lingvitae As | Polynucleotide Ligation Reactions |
FR2866493B1 (fr) | 2004-02-16 | 2010-08-20 | Commissariat Energie Atomique | Dispositif de controle du deplacement d'une goutte entre deux ou plusieurs substrats solides |
WO2005089508A2 (en) | 2004-03-18 | 2005-09-29 | Atom Sciences, Inc. | Dna sequence detection by limited primer extension |
FR2868638B1 (fr) | 2004-03-30 | 2006-05-19 | Sagem | Procede d'echange d'informations entre deux reseaux fonctionnant sous des protocoles de routages differents |
KR100624420B1 (ko) * | 2004-04-10 | 2006-09-19 | 삼성전자주식회사 | 마이크로어레이에 대한 정보가 스팟의 형태로 저장되어있는 마이크로어레이, 그를 제조하는 방법 및 그를이용하는 방법 |
CA2563168A1 (en) | 2004-04-14 | 2005-11-17 | President And Fellows Of Harvard College | Nucleic-acid programmable protein arrays |
RU2270254C2 (ru) | 2004-04-30 | 2006-02-20 | Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук | Способ идентификации трансгенных последовательностей днк в растительном материале и продуктах на его основе, набор олигонуклеотидов и биочип для осуществления этого способа |
DE102004022263A1 (de) * | 2004-05-06 | 2005-12-15 | Clondiag Chip Technologies Gmbh | Vorrichtung und Verfahren zum Nachweis von molekularen Wechselwirkungen |
WO2005113804A1 (en) | 2004-05-20 | 2005-12-01 | Trillion Genomics Limited | Use of mass labelled probes to detect target nucleic acids using mass spectrometry |
US7906276B2 (en) | 2004-06-30 | 2011-03-15 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
FR2872715B1 (fr) | 2004-07-08 | 2006-11-17 | Commissariat Energie Atomique | Microreacteur goutte |
FR2872809B1 (fr) | 2004-07-09 | 2006-09-15 | Commissariat Energie Atomique | Methode d'adressage d'electrodes |
WO2006073504A2 (en) | 2004-08-04 | 2006-07-13 | President And Fellows Of Harvard College | Wobble sequencing |
US7608434B2 (en) | 2004-08-04 | 2009-10-27 | Wisconsin Alumni Research Foundation | Mutated Tn5 transposase proteins and the use thereof |
JP2006058031A (ja) | 2004-08-17 | 2006-03-02 | Hitachi High-Technologies Corp | 化学分析装置 |
US7776547B2 (en) * | 2004-08-26 | 2010-08-17 | Intel Corporation | Cellular analysis using Raman surface scanning |
US20060228758A1 (en) | 2004-09-13 | 2006-10-12 | Xencor, Inc. | Analysis of MHC-peptide binding interactions |
JP2008513782A (ja) | 2004-09-17 | 2008-05-01 | パシフィック バイオサイエンシーズ オブ カリフォルニア, インコーポレイテッド | 分子解析のための装置及び方法 |
WO2006041194A1 (ja) | 2004-10-15 | 2006-04-20 | Japan Science And Technology Agency | mRNA-ピューロマイシン-タンパク質連結体作製用リンカー |
ES2503738T3 (es) | 2004-11-12 | 2014-10-07 | Asuragen, Inc. | Procedimientos y composiciones que implican miARN y moléculas inhibidoras de miARN |
US7183119B2 (en) * | 2004-11-15 | 2007-02-27 | Eastman Kodak Company | Method for sensitive detection of multiple biological analytes |
US7745143B2 (en) | 2004-11-19 | 2010-06-29 | Plexera, Llc | Plasmon resonance biosensor and method |
EP1828412B2 (en) | 2004-12-13 | 2019-01-09 | Illumina Cambridge Limited | Improved method of nucleotide detection |
GB0427236D0 (en) | 2004-12-13 | 2005-01-12 | Solexa Ltd | Improved method of nucleotide detection |
US20060292586A1 (en) | 2004-12-17 | 2006-12-28 | Schroth Gary P | ID-tag complexes, arrays, and methods of use thereof |
JP2008526877A (ja) | 2005-01-05 | 2008-07-24 | エージェンコート パーソナル ジェノミクス | 可逆的ヌクレオチドターミネーターおよびその使用 |
US7458661B2 (en) | 2005-01-25 | 2008-12-02 | The Regents Of The University Of California | Method and apparatus for promoting the complete transfer of liquid drops from a nozzle |
EP1841879A4 (en) | 2005-01-25 | 2009-05-27 | Population Genetics Technologi | ISOTHERMAL DNA AMPLIFICATION |
BRPI0607213B1 (pt) | 2005-01-28 | 2017-04-04 | Univ Duke | aparelho para manipulação de gotículas em uma placa de circuito impresso |
CA2596117A1 (en) | 2005-02-03 | 2006-08-10 | Perkinelmer Las, Inc. | Ultra-sensitive detection systems using multidimension signals |
US7393665B2 (en) | 2005-02-10 | 2008-07-01 | Population Genetics Technologies Ltd | Methods and compositions for tagging and identifying polynucleotides |
US7407757B2 (en) | 2005-02-10 | 2008-08-05 | Population Genetics Technologies | Genetic analysis by sequence-specific sorting |
US20060199207A1 (en) | 2005-02-24 | 2006-09-07 | Matysiak Stefan M | Self-assembly of molecules using combinatorial hybridization |
US7727721B2 (en) | 2005-03-08 | 2010-06-01 | California Institute Of Technology | Hybridization chain reaction amplification for in situ imaging |
US7601498B2 (en) | 2005-03-17 | 2009-10-13 | Biotium, Inc. | Methods of using dyes in association with nucleic acid staining or detection and associated technology |
US7776567B2 (en) | 2005-03-17 | 2010-08-17 | Biotium, Inc. | Dimeric and trimeric nucleic acid dyes, and associated systems and methods |
US7303880B2 (en) | 2005-03-18 | 2007-12-04 | Wisconsin Alumni Research Foundation | Microdissection-based methods for determining genomic features of single chromosomes |
US7229769B2 (en) | 2005-03-25 | 2007-06-12 | Illumina, Inc. | Compositions and methods for detecting protease activity |
ATE406463T1 (de) | 2005-04-06 | 2008-09-15 | Maurice Stroun | Methode zur krebsdiagnose mittels nachweis von dna und rna im kreislauf |
GB0508983D0 (en) | 2005-05-03 | 2005-06-08 | Oxford Gene Tech Ip Ltd | Cell analyser |
US8623628B2 (en) | 2005-05-10 | 2014-01-07 | Illumina, Inc. | Polymerases |
US20070003954A1 (en) | 2005-05-12 | 2007-01-04 | The Board Of Regents Of The University Of Texas System | Protein and antibody profiling using small molecule microarrays |
ATE502120T1 (de) | 2005-05-12 | 2011-04-15 | Affymetrix Inc | Multiplex-assays für verzweigtkettige dna |
AU2006247067B2 (en) | 2005-05-18 | 2012-06-07 | Novartis Ag | Methods for diagnosis and treatment of proliferative disorders mediated by CD40 signaling |
US20060263789A1 (en) | 2005-05-19 | 2006-11-23 | Robert Kincaid | Unique identifiers for indicating properties associated with entities to which they are attached, and methods for using |
CN100526453C (zh) | 2005-05-20 | 2009-08-12 | 麦克奥迪实业集团有限公司 | 激光显微切割后细胞收集方法 |
CA2609328A1 (en) | 2005-05-26 | 2006-11-30 | The Trustees Of Boston University | Quantification of nucleic acids and proteins using oligonucleotide mass tags |
US8486629B2 (en) | 2005-06-01 | 2013-07-16 | Bioarray Solutions, Ltd. | Creation of functionalized microparticle libraries by oligonucleotide ligation or elongation |
WO2007145612A1 (en) | 2005-06-06 | 2007-12-21 | 454 Life Sciences Corporation | Paired end sequencing |
ATE528644T1 (de) | 2005-06-07 | 2011-10-15 | Centre Nat Rech Scient | Verwendung ionischer matrizen zur analyse von gewebeabschnitten durch maldi-massenspektrometrie |
GB0511717D0 (en) | 2005-06-09 | 2005-07-13 | Babraham Inst | Repeatable protein arrays |
CA2611743C (en) | 2005-06-15 | 2019-12-31 | Callida Genomics, Inc. | Nucleic acid analysis by forming and tracking aliquoted fragments of a target polynucleotide |
ES2434915T3 (es) | 2005-06-20 | 2013-12-18 | Advanced Cell Diagnostics, Inc. | Detección múltiplex de ácidos nucleicos |
US7873193B2 (en) | 2005-06-21 | 2011-01-18 | Carl Zeiss Microimaging Gmbh | Serial section analysis for computer-controlled microscopic imaging |
DK2292788T3 (da) | 2005-06-23 | 2012-07-23 | Keygene Nv | Strategier til identifikation og detektion af polymorfismer med højt gennemløb |
WO2007005649A2 (en) | 2005-06-30 | 2007-01-11 | Applera Corporation | Proximity probing of target proteins comprising restriction and/or extension field |
US7883848B2 (en) | 2005-07-08 | 2011-02-08 | Olink Ab | Regulation analysis by cis reactivity, RACR |
JP4822753B2 (ja) | 2005-07-11 | 2011-11-24 | 一般社団法人オンチップ・セロミクス・コンソーシアム | 細胞構成物質分取チップならびに細胞構成物質解析システム及びこれらを用いる細胞構成物質解析法 |
GB0514936D0 (en) | 2005-07-20 | 2005-08-24 | Solexa Ltd | Preparation of templates for nucleic acid sequencing |
US20070020640A1 (en) | 2005-07-21 | 2007-01-25 | Mccloskey Megan L | Molecular encoding of nucleic acid templates for PCR and other forms of sequence analysis |
US20070023292A1 (en) | 2005-07-26 | 2007-02-01 | The Regents Of The University Of California | Small object moving on printed circuit board |
US7805081B2 (en) | 2005-08-11 | 2010-09-28 | Pacific Biosciences Of California, Inc. | Methods and systems for monitoring multiple optical signals from a single source |
WO2007027653A1 (en) | 2005-09-01 | 2007-03-08 | Promega Corporation | Cell-based luminogenic and nonluminogenic proteasome assays |
WO2007030373A2 (en) | 2005-09-07 | 2007-03-15 | St. Jude Children's Research Hospital | Method for in situ hybridization analysis |
JP2007074967A (ja) | 2005-09-13 | 2007-03-29 | Canon Inc | 識別子プローブ及びそれを用いた核酸増幅方法 |
CA2910861C (en) | 2005-09-29 | 2018-08-07 | Michael Josephus Theresia Van Eijk | High throughput screening of mutagenized populations |
US7405281B2 (en) | 2005-09-29 | 2008-07-29 | Pacific Biosciences Of California, Inc. | Fluorescent nucleotide analogs and uses therefor |
WO2007041689A2 (en) | 2005-10-04 | 2007-04-12 | President And Fellows Of Harvard College | Methods of site-specific labeling of molecules and molecules produced thereby |
GB0522310D0 (en) | 2005-11-01 | 2005-12-07 | Solexa Ltd | Methods of preparing libraries of template polynucleotides |
US20070116612A1 (en) | 2005-11-02 | 2007-05-24 | Biopath Automation, L.L.C. | Prefix tissue cassette |
WO2007120208A2 (en) | 2005-11-14 | 2007-10-25 | President And Fellows Of Harvard College | Nanogrid rolling circle dna sequencing |
EP1957979A1 (en) | 2005-11-25 | 2008-08-20 | Koninklijke Philips Electronics N.V. | Magnetic biosensor for determination of enzymic activity |
WO2007100392A2 (en) | 2005-11-30 | 2007-09-07 | Biotium, Inc. | Enzyme substrate comprising a functional dye and associated technology and methods |
US20070161029A1 (en) | 2005-12-05 | 2007-07-12 | Panomics, Inc. | High throughput profiling of methylation status of promoter regions of genes |
US7803751B2 (en) | 2005-12-09 | 2010-09-28 | Illumina, Inc. | Compositions and methods for detecting phosphomonoester |
US20070141718A1 (en) | 2005-12-19 | 2007-06-21 | Bui Huy A | Reduction of scan time in imaging mass spectrometry |
US20070178503A1 (en) | 2005-12-19 | 2007-08-02 | Feng Jiang | In-situ genomic DNA chip for detection of cancer |
DK1966394T3 (da) | 2005-12-22 | 2012-10-29 | Keygene Nv | Forbedrede strategier til transkriptprofilering under anvendelse af high throughput-sekventeringsteknologier |
DK2789696T3 (en) | 2005-12-22 | 2016-02-29 | Keygene Nv | A method for high-throughput AFLP-based polymorphism |
EP1985092B1 (en) | 2005-12-23 | 2011-07-06 | Telefonaktiebolaget LM Ericsson (publ) | Method and apparatus for solving data packet traffic congestion. |
ES2374788T3 (es) | 2005-12-23 | 2012-02-22 | Nanostring Technologies, Inc. | Nanoinformadores y métodos para su producción y uso. |
CN101395281B (zh) | 2006-01-04 | 2013-05-01 | 骆树恩 | 用于核酸作图和鉴定核酸的精细结构变化的方法以及用途 |
US7537897B2 (en) * | 2006-01-23 | 2009-05-26 | Population Genetics Technologies, Ltd. | Molecular counting |
WO2007087310A2 (en) | 2006-01-23 | 2007-08-02 | Population Genetics Technologies Ltd. | Nucleic acid analysis using sequence tokens |
WO2007087339A2 (en) | 2006-01-24 | 2007-08-02 | Perkinelmer Las, Inc. | Multiplexed analyte quantitation by two-dimensional planar electrochromatography |
WO2007092538A2 (en) | 2006-02-07 | 2007-08-16 | President And Fellows Of Harvard College | Methods for making nucleotide probes for sequencing and synthesis |
CA2643700A1 (en) | 2006-02-24 | 2007-11-22 | Callida Genomics, Inc. | High throughput genome sequencing on dna arrays |
SG10201405158QA (en) | 2006-02-24 | 2014-10-30 | Callida Genomics Inc | High throughput genome sequencing on dna arrays |
JP5237126B2 (ja) | 2006-03-01 | 2013-07-17 | キージーン ナムローゼ フェンノートシャップ | ライゲーションアッセイを用いてハイスループットシークエンスに基づき遺伝子関連配列を検出する方法 |
EP2021503A1 (en) | 2006-03-17 | 2009-02-11 | Solexa Ltd. | Isothermal methods for creating clonal single molecule arrays |
US20070231823A1 (en) * | 2006-03-23 | 2007-10-04 | Mckernan Kevin J | Directed enrichment of genomic DNA for high-throughput sequencing |
US8975216B2 (en) | 2006-03-30 | 2015-03-10 | Pacific Biosciences Of California | Articles having localized molecules disposed thereon and methods of producing same |
CN101460953B (zh) | 2006-03-31 | 2012-05-30 | 索雷克萨公司 | 用于合成分析的序列的系统和装置 |
EP2963127B1 (en) | 2006-04-04 | 2017-08-16 | Keygene N.V. | High throughput detection of molecular markers based on restriction fragments |
CA2680061C (en) | 2006-04-18 | 2015-10-13 | Duke University | Droplet-based biochemistry |
US8383338B2 (en) | 2006-04-24 | 2013-02-26 | Roche Nimblegen, Inc. | Methods and systems for uniform enrichment of genomic regions |
WO2007127458A2 (en) | 2006-04-28 | 2007-11-08 | Nsabp Foundation, Inc. | Methods of whole genome or microarray expression profiling using nucleic acids |
WO2007133703A2 (en) | 2006-05-10 | 2007-11-22 | Dxterity Diagnostics | Detection of nucleic acid targets using chemically reactive oligonucleotide probes |
JP2007304043A (ja) | 2006-05-15 | 2007-11-22 | Canon Inc | プローブ固定担体の製造方法 |
US7941279B2 (en) | 2006-05-22 | 2011-05-10 | Nanostring Technologies, Inc. | Systems and methods for analyzing nanoreporters |
US20080132429A1 (en) | 2006-05-23 | 2008-06-05 | Uchicago Argonne | Biological microarrays with enhanced signal yield |
ES2553141T3 (es) | 2006-05-27 | 2015-12-04 | Fluidigm Canada Inc. | Marcadores elementales de cadena principal polimérica |
WO2008002502A2 (en) | 2006-06-23 | 2008-01-03 | Illumina, Inc. | Devices and systems for creation of dna cluster arrays |
JP2009542222A (ja) | 2006-06-29 | 2009-12-03 | ジーイー・ヘルスケア・バイオサイエンス・アクチボラグ | チャンバー装置 |
US8178316B2 (en) | 2006-06-29 | 2012-05-15 | President And Fellows Of Harvard College | Evaluating proteins |
AT503862B1 (de) | 2006-07-05 | 2010-11-15 | Arc Austrian Res Centers Gmbh | Pathogen-identifizierung anhand eines 16s oder 18s-rrna mikroarray |
JP4881950B2 (ja) | 2006-07-10 | 2012-02-22 | 株式会社日立ハイテクノロジーズ | 液体搬送デバイス |
EP3536396B1 (en) | 2006-08-07 | 2022-03-30 | The President and Fellows of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
WO2008022332A2 (en) | 2006-08-18 | 2008-02-21 | Board Of Regents, The University Of Texas System | System, method and kit for replicating a dna array |
US20080047835A1 (en) | 2006-08-22 | 2008-02-28 | Macconnell William P | Genomic DNA Purifier |
CA2662521C (en) | 2006-09-01 | 2016-08-09 | Pacific Biosciences Of California, Inc. | Substrates, systems and methods for analyzing materials |
US7754429B2 (en) | 2006-10-06 | 2010-07-13 | Illumina Cambridge Limited | Method for pair-wise sequencing a plurity of target polynucleotides |
WO2008051530A2 (en) | 2006-10-23 | 2008-05-02 | Pacific Biosciences Of California, Inc. | Polymerase enzymes and reagents for enhanced nucleic acid sequencing |
US20080108804A1 (en) | 2006-11-02 | 2008-05-08 | Kabushiki Kaisha Dnaform | Method for modifying RNAS and preparing DNAS from RNAS |
US9266076B2 (en) | 2006-11-02 | 2016-02-23 | The Regents Of The University Of California | Method and apparatus for real-time feedback control of electrical manipulation of droplets on chip |
US20110045462A1 (en) | 2006-11-14 | 2011-02-24 | The Regents Of The University Of California | Digital analysis of gene expression |
US9201063B2 (en) | 2006-11-16 | 2015-12-01 | General Electric Company | Sequential analysis of biological samples |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
EP3285067B1 (en) | 2006-12-14 | 2022-06-22 | Life Technologies Corporation | Apparatus for measuring analytes using fet arrays |
CN101221182A (zh) | 2007-01-08 | 2008-07-16 | 山东司马特生物芯片有限公司 | 一种荧光蛋白质芯片血清肿瘤系列诊断新方法 |
WO2008093098A2 (en) | 2007-02-02 | 2008-08-07 | Illumina Cambridge Limited | Methods for indexing samples and sequencing multiple nucleotide templates |
WO2008098100A2 (en) | 2007-02-07 | 2008-08-14 | Perscitus Biosciences, Llc | Detection of molecule proximity |
EP2118344B1 (en) | 2007-02-12 | 2014-07-23 | Proteonova, Inc. | GENERATION OF LIBRARY OF SOLUBLE RANDOM POLYPEPTIDES LINKED TO mRNA |
KR100819006B1 (ko) | 2007-02-13 | 2008-04-03 | 삼성전자주식회사 | 마이크로 어레이용 마스크 세트, 이의 제조 방법, 및마스크 세트를 이용한 마이크로 어레이의 제조 방법 |
US8153782B2 (en) | 2007-02-14 | 2012-04-10 | Eastman Chemical Company | Reformation of ionic liquids |
KR101017808B1 (ko) | 2007-04-04 | 2011-02-28 | 엔에이치엔(주) | 편집 파일 자동 생성 방법 및 그 장치 |
EP2145180B1 (en) | 2007-04-13 | 2013-12-04 | Sequenom, Inc. | Comparative sequence analysis processes and systems |
CA2687804A1 (en) | 2007-05-23 | 2008-12-04 | Oregon Health & Science University | Microarray systems and methods for identifying dna-binding proteins |
US20090105959A1 (en) | 2007-06-01 | 2009-04-23 | Braverman Michael S | System and method for identification of individual samples from a multiplex mixture |
US8926811B2 (en) | 2007-06-27 | 2015-01-06 | Digital Biosystems | Digital microfluidics based apparatus for heat-exchanging chemical processes |
US7635566B2 (en) | 2007-06-29 | 2009-12-22 | Population Genetics Technologies Ltd. | Methods and compositions for isolating nucleic acid sequence variants |
JP2009025385A (ja) | 2007-07-17 | 2009-02-05 | Nitto Denko Corp | フィルム状光導波路の製造方法 |
US20100112590A1 (en) | 2007-07-23 | 2010-05-06 | The Chinese University Of Hong Kong | Diagnosing Fetal Chromosomal Aneuploidy Using Genomic Sequencing With Enrichment |
AU2008282557A1 (en) | 2007-07-27 | 2009-02-05 | Ensemble Discovery Corporation | Detection assays and use thereof |
JP2009036694A (ja) | 2007-08-03 | 2009-02-19 | Tokyo Medical & Dental Univ | 空間分布を保った細胞内生体物質の解析方法 |
EP2191011B1 (en) | 2007-08-29 | 2017-03-29 | Illumina Cambridge Limited | Method for sequencing a polynucleotide template |
US9388457B2 (en) | 2007-09-14 | 2016-07-12 | Affymetrix, Inc. | Locus specific amplification using array probes |
EP2201143B2 (en) | 2007-09-21 | 2016-08-24 | Katholieke Universiteit Leuven | Tools and methods for genetic tests using next generation sequencing |
EP2053132A1 (en) | 2007-10-23 | 2009-04-29 | Roche Diagnostics GmbH | Enrichment and sequence analysis of geomic regions |
US8518640B2 (en) | 2007-10-29 | 2013-08-27 | Complete Genomics, Inc. | Nucleic acid sequencing and process |
US8592150B2 (en) | 2007-12-05 | 2013-11-26 | Complete Genomics, Inc. | Methods and compositions for long fragment read sequencing |
KR20090081260A (ko) | 2008-01-23 | 2009-07-28 | 삼성전자주식회사 | 마이크로 어레이 혼성화 검출 방법 |
DE102008014687A1 (de) | 2008-03-18 | 2009-09-24 | Smartrac Ip B.V. | Lagenverbund für einen Kartenkörper und Verfahren zur Herstellung des Lagenverbunds |
GB2470672B (en) | 2008-03-21 | 2012-09-12 | Nugen Technologies Inc | Methods of RNA amplification in the presence of DNA |
US20090253163A1 (en) | 2008-04-02 | 2009-10-08 | General Electric Company | Iterative staining of biological samples |
DE102008023438B4 (de) | 2008-05-14 | 2011-06-30 | Bruker Daltonik GmbH, 28359 | Verfahren zur Analyse von Gewebeschnitten |
US8093064B2 (en) | 2008-05-15 | 2012-01-10 | The Regents Of The University Of California | Method for using magnetic particles in droplet microfluidics |
DE102008025656B4 (de) | 2008-05-28 | 2016-07-28 | Genxpro Gmbh | Verfahren zur quantitativen Analyse von Nukleinsäuren, Marker dafür und deren Verwendung |
US20100120097A1 (en) | 2008-05-30 | 2010-05-13 | Board Of Regents, The University Of Texas System | Methods and compositions for nucleic acid sequencing |
GB0811574D0 (en) | 2008-06-24 | 2008-07-30 | Trillion Genomics Ltd | Characterising planar samples by mass spectrometry |
US8198028B2 (en) | 2008-07-02 | 2012-06-12 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US20100035249A1 (en) | 2008-08-05 | 2010-02-11 | Kabushiki Kaisha Dnaform | Rna sequencing and analysis using solid support |
CA2733609C (en) | 2008-08-14 | 2018-03-06 | Nanostring Technologies, Inc. | Stable nanoreporters |
CN102203287B (zh) | 2008-08-26 | 2017-09-19 | 弗卢迪格姆公司 | 增加样本和/或靶通量的测定方法 |
US20100055733A1 (en) | 2008-09-04 | 2010-03-04 | Lutolf Matthias P | Manufacture and uses of reactive microcontact printing of biomolecules on soft hydrogels |
EP2163900A1 (en) | 2008-09-04 | 2010-03-17 | Commissariat A L'energie Atomique | New method of imaging by mass spectrometry and new mass tag associated trityl derivatives |
US8586310B2 (en) | 2008-09-05 | 2013-11-19 | Washington University | Method for multiplexed nucleic acid patch polymerase chain reaction |
JP5184642B2 (ja) | 2008-09-08 | 2013-04-17 | 株式会社日立製作所 | Dna検出装置、及びdna検出デバイス、並びにdna検出方法 |
US8383345B2 (en) | 2008-09-12 | 2013-02-26 | University Of Washington | Sequence tag directed subassembly of short sequencing reads into long sequencing reads |
CN102292635B (zh) | 2008-09-22 | 2015-04-01 | 霍夫曼-拉罗奇有限公司 | 微阵列底物上的生物材料的选择性处理 |
US8404445B2 (en) | 2008-09-30 | 2013-03-26 | Abbvie Inc. | Antibody libraries |
AU2009302248B2 (en) | 2008-10-08 | 2014-03-06 | Sage Science, Inc. | Multichannel preparative electrophoresis system |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US9080211B2 (en) | 2008-10-24 | 2015-07-14 | Epicentre Technologies Corporation | Transposon end compositions and methods for modifying nucleic acids |
US9751084B2 (en) | 2008-10-28 | 2017-09-05 | Emd Millipore Corporation | Biological culture assembly |
CN104195227B (zh) | 2008-11-07 | 2017-04-12 | 适应生物技术公司 | 通过序列分析监测状况的方法 |
US8748103B2 (en) | 2008-11-07 | 2014-06-10 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
WO2010081114A2 (en) | 2009-01-12 | 2010-07-15 | 20/20 Genesystems, Inc. | Oligonucleotide-coated affinity membranes and uses thereof |
KR101059565B1 (ko) | 2009-02-11 | 2011-08-26 | 어플라이드 프레시젼, 인코포레이티드 | 밝은 기준점 표지를 갖는 마이크로어레이 및 그로부터 광 데이터를 수집하는 방법 |
CN102625850B (zh) | 2009-04-03 | 2014-11-26 | 蒂莫西·Z·刘 | 多重核酸检测方法和系统 |
WO2010126614A2 (en) | 2009-04-30 | 2010-11-04 | Good Start Genetics, Inc. | Methods and compositions for evaluating genetic markers |
US9085798B2 (en) | 2009-04-30 | 2015-07-21 | Prognosys Biosciences, Inc. | Nucleic acid constructs and methods of use |
RU2410439C1 (ru) | 2009-07-06 | 2011-01-27 | Российская Федерация, От Имени Которой Выступает Министерство Образования И Науки Российской Федерации | Способ абляции целевой днк с поверхности днк-биочипов |
WO2011008831A2 (en) | 2009-07-14 | 2011-01-20 | University Of Florida Research Foundation, Inc. | Mass tags for spectrometric analysis of immunoglobulins |
KR101029343B1 (ko) | 2009-07-30 | 2011-04-13 | 한국과학기술연구원 | 면역분석 기반의 항원 검출용 키트 및 항원 검출 방법 |
WO2011014811A1 (en) | 2009-07-31 | 2011-02-03 | Ibis Biosciences, Inc. | Capture primers and capture sequence linked solid supports for molecular diagnostic tests |
EP2460011A2 (en) | 2009-07-31 | 2012-06-06 | Prognosys Biosciences, Inc. | Assay tools and methods of use |
EP2467479B1 (en) | 2009-08-20 | 2016-01-06 | Population Genetics Technologies Ltd | Compositions and methods for intramolecular nucleic acid rearrangement |
EP2473842A4 (en) | 2009-09-01 | 2014-03-19 | Univ Oregon Health & Science | ELECTROPHORESIS DEVICE WITH REVERSIBLE STROM GEL FOR THE SEPARATION OF BIOLOGICAL MACROMOLECULES |
SG169918A1 (en) | 2009-10-02 | 2011-04-29 | Fluidigm Corp | Microfluidic devices with removable cover and methods of fabrication and application |
US9557330B2 (en) | 2009-10-09 | 2017-01-31 | Invisible Sentinel, Inc. | Device for detection of analytes and uses thereof |
JP5954876B2 (ja) | 2009-10-13 | 2016-07-20 | ナノストリング テクノロジーズ, インコーポレイテッド | ナノレポーターによるタンパク質の検出 |
US20120277113A1 (en) | 2009-11-18 | 2012-11-01 | Ruo-Pan Huang | Array-based proximity ligation association assays |
US20120245053A1 (en) | 2009-12-04 | 2012-09-27 | Hitachi, Ltd. | GENE EXPRESSION ANALYSIS METHOD USING TWO DIMENSIONAL cDNA LIBRARY |
CN102648294A (zh) | 2009-12-07 | 2012-08-22 | 普罗格诺西斯生物科学公司 | 肽展示阵列 |
CN102648295B (zh) | 2009-12-07 | 2017-08-08 | 伊鲁米那股份有限公司 | 用于多重基因分型的多样品索引 |
US8835358B2 (en) | 2009-12-15 | 2014-09-16 | Cellular Research, Inc. | Digital counting of individual molecules by stochastic attachment of diverse labels |
WO2011094669A1 (en) | 2010-01-29 | 2011-08-04 | Advanced Cell Diagnostics, Inc. | Methods of in situ detection of nucleic acids |
EP2354242A1 (en) | 2010-02-03 | 2011-08-10 | Epiontis GmbH | Assay for determining the type and/or status of a cell based on the epigenetic pattern and the chromatin structure |
EP2516681B1 (en) | 2010-02-11 | 2017-10-18 | Nanostring Technologies, Inc | Compositions and methods for the detection of preferably small rnas by bridge hybridisation and ligation |
EP2536818B1 (en) | 2010-02-18 | 2018-10-03 | Bima Limited | Immobilised-bead immunomultiplex assay |
JP5665021B2 (ja) | 2010-03-08 | 2015-02-04 | 国立大学法人東京農工大学 | 融合mhc分子連結磁気微粒子、抗原ペプチドのスクリーニング方法、組換えベクター、及び磁性細菌の形質転換体 |
WO2011112634A2 (en) | 2010-03-08 | 2011-09-15 | California Institute Of Technology | Molecular indicia of cellular constituents and resolving the same by super-resolution technologies in single cells |
CN102834526B (zh) | 2010-04-05 | 2015-12-02 | 普罗格诺西斯生物科学公司 | 空间编码的生物学测定 |
US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
WO2011127006A1 (en) | 2010-04-05 | 2011-10-13 | Prognosys Biosciences, Inc. | Co-localization affinity assays |
US20130059741A1 (en) | 2010-05-13 | 2013-03-07 | Illumina, Inc. | Binding assays for markers |
ES2697974T3 (es) | 2010-06-09 | 2019-01-30 | Keygene Nv | Códigos de barras de secuencia combinatoria para selección de alto rendimiento |
US9291597B2 (en) | 2010-07-02 | 2016-03-22 | Ventana Medical Systems, Inc. | Detecting targets using mass tags and mass spectrometry |
WO2012012772A2 (en) | 2010-07-22 | 2012-01-26 | The Johns Hopkins University | Drug eluting hydrogels for catheter delivery |
GB201013767D0 (en) | 2010-08-17 | 2010-09-29 | Isis Innovation | Identification of ligands and their use |
CN110878345A (zh) | 2010-09-21 | 2020-03-13 | 安捷伦科技有限公司 | 通过分子计数提高等位基因调用的置信度 |
JP5986572B2 (ja) | 2010-09-24 | 2016-09-06 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 固定化プライマーを使用した標的dnaの直接的な捕捉、増幅、および配列決定 |
US9110079B2 (en) | 2010-09-29 | 2015-08-18 | Biomerieux | Method and kit for establishing an in vitro prognosis on a patient exhibiting SIRS |
CA2814049C (en) | 2010-10-08 | 2021-07-13 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
WO2012049316A1 (en) | 2010-10-15 | 2012-04-19 | Olink Ab | Dynamic range methods |
EP4328321A3 (en) | 2010-10-22 | 2024-05-29 | Cold Spring Harbor Laboratory | Varietal counting of nucleic acids for obtaining genomic copy number information |
EP2632593B1 (en) | 2010-10-27 | 2021-09-29 | Illumina, Inc. | Flow cells for biological or chemical analysis |
WO2012058638A2 (en) | 2010-10-29 | 2012-05-03 | President And Fellows Of Harvard College | Nucleic acid nanostructure barcode probes |
US20130035259A1 (en) | 2010-11-22 | 2013-02-07 | The University Of Chicago | Methods and/or Systems Producing and Providing Sets of Oligonucleotide Conjugates for Assays and Detections |
US20140121118A1 (en) | 2010-11-23 | 2014-05-01 | Opx Biotechnologies, Inc. | Methods, systems and compositions regarding multiplex construction protein amino-acid substitutions and identification of sequence-activity relationships, to provide gene replacement such as with tagged mutant genes, such as via efficient homologous recombination |
US9163281B2 (en) | 2010-12-23 | 2015-10-20 | Good Start Genetics, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
CA2823621C (en) | 2010-12-30 | 2023-04-25 | Foundation Medicine, Inc. | Optimization of multigene analysis of tumor samples |
US8951781B2 (en) | 2011-01-10 | 2015-02-10 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US10196691B2 (en) | 2011-01-25 | 2019-02-05 | Almac Diagnostics Limited | Colon cancer gene expression signatures and methods of use |
US8551708B2 (en) | 2011-02-15 | 2013-10-08 | Leica Biosystems Newcastle Ltd. | Methods for localized in situ detection of mRNA |
WO2012129363A2 (en) | 2011-03-24 | 2012-09-27 | President And Fellows Of Harvard College | Single cell nucleic acid detection and analysis |
EP3150750B1 (en) | 2011-04-08 | 2018-12-26 | Prognosys Biosciences, Inc. | Peptide constructs and assay systems |
GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
EP2697397B1 (en) | 2011-04-15 | 2017-04-05 | The Johns Hopkins University | Safe sequencing system |
ES2597032T3 (es) | 2011-05-04 | 2017-01-13 | HTG Molecular Diagnostics, Inc | Mejoras en un ensayo cuantitativo de protección contra la nucleasa (qNPA) y secuenciación (qNPS) |
CN108342453A (zh) | 2011-05-09 | 2018-07-31 | 富鲁达公司 | 基于探针的核酸检测 |
KR20140023326A (ko) | 2011-06-06 | 2014-02-26 | 비오까르띠 에스아 | 이온성 계면활성제에 의한 세포의 선택적 용해 |
EP2739752B1 (en) | 2011-08-03 | 2017-07-19 | Bio-Rad Laboratories, Inc. | Filtering small nucleic acids using permeabilized cells |
EP3623481B1 (en) | 2011-09-23 | 2021-08-25 | Illumina, Inc. | Compositions for nucleic acid sequencing |
WO2013063382A2 (en) | 2011-10-28 | 2013-05-02 | Illumina, Inc. | Microarray fabrication system and method |
US8987174B2 (en) | 2011-10-28 | 2015-03-24 | Prognosys Biosciences, Inc. | Methods for manufacturing molecular arrays |
AU2012336040B2 (en) | 2011-11-07 | 2015-12-10 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
EP2788499B1 (en) | 2011-12-09 | 2016-01-13 | Illumina, Inc. | Expanded radix for polymeric tags |
US9803188B2 (en) | 2011-12-22 | 2017-10-31 | Ibis Biosciences, Inc. | Systems and methods for isolating nucleic acids |
WO2014163886A1 (en) | 2013-03-12 | 2014-10-09 | President And Fellows Of Harvard College | Method of generating a three-dimensional nucleic acid containing matrix |
SG11201404899VA (en) | 2012-02-14 | 2014-10-30 | Univ Cornell | Method for relative quantification of nucleic acid sequence, expression, or copy changes, using combined nuclease, ligation, and polymerase reactions |
LT3363901T (lt) | 2012-02-17 | 2021-04-12 | Fred Hutchinson Cancer Research Center | Kompozicijos ir būdai, skirti tiksliam mutacijų nustatymui |
CA2867293C (en) | 2012-03-13 | 2020-09-01 | Abhijit Ajit PATEL | Measurement of nucleic acid variants using highly-multiplexed error-suppressed deep sequencing |
US9896709B2 (en) | 2012-03-13 | 2018-02-20 | Swift Biosciences, Inc. | Methods and compositions for size-controlled homopolymer tailing of substrate polynucleotides by a nucleic acid polymerase |
PT2828218T (pt) | 2012-03-20 | 2020-11-11 | Univ Washington Through Its Center For Commercialization | Métodos para baixar a taxa de erro da sequenciação paralela massiva de adn utilizando sequenciação duplex de consensus |
ES2945311T3 (es) | 2012-03-26 | 2023-06-30 | Univ Johns Hopkins | Detección rápida de aneuploidía |
EP2647426A1 (en) | 2012-04-03 | 2013-10-09 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Replication of distributed nucleic acid molecules with preservation of their relative distribution through hybridization-based binding |
KR102118211B1 (ko) | 2012-04-03 | 2020-06-02 | 일루미나, 인코포레이티드 | 핵산 서열분석에 유용한 통합 광전자 판독 헤드 및 유체 카트리지 |
EP2659977B1 (en) | 2012-05-02 | 2019-04-24 | IMEC vzw | Microfluidics system for sequencing |
US9012022B2 (en) | 2012-06-08 | 2015-04-21 | Illumina, Inc. | Polymer coatings |
US8895249B2 (en) | 2012-06-15 | 2014-11-25 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US20140378345A1 (en) | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20160002731A1 (en) | 2012-10-01 | 2016-01-07 | Adaptive Biotechnologies Corporation | Immunocompetence assessment by adaptive immune receptor diversity and clonality characterization |
US9593365B2 (en) | 2012-10-17 | 2017-03-14 | Spatial Transcriptions Ab | Methods and product for optimising localised or spatial detection of gene expression in a tissue sample |
SG11201504334WA (en) | 2012-12-10 | 2015-07-30 | Resolution Bioscience Inc | Methods for targeted genomic analysis |
US9512422B2 (en) | 2013-02-26 | 2016-12-06 | Illumina, Inc. | Gel patterned surfaces |
ES2878525T3 (es) | 2013-03-13 | 2021-11-19 | Illumina Inc | Dispositivos fluídicos multicapa y procedimientos para su fabricación |
EP4253558A1 (en) | 2013-03-15 | 2023-10-04 | The Board of Trustees of the Leland Stanford Junior University | Identification and use of circulating nucleic acid tumor markers |
ES2754177T3 (es) | 2013-06-12 | 2020-04-16 | Massachusetts Gen Hospital | Métodos para la detección multiplexada de moléculas diana y sus usos |
CN105849275B (zh) | 2013-06-25 | 2020-03-17 | 普罗格诺西斯生物科学公司 | 检测样品中生物靶标的空间分布的方法和系统 |
ES2899618T3 (es) | 2013-07-01 | 2022-03-14 | Illumina Inc | Funcionalización de superficie exenta de catalizador e injerto de polímero |
CN105745528A (zh) | 2013-10-07 | 2016-07-06 | 赛卢拉研究公司 | 用于以数字方式对阵列上的特征进行计数的方法和系统 |
EP3149476B1 (en) | 2014-05-30 | 2022-02-16 | The Regents of The University of California | Subcellular western blotting of single cells |
SG11201610177UA (en) | 2014-06-06 | 2017-01-27 | Herlev Hospital | Determining antigen recognition through barcoding of mhc multimers |
US11585806B2 (en) | 2014-06-13 | 2023-02-21 | Immudex Aps | General detection and isolation of specific cells by binding of labeled molecules |
JP6838969B2 (ja) | 2014-06-26 | 2021-03-03 | 10エックス ジェノミクス, インコーポレイテッド | 個々の細胞または細胞集団由来の核酸の分析方法 |
AU2015284464B2 (en) | 2014-06-30 | 2021-06-17 | Illumina, Inc. | Methods and compositions using one-sided transposition |
WO2016007839A1 (en) | 2014-07-11 | 2016-01-14 | President And Fellows Of Harvard College | Methods for high-throughput labelling and detection of biological features in situ using microscopy |
CN107208157B (zh) | 2015-02-27 | 2022-04-05 | 贝克顿迪金森公司 | 用于条形编码核酸以用于测序的方法和组合物 |
ES2836802T3 (es) | 2015-02-27 | 2021-06-28 | Becton Dickinson Co | Códigos de barras moleculares espacialmente direccionables |
EP4119677B1 (en) | 2015-04-10 | 2023-06-28 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
SG10202107055SA (en) | 2015-07-17 | 2021-08-30 | Nanostring Technologies Inc | Simultaneous quantification of a plurality of proteins in a user-defined region of a cross-sectioned tissue |
EP3325650B1 (en) | 2015-07-17 | 2024-01-03 | Nanostring Technologies, Inc. | Simultaneous quantification of gene expression in a user-defined region of a cross-sectioned tissue |
CA2993463A1 (en) | 2015-07-27 | 2017-02-02 | Illumina, Inc. | Spatial mapping of nucleic acid sequence information |
US10768141B2 (en) | 2015-09-11 | 2020-09-08 | The Regents Of The University Of California | Isoelectric focusing arrays and methods of use thereof |
US10078895B2 (en) | 2015-12-30 | 2018-09-18 | Case Western Reserve University | Prediction of recurrence of non-small cell lung cancer with tumor infiltrating lymphocyte (TIL) graphs |
US20190218276A1 (en) | 2016-03-21 | 2019-07-18 | The Broad Institute, Inc. | Methods for determining spatial and temporal gene expression dynamics in single cells |
WO2018045181A1 (en) | 2016-08-31 | 2018-03-08 | President And Fellows Of Harvard College | Methods of generating libraries of nucleic acid sequences for detection via fluorescent in situ sequencing |
CN109923216A (zh) | 2016-08-31 | 2019-06-21 | 哈佛学院董事及会员团体 | 将生物分子的检测组合到使用荧光原位测序的单个试验的方法 |
GB201619458D0 (en) | 2016-11-17 | 2017-01-04 | Spatial Transcriptomics Ab | Method for spatial tagging and analysing nucleic acids in a biological specimen |
US10011872B1 (en) | 2016-12-22 | 2018-07-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
WO2020047004A2 (en) | 2018-08-28 | 2020-03-05 | 10X Genomics, Inc. | Methods of generating an array |
WO2020076979A1 (en) | 2018-10-10 | 2020-04-16 | Readcoor, Inc. | Surface capture of targets |
WO2020123309A1 (en) | 2018-12-10 | 2020-06-18 | 10X Genomics, Inc. | Resolving spatial arrays by proximity-based deconvolution |
US20210189475A1 (en) | 2018-12-10 | 2021-06-24 | 10X Genomics, Inc. | Imaging system hardware |
WO2020219901A1 (en) | 2019-04-26 | 2020-10-29 | 10X Genomics, Inc. | Imaging support devices |
US20210140982A1 (en) | 2019-10-18 | 2021-05-13 | 10X Genomics, Inc. | Identification of spatial biomarkers of brain disorders and methods of using the same |
EP4025711A2 (en) | 2019-11-08 | 2022-07-13 | 10X Genomics, Inc. | Enhancing specificity of analyte binding |
EP4055185A1 (en) | 2019-11-08 | 2022-09-14 | 10X Genomics, Inc. | Spatially-tagged analyte capture agents for analyte multiplexing |
EP4058598A1 (en) | 2019-11-13 | 2022-09-21 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US20210199660A1 (en) | 2019-11-22 | 2021-07-01 | 10X Genomics, Inc. | Biomarkers of breast cancer |
WO2021133849A1 (en) | 2019-12-23 | 2021-07-01 | 10X Genomics, Inc. | Methods for spatial analysis using rna-templated ligation |
US20210198741A1 (en) | 2019-12-30 | 2021-07-01 | 10X Genomics, Inc. | Identification of spatial biomarkers of heart disorders and methods of using the same |
US20210214785A1 (en) | 2020-01-13 | 2021-07-15 | Spatial Transcriptomics Ab | Methods of decreasing background on a spatial array |
US20210223227A1 (en) | 2020-01-17 | 2021-07-22 | Spatial Transcriptomics Ab | Electrophoretic system and method for analyte capture |
US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
US20210222253A1 (en) | 2020-01-21 | 2021-07-22 | 10X Genomics, Inc. | Identification of biomarkers of glioblastoma and methods of using the same |
US20210230681A1 (en) | 2020-01-24 | 2021-07-29 | 10X Genomics, Inc. | Methods for spatial analysis using proximity ligation |
US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
US20210238664A1 (en) | 2020-02-03 | 2021-08-05 | 10X Genomics, Inc. | Methods for preparing high-resolution spatial arrays |
US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
US11835462B2 (en) | 2020-02-11 | 2023-12-05 | 10X Genomics, Inc. | Methods and compositions for partitioning a biological sample |
US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
-
2011
- 2011-04-05 CN CN201180017696.3A patent/CN102834526B/zh active Active
- 2011-04-05 CN CN201510755990.4A patent/CN105385756B/zh active Active
- 2011-04-05 AU AU2011237729A patent/AU2011237729B2/en not_active Ceased
- 2011-04-05 ES ES11766613.1T patent/ES2555106T3/es active Active
- 2011-04-05 JP JP2013503861A patent/JP5893607B2/ja not_active Expired - Fee Related
- 2011-04-05 HU HUE11766613A patent/HUE026666T2/en unknown
- 2011-04-05 US US13/080,616 patent/US9371598B2/en active Active
- 2011-04-05 DK DK11766613.1T patent/DK2556171T3/en active
- 2011-04-05 PT PT117666131T patent/PT2556171E/pt unknown
- 2011-04-05 SI SI201130675T patent/SI2556171T1/sl unknown
- 2011-04-05 PL PL11766613T patent/PL2556171T3/pl unknown
- 2011-04-05 KR KR1020127029015A patent/KR101866401B1/ko active IP Right Grant
- 2011-04-05 EP EP11766613.1A patent/EP2556171B1/en active Active
- 2011-04-05 WO PCT/US2011/031308 patent/WO2011127099A1/en active Application Filing
- 2011-04-05 RS RS20150814A patent/RS54482B1/en unknown
- 2011-04-05 CA CA2794522A patent/CA2794522C/en active Active
-
2013
- 2013-08-13 HK HK13109501.8A patent/HK1182143A1/zh unknown
-
2015
- 2015-11-30 HR HRP20151294TT patent/HRP20151294T1/hr unknown
- 2015-12-01 SM SM201500301T patent/SMT201500301B/it unknown
-
2016
- 2016-06-20 US US15/187,661 patent/US10308982B2/en active Active
- 2016-08-31 HK HK16110362.1A patent/HK1222210A1/zh unknown
-
2019
- 2019-02-14 US US16/276,235 patent/US10480022B2/en active Active
- 2019-02-14 US US16/276,260 patent/US10662467B2/en active Active
- 2019-05-02 US US16/402,098 patent/US10472669B2/en active Active
- 2019-06-03 US US16/430,015 patent/US20190300943A1/en not_active Abandoned
- 2019-06-03 US US16/430,109 patent/US20190300944A1/en not_active Abandoned
- 2019-06-07 US US16/435,295 patent/US10996219B2/en active Active
- 2019-06-07 US US16/435,176 patent/US20190323071A1/en not_active Abandoned
- 2019-06-11 US US16/437,637 patent/US10494667B2/en active Active
- 2019-06-17 US US16/443,771 patent/US20190309355A1/en not_active Abandoned
- 2019-10-22 US US16/660,234 patent/US10662468B2/en active Active
- 2019-10-30 US US16/669,246 patent/US10982268B2/en active Active
- 2019-10-31 US US16/670,603 patent/US10612079B2/en active Active
-
2020
- 2020-01-03 US US16/734,237 patent/US20200140935A1/en not_active Abandoned
- 2020-01-03 US US16/734,216 patent/US10619196B1/en active Active
- 2020-03-11 US US16/816,177 patent/US10914730B2/en active Active
- 2020-03-11 US US16/816,192 patent/US10962532B2/en active Active
- 2020-04-01 US US16/837,924 patent/US10983113B2/en active Active
-
2021
- 2021-01-08 US US17/145,210 patent/US11067567B2/en active Active
- 2021-05-14 US US17/321,090 patent/US11156603B2/en active Active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5893607B2 (ja) | 空間コード化生物学的アッセイ | |
US11479810B1 (en) | Spatially encoded biological assays | |
AU2014203638B2 (en) | Spatially encoded biological assays |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140404 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140404 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150623 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150924 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151218 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160126 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160224 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5893607 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |