ДЕТЕКЦИЯ НУКЛЕОТИДНОЙ ВАРИАЦИИ В НУКЛЕИНОВОКИСЛОТНОЙ ПОСЛЕДОВАТЕЛЬНОСТИ-МИШЕНИ В АНАЛИЗЕ С РАСЩЕПЛЕНИЕМ И УДЛИНЕНИЕМ ЗОНДИРУЮЩЕГО И МЕТЯЩЕГО ОЛИГОНУКЛЕОТИДА (РТО)

Настоящее изобретение относится к области биотехнологии, конкретно к способу для детекции нуклеотидных вариаций посредством анализа с расщеплением и удлинением зондирующего и метящего олигонуклеотида (анализа РТОСЕ), и может быть использовано в медицине. Изобретение предлагает применение PTO-NV, содержащего сайт распознавания нуклеотидной вариации, расположенный на 5’-концевой части 3’-концевого узнающего мишень участка для селективности PTO в отношении конкретной нуклеотидной вариации. 4 н. и 35 з.п. ф-лы, 35 ил., 18 табл., 10 пр.

ИММОБИЛИЗАЦИЯ МОДИФИЦИРОВАННОГО ОЛИГОНУКЛЕОТИДА НА ПОЛИМЕРНОМ СУБСТРАТЕ ПОСРЕДСТВОМ ФИЗИЧЕСКОЙ АДСОРБЦИИ

Группа изобретений относится к области биотехнологии. Предложен способ иммобилизации меченого олигонуклеотида, способ иммобилизации интересующей молекулы (варианты), микрочип, диагностический набор для определения нуклеиновой кислоты, а также применение присоединенной к олигонуклеотиду метки для иммобилизации меченого олигонуклеотида на немодифицированном полимерном субстрате. Способ иммобилизации меченого олигонуклеотида включает получение включающей жидкость и меченый олигонуклеотид смеси, нанесение смеси на немодифицированный циклический олефиновый полимер, причем олигонуклеотид иммобилизуют на полимере посредством физической адсорбции с помощью метки олигонуклеотида, где метка ковалентно связана с олигонуклеотидом. Способ иммобилизации интересующей молекулы включает стадии указанного выше способа, где в одном варианте меченый олигонуклеотид включает интересующую молекулу, а в другом варианте способ дополнительно включает гибридизацию олигонуклеотида с интересующей молекулой. Микрочип ...

СИСТЕМА И СПОСОБ ДЛЯ РАСПРОСТРАНЕНИЯ ИНФОРМАЦИИ С ИСПОЛЬЗОВАНИЕМ МОДИФИЦИРОВАННЫХ НУКЛЕИНОВЫХ КИСЛОТ

Настоящее изобретение относится к области биоинформатики. Предложен способ для приготовления улучшенной вычислительной системы, основанной на нуклеиновых кислотах, включающий синтезирование в водном растворе варианта системы молекулярных вычислений, отличающегося включением химической модификации, изменяющей энергию гибридизации молекул нуклеиновых кислот в системе. Также рассмотрена вычислительная система, основанная на нуклеиновых кислотах и содержащая химические модификации в соответствии со способом по настоящему изобретению. Предложенное изобретение позволяет увеличивать вероятность желаемых событий связывания молекул нуклеиновых кислот в составе системы. 2 н. и 14 з.п. ф-лы, 8 ил.

СПОСОБ ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКИ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ НА ОСНОВЕ АНАЛИЗА МИКРОРНК ПЛАЗМЫ КРОВИ

Изобретение относится к области медицины, в частности к онкологии и молекулярной биологии, и предназначено для дифференциальной диагностики рака предстательной железы (РПЖ). В плазме крови пациента методом микрочипового анализа измеряют экспрессию микроРНК hsa-miR-619-5p и hsa-miR-1184. При величинах экспрессии микроРНК hsa-miR-619-5p в log2-шкале более 1,25 и микроРНК hsa-miR-1184 более 3,5 диагностируют РПЖ. Если величина экспрессии микроРНК hsa-miR-619-5p в log2-шкале менее 1,25 и микроРНК hsa-miR-1184 менее 3,5, диагностируют доброкачественную гиперплазию предстательной железы (ДГПЖ). Изобретение обеспечивает получение новых диагностических маркеров РПЖ и ДГПЖ, позволяющих при сопоставимой достоверности и специфичности осуществлять дифференциальную диагностику РПЖ и ДГПЖ. 3 табл., 6 пр.

СПОСОБ ВЫБОРА ТАКТИКИ ЛЕЧЕНИЯ ПАЦИЕНТОВ С АНТИПСИХОТИК-ИНДУЦИРОВАННЫМИ ЭКСТРАПИРАМИДНЫМИ РАССТРОЙСТВАМИ

Изобретение относится к медицине, а именно к психиатрии, неврологии и клинической фармакологии, и может быть использовано для выбора тактики лечения пациентов с антипсихотик-индуцированными экстрапирамидными расстройствами. Определяют особенности генотипа пациентов посредством микрочипов. При выявлении гомозигот GG варианта rs1799732 (4750dup) гена DRD2, гомозигот ТТ варианта rs1045642 гена АВСВ1 и гомозигот АА варианта CYP2D6*4 (rs3892097) гена CYP2D6 определяют фенотип антипсихотик-индуцированного паркинсонизма. При выявлении гомозигот ТТ варианта rs6275 (67525 Т>С) гена DRD2 и гомозигот ТТ варианта CYP3A5*6 (rs10264272 C>Т) гена CYP3A5 определяют фенотип антипсихотик-индуцированной тардивной дискинезии. При выявлении гомозигот СС варианта rs1800498 (59414 Т>С) гена DRD2, гомозигот ТТ варианта rs1128503 гена АВСВ1 и гомозигот ТТ варианта CYP3A5*6 (rs10264272 C>Т) гена CYP3A5 определяют фенотип антипсихотик-индуцированной акатизии. В соответствии с фенотипом пациента осуществляют выбор ...

СПОСОБ ПОИСКА МОЛЕКУЛЯРНЫХ МАРКЕРОВ ПАТОЛОГИЧЕСКОГО ПРОЦЕССА ДЛЯ ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКИ, МОНИТОРИНГА И ТАРГЕТНОЙ ТЕРАПИИ

Изобретение относится к области биотехнологии и медицины. Предложен способ поиска молекулярных маркеров патологического процесса для дифференциальной диагностики, мониторинга и таргетной терапии. Способ включает получение транскриптомных данных от пациентов с исследуемой патологией (патология исследования), пациентов с заболеванием иной этиологии со схожей клинической картиной (патология сравнения) и клинически здоровых доноров сопоставимого возраста и пола (норма). Осуществляют идентификацию молекулярных маркеров исследуемой патологии. Изобретение обеспечивает оптимизацию способов дифференциальной диагностики, мониторинга и специфической терапии. 3 табл., 1 пр.

ДЕТЕКЦИЯ НУКЛЕИНОВОКИСЛОТНОЙ ПОСЛЕДОВАТЕЛЬНОСТИ-МИШЕНИ В АНАЛИЗЕ С ГИБРИДИЗАЦИЕЙ СИГНАЛЬНОГО ОЛИГОНУКЛЕОТИДА, ЗАВИСЯЩЕЙ ОТ РАСЩЕПЛЕНИЯ И УДЛИНЕНИЯ ЗОНДИРУЮЩЕГО И МЕТЯЩЕГО ОЛИГОНУКЛЕОТИДА

... 1. Способ детекции нуклеиновокислотной последовательности-мишени из ДНК или смеси нуклеиновых кислот в анализе с PCE-SH (гибридизацией сигнального олигонуклеотида, зависящей от расщепления и удлинения РТО), включающийа) гибридизацию нуклеиновокислотной последовательности-мишени с располагающимся против хода транскрипции олигонуклеотидом и зондирующим и метящим олигонуклеотидом (РТО); при этом располагающийся против хода транскрипции олигонуклеотид содержит гибридизующуюся нуклеотидную последовательность, комплементарную нуклеиновокислотной последовательности-мишени; РТО содержит (1) 3′-концевой узнающий мишень участок, содержащий гибридизующуюся нуклеотидную последовательность, комплементарную нуклеиновокислотной последовательности-мишени, и (2) 5′-концевой тегирующий участок, содержащий нуклеотидную последовательность, не комплементарную нуклеиновокислотной последовательности-мишени; при этом 3′-концевой узнающий мишень участок РТО гибридизуется с нуклеиновокислотной последовательностью-мишенью ...

ЦИФРОВОЙ АНАЛИЗ МОЛЕКУЛЯРНЫХ АНАЛИЗИРУЕМЫХ ВЕЩЕСТВ С ПОМОЩЬЮ ЭЛЕКТРИЧЕСКИХ СПОСОБОВ

СПОСОБ ОБНАРУЖЕНИЯ НАЛИЧИЯ МИКРООРГАНИЗМОВ В БИОЛОГИЧЕСКОМ ОБРАЗЦЕ

... 1. Способ определения наличия определенных микроорганизмов в биологическом образце, причем микроорганизмы представляют собой бактерии, грибки, вирусы и простейшие, включающий: ! (а) иммобилизацию биологического образца на и/или в твердом субстрате в одном первом местоположении; ! (б) перенос иммобилизованного биологического образца, по меньшей мере, в другое местоположение и осуществление стадии экстракции на твердом субстрате таким образом, чтобы экстрагировалась ДНК любого микроорганизма, иммобилизованная на и/или в твердом субстрате; ! (в) амплификацию нуклеиновой кислоты на ДНК микроорганизмов, экстрагированных на стадии (б), причем стадия амплификации относится к амплификации, по меньшей мере, одной высококонсервативной последовательности одного или более определенных микроорганизмов, а амплифицированные последовательности именуются целевыми последовательностями; ! (г) смешение целевых последовательностей с последовательностями совокупности праймеров, содержащихся на диагностической ...

ПАНЕЛЬ И СПОСОБ ПОЛУЧЕНИЯ ПРОСТРАНСТВЕННОЙ ИНФОРМАЦИИ О НУКЛЕИНОВЫХ КИСЛОТАХ

Изобретение относится к области биотехнологии. Описана группа изобретений, включающая панель нуклеиновых кислот для получения пространственной информации о нуклеиновой кислоте в образце, набор для получения пространственной информации о нуклеиновой кислоте в образце (варианты), способ изготовления панели нуклеиновых кислот для получения пространственной информации о нуклеиновой кислоте в биологическом образце и способ получения пространственной информации о нуклеиновой кислоте в образце (варианты). В одном варианте реализации панель нуклеиновых кислот включает в себя твердую подложку с многочисленными видами последовательностей-носителей, присоединенных к ее поверхности, где каждый вид последовательности-носителя занимает в панели отличное от другого вида положение, где множественные копии последовательности-носителя представляют собой продукт амплификации, образованный посредством амплификации с применением в качестве матрицы последовательности, комплементарной последовательности-носителю ...

НАБОР ИЛИ УСТРОЙСТВО ДЛЯ ОБНАРУЖЕНИЯ РАКА ЛЕГКОГО И СПОСОБ ОБНАРУЖЕНИЯ

4С

... 1. Способ анализа частоты взаимодействия нуклеотидной последовательности-мишени с одной или несколькими представляющими интерес нуклеотидными последовательностями (например, одним или несколькими геномными локусами), включающий в себя стадии ! (a) получения образца поперечно сшитой ДНК; ! (b) расщепления поперечно сшитой ДНК первым ферментом рестрикции; ! (c) лигирования поперечно сшитых нуклеотидных последовательностей; ! (d) удаления поперечных сшивок; ! (e) расщепления нуклеотидных последовательностей вторым ферментом рестрикции; ! (f) лигирования одной или нескольких последовательностей ДНК с известным составом нуклеотидов с доступным сайтом (сайтами) расщепления вторым ферментом рестрикции, который фланкирует одну или несколько представляющих интерес нуклеотидных последовательностей; ! (g) амплификации одной или нескольких представляющих интерес нуклеотидных последовательностей с использованием по меньшей мере двух олигонуклеотидных праймеров, при этом каждый праймер гибридизуется ...

БИОЛОГИЧЕСКИЕ МАРКЕРЫ И СПОСОБЫ ПРОГНОЗИРОВАНИЯ ВОСПРИИМЧИВОСТИ К АНТАГОНИСТАМ В-КЛЕТОК

... 1. Биомаркер для прогнозирования восприимчивости пациента к терапевтическому агенту, включающему антагонист В-клеток, где биомаркер включает повышенный общий уровень мРНК плазматических клеток/плазмабластов в биологическом образце, полученном от пациента, по сравнению с общим уровнем мРНК плазматических клеток/плазмабластов в биологическом образце, полученном от контрольного субъекта, или по сравнению с пороговым значением общего уровня мРНК плазматических клеток/плазмабластов.2. Биомаркер по п.1, дополнительно включающий низкий уровень общей мРНК наивных/зрелых В-клеток в биологическом образце пациента по сравнению с уровнем общей мРНК наивных/зрелых В-клеток в биологическом образце контрольного субъекта или по сравнению с пороговым значением общего уровня мРНК наивных/зрелых В-клеток.3. Биомаркер по п.1, отличающийся тем, что биологическим образцом является цельная кровь.4. Биомаркер по п.1, отличающийся тем, что пациент болен ревматоидным артритом или предполагается, что он болен ревматоидным ...

НАБОР ОЛИГОНУКЛЕОТИДНЫХ ПРАЙМЕРОВ И ЗОНДОВ ДЛЯ ГЕНОТИПИРОВАНИЯ ПОЛИМОРФНЫХ ЛОКУСОВ ДНК, АССОЦИИРОВАННЫХ С РИСКОМ РАЗВИТИЯ СПОРАДИЧЕСКОЙ ФОРМЫ БОЛЕЗНИ АЛЬЦГЕЙМЕРА В РОССИЙСКИХ ПОПУЛЯЦИЯХ

... 1. Набор олигонуклеотидных праймеров и зондов для анализа генетического полиморфизма в локусах ДНК ApoE (rs429358, rs7412), ApoJ (rs11136000) и GAB2 (rs2373115), предусматривающего следующие стадии:(а) - амплификация полиморфных фрагментов генов ApoE, ApoJ и GAB2 с помощью мультиплексной «гнездной» двухэтапной ПЦР, в которых в качестве матрицы для амплификации используется образец ДНК; при проведении ПЦР используется набор праймеров с последовательностями, представленными в SEQ ID NO: 9-20; в результате чего, на втором этапе ПЦР образуется флуоресцентно меченый ПЦР-продукт;в мультиплексной реакции I этапа используют праймеры: 9, 10, 13, 14, 17, 18;в мультиплексной реакции II этапа используют праймеры: 11, 12, 15, 16, 19, 20;реакционная смесь на первом этапе ПЦР содержит 5 пкмоль каждого праймера, 67 мМ Трис_HCl, pH 8.6, 166 мМ (NH4)2SO4, 1.5 мМ MgCl2, 0.2 мМ каждого из dNTP, 2.5 ед. акт. Taq-полимеразы и матрицу в количестве не менее 10 нг геномной ДНК. Реакция проводится в следующем режиме ...

СПОСОБЫ ЛЕЧЕНИЯ, ДИАГНОСТИКИ И МОНИТОРИНГА РЕВМАТОИДНОГО АРТРИТА

... 1. Способ диагностики молекулярного субтипа RA у субъекта, причем способ включает измерение в биологическом образце, полученном от субъекта, экспрессии одного гена или их комбинации или экспрессии одного белка или их комбинации, кодируемой одним геном или их комбинацией, где один ген или их комбинация выбраны из любого из перечисленных в таблице 1, в таблице 5, в таблице 10, CXCL13, FcRH5, sFcRH5, LTβ, ICAM3, IL18, PACAP, TNFRSF7, IgJ, IGM, IgG и XBP1, где повышенная экспрессия одного гена или их комбинации или повышенная экспрессия одного белка или их комбинации является индикатором молекулярного субтипа RA.2. Способ по п. 1, в котором биологический образец представляет собой синовиальную ткань.3. Способ по п. 2, в котором экспрессию одного гена или их комбинации измеряют с использованием способа на основе ПЦР или на основе чипа микроматрицы.4. Способ по п. 1, в котором комбинация генов включает XBP1, SMPDL3B, LOC255458, LOC339562, PIM2, SLC2A11, FAM46C, NDP52, CD79A, SLC38A1, IGLL1, LOC91316 ...

ДИФФЕРЕНЦИАЛЬНЫЕ КАРТИНЫ ЭКСПРЕССИИ ГЕНОВ, КОТОРЫЕ ПРЕДСКАЗЫВАЮТ ХЕМОЧУВСТВИТЕЛЬНОСТЬ И ХЕМОРЕЗИСТЕНТНОСТЬ К ДОЦЕТАКСЕЛУ

... 1. Способ скрининга пациента в отношении ответа на терапию доцетакселом, включающий в себя стадии: получения образца опухоли от пациента; выделения РНК из образца; определения относительной экспрессии отдельных нуклеиновых кислот в РНК, по меньшей мере, 10 нуклеиновых кислот, выбранных из группы, состоящей из SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, ...

ETIKETTIERREAGENZ UND NACHWEISMETHODE

VERANKERTE STRANGVERDRÄNGUNGS-AMPLIFIZIERUNG AUF EINEM ELEKTRONISCH ADRESSIERBAREN MIKROCHIP

Auf einer Oberfläche befestigte multifunktionelle Polymere-Netzwerke für Sensorchips

Messgerät für das automatisierte Testen von Wafern

Messgerät für das automatisierte Testen von Wafern, dadurch gekennzeichnet, dass dieses Folgendes umfasst: eine Ladevorrichtung, wobei an einer Seite mindestens ein Bereich für die Vorbehandlung, ein Bereich für die Reinigung und Extraktion, ein Bereich für die rückwärts gerichtete Aufzeichnung und Trennung und ein Bereich für die Reaktion und die Aufnahme der Wafer gebildet werden, und diese werden verwendet, um eine Befüllung vorzunehmen wobei dabei das Messobjekt getestet wird und um die Reaktion auszuführen, einen Bewegungsmechanismus wobei dieser mit der Ladevorrichtung verbunden wird, und dieser wird verwendet, um beim Messvorgang die Ladevorrichtung zu schütteln oder zu vibrieren, und es findet eine gewünschte Mischung aus der Beibehaltung des Messobjekts in der Ladevorrichtung sowie des Edukts und der angeordneten Wafer statt, einen Temperatursteuerungsmechanismus wobei dieser mit der Ladevorrichtung verbunden wird, und dieser wird verwendet um beim Messvorgang die Temperatur in ...

Verfahren und Vorrichtung zur Analyse von Polynucleotid-Sequenzen.

Vorrichtung zum Nachweis von fluoreszenten, der Bindung eines Liganden auf einem Substrat entsprechenden Merkmalen

Bauteil zur Interaktionsanalyse mit Kooperationseffekte ausbildenden Probenmolekülspezies

Die Erfindung betrifft ein Bauteil mit einem Träger und mit auf dem Träger in definierter Anordnung angeordneten Probenmolekülfeldern, wobei jedes Probenmolekülfeld Probenmoleküle zumindest einer Probenmolekülspezies trägt, und wobei eine Zuordnung zwischen den geometrischen Positionen der Probenmolekülfelder innerhalb des Bauteils und den Probenmolekülspezies der Probenmolekülfelder getroffen ist. Sie ist dadurch gekennzeichnet, daß jedes Probenmolekülfeld Probenmoleküle einer jeweils selektierten, unterschiedlichen Probenmolekülspeziesgruppe trägt, wobei Gruppenelemente jeder Probenmolekülspeziesgruppe gemeinsam unter Ausbildung von kooperativen Effekten an ein defindiertes Targetmolekül binden.

Kit, Verfahren und Mikroarray zur Bestimmung des Geschlechtes eines menschlichen Fötus

The invention relates to a diagnosis kit for determining the sex of a human foetus from a maternal blood sample, comprising at least one pair of oligonucleotides (reverse primer, forward primer), the two oligonucleotides of a pair being suitable as a primers for amplifying one of the two complementary strands of the DNA segment sought, respectively, by means of polymerase chain reaction, said DNA segment being part of the human Y chromosome.

VERWENDUNG VON VEREINIGTEN SONDEN ZUR GENETISCHEN ANALYSE

DNA Chip, PNA Chip, sowie Herstellungsverfahren

DETEKTION UND CHARAKTERISIERUNG DER AKTIVITÄT VON PROTEINEN, WELCHE AN DER REPARATUR VON DNA-LÄSIONEN BETEILIGT SIND

System und Verfahren zum Testen von Nukleinsäuremolekülen

NANOPARTIKEL MIT DARAN ANGEHEFTETEN OLIGONUKLEOTIDEN SOWIE DEREN VERWENDUNGEN

EXPRESSIONSNACHWEIS DURCH HYBRIDISIERUNG AN OLIGONUKLEOTIDARRAYS HOHER BELEGUNGSDICHTE

MASSENMARKIERTE HYBRIDISIERUNGSSONDEN

ECHTZEIT-PCR VON ZIELEN AUF EINEM MIKROARRAY

VERFAHREN ZUM NACHWEIS VON EGFR-MUTATIONEN IN BLUTPROBEN

VERWENDUNG VON OLIGONUKLEOTIDSONDEN UND VERFAHREN ZUR GENOMISCHEN TYPISIERUNG VON ERYTHROZYTENSYSTEMEN

Prostate stem cell

A method and a kit for diagnosing cervical cancer

Human genome-derived single exon nucleic acid probes useful for analysis of gene expression in human hela cells or other human cervical epithelial cells

Arrays and design thereof where probe abundance is varied in predetermined manner

A method for designing an array (12) is provided. This method includes grouping probes into a plurality of ranked groups of probes, designing an array (12) comprising the ranked groups of probes, wherein the array (12) contains more replicates of probes in a higher ranked group as compared to probes of a lower ranked group. The groups of probes are ranked either arbitrarily or using experimental data, location, function or expression and the number of probes are determined by the abundance of target for the probe in a sample. A computer readable media and a computer executable method are used for designing or fabricating the array. The resulting array is used for analysis of samples by evaluating binding to the probes.

Method for the preparation of a probe for nucleic acid hybridization

Arrays of protein variants

By highly homologous or related it is meant those DNA coding sequences which share a common sequence and which differ only by one or more naturally occurring mutations such as single nucleotide polymorphisms, deletions or insertions, or those sequences which are considered to be haplotypes (a haplotype being a combination of variations or mutations on a chromosome, usually within the context of a particular gene). Such highly homologous or related DNA coding sequences are generally naturally occurring variants of the same gene. Arrays according to the invention have multiple for example, two or more, individual proteins deposited in a spatially defined pattern on a surface in a form whereby the properties, for example the activity or function of the proteins can be investigated or assayed in parallel by interrogation of the array.

Human genome-derived single exon nucleic acid probes useful for analysis of gene expression in human breast and HBL 100 cells

A single exon nucleic acid microarray comprising a plurality of single exon nucleic acid probes for measuring gene expression in a sample derived from human HBL 100 cells is described. Also described are single exon nucleic acid probes expressed in the HBL 100 cells and their use in methods for detecting gene expression.

Chip for detection or analysis of biologically active substance

Microarray hybridization assay methods

Probe with hairpin and template sections for biochip testing

A detection oligomer 2 and method for controlling the quality of a biochip using the detection oligomer are provided. The detection oligomer 2 includes a template 100 complimentary to a specific sequence of an oligomer and has a first end (3') and second end, and a hairpin 200 connected to the first end of the template. The stem-loop 210, 230 may include a restriction enzyme or nuclease site 215 on both strands. The template extension or tail 100 may have a have a fluorescent label 300 attached at the second (5') end. In use, the probe hybridises to other complementary probes immobilised on a biochip; the free end of the hairpin is ligated to the free end of the immobilised probe (fig. 4B); hybridisation is then removed. Further steps may include washing to remove unligated probes (fig. 4C), re-hybridisation and detecting the remaining attached probes using labels (figs. 4E and 5), then detaching the detection probes using the endonuclease sites.

Prediction of adverse side effects of drugs

Membrane bound nucleic acid nanopores

Method for obtaining aptamer using microarrays

Electrically active combinatorial-chemical (EACC) chip for biochemical analyte detection

Apparatus and methods are disclosed for electrically active combinatorial-chemical (EACC) chips for biochemical analyte detection. An apparatus includes a substrate that has an array of regions defining multiple cells, wherein each of the cells includes a reaction cavity that contains multiple functional binding groups. A method of detecting an analyte providing the reaction cavity between a source and a drain or a pair of electrodes, applying a voltage and monitoring a parameter indicative of an analyte characteristic. A process of fabricating an EACC include bonding an analyte to the multiple functional binding groups of each reaction cavity, and forming an analyte sensing structure including the substrate.

Biochip and method of fabrication

A method of fabricating a biochip and a biochip fabricated by the method are provided. The method comprises providing a substrate including a plurality of first areas 20 separated from each other by a second area 30, forming a plurality of activation patterns 100 on each of the first areas, coupling a plurality of probes to each of the activation patterns, and cutting the substrate along the second area to form a plurality of chips. Also claimed is a biochip comprising an array region, a non-array region, a substrate and a probe cell array formed on or in the array region, wherein a surface of the substrate is at least partially exposed in the array region.

Arrays comprising immobilized primer pair spots for amplifying target nucleic acids

Arrays are disclosed comprising a substrate and a plurality of oligonucleotide primer spots immobilised thereon, wherein within each spot a population of primer pairs for specifically amplifying a target nucleic acid (NA) by PCR is immobilised upon the substrate such that the 3 ends of said primers can be extended, at least two of said oligonucleotide primer spots being adapted to amplify different target NAs. Methods of amplifying target NAs using the arrays are claimed (effectively utilising bridge amplification techniques). Methods of preparing oligonucleotide primer spots on an array are also claimed, wherein the methods may comprise steps of immobilising a population of a combined primer construct comprising first and second primers linked via a cleavable linkage, or wherein the methods comprise immobilising one of the primers and then covalently linking or recombining a proportion of the immobilised primers with the second primer of the primer pair.

Human genome-derived single exon nucleic acid probes useful for anlaysis of gene expression in human hela cells or other human cervical epithelial cells

Human genome-derived single exon nucleic acid probes useful for analysis of gene expression in human breast and BT 474 cells

Microarrays having multiple oligonucleotides in single array features

The present invention is a method for synthesizing microarrays having different oligonucleotides present within one feature area of the array. The method utilizes the techniques common to miccroarray synthesis, but limits the duration in which selected feature areas on the array are initially dosed with light so as to only deprotect a calculated ratio of the compounds forming the array's binding layer. The compounds initially deprotected are capped with a nonphotosensitive protecting group, such as di-methoxy-trityl, to inhibit their involvement in the synthesis of a first group of DNA strands built onto the array. Once the first group of DNA strands have been synthesized, the original deprotected group may then be further processed to build one or more groups of DNA strands in the same feature area as the first group of DNA strands. The present invention also includes microarrays manufactured using the method.

Microarrays having multiple oligonucleotides in single array features

Polynucleotide analysis using combinatorial PCR

Systems, methods, and devices for sample collection, stabilization and preservation

Biopolymer arrays and their fabrication

Arrayed polynucleotides and their use in genome analysis

Detection oligomer and method for controlling quality of biochip using detection oligomer

Biopolymeric arrays

Diagnostic methods and apparatus

Method for transposase-mediated spatial tagging and analysing genomic DNA in a biological specimen

Gene sequencer and methods.

A gene sequencer, bio-comapct disk and sample preparation methodology are described. Constant length oligonucleotides are prepared and, in conjuction with the bio-compact disk and apparatus described, used in gene sequencing and strategies therefor.

Gene sequencer and methods

ANALYSIS CHIP WITH REFERENCE SCALE KITS AND ANALYSIS METHODS

GENES AND POLYPEPTIDE IN CONNECTION WITH HUMAN PANKREASKARZINOMEN

USE OF A TYPE III-RESTRICTION ENZYME FOR THE ISOLATION OF MORE THAN 25 NUCLEOTIDES COMPREHENSIVE ONE SEQUENCE TAGS

NUCLEIC ACID PROOF PROCEDURE WITH UNIVERSAL PRIMING

SHORTENED PROCEEDINGS FOR THE DETECTION OF MICROORGANISMS IN FOOD SAMPLES

MATRIX SCREENING PROCEDURE

LIGHT-ADJUSTED, ELECTRICALKINETIC COMPOSITION OF PARTICLES AT SURFACES

MOLECULAR MARKING SYSTEM

PROCEDURE FOR THE DETERMINATION OF A ANALYTEN

PROCEDURE FOR THE DEVELOPMENT FROM GENE CORRODING TO DIAGNOSTIC AND THERAPEUTIC PURPOSES ON BASIS OF THE EXPRESS ION AND METHYLIERUNGSSTATUS THE GENES

PROCEDURE AND KIT FOR DETECTION AND/OR QUANTIFICATION OF THE HOMOLOGOUS NUCLEOTIDE SEQUENCES ON AN ARRAY

DETECTION OF NUCLEIC ACIDS

POLYNUKLEOTIDMATRIX BASED PROCEDURE FOR THE IDENTIFICATION OF MICROORGANISMS

PROCEDURE WITH RELATIONSHIP WITH LINEAR BEACONS

UNIVERSAL DAY ASSAY

METHODE ZUR 5-METHYLCYTOSIN-DETEKTION

The present invention provides a method for the detection of 5-methylcytosine, characterized in that either a 5-methylcytosine specific binding moiety or a nucleotide analyte is attached to the tip of a single molecule force spectroscopy (SMFS) probe and the other of the 5-methylcytosine specific binding moiety or the nucleotide analyte is attached to a carrier, wherein the SMFS probe is brought into contact to the carrier and is detached and the detachment force is measured through an SMFS detection means; as well as an SMFS probe and an SMFS apparatus for said method.

PROOF OF CHROMOSOMALER DISTURBANCES

PROCEDURE FOR THE IMPROVEMENT OF THE EFFICIENCY OF THE POLYNUKLEOTIDSEQUENZIERUNG

PROCEDURE AND COMPOSITIONS FOR THE PROOF OF NUCLEIC ACIDS IN A BIOLOGICAL SAMPLE

PROCEDURE FOR THE CALIBRATION AND CONTROL OF METHYLIERUNGSANALYSE METHODS BY NOT METHYLIERTER DNA

CARBON ELECTRODE SURFACE FOR THE CONNECTION OF DNA AND PROTEIN MOLECULES TO IT

INCREASE OF THE SENSITIVITY AND SPECIFICITY OF HYBRIDIZING EXPERIMENTS WITH NUCLEIC ACID CHIP

PROCEDURE FOR THE ANALYSIS OF MAKROMOLEKULEN

PROCEDURE FOR THE PROOF OF NUCLEIC ACIDS BY AMPLIFICATION ON AN ARRAY

IN KANZERÍSEN MAMMAZELLEN DIFFERENTIAL EXPRIMIERTE GENE PRODUCTS AND YOUR USE PROCEDURES

MICRO ARRAY DEVICES WITH CONTROLLABLE REACTION VOLUME

DEVICE AND PROCEDURE FOR THE PROOF OF DNA IN BIOLOGICAL SAMPLES

REAL TIME PCR OF GOALS ON A MICRO ARRAY

NUCLEOTIDE CARRIER FOR THE DIAGNOSIS AND THERAPY OF ORAL ILLNESSES

FIBRE OPTICS PROCEDURE FOR THE DETECTION OF SPECIFIC CONNECTION REACTIONS ACCORDING TO THE SCATTERED LIGHT METHOD

FABRIC-SPECIFIC CONNEXIN-40-GENMUTATIONEN

IDENTIFICATION OF A ERBB2 GENE EXPRESS ION SIGNATURE WITH CANCER OF THE BREAST

DIRECT SNP PROOF WITH NICHTAMPLIFIZIERTER DNA

ARTICLES ALSO ON IT ANGEORDETEN LOCATED MOLECULES AND MANUFACTURING PROCESSES FOR IT

Marker for Liver-Cancer Diagnosis and Recurrence and Survival Prediction, a Kit Comprising the Same, and Prognosis Prediction in Liver-Cancer Patients Using the Marker

A composition for detecting a marker for the diagnosis or prognosis of liver cancer is disclosed. The composition includes an agent capable of assessing the expression level of UQCRH (ubiquinol-cytochrome c reductase hinge protein). In addition, a kit having the composition, a microarray for the diagnosis of liver cancer using the marker, and a method for detecting the marker, and predicting recurrence following surgery in liver cancer patients are disclosed. The marker is able to contribute to the early diagnosis of liver cancer and prediction of recurrence following surgery and survival of liver cancer patients who have undergone hepatic resection, and also is significant for being a promising therapeutic target for liver cancer.

Antireflective Coatings for High-Resolution Photolithographic Synthesis of DNA Array

The present invention provides an array of polymers and methods of forming arrays of polymers by providing a substrate having a first layer including one or more dielectric coatings on a solid support and a second layer including a plurality of polymers disposed on the first layer. The invention also provides methods for forming an array of polymers on a substrate using light-directed synthesis by providing a substrate having a first layer including one or more dielectric coatings on a solid support, derivatizing the first layer by contacting the first layer with a silanation reagent, and a second layer disposed on said first layer wherein the second layer includes functional groups protected with a photolabile protecting group.

Methods and systems for monitoring reactions

Methods and systems for monitoring reactions by observing signals deriving from those reactions, using signal processing that allows differentiation between signals that are otherwise optically overlapping by conventional detection methods. Centroid determination is used to identify signal sources that are presenting confounding overlapping signals due to their physical proximity, and/or to identify discrete signals from different reaction centers.

Universal Tags, Probes and Detection Methods For Multiple Targets Detection of Biomolecules

The present invention provides universal tags, probes and detection methods for multiple targets detection of biomolecules. The universal tag in the present invention is a fragment of DNA, RNA, peptide nucleic acid, or LNA, and is 3-20 mer in length. The probe in the present invention contains in order from 3′ terminus to 5′ terminus, a nucleotide sequence which is reverse complementary to a target molecule or a portion of the target molecule, and a nucleotide sequence which is reverse complementary to the universal tag; or said probe contains in order from 3′ terminus to 5′ terminus, a nucleotide sequence which is reverse complementary to the universal tag, and a nucleotide sequence which is reverse complementary to a target molecule or a portion of the target molecule.

Method for Detecting and Quantitating Multiple-Subcellular Components

A method for detecting and quantitating multiple and unique fluorescent signals from a cell sample is provided. The method combines immunohistochemistry and a fluorescent-labeled in situ hybridization techniques. The method is useful for identifying specific subcellular components of cells such as chromosomes and proteins.

Methods and apparatus for nanoparticle-assisted nucleic acid hybridization and microarray analysis

The invention provides nucleic acid hybridization methods for detecting target nucleic acid sequences wherein complexes comprising nanoparticles non-covalently associated with single-stranded tartlet nucleic acid molecules are incubated with immobilized probe nucleic acid molecules. Because the nanoparticles function as competitors in the hybridization reaction between the target nucleic acid molecules and the probe nucleic acid molecules. The methods provide a high degree of discrimination between a perfectly matched target sequence and a sequence having at least a single-base-pair mismatch, even when the hybridization reaction is performed at room temperature. The invention also provides microarray methods and apparatus which incorporate the nanoparticle-assisted hybridization methods.

Methods and devices for molecular association and imaging

The present invention is directed to devices and methods for molecular association, particularly to devices and methods for hybridization of nucleic acids utilizing temperature gradients and imaging thereof. In one aspect, a molecular hybridization system generally includes a substrate having a plurality of molecular probes attached thereto, the plurality of probes being generally present in multiple copies arranged in localized formations on the surface of the substrate. The molecular hybridization system further generally includes a chamber that encloses the plurality of molecular probes such that a fluid containing sample may be applied and kept in contact with the substrate having the probes thereon. The molecular hybridization system also includes a temperature affecting system that generally produces at least one desired temperature on the surface of the substrate and in the adjacent fluid within the chamber.

Rna labeling method

A method of sample analysis is provided. In certain embodiments, the method involves: a) obtaining a fragmented RNA sample comprising fragments of long RNA molecules and short RNA molecules; b) ligating an adaptor to an end of the RNA of the fragmented RNA sample to produce an adaptor-ligated sample; c) hybridizing said adaptor-ligated sample to an array of nucleic acid probes; and d) reading said array to obtain an estimate of the abundance of a long RNA in the RNA sample and an estimate of the abundance a small RNA in the RNA sample.

Markers for endometrial cancer

The invention relates to the surprising finding that biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1 R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, S0CS2, and DCN are differentially expressed in control samples as compared to samples from patients having endometrial cancer and are therefore useful for detecting endometrial cancer. In particular these biomarkers having excellent sensitivity, specificity, and/or the ability to separate affected from non affected individuals. Furthermore, the inventors found that the differential expression of these biomarkers in primary endometrial cancer tumor tissue is correlated to their expression level in uterine fluid samples as compared to control values. Thus these biomarkers are robust in that they are found to be differentially expressed in several different types of samples from affected individuals.

Methods and arrays for profiling dna methylation

This invention provides methods and arrays for determination of the methylation patterns at single-nucleotide resolution by array-based hybrid selection and next-generation sequencing of bisulfite-treated DNA.

Method for making populations of defined nucleic acid molecules

The present invention provides methods of making a population of nucleic acid molecules, wherein each nucleic acid molecule comprises a predetermined nucleic acid sequence, each of said methods comprising the steps of: (a) synthesizing, on a substrate, a population of nucleic acid molecules wherein: i) each synthesized nucleic acid molecule comprises a predetermined nucleic acid sequence; and ii) each synthesized nucleic acid molecule is localized to a defined area of said substrate; (b) harvesting said population of synthesized nucleic acid molecules from said substrate to yield harvested nucleic acid molecules; and (c) introducing said harvested nucleic acid molecules into vector molecules.

Methods for Diagnosing Colon Cancer Using MicroRNAs

The present invention provides novel methods and compositions for the diagnosis and treatment of solid cancers. The invention also provides methods of identifying inhibitors of tumorigenesis.

Arrays of microparticles and methods of preparation thereof

This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

GENE EXPRESSION ANALYSIS METHOD USING TWO DIMENSIONAL cDNA LIBRARY

The present invention provides a method and/or means for collecting and analyzing an individual cell in a tissue, and at the same time, quantitatively monitoring the expression levels of various genes while keeping two-dimensional information in the tissue. Specifically, the present invention provides a method comprising preparing a cDNA library from mRNA while keeping two-dimensional cellular distribution information and obtaining the gene expression levels at any site or all sites at a level of single cell. More specifically, the present invention provides a method comprising preparing a cDNA library in a sheet-form from mRNA while keeping two-dimensional cellular distribution information and repeatedly using the cDNA library in the detection of the gene expression, thereby allowing measurement of the expression distribution for a number of genes at a high accuracy.

Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays

The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support.

Potentiometric dna microarray, process for producing the same and method of analyzing nucleic acid

A DNA microarray system whereby measurement can be performed at a low running cost, a low price and yet a high accuracy. A nucleic acid probe ( 3 ) is immobilized on the surface of a gate insulator of an electric field effect transistor and then hybridized with a target gene on the surface of the gate insulator. A change in the surface electric charge density thus arising is detected by using the electric effect.

Detection method for microarray

Described is a means for objectively determining hybridization failure in addition to performance degradation, insufficient washing and the like in a microarray. In particular a method for detecting the hybridization between a probe polynucleotide and a target polynucleotide by using a microarray is presented.

Non-Invasive Diagnosis of Graft Rejection in Organ Transplant Patients

The disclosure provides methods, devices, compositions and kits for diagnosing or predicting transplant status or outcome in a subject who has received a transplant. The methods comprise determining the presence or absence of one or more nucleic acids from a donor transplant, wherein said one or more nucleic acids from said donor are identified based on a predetermined marker profile, and diagnosing or predicting transplant status or outcome based on the presence or absence of said one or more nucleic acids.

Identification of Tumors

The invention provides methods for the use of gene expression measurements to classify or identify tumors in samples obtained from a subject in a clinical setting, such as in cases of formalin fixed, paraffin embedded (FFPE) samples.

COMPOSITIONS AND METHODS FOR CLASSIFYING LUNG CANCER AND PROGNOSING LUNG CANCER SURVIVAL

The application provides methods of prognosmg, diagnosing, screening and classifying lung cancer patients into poor survival groups or good survival groups. A number of altered genomic regions have been identified that distinguish subtype of lung adenocarcinoma (ADC), specifically between bronchioloalveolar carcinoma (BAC) and invasive ADC with BAC features (AWBF), and genes and biomarkers whose expression are altered in individuals with pulmonary ADC according to different survival outcomes. The amplification and/or deletion of these genomic regions, and/or the biomarker expression profiles can be used to classify patients with ADC into a BAC group with excellent survival outcome, or an invasive ADC with BAC features group with higher risk of developing metastatic recurrence and poorer survival outcome. The application also includes kits for use in the methods of the application. 1. A method of classifying a subject with lung adenocarcinoma , comprising the steps:(a) determining the expression level of one or more biomarkers in a test sample from the subject, wherein the one or more biomarkers are selected from Table 1, 2, 3 and/or 4;(b) comparing the expression of the one or more biomarkers with a control, and(c) classifying the subject with lung adenocarcinoma into a bronchioloalveolar carcinoma (BAC) group or invasive adenocarcinoma (ADC) group or a poor survival group or a good survival group according to a difference or a similarity in the expression of the one or more biomarkers between the control and the test sample.2. The method of for classifying or prognosing a subject with lung adenocarcinoma claim 1 , comprising the steps:a) obtaining a subject biomarker expression profile in a sample of the subject;b) obtaining one or more biomarker reference expression profiles associated with a disease subtype, wherein the subject biomarker expression profile and the biomarker reference profile each has a plurality of values, each value representing an expression ...

METHODS FOR SCREENING Th2 INFLAMMATORY DISEASES

The present invention provides a method for screening for a Th2 inflammatory disease in a subject comprising the steps of: assaying a miR-21 expression level in a biological sample from the subject, and comparing the miR-21 expression level in the biological sample from the subject to the miR-21 expression level in a control, wherein an increase in the miR-21 expression level in the biological sample from the subject compared to the miR-21 expression level in the control indicates the presence of Th2 inflammatory disease in the subject. 1. A method of screening for a Th2 inflammatory disease in a subject , the method comprising the steps of:assaying miR-21 expression level in a biological sample from the subject by at least one of quantitative PCR, a microarray, or in situ hybridization; andcomparing miR-21 expression level in the biological sample from the subject to miR-21 expression level in a control; anddetermining the subject has a Th2 inflammatory disease if there is an increase in miR-21 expression level in the biological sample from the subject compared to miR-21 expression level in the control.2. The method of claim 1 , further comprising the step of developing a treatment plan if the increase in miR-21 expression level in the biological sample from the subject is at least 5-fold compared to miR-21 expression level in the control.3. The method of claim 1 , wherein the biological sample is selected from the group consisting of blood claim 1 , serum claim 1 , a biopsy sample claim 1 , a tissue sample claim 1 , a cell suspension claim 1 , saliva claim 1 , oral fluid claim 1 , cerebrospinal fluid claim 1 , lymph claim 1 , urine claim 1 , gastric fluid claim 1 , synovial fluid claim 1 , mucus claim 1 , sputum claim 1 , and mixtures thereof.4. The method of claim 1 , wherein the disease is selected from the group consisting of allergic asthma claim 1 , eosinophilic esophagitis claim 1 , allergic rhinitis claim 1 , atopic dermatitis claim 1 , and combinations ...

Method of selecting induced pluripotent stem cell

The present invention provides a method of selecting a highly safe induced pluripotent stem cell, which includes comprehensively detecting the sequence of an expression vector used for induction of the induced pluripotent stem cell, in the nucleic acid in the cell, and a kit used for the method.

Compositions, Kits, and Methods for Identification, Assessment, Prevention, and Therapy of Cancer

The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

Pancreatic cancer markers, and detecting methods, kits, biochips thereof

The present invention provides microRNAs for assessing the status of pancreatic cancer in a subject, and provides methods, kits, and biochips for detecting said microRNAs.

Method and kit for discriminating between breast cancer and benign breast disease

A method and kit are related to discriminating between breast cancer and benign breast disease by the determination of the expression level of at least one target gene including a nucleic acid sequence selected from the nucleic acid sequences set forth in SEQ ID NOs: 1, 2 or 3, 4 and 5 or 6 to obtain an expression profile for the patient, and the comparison of the expression profile of the patient with expression profiles of target genes from patients previously clinically classified as breast cancer and expression profiles of target genes from patients previously clinically classified as benign breast disease.

METHOD AND KIT FOR THE PROGNOSIS OF COLORECTAL CANCER

A method and kit for the prognosis of colorectal cancer where the method includes the steps of: a) obtaining a peripheral blood sample and extracting total RNA from the sample, b) contacting the total RNA with at least one reagent specific for at least one NK cell gene and no more than 25 specific reagents for 25 NK cell genes, c) determining the expression level of at least one and at most 25 NK cell genes to obtain an expression profile for the patient, d) analyzing the expression profile with expression profiles previously clinically classified as a good prognosis and as a poor prognosis, wherein if the expression profile is clustered with the poor prognosis profiles, then the patient is determined to have a poor prognosis, and if the expression profile is clustered with the good prognosis profiles, then the patient is determined to have a good prognosis. 1. A method for determining the prognosis of a colorectal cancer in a peripheral blood sample from a patient , the method comprising:a) obtaining the peripheral blood sample and extracting total RNA from the blood sample,b) contacting the total RNA with at least one reagent that is specific for at least one NK cell gene and no more than 25 specific reagents for 25 NK cell genes,c) determining the expression level of the at least one NK cell gene and of the most 25 NK cell genes to obtain an expression profile for the patient, if the expression profile for the patient is clustered with the expression profiles from patients previously clinically classified as a poor prognosis, then the patient is determined to have a poor prognosis, and', 'if the expression profile for the patient is clustered with the expression profiles from patients previously clinically classified as a good prognosis, then the patient is determined to have a good prognosis., 'd) performing analysis of the expression profile of the patient with expression profiles of NK cell genes from patients previously clinically classified as a good ...

METHODS FOR ASSESSING ENDOMETRIUM RECEPTIVITY OF A PATIENT

The present invention relates to a method for assessing the endometrium receptivity of a patient, comprising a step consisting of measuring the expression level of eleven genes in an endometrial biopsy sample obtained from said patient wherein said genes are MFAP5, ANGPTL1, PROK1, NLF2, LAMB3, BCL2L10, CD68, TRPC4, SORCS1, FST and KRT80. 14-. (canceled)6. The method of claim 5 , wherein said step of measuring is carried out by determining a quantity of mRNA associated with expression of said eleven genes claim 5 , or determining a quantity of proteins encoded by said eleven genes.7. The method of claim 5 , wherein all of said eleven genes are overexpressed.8. The method of claim 5 , wherein said step of proceeding with IVF procedures includes a step of implanting an embryo.9. The method of claim 8 , wherein the embryo is autologous.10. A method of obtaining a blastocyst claim 8 , comprising the steps ofmeasuring an expression level of eleven genes in an endometrial biopsy sample from a patient, wherein the eleven genes are MFAP5, ANGPTL1, PROK1, NLF2, LAMB3, BCL2L10, CD68, TRPC4, SORCS1, FST and KRT80;concluding that the endometrium of the patient is receptive if at least one of the eleven genes is overexpressed,preparing competent endometrial cells from an endometrial explant from the patient;coculturing the competent endometrial cells with an embryo to obtain a blastocyst.11. A method of in vitro fertilization (IVF) claim 8 , comprising the steps ofmeasuring an expression level of eleven genes in an endometrial biopsy sample from the patient, wherein the eleven genes are MFAP5, ANGPTL1, PROK1, NLF2, LAMB3, BCL2L10, CD68, TRPC4, SORCS1, FST and KRT80; andconcluding that the endometrium of the patient is receptive if at least one of the eleven genes is overexpressed,preparing competent endometrial cells from an endometrial explant from the patient;coculturing the competent endometrial cells with an embryo to obtain a blastocyst; andimplanting the blastocyst into the ...

METHODS AND USES RELATING TO THE IDENTIFICATION OF COMPOUND INVOLVED IN PAIN AS WELL AS METHODS OF DIAGNOSING ALGESIA

The present invention relates to a method of identifying a compound involved in pain, the use of Ifi205 nucleic acid or Ifi205 protein for identifying a compound involved in pain as well as methods of diagnosing algesia involving the same. 1. A method of identifying a compound involved in pain , the method comprising the steps of:a) providing a test system comprising Ifi205 nucleic acid,b) contacting the test system with a test compound, andc) determining the effect of the test compound on the test system,wherein the test compound is identified as a compound involved in pain, when a significant effect of the test compound on the test system relative to a control is detected.2. A method of identifying a compound involved in pain , the method comprising the steps of:a) providing a test system comprising Ifi205 protein or a functionally active variant thereof,a) contacting the test system with a test compound, andb) determining the effect of the test compound on the test system,wherein the test compound is identified as a compound involved in pain, when a significant effect of the test compound on the test system relative to a control is detected.3. (canceled)4. The method of or , wherein the compound involved in pain alters signal transduction upstream or downstream of the Ifi205 protein.5. The method of or , wherein the compound involved in pain alters expression of the Ifi205 gene.6. The method of or , wherein the compound involved in pain binds to the Ifi205 nucleic acid or the Ifi205 protein.78-. (canceled)9. The method of or , wherein the test system is in a cell.10. The method of or , wherein the method is a high-through-put method.11. The method of or , wherein the pain is neuropathic pain.1214-. (canceled)15. A method of diagnosing algesia , comprising the steps ofa) determining the level expression of the Ifi205 gene in a subject's sample, andb) identifying the subject as algesic, if the level expression of the Ifi205 gene is increased in the subject's sample ...

Microarray-based sample analysis system

A microarray-based sample analysis (MBSA) system includes a cartridge holder adapted to receive a replaceable cartridge that is configured to receive a detachable, replaceable sample analysis unit containing one or more reaction chambers for sample analysis; a fluid control subsystem that controls fluid flow; and an optical subsystem configured to capture an image of the microarray.

Means and Methods for Determining Risk of Cardiovascular Disease

The invention relates to medicine, in particular to internal medicine and/or cardiology. The present invention provides means and methods for typing a sample and identifying and/or treating a patient suffering from or at risk of suffering from cardiovascular disease by measuring mi RNA present in a sample of said patient. The present invention further provides means and methods for identifying new cardiovascular disease therapies.

Method for Predicting a Therapy Response in Subjects with Multiple Sclerosis

A method is provided for determining the efficacy of interferon-beta (IFN-β) therapy in a subject with multiple sclerosis. One step of the method can include obtaining a biological sample from the subject. After obtaining the biological sample, the expression level of at least one interferon-regulated gene (IRG) and/or variant thereof can be determined. Increased or decreased expression of the at least one IRG and/or variant thereof as compared to a control may indicate that the subject will respond poorly to IFN-β therapy. 1. A method of determining the efficacy of interferon-beta (IFN-β) therapy in a subject with multiple sclerosis (MS) , the method comprising the steps of:obtaining a biological sample from the subject; anddetermining the expression level of at least one interferon-regulated gene (IRG) and/or variant thereof;wherein increased or decreased expression of the at least one IRG and/or variant thereof as compared to a control indicates that the subject will respond poorly to IFN-β therapy.2. The method of claim 1 , the biological sample comprising whole blood.3. The method of claim 2 , further comprising isolating RNA from the whole blood sample.4. The method of claim 1 , further including administering a dose of IFN-β to the subject prior to obtaining the biological sample.5. The method of claim 4 , further including obtaining the biological sample in less than about 12 hours after administration of the IFN-β dose.6. A method for screening an agent that can be used to treat MS claim 4 , the method comprising the steps of:providing a population of peripheral blood mononuclear cells (PBMCs) from a subject with MS that is a poor responder to IFN-β therapy;administering an agent to the PBMCs; anddetermining the expression level of at least one IRG and/or variant thereof in one or more of the PBMCs.7. The method of claim 6 , wherein increased or decreased expression of the at least one IRG and/or variant thereof as compared to a control indicates that the ...

SELECTION OF COMPARTMENTALISED SCREENING

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids. 174-. (canceled)75. A method for analyzing a reaction product , the method comprising:providing a plurality of droplets in a reservoir, at least one of the droplets comprising molecules for a reaction;conducting a reaction in the at least one droplets; andmoving the droplets through a channel and past a detector, thereby detecting a reaction product in at least one of the at least one droplets.76. The method according to claim 75 , wherein the reaction is conducted in the reservoir.77. The method according to claim 75 , wherein the droplets are separated by an immiscible fluid.78. The method accordingly to claim 77 , wherein the droplets and the immiscible fluid have different buoyancies.79. The method according to claim 78 , wherein the buoyancy differences assist droplet collection by separating at least a portion of the immiscible fluid from the droplets.80. The method according to claim 75 , wherein the droplets are monodisperse within the channel.81. The method according to claim 77 , wherein the immiscible fluid is an oil82. The method according to claim 81 , wherein the oil is a fluorinated oil.83. The method according to claim 81 , wherein the oil comprises a surfactant.84. The method according to claim 83 , wherein the surfactant the surfactant is a fluorosurfactant.85. The method according to claim 75 , wherein the reaction is a temperature controlled reaction.86. The method according to claim 75 , wherein the molecules comprise one or more cells claim 75 , virus particles claim 75 , bacteria claim 75 , beads claim 75 , protein molecules claim 75 , nucleic acid molecules claim 75 , or any combination thereof.87. The ...

Quantitative, Highly Multiplexed Detection of Nucleic Acids

This invention provides methods of detecting and quantifying target nucleic acids in samples in multiplexed single chamber reactions. Consumables incorporating chambers optimized to reduce signal background proximal to high efficiency arrays are provided, as well as methods of use. Devices and systems configured to use the consumables to practice the methods are a feature of the invention. 1. A method of detecting a target nucleic acid sequence in a sample , comprising:performing an amplification reaction on the sample with a polymerase enzyme that possesses nuclease activity, in the presence of a reagent comprising first probes that comprise a first portion complementary to the target nucleic acid sequence and a second portion not complementary to the first target nucleic acid sequence, the second portion comprising a first quencher moiety coupled to the second portion at a first position, such that the second portion is cleaved from the first portion as a first probe fragment, when the target nucleic acid sequence is amplified;hybridizing the first probe fragment to capture probes immobilized upon a substrate, wherein the capture probes comprise a fluorophore that is at least partially quenched by the first quencher moiety, the fluorophore coupled to a second position on the capture probes such that upon hybridization of the probe fragments to the capture probes, the fluorophore is at least partially quenched by the quencher; anddetecting the presence of the target sequence based upon the quenching of the fluorophore on the capture probes.2. The method of claim 1 , wherein:the amplification reagent comprises a plurality of different probes having a plurality of different first portions complementary to different target nucleic acid sequences, and different second portions not complementary to the plurality of target nucleic acid sequences, the second portions each comprising a quencher moiety coupled to the first position, the plurality of second portions being ...

GENE-EXPRESSION PROFILING WITH REDUCED NUMBERS OF TRANSCRIPT MEASUREMENTS

The present invention provides compositions and methods for making and using a transcriptome-wide gene-expression profiling platform that measures the expression levels of only a select subset of the total number of transcripts. Because gene expression is believed to be highly correlated, direct measurement of a small number (for example, 1,000) of appropriately-selected transcripts allows the expression levels of the remainder to be inferred. The present invention, therefore, has the potential to reduce the cost and increase the throughput of full-transcriptome gene-expression profiling relative to the well-known conventional approaches that require all transcripts to be measured. 1. A method for creating a transcriptome-wide expression profile , comprising: i) a plurality of sample transcripts derived from a biological sample;', 'ii) a plurality of centroid transcripts comprising at least a portion of said sample transcripts, said remaining sample transcripts being non-centroid transcripts;, 'a) providingb) measuring the expression level of said plurality of centroid transcripts; andc) inferring the expression levels of said non-centroid transcripts from said centroid transcript expression levels, thereby creating a genome-wide expression profile.2. A method according to claim 1 , wherein the plurality of centroid transcripts is less than the plurality of sample transcripts.3. A method according to claim 1 , wherein the plurality of centroid transcripts is provided bya) performing computational analysis on a library of transcriptome-wide transcript expression data, such that a plurality of transcript clusters are created, wherein the number of said clusters is less than the total number of transcripts in the library;b) identifying a centroid transcript within each of said transcript clusters thereby creating a plurality of centroid transcripts, said remaining transcripts being non-centroid transcripts;c) determining the ability of the measurements of the ...

METHODS OF IDENTIFYING INTERACTIONS BETWEEN GENOMIC LOCI

The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci. 1. A method , comprising: i) a nuclear matrix comprising a first region and a second region; and', 'ii) a junction marker;, 'a) providing;'}b) incorporating the labeled linker into the nuclear matrix; andc) identifying an interaction frequency within the nuclear matrix.2. The method of claim 1 , wherein said method further comprises fragmenting the nuclear matrix into fragments.3. The method of claim 1 , wherein said junction marker comprises biotin.4. The method of claim 1 , wherein said first and second regions are located on the same chromosome.5. The method of claim 1 , wherein said first and second regions are located on different chromosomes.6. The method of claim 1 , wherein said interaction frequency identifies a long range interaction.7. The method of claim 1 , wherein said interaction frequency identifies a short range interaction.8. The method of claim 1 , wherein said interaction frequency identifies a close neighbor interaction.9. The method of claim 1 , wherein said nuclear matrix is derived from a human cell nucleus.10. The method of claim 1 , wherein said nuclear matrix is derived from a yeast cell nucleus.11. A method claim 1 , comprising; i) a cell comprising at least one chromosome, wherein said at least one chromosome comprises a first region and a second region; and', 'ii) a junction marker;, 'a) providing;'}b) extracting said at least one chromosome from said cell;c) incorporating said junction marker into said extracted chromosome; andd) identifying an interaction frequency involving the chromosome.12. The method of claim 11 , ...

MICROARRAYS

Disclosed is a method of producing a two dimensional microarray using a three dimensional or structured microarray. The invention involves forming defined functionalized areas by layering an inert material over the surface structures of the three dimensional microarray. Sufficient of the inert material and of the top of the surface structures are then removed to expose defined areas of the surface structures within the inert material. 1113-. (canceled)115. A microarray as claimed in claim 114 , wherein the base material is formed from a plastics material claim 114 , a metal claim 114 , a ceramic claim 114 , an oxide claim 114 , silicon claim 114 , a photoresist claim 114 , a polymer substrate claim 114 , or glass.116. A microarray as claimed in claim 114 , wherein the base material has a thickness of between about 500 microns and about 2 mm.117. A microarray as claimed in claim 114 , wherein the base material has a three-dimensional (3D) pattern on the surface in contact with the inert material claim 114 , the tops of the 3D structure protruding or being otherwise exposed from the inert material and defining the functionalized areas.118. A microarray as claimed in claim 114 , wherein the base material has a flat surface claim 114 , and wherein the defined functionalized areas are formed by lithographic claim 114 , printing or masking techniques.119. A microarray as claimed in claim 114 , wherein a patterned layer is attached to or formed onto the underside of the base material to disperse light across the surface where light is passed through the microarray for measurement purposes.120. A microarray as claimed in claim 114 , wherein the inert material:(a) is applied to the surface of the base material between the defined functionalized areas using evaporation, painting, deposition, sputtering, plasma treatment, spray coating, dip coating or spin coating; and/or(b) is selected from gold or silver or chromium, a polymer, or an oil or a combination of any of gold, ...

DETECTION OF TARGET NUCLEIC ACID SEQUENCES BY PTO CLEAVAGE AND EXTENSION ASSAY

The present invention relates to the detection of a target nucleic acid sequence by a PTOCE (PTO Cleavage and Extension) assay. The present invention detects a target nucleic acid sequence in which the PTO (Probing and Tagging Oligonucleotide) hybridized with the target nucleic acid sequence is cleaved to release a fragment and the fragment is hybridized with the CTO (Capturing and Templating Oligonucleotide) to form an extended duplex, followed by detecting the presence of the extended duplex. The extended duplex provides signals (generation, increase, extinguishment or decrease of signals) from labels indicating the presence of the extended duplex and has adjustable Tm value, which are well adoptable for detection of the presence of the target nucleic acid sequence. 1. A method for detecting a target nucleic acid sequence from a DNA or a mixture of nucleic acids by a PTOCE (PTO Cleavage and Extension) assay , comprising:(a) hybridizing the target nucleic acid sequence with an upstream oligonucleotide and a PTO (Probing and Tagging Oligonucleotide); wherein the upstream oligonucleotide comprises a hybridizing nucleotide sequence complementary to the target nucleic acid sequence; the PTO comprises (i) a 3′-targeting portion comprising a hybridizing nucleotide sequence complementary to the target nucleic acid sequence and (ii) a 5′-tagging portion comprising a nucleotide sequence non-complementary to the target nucleic acid sequence; wherein the 3′-targeting portion is hybridized with the target nucleic acid sequence and the 5′-tagging portion is not hybridized with the target nucleic acid sequence; the upstream oligonucleotide is located upstream of the PTO;(b) contacting the resultant of the step (a) to an enzyme having a 5′ nuclease activity under conditions for cleavage of the PTO; wherein the upstream oligonucleotide or its extended strand induces cleavage of the PTO by the enzyme having the 5′ nuclease activity such that the cleavage releases a fragment ...

Digital Counting of Individual Molecules by Stochastic Attachment of Diverse Label-Tags

Compositions, methods and kits are disclosed for high-sensitivity counting of individual molecules by stochastic labeling of a identical molecules in mixtures of molecules by attachment of a unique label-tags from a diverse pool of label tags to confer uniqueness to otherwise identical or indistinguishable events. Individual occurrences of target molecules randomly choose from a non-depleting reservoir of diverse label-tags. Labeled molecules may be detected by hybridization or sequencing based methods. Molecules that would otherwise be identical in information content are labeled to create a separately detectable product that can be distinctly detected. The disclosed stochastic transformation methods reduce the problem of counting molecules from one of locating and identifying identical molecules to a series of binary digital questions detecting whether preprogrammed label-tags are present. The methods may be used, for example, to count a given species of molecule within a sample. 1. A method for counting individual occurrences of at least one species of target molecule in a mixture of nucleic acids having an unknown number of target molecule occurrences , the method comprising:(a) combining the mixture with a pool of label-tags, wherein the pool of label-tags comprises multiple copies of each of a plurality of different label-tag sequences;(b) attaching label-tags from the pool of label-tags to individual occurrences of the at least one species of target molecule in a random manner to obtain label-tag-target molecules, wherein different occurrences of a species of target molecule attach to different label-tag sequences from the plurality of different label-tag sequences, thereby obtaining a plurality of unique label-tag-target molecules;(c) optionally amplifying the unique label-tag-target molecules;(d) detecting each type of unique label-tag-target molecule; and(e) counting the number of unique label-tag-target molecules that are detected to obtain a count of the ...

ARBITRARY ASSEMBLY OF NANO-OBJECTS INTO DESIGNED 1D AND 2D ARRAYS

The present invention is directed to nanoscale fabrication of nano-materials with application in electronics, energy conversion, bio-sensing and others. Specifically, the invention is directed to arbitrary, that is periodic and non-periodic, assembly of nano-objects on I D and 2D arrays. The present invention utilizes self-organization properties of nanoscale bio-encoded building blocks, programmability of biomolecular interactions, and simple processing techniques for providing arbitrary by-design fabrication capability. Specifically, the present invention utilizes double stranded DNA attached to a surface and intercalating PNA-DNA hybrids attached to nano-objects to bind the nano-objects to the dsDNA in a site specific manner. The present invention allows for an integration of a large number of nano-components in unified well-defined systems. Accordingly, the present invention is applicable for fabrication of I D and 2D structures of various by-design placements of nano-objects of multiple types, including metal, semiconducting and organic nano-objects. 1. An array comprising:a surface having an anchoring point;a strand of nucleic acids attached to the surface at the anchoring point;an intercalator; anda nano-object,wherein one end of the intercalator binds to a specific sequence on the strand of nucleic acids and a second end of the intercalator binds to the nano-object.2. The array according to claim 1 , wherein the surface is a solid support made of silicon.3. The array according to claim 1 , wherein the anchoring point is a nucleic acid sequence claim 1 , biotin claim 1 , or streptavidin.4. The array according to claim 1 , wherein the strand of nucleic acids is DNA.5. The array according to claim 1 , wherein the strand of nucleic acids is a lithographic DNA.6. The array according to claim 1 , wherein the intercalator is a strand of nucleic acids claim 1 , a protein claim 1 , an organic compound claim 1 , or a combination thereof.7. The array according to claim ...

Gene expression profiles and methods of use

The present invention relates to gene expression profiles, microarrays comprising nucleic acid sequences representing gene expression profiles, and methods of using expression profiles and microarrays. The invention also provides methods and compositions for diagnostic assays for detecting cancer and therapeutic methods and compositions for treating cancer. The invention also provides methods for designing, identifying, and optimizing therapeutics for cancer. 1. A method to monitor the response of a patient being treated for cancer by administering an anti-cancer agent , comprising the steps of:(a) determining the level of expression of one or more genes or gene products in a first biological sample taken from the patient prior to treatment with the anti-cancer agent;(b) determining the level of expression of one or more genes or gene products in at least a second biological sample taken from the patient subsequent to the treatment with the anti-cancer agent; and(c) comparing the level of expression of one or more one genes(s) or gene products in the second biological sample with the level of expression of one or more one genes(s) or gene products in the first biological sample;wherein a change in the level of expression of one or more genes or gene products in the second biological sample compared to the level of expression of one or more genes or gene products in the first biological sample indicates the efficacy of the treatment with the anti-cancer agent.2. The method of claim 1 , wherein the anti-cancer agent is a multi-kinase inhibitor.3. The method of wherein one or more genes are selected from the group consisting of genes listed in Table 1.4. The method of claim 2 , wherein the multi-kinase inhibitor is sorafenib.5. A method to predict the response of a patient to an anti-cancer agent claim 2 , comprising the steps of:(a) determining the level of expression of one or more genes or gene products in a first biological sample taken from the patient prior to ...

NON-FOULING POLYMERIC SURFACE MODIFICATION AND SIGNAL AMPLIFICATION METHOD FOR BIOMOLECULAR DETECTION

An article such as a biosensor having a nonfouling surface thereon is described. The article comprises: (a) a substrate having a surface portion; (b) a linking layer on the surface portion; (c) a polymer layer comprising brush molecules formed on the linking layer; and (d) optionally but preferably, a first member of a specific binding pair (e.g., a protein, peptide, antibody, nucleic acid, etc.) coupled to the brush molecules. The polymer layer is preferably formed by the process of surface-initiated polymerization (SIP) of monomeric units thereon. Preferably, each of the monomeric units comprises a monomer (for example, a vinyl monomer) core group having at least one protein-resistant head group coupled thereto, to thereby form the brush molecule on the surface portion. Methods of using the articles are also described. 1. A biomolecular detector , comprising:(a) a substrate having a surface portion;(b) a linking layer on said surface portion; and(c) a polymer layer formed on said linking layer by the process of surface-initiated polymerization of monomeric units thereon, with each of said monomeric units comprising a monomer core group having at least one protein-resistant head group coupled thereto, to thereby form a brush molecule on said surface portion;said brush molecule comprising a stem formed from the polymerization of said monomer core groups, and a plurality of branches formed from said head group projecting from said stem; and(d) a first member of a specific binding pair coupled to said brush molecule.2. The detector of claim 1 , wherein said member of a specific binding pair further comprises an extended nucleic acid conjugated thereto claim 1 , said extended nucleic acid produced by the process of enzymatic extension with terminal transferase.3. The detector of claim 1 , wherein said first member is a first nucleic acid claim 1 , said detector optionally further comprising a second nucleic acid as a second member of said binding pair hybridized to ...

Arrays of Nucleic Acid Probes for Analyzing Biotransformation Genes

The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the biotransformation genes, such as cytochromes P450. For example, one such array comprises four probe sets. A first probe set comprises a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence from a biotransformation gene, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence. Second, third and fourth probe sets each comprise a corresponding probe for each probe in the first probe set. The probes in the second, third and fourth probe sets are identical to a sequence comprising the corresponding probe from the first probe set or a subsequence of at least three nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the four corresponding probes from the four probe sets. 1. An array of nucleic acid probes immobilized on a solid support , the array comprising at least two sets of probes ,(1) a first probe set comprising a plurality of probes, each probe comprising a segment of at least six nucleotides exactly complementary to a subsequence of a reference sequence, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence,(2) a second probe set comprising a corresponding probe for each probe in the first probe set, the corresponding probe in the second probe set being identical to a sequence comprising the corresponding probe from the first probe set or a subsequence of at least six nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the two corresponding probes from the first and ...

Systems and methods for high speed array printing and hybridization

Novel and improved systems and methods for high speed arraying, hybridization, quantitative development and/or assaying are provided. Some embodiments provide a web based arraying format. Some other embodiments provide a sheet based arraying format. Some embodiments use a drop on drop assaying or hybridization mode. In some embodiments, a substantially inert substrate is utilized. In some other embodiments, an interactive substrate is utilized.

Methods for inhibition of cell proliferation, synergistic transcription modules and uses thereof

The invention provides for methods for treating nervous system cancers in a subject. The invention further provides methods for treating nervous system tumor cell invasion, migration, proliferation, and angiogenesis associated with nervous system tumors.

METHODS FOR MULTIPLEXED SELECTION OF FUNCTIONAL LIGANDS

The present invention relates to methods for generating functional biomolecules. In one exemplary aspect of the invention, generation of functional biomolecules may be performed against multiple targets simultaneously within a single system. In general, a plurality of targets may be disposed within in a single reaction volume and a library of biomolecules, such as a nucleic acid library, may be applied to the reaction volume. The members of the library that do not bind to any of the plurality of targets under given conditions may then be partitioned. The remaining members of the library may then be marked and/or tagged, such as to identify the particular target or targets to which the member of the library binds. The binding members of the library may then be isolated and, by virtue of the marking or tagging, be matched to a particular target or targets. 2. The method of claim 1 , wherein said aptamers and said identifiers further comprise constant priming regions.3. The method of claim 2 , wherein said attaching comprises hybridizing said constant region of said identifiers to said constant region of said aptamers.4. The method of claim 2 , further comprising performing a nucleic acid extension reaction on any of said hybridized oligonucleotide and aptamer to produce an extension product comprising said identity sequence and a complementary sequence to said aptamer claim 2 , or their complements.5. The method of claim 4 , further comprising sequencing said extension product to determine the original sequence of said aptamer and the predetermined position to which said aptamer was bound.6. The method of claim 4 , further comprising adding primers substantially complementary to said constant priming regions.7. The method of claim 1 , wherein each of said target spots comprises a different target molecule.8. The method of claim 1 , wherein said target spots are obtained by contacting a library of oligonucleotides with a plurality of target molecules disposed on a ...

METHODS AND COMPOSITIONS INVOLVING MIRNA EXPRESSION LEVELS FOR DISTINGUISHING PANCREATIC CYSTS

Embodiments concern methods and compositions for evaluating a pancreatic cyst in a patient based on the expression levels of one or more miRNAs to determine whether the pancreatic cyst is a low or high risk lesion and in further need of treatment such as resection. 1. A method for evaluating a pancreatic cyst in a patient comprising:a) measuring from a pancreatic cyst sample from the patient the level of expression of at least two of the following biomarker miRNAs: miR-24, miR-30a-3p, miR-92a, miR-18a, miR-342-3p, miR-99b, miR-106b, miR-142-3p, or miR-532-3;b) comparing the level of expression each biomarker miRNA to the level of expression of another biomarker miRNA;c) calculating a diagnostic score that indicates the probability the pancreatic cyst is a low risk or high risk lesion, wherein the diagnostic score is based on comparisons between the expression levels of the biomarker miRNAs to the expression level of at least one other biomarker miRNA.214.-. (canceled)15. The method of claim 1 , wherein the pancreas sample is a cystic fluid sample.16. The method of claim 15 , wherein the sample is obtained by fine needle aspirate.1723.-. (canceled)24. The method of claim 16 , further comprising determining diffpair values after measuring and comparing the level of expression of miRNAs claim 16 , where the diff pair values are calculated from at least two of the following diffpairs: miR-24/miR-30a-3p; miR-18a/miR-92a; miR-24/miR-342-3p; miR-24/miR-99b; miR-106b/miR-92a; miR-142-3p/miR-92a; or miR-30a-3p/miR-532-3p.2529.-. (canceled)30. The method of claim 24 , further comprising measuring the level of expression of at least one of the following miRNAs: miR-15a claim 24 , miR-16 claim 24 , miR-21 claim 24 , miR-17-5p claim 24 , miR-100 claim 24 , miR-107 claim 24 , miR-155 claim 24 , miR-181a claim 24 , miR-181c claim 24 , miR-210 claim 24 , miR-221 claim 24 , or miR-223.3132.-. (canceled)33. The method of claim 1 , wherein the diagnostic score is based on determined ...

Discrete states for use as biomarkers

The present invention describes the use of discrete states and signatures for classifying samples.

METHOD FOR PREDICTING THERAPEUTIC EFFECT OF IMMUNOTHERAPY ON CANCER PATIENT, AND GENE SET AND KIT TO BE USED IN THE METHOD

Provided is a gene set which is useful for predicting the therapeutic effect of an immunotherapy on a cancer patient. Also provided is a method for examining whether an immunotherapy is efficacious or not, said method comprising quantifying the expression amount of each of the genes constituting the aforesaid gene set. This examination method is useful for determining a therapeutic strategy for the cancer patient. 1. A method for predicting effect of immunotherapy on a cancer patient , comprising a step of measuring an expression level of each of at least one gene selected from the group of genes shown in Table 1 , 19 , 34 or 35 in a sample obtained from the cancer patient before the immunotherapy.2. The method according to claim 1 , wherein an expression level of each of LOC653600 claim 1 , TNFRSF19 claim 1 , P4HA1 and SYNE1 is measured.3. (canceled)4. The method according to claim 1 , wherein an expression level of each of DEFA1 claim 1 , DEFA4 claim 1 , CEACAM8 and MPO is measured.5. (canceled)6. The method according to claim 1 , wherein an expression level of each of LRRN3 claim 1 , PCDH17 claim 1 , HIST1H4C and PGLYRP1 is measured.7. The method according to claim 1 , further comprising a step of determining a prognosis of the patient by discriminant analysis using the expression level.8. The method according to claim 1 , for predicting a poor prognosis group.9. The method according to claim 1 , wherein the immunotherapy is peptide vaccine therapy.10. The method according to claim 1 , wherein the cancer is prostate cancer.11. The method according to claim 1 , wherein the sample obtained from the cancer patient is blood.12. A gene set for predicting effect of immunotherapy on a cancer patient claim 1 , comprising at least one gene selected from the group of genes shown in Table 1 claim 1 , 19 claim 1 , 34 or 35.13. The gene set according to claim 12 , wherein the gene set comprises at least one gene selected from the group of genes shown in Table 2 or 22.14. The ...

Compositions and methods for the treatment of immune related diseases

The present invention relates to compositions containing novel proteins and methods of using those compositions for the diagnosis and treatment of immune related diseases.

IDENTIFICATION OF MULTIGENE BIOMARKERS

Methods for identifying multigene biomarkers for predicting sensitivity or resistance to an anti-cancer drug of interest, or multigene cancer prognostic biomarkers are disclosed. The disclosed methods are based on the classification of the mammalian genome into 51 transcription clusters, i.e., non-overlapping, functionally relevant groups of genes whose intra-group transcript levels are highly correlated. Also disclosed are specific multigene biomarkers for predicting sensitivity or resistance to tivozanib, or rapamycin, and a specific multigene biomarker for determining breast cancer prognosis, all of which were identified using the methods disclosed herein. 2. The method of claim 1 , wherein the PGS comprises a 10-gene subset of TC50 selected from the group consisting of:(a) MRC1, ALOX5AP, TM6SF1, CTSB, FCGR2B, TBXAS1, MS4A4A, MSR1, NCKAP1L, and FLI1; and(b) LAPTM5, FCER1G, CD48, BIN2, C1QB, NCF2, CD14, TLR2, CCL5, and CD163.3. The method of claim 1 , further comprising the step of performing a threshold determination analysis claim 1 , thereby generating a defined threshold claim 1 , wherein the threshold determination analysis comprises a receiver operator characteristic curve analysis.4. The method of claim 1 , wherein the relative expression level of each gene in the PGS is measured by a method selected from the group consisting of: (a) DNA microarray analysis claim 1 , (b) qRT-PCR analysis claim 1 , (c) qNPA analysis claim 1 , (d) a molecular barcode-based assay claim 1 , and (e) a multiplex bead-based assay. This application is a divisional of U.S. patent application Ser. No. 13/669,275, filed Nov. 5, 2012, which claims the benefit of and priority to U.S. provisional application Ser. No. 61/579,530, filed Dec. 22, 2011; the entire contents of each of which are incorporated herein by reference.The field of the invention is molecular biology, genetics, oncology, bioinformatics and diagnostic testing.Most cancer drugs are effective in some patients, but not ...

MONITORING OF IMMUNE SYSTEM USING PERIPHERAL BLOOD MICRO-RNA EXPRESSION PROFILE ANALYSIS AND USES THEREOF

The present invention relates to a method for monitoring the immune system of an individual, which comprises measuring, preferably by quantitative RT-PCR, the expression level of at least one microRNA (miRNA) gene product in a peripheral blood sample or in a biological fluid sample, and comparing said measured expression level with a reference level. In particular, the at least one miRNA gene product, which the method of the invention measures, is expressed by lymphocyte populations of an individual, in particular by naive CD4+T, TH1, TH2 and TH17 lymphocytes. The method of the invention is useful for the diagnosis, prognosis, prevention, control and/or the treatment of a pathological condition caused by or associated with an immune system dysfunction. Moreover, the method of the present invention is useful for monitoring, in an individual, the evolution of conditions mediated by the immune system, such as the response to a vaccination. 1. A method for monitoring the immune system of an individual , comprising the steps of:a) measuring the expression level of at least one miRNA gene product selected from among SEQ ID NO: 1-154 or combinations thereof; and 'wherein said measuring of the expression level of at least one miRNA gene product is carried out in an isolated sample of peripheral blood or biological fluid.', 'b) comparing said measured expression level with a reference level,'}2. The method according to claim 1 , wherein said individual is affected by a pathological condition caused by or associated with a dysfunction of said immune system claim 1 , or said individual undergoes a vaccination.3. The method according to claim 1 , for the diagnosis claim 1 , prognosis or prevention of a pathological condition caused by or associated with a dysfunction of said immune system claim 1 , or for evaluating the risk of the functionality of said immune system being compromised claim 1 , or for monitoring the effectiveness of a therapeutic treatment for said pathological ...

DNA INTERCALATOR DETECTION

A DNA intercalator detection system can include a filtration unit a control sample conditioner operably coupled with the filtration unit and an analytic unit operably coupled with the filtration unit and control sample conditioner and having an electronic chemical array (ECA) reaction component. A data processing unit is operably coupled with the analytic unit and configured to compare and determine a difference between electronic data of a test sample and a conditioned control sample from the ECA reaction component. The difference provides an indication of whether or not a DNA intercalator is present in the test sample. 1. A DNA intercalator detection system , the system comprising:a control sample conditioner unit configured to receive a control sample and to remove one or more DNA intercalators from the control sample so as to produce a conditioned control sample;an analytic unit having a first inlet fluidly coupled to the control sample conditioner unit and configured to receive the conditioned control sample and a second inlet configured to receive a test sample, wherein the analytic unit has one or more electronic chemical arrays configured to assay the test sample and configured to assay the conditioned control sample; anda data processing unit operably coupled with the analytic unit and configured to compare and to determine a difference between an electronic current of the test sample with an electronic current of the conditioned control sample from the analytic unit, said difference providing an indication of whether or not a DNA intercalator is present in the test sample.2. The system of claim 1 , further comprising a filtration unit having an outlet fluidly coupled to an inlet of the control sample conditioner unit and an outlet fluidly coupled to an inlet of the analytic unit claim 1 , wherein the filtration unit includes filter components configured to separate environmental and/or biological materials from an environmental sample to provide the test ...

Microfluidic devices

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.

Direct Clone Analysis and Selection Technology

The present invention describes a spatial addressing technique that uses a very high-density micro-pore array for high-throughput screening of biological interactions. The therapeutic, diagnostic and drug-discovery implications of being able to identify, select and characterize specific protein-protein, protein-DNA and/or protein-carbohydrate interactions from heterogeneous populations of millions (to billions) of cells is discussed. Importantly, this technique possesses the screening and selection capacity of current display-based screening systems (i.e., millions-billions) but with greater efficiency and shorter time.

PATTERNED DEVICES AND METHODS FOR DETECTING ANALYTES

Disclosed herein are devices for the detection of target molecules and methods for their use and production. The disclosed devices may include optically decipherable patterns that facilitate an understanding of binding events between a target molecule and a detection molecule. In one example, a device includes a macroscopic pattern constructed using microscopic elements that can be chromogenically developed to memorialize a binding event. In another example, a device includes characters that can be chromogenically developed using an automated slide staining instrument to memorialize a binding event. 1. A device comprisinga substrate with at least one substrate surface anda plurality of immobilized detection molecules bound to the substrate surface,wherein the plurality of immobilized detection molecules are patterned on the substrate surface to form at least one optically decipherable pattern.2. The device of claim 1 , wherein the detection molecules are oligonucleotides or peptides.3. The device of claim 1 , wherein the optically decipherable pattern includes a shape pattern and/or a positional pattern.4. The device of claim 1 , wherein the at least one optically decipherable pattern is a glyph rendered from a character selected from the Universal Character Set claim 1 , defined by the International Standard ISO/IEC 10646.5. The device of claim 3 , wherein the glyph is associated with a typeface claim 3 , the typeface having a typographic size of between about 1 and about 216 points or between about 3 and about 96 points claim 3 , wherein one point is 1/72 of inch.6. The device of claim 1 , wherein the plurality of detection molecules includes a first immobilized detection molecule that is specific to a first target molecule and a second immobilized detection molecule that is specific to a first control molecule.7. The device of claim 6 , wherein the first immobilized detection molecule is patterned on the substrate surface to form a first character and the second ...

METHOD AND KIT FOR CLASSIFYING A PATIENT

Provided is a Suppressive Subtractive Hybridization-Oligonucleotide Microarray (SSH-OM) method for the prediction of treatment response for personalized medicine applications and for the prediction of cancer classes and subclasses. 1. A method for classifying a patient comprising(a) isolating a total RNA sample from the patient;(b) subjecting the total RNA to ribosomal RNA reduction, mRNA species enrichment and fragmentation;(c) subtracting a first aliquot of the fragmented mRNA against a first reference pool of complementary RNA (cRNA);(d) independently subtracting a second aliquot of the fragmented mRNA against a second reference pool of cRNA;(e) independently amplifying the subtracted mRNA of (c) and (d) to produce first and second amplified RNAs, respectively;(f) independently hybridizing the first and second amplified RNAs to oligonucleotide microarrays to generate first and second patterns of hybridization;(g) comparing the first and second patterns of hybridization to controls to classify the patient.2. The method of claim 1 , wherein the first and second reference pool cRNA are respectively from responders and non-responders to treatment and the patient is classified as a responder or non-responder to treatment.3. The method of claim 2 , wherein the controls comprise oligonucleotides microarray hybridization patterns of responders and non-responders to treatment.4. The method of or claim 2 , wherein the treatment is lung cancer surgery or adjuvant therapy.5. The method of claim 1 , wherein the patient is classified as having a particular class of cancer.6. The method of claim 5 , wherein the cancer is lung cancer.7. The method of claim 6 , wherein the lung cancer is classified as non-small-cell lung carcinoma claim 6 , small-cell lung carcinoma claim 6 , cardinoid claim 6 , or sarcoma.8. The method of claim 7 , wherein the non-small-cell lung carcinoma is subclassified as adenocarcinoma claim 7 , squamous cell carcinoma or Large Cell carcinoma.9. The method ...

Method for Active Hybridization in Microarrays with Denaturing Function

A method for active hybridization in microarrays includes pumping an already prepared sample through a denaturing unit with a microarray and then through a reaction region which is spatially separate from the denaturing unit. The denatured reactive sample components are hybridized in the reaction region. 1. A method for active hybridization to at least one probe of a microarray , comprising:a. providing a sample liquid containing reactive constituents,b. introducing the sample liquid into a pump route comprising at least one pump unit, at least one temperature-controlled denaturation unit and at least one temperature-controlled reaction area which is spatially separated from the at least one temperature-controlled denaturation unit and has at least one microarray,c. pumping the sample liquid,d. denaturing the reactive constituents of the sample liquid in the at least one temperature-controlled denaturation unit ande. hybridizing the denatured constituents to at least one probe of the at least one microarray in the at least one temperature-controlled reaction area.2. The method as claimed in claim 1 , wherein the at least one pump unit and the at least one temperature-controlled denaturation unit form a structural unit.3. The method as claimed in claim 1 , further comprising cooling the sample liquid after denaturing in the at least one temperature-controlled denaturation unit and before hybridizing in the at least one temperature-controlled reaction area.4. The method as claimed in claim 1 , further comprising detecting the microarray after hybridizing the denatured constituents in step e.5. The method as claimed in claim 1 , wherein the at least one pump unit comprises one of a micromembrane pump and a peristaltic micropump.6. The method as claimed in claim 5 , wherein the at least one pump unit is integrated within the pump route or is arranged off chip.7. The method as claimed in claim 1 , wherein the pump route is arranged as a circuit and a uniform claim 1 , ...

MICROARRAY-BASED ASSAY INTEGRATED WITH PARTICLES FOR ANALYZING MOLECULAR INTERACTIONS

A microarray-based assay is provided, which is used for analyzing molecular interactions, including polynucleotides, polypeptides, antibodies, small molecule compounds, peptides and carbohydrates. Such method comprises coupling a target molecule to a particle and then binding to a probe molecule on microarray. In particular, multiplexed genetic analysis of nucleic acid fragments can be implemented. Specific genes, single nucleotide polymorphisms or gene mutations, such as deletions, insertions, and indels, can be identified. Coupled with microarray, the particles, themselves or further modified, facilitate the detection of results with non-expensive devices or even naked eyes. This technology enables the detection and interpretation of molecular interactions in an efficient and cost effective way. 199-. (canceled)100. A method for detecting a target molecule using a microarray , which method comprises:a) coupling the target molecule to a particle;b) binding the target molecule to a probe molecule immobilized on the microarray; andc) detecting the interaction between the target molecule and the probe molecule,wherein the target molecule is selected from the group consisting of a polypeptide, an antibody, a small molecule compound, a peptide and a carbohydrate.101. A method for detecting a target molecule using a microarray , which method comprises:a) coupling a double stranded target molecule to a particle;b) recovering a single stranded target molecule coupled to the particle;c) binding the single stranded target molecule to a probe molecule immobilized on the microarray; andd) detecting the interaction between the target molecule and the probe molecule,wherein the target molecule is a polynucleotide.102. The method according to or , wherein the particle and/or the target molecule is modified with a functional group selected from the group consisting of a chemical group , a polynucleotide , a polypeptide , an antibody , a small molecule compound , a peptide and a ...

INTEGRATED SEMICONDUCTOR BIOARRAY

A biosensor array, system and method for affinity based assays that are able to simultaneously obtain high quality measurements of the binding characteristics of multiple analytes, and that are able to determine the amounts of those analytes in solution. The invention also provides a fully integrated bioarray for detecting real-time characteristics of affinity based assays. 145-. (canceled)46. A method comprising: a solid substrate comprising an array of semiconductor-based optical sensors;', 'an optical filter layer integrated on top of the solid substrate;', 'and', 'a molecular recognition layer in contact with the optical coupling filter layer and comprising a plurality of different probes, with different probes immobilized to the surface at different addressable locations;, 'contacting a fluid containing a target analyte with a fully integrated biosensor array comprisingilluminating the biosensor;detecting fluorescence on the biosensor;correlating the detected fluorescence with binding of the target analyte with the probes.47. The method of claim 46 , in which:the contacting fluid volume comprises a plurality of different analytes, wherein the probes are capable of specifically binding to the analytes; andthe step of detecting fluorescence on the biosensor comprises measuring the fluorescence signals at multiple time points while the fluid volume is in contact with the substrate, wherein the fluorescence signals measured at multiple time points can be correlated with the amount of binding of the analytes with the probes as a function of time.48. The method of further comprising the step of:using the signals measured at multiple time points to determine the original concentration of an analyte in the fluid volume.49. The method of wherein a change in the signals with time correlates with the amount of the analytes bound to the probes.50. The method of claim 46 , further comprising the steps of:performing a nucleic acid amplification on two or more nucleotide ...

Method for Detecting Nucleic Acids

A method for simultaneously detecting at least one specific DNA target molecule in a plurality of samples by means of nucleic acid amplification is provided. The method comprising: bringing at least two DNA samples comprising DNA in contact with forward and reverse primers, which in the 3′ portion contain a nucleotide sequence that is complementary to the amplifying DNA target molecule, and which in the 5′ portion comprises an oligonucleotide having an artificial DNA sequence that is associated with the individual samples; amplifying the samples; contacting the amplified samples with a solid substrate on which oligonucleotides are immobilized at a preselected site, said oligonucleotides comprising at the 3′ ends the artificial DNA sequence associated with the individual samples; and ascertaining binding of the amplification products at the oligonucleotides immobilized on the solid substrate. 1. A method for simultaneously detecting at least one specific target DNA molecule in a plurality of samples by means of nucleic acid amplification , comprising the following steps:a) providing at least two samples comprising DNA,b) contacting the samples from step a) with a forward primer and a reverse primer comprising a 3′ and a 5′ portion, wherein the forward and the reverse primer each have a nucleotide sequence in the 3′ portion that is complementary to the DNA target molecule to be amplified and the forward or the reverse primer comprises an oligonucleotide in the 5′ portion that has an artificial sequence which is associated with the individual samples,c) amplifying the samples from step b),d) contacting the amplified samples from step c) with a solid support on which oligonucleotides are immobilized at a preselected site, wherein said oligonucleotides comprise at the 3′ end thereof the artificial sequence which is associated with the individual samples, ande) detecting the binding of the amplification products from step c) to the oligonucleotides immobilized on the ...

MULTIPLEX NUCLEIC ACID REACTIONS

A method for detecting nucleic acids by (a) providing a sample having target nucleic acids, each nucleic acid having contiguous first, second, and third domains; (b) contacting the sample with probe sets to form hybridization complexes, wherein each probe set includes (i) a first probe having a sequence that is complementary to the first domain; and (ii) a second probe having a sequence substantially complementary to the third domain; (c) extending the first probes along the second domains of the complexes while the complexes are immobilized on a solid support; (d) ligating the extended first probes to the second probes to form templates; (e) amplifying the templates with primers that are complementary to the first and second priming sequences to produce amplicons; and (f) detecting the amplicons on the surface of a nucleic acid array. 1. A method for detecting different target nucleic acids in a sample , each nucleic acid comprising , from 3′ to 5′: contiguous first , second , and third target domains , comprising:(a) providing a sample having different target nucleic acids; (i) a first probe comprising, from 5′ to 3′: a first priming sequence and a sequence that is substantially complementary to the first target domain; and', '(ii) a second probe comprising 5′ to 3′: a sequence substantially complementary to the third target domain, and a second priming sequence,', 'wherein at least one probe in each of the different probe sets contains a distinct adapter sequence not native to the target nucleic acid;, '(b) contacting the sample with a plurality of at least 100 different probe sets to form hybridization complexes with the different target nucleic acids, wherein each probe set comprises 'wherein the hybridization complexes are immobilized on a solid support when contacted with the extension enzyme and the nucleotides;', '(c) contacting the hybridization complexes with an extension enzyme and nucleotides, wherein the first probes are extended along the second ...

In vitro method for predicting whether a compound is genotoxic in vivo

The invention is in the field of genomics and it provides an in vitro method for predicting whether a compound is genotoxic in vivo. It provides a method that employs the analysis of expression profiles of microRNAs in cells exposed to a potentially genotoxic compound. It was found that differential expression of a number of microRNAs could reliably predict whether a compound was a genotoxic or a non-genotoxic compound.

Method for identifying immunoreactive peptides

The invention relates to a method for identifying immunoreactive peptides. According to said method, a sample of tumorous and corresponding healthy tissue is first provided, the tumor-specific expression profile is subsequently determined and antigenic peptides are isolated from the tumorous tissue and analyzed. The respective data that has been obtained is then matched and peptides are identified on the basis of said data.

PORTABLE GENETIC DETECTION AND ANALYSIS SYSTEM AND METHOD

A portable detector is disclosed for detecting certain analytes of interest, such as genetic material (e.g., nucleic acids). The detector includes a reading component for the detection of the analytes, and control circuitry for controlling operation of the reading component. Processing circuitry may be included to perform both primary analysis of acquired data, and where desired, secondary analysis. Where desired, some or all of the computationally intensive tasks may be off-loaded to enhance the portability and speed of the device. The device may incorporate various types of interface, technologies for reading and analysis, positioning system interfaces, and so forth. A number of exemplary use cases and methods are also disclosed. 1. A portable genetic detector comprising:a reading component configured to detect nucleic acids of interest in a biological sample introduced into the detector;a control system configured to control operation of the reading component; anda communications component configured to transmit data produced by the reading component to a remote computer system for analysis.2. The detector of claim 1 , comprising a sample receiving component configured to receive and prepare the biological sample on a support for genetic analysis.3. The detector of claim 2 , wherein the sample receiving component is controlled by the control system.4. The detector of claim 1 , wherein the detector has a form factor suitable for hand-held operation.5. The detector of claim 1 , comprising memory circuitry for storing at least some of the data produced by the reading component.6. The detector of claim 1 , comprising a processing system configured to perform at least primary analysis of the data produced by the reading component to create processed data.7. The detector of claim 6 , wherein the primary analysis comprises eliminating image data not corresponding to locations on the support having detectable nucleic acids.8. The detector of claim 6 , wherein at least ...

Sensor

A sequencer that measures a nucleic acid sequence in a nucleic acid strand includes: a base material having a surface made of silicon, and a fibrous protrusion that is made of silicon dioxide and is directly joined to the surface of the base material made of silicon, wherein a plurality of the nucleic acid strands are fixed onto the fibrous protrusion.

REAL-TIME AMPLIFICATION AND MICRO-ARRAY BASED DETECTION OF NUCLEIC ACID TARGETS IN A FLOW CHIP ASSAY

The present method is related to a method for identification and/or quantification of at least one polynucleotide target compound present in a biological sample among possible other ones by its amplification in a cycling flow chip solution passing through different temperatures required for the amplification and its detection in real-time onto a micro-array of specific capture molecules. 1. A method for performing real-time amplification and detection of target polynucleotide molecule(s) present in a sample , comprising the steps of:a) providing a flow chip device comprising:{'sup': '2', 'b': '1', 'a flow channel having a section comprised between 0.01 and 10 mmand a volume V, wherein the flow channel is configured such that a solution introduced into the flow channel is cycled through the flow channel,'}{'b': 2', '2', '1, 'a detection chamber in fluid communication with the flow channel, said detection chamber having an optically transparent solid support and a micro-array comprising more than 4 capture molecules being immobilized in localized areas of the surface of said transparent solid support, wherein said chamber has a height lower than 1 mm and a volume V, and wherein the ratio V/V is between 0.001 and 0.5,'}at least 2 different temperature regions at which temperature is regulated, each temperature region being located at a different location of the flow channel, wherein one temperature region comprises the detection chamber and has a temperature allowing the hybridization of the target polynucleotide molecules to the capture molecules,{'b': 3', '3', '1', '2, 'b) introducing a solution having a volume V and containing target polynucleotide molecules into the flow channel and reagents for polynucleotide molecule amplification, wherein the ratio V/(V+V) is higher than 0.02 and lower than 1,'}c) submitting the solution to at least 5 amplification cycles to obtain labeled target polynucleotide molecules, wherein one amplification cycle is obtained by cycling ...

PROBES UTILIZING UNIVERSAL TAGS, A KIT COMPRISING THE SAME AND DETECTION METHODS

The present invention provides a kit and a detection method for multiple targets detection of biomolecules. The kit comprises a universal tag, a probe and an optional instruction for using the same. The universal tag in the present invention is a fragment of DNA, RNA, peptide nucleic acid, or LNA, and is 3-20 mer in length. The probe in the present invention contains in order from 3′ terminus to 5′ terminus, a nucleotide sequence which is reverse complementary to a target molecule or a portion of the target molecule, and a nucleotide sequence which is reverse complementary to the universal tag; or said probe contains in order from 3′ terminus to 5′ terminus, a nucleotide sequence which is reverse complementary to the universal tag, and a nucleotide sequence which is reverse complementary to a target molecule or a portion of the target molecule. 1. A multiple targets detection method of biomolecules ,characterized in that the method comprises steps of:1) preparing universal tags labeled with indicators, wherein the indicators are selected from the group consisting of fluorescent dyes, quantum dots, nanogolds, isotopes, biotins, and combinations thereof;2) preparing probes;3) linking the probes to a modified solid phase support to form probe arrays;4) dissolving the universal tags and samples to be tested into a hybridization solution to hybridize with the probe arrays; or hybridizing the samples to be tested with the probes first, then hybridizing the universal tags with the probe arrays after rinsing;5) rinsing to remove the redundant samples and the redundant universal tags; and6) detecting the presence or absence of the indicators on the probe arrays with a fluorescence microscope, a flat scanner, or an array scanner, wherein:the biomolecules are selected from the group of molecules consisting of DNA, RNA, protein and/or saccharide;the universal tag is a fragment of DNA, RNA, peptide nucleic acid, or LNA, and is 3-20 mer in length;the probe contains in order from ...

Multiplex branched-chain DNA assays

Methods of detecting two or more nucleic acids in a multiplex branched-chain DNA assay are provided. Different nucleic acids are captured through cooperative hybridization events on different, identifiable subsets of particles or at different selected positions on a spatially addressable solid support. Compositions, kits, and systems related to the methods are also described. 1139.-. (canceled)140. A method of detecting ten or more different target nucleic acids of interest , the method comprising:providing a sample comprising nucleic acids;providing a solid phase having associated therewith ten or more different capture probes;providing ten or more subsets of n capture extenders, wherein n is at least two, wherein each subset of n capture extenders is capable of hybridizing to a different target nucleic acid, and wherein the capture extenders in each subset are capable of hybridizing to one of the capture probes and thereby associating each subset of n capture extenders with the solid phase;contacting the sample, the solid phase, and the subsets of n capture extenders;hybridizing any of the different target nucleic acids present in the sample to its complementary subset of n capture extenders and hybridizing the subset of n capture extenders to its complementary capture probe, thereby capturing the target nucleic acid on the solid phase,{'sub': 'm', 'wherein the hybridizing the subset of n capture extenders to the complementary capture probe is performed at a hybridization temperature which is greater than a melting temperature Tof a complex between each individual capture extender and its complementary capture probe;'}hybridizing one or more label extenders to target nucleic acids captured on the solid phase;hybridizing a preamplifier to the label extenders, hybridizing a plurality of amplification multimers to the preamplifier, and hybridizing a plurality of label probes to each of the amplification multimers, wherein each of the label probes comprises or binds a ...

ASSEMBLIES FOR MULTIPLEX BINDING ASSAYS

Assay plate assemblies are disclosed. The assemblies include an assay plate that has a top side, a bottom side, and at least one well accessible from the top side of the plate. The well includes a side surface and a bottom surface, with at least one secondary container protruding through the bottom surface and into an interior volume of the well. The assemblies further include a dispenser plate that is adapted to be positioned adjacent to the top side of the assay plate. The dispenser is further configured to provide one or more reagents to one or more secondary containers of at least one well of the assay plate. 1. An assay plate assembly , which comprises:(a) an assay plate that comprises a top side, a bottom side, and at least one well accessible from the top side of the plate, wherein the well comprises a side surface and a bottom surface, wherein at least one secondary container protrudes through the bottom surface and into an interior volume of the well; and(b) a dispenser plate that is adapted to be positioned adjacent to the top side of the assay plate and to provide one or more reagents to one or more secondary containers of at least one well of the assay plate.2. The assay plate assembly of claim 1 , wherein the secondary container comprises a capillary tube that (a) begins at a location that protrudes through the bottom surface and into an interior volume of the well and (b) ends at a location that extends beyond a bottom side of the assay plate.3. The assay plate assembly of claim 2 , wherein the bottom side of the assay plate comprises a recess around each secondary container at the location that extends beyond the bottom side of such assay plate.4. The assay plate assembly of claim 3 , wherein the side surface of the at least one well comprises a notch claim 3 , which is configured to receive and be positioned adjacent to a correspondingly configured aligning element of the dispenser plate claim 3 , such that when the notch of the well and the aligning ...

MULTIPLEX DECODING OF ARRAY SENSORS WITH MICROSPHERES

The invention relates to compositions and methods for multiplex decoding of microsphere array sensors. 126.-. (canceled)27. A system for decoding the position of one or more bioactive agents on an array , comprising:an array comprising a plurality of bioactive agents randomly distributed at sites of said array, wherein each of a plurality of said sites further comprises at least a first and a second identifier binding ligand (IBL), wherein said first IBL and said second IBL each comprise different nucleic acid sequences;a first decoder binding ligand (DBL) adapted to bind to the first IBL, wherein binding of the first DBL with the first IBL comprises a detectable signal indicative of the location of the first IBL;a second DBL adapted to bind to the second IBL, wherein binding of the second DBL with the second IBL comprises a detectable signal indicative of the location of the second IBL; andwherein the location of the first and second IBLs is indicative of the position of one or more bioactive agents on said array.28. The system of claim 27 , wherein said array comprises glass or plastic.29. The system of claim 27 , wherein said array comprises a fiber optic bundle.30. The system of claim 27 , wherein said array comprises a flat planar surface.31. The system of claim 30 , wherein said flat planar surface comprises one or more depressions.32. The system of claim 27 , wherein said plurality of bioactive agents and said first and second IBLs each comprise a nucleic acid.33. The system of claim 32 , wherein said nucleic acid is selected from the group consisting of DNA and RNA.34. The system of claim 32 , wherein said nucleic acid is single-stranded.35. The system of claim 27 , wherein said one of said first and second IBLs comprises substantially the same nucleic acid sequence as one or more bioactive agents.36. The system of claim 27 , wherein the first IBL and the second IBL each comprise different nucleic acid sequences.37. The system of claim 32 , wherein said ...

INTEROGATORY CELL-BASED ASSAYS FOR IDENTIFYING DRUG-INDUCED TOXICITY MARKERS

Described herein is a discovery Platform Technology for analyzing a drug-induced toxicity condition, such as cardiotoxicity via model building. 1. A method for identifying a drug that causes or is at risk for causing drug-induced cardiotoxicity , comprising: comparing (i) a level of expression of one or more biomarkers present in a first cell sample obtained prior to the treatment with the drug; with (ii) a level of expression of the one or more biomarkers present in a second cell sample obtained following the treatment with the drug; wherein the one or more biomarkers is selected from the markers listed in table 2; wherein a modulation in the level of expression of the one or more biomarkers in the second sample as compared to the first sample is an indication that the drug causes or is at risk for causing drug-induced cardiotoxicity.2. A method for identifying a rescue agent that can reduce or prevent drug-induced cardiotoxicity comprising: (i) determining a normal level of expression of one or more biomarkers present in a first cell sample obtained prior to the treatment with a cardiotoxicity inducing drug; (ii) determining a treated level of expression of the one or more biomarkers present in a second cell sample obtained following the treatment with the cardiotoxicity inducing drug to identify one or more biomarkers with a change of expression in the treated cell sample; (iii) determining the level of expression of the one or more biomarkers with a changed level of expression in the cardiotoxicity inducing drug treated sample present in a third cell sample obtained following the treatment with the cardiotoxicity inducing drug and the rescue agent; and (iv) comparing the level of expression of the one or more biomarkers determined in the third sample with the level of expression of the one or more biomarkers present in the first sample; wherein the one or more biomarkers is selected from the markers listed in table 2; and wherein a normalized level of expression ...

METHOD FOR DETERMINING THE NEURODEVELOPMENTAL TOXICITY OF A COMPOUND IN VITRO

This invention is in the field of medical molecular diagnostics. It provides methods and means for the in vitro detection of the neurodevelopmental toxicity of a compound by determining the gene expression of a limited number of genes. More in particular, it relates to a method for determining the likelihood that a compound is neurodevelopmental toxic, comprising the steps of: providing embryonic stem cells, allowing the stem cells to form embryoid bodies, allowing the embryoid bodies to differentiate into neural cells, in the presence of said compound, thereby creating a neural differentiation culture, extracting total RNA from the cells in said neural differentiation culture, determining the expression levels of genes Hoxb6, Nrk, 1700011H14Rik and Tph1, comparing the expression levels with a predetermined reference value and determining the increase or decrease of the expression level relative to the reference value, wherein a relative increase or decrease in expression value of more than 20% indicates that a compound is neurodevelopmental toxic. 2. The method according to claim 1 , wherein step c is carried out 3 days after the start of step b.3. The method according to claim 1 , wherein step d is carried out 1 day after step c.4. The method according to claim 1 , wherein a retinoid is used for inducing the embryoid bodies to differentiate into a neural lineage.5. The method according to claim 1 , wherein the expression level of the genes is determined by quantitative amplification of nucleic acid.6. The method according to wherein the amplification of nucleic acid includes a polymerase chain reaction.7. The method according to claim 1 , further comprising determining the expression level of at least one gene selected from the group consisting of Prickle1 claim 1 , Scara3 claim 1 , Tgfb2 claim 1 , Crabp1 claim 1 , and Hoxb5.8. The method according to claim 1 , wherein the expression level of genes Hoxb6 claim 1 , Nrk claim 1 , 1700011H14Rik claim 1 , Tph1 claim 1 ...

MICROARRAY SYSTEM WITH IMPROVED SEQUENCE SPECIFICITY

The invention provides a novel array method for nucleic acid sequence detection with improved specificity which allows for detection of genetic variation, from simple SNPs (where the variation occurs at a fixed position and is of limited allelic number) to more complex sequence variation patterns (such as with multigene families or multiple genetic strains of an organism where the sequence variation between the individual members is neither fixed nor consistent). The array is comprised of short, synthetic oligonucleotide probes attached to a solid surface which are hybridized to single-stranded targets. Single stranded targets can be produced using a method that employs primers modified on the 5′ end to prohibit degradation by a 5′-exonuclease that is introduced to degrade the unprotected strand. The invention further provides for printing buffers/solutions for the immobilization of oligonucleotide probes to an array surface. The invention also provides hybridization and wash buffers and conditions to maximize hybridization specificity and signal intensity, and reduce hybridization times. 16-. (canceled)7. A method of detecting the presence of a specific nucleic acid sequence within a pool of detectably labeled target polynucleotides by hybridization to one or more oligonucleotide probes attached to a support comprising:contacting the support with the polynucleotide under high stringency conditions in a buffer comprising a tertiary alkyl ammonium salt and formamide for a period of about 6 hours or less;removing unhybridized target polynucleotides from the support by washing the support under high stringency conditions for a period about 30 minutes or less; anddetecting the presence or absence of labeled target polynucleotides on the washed support.8. The method of claim 7 , wherein the buffer comprises about 2M to about 3M tetramethyl ammonium chloride (TMAC).9. The method of claim 8 , wherein the concentration of TMAC is about 2.5M.10. The method of claim 7 , ...

Specific biomarker for identification of exposure to lower aliphatic saturated aldehydes and the method of identification using the same

The present invention relates to a biomarker for the identification of specific exposure to lower aliphatic saturated aldehydes which are volatile organic compounds exposed in the environment, and a method for the identification of specific exposure to lower aliphatic saturated aldehydes using the same, precisely a biomarker which is up- or down-regulated specifically by lower aliphatic saturated aldehyde exposure and a method for the identification of specific exposure to lower aliphatic saturated aldehydes using the biomarker. The biomarker of the present invention is the reacted genes selected by using DNA microarray chip, which can be effectively used for the monitoring and evaluation of lower aliphatic saturated aldehyde contamination in the environment samples and at the same time as a tool for the investigation of the toxic mechanism induced specifically by lower aliphatic saturated aldehydes.

MicroRNAs For Identification Of Exposure To Lower Aliphatic Saturated Aldehydes And The Method Of Identification Using Thereof

The present invention relates to a biomarker for the identification of exposure to lower aliphatic saturated aldehydes by using micro RNA and a method for the identification of exposure to lower aliphatic saturated aldehydes using the same. In this invention, the micro RNA at least 1.5 fold up-regulated by exposure to lower aliphatic saturated aldehydes and the micro RNA up to 0.66 fold down-regulated by the same were selected. These two micro RNAs can be effectively used as the biomarker for the monitoring of lower aliphatic saturated aldehydes and for the risk assessment thereby and at the same time as a tool to investigate the mechanism of toxicity caused by such lower aliphatic saturated aldehydes. 1. A method for the identification of exposure to lower aliphatic saturated aldehydes , comprising the following steps:{'i': Homo sapiens', 'Homo sapiens, '1) measuring an expression level of micro RNA accession number (miRbase) MIMAT0003258 (hsa-miR-590-5p, miR-590-5p; SEQ. ID. NO: 1), and micro RNA accession number (miRbase) MIMAT0000085 (hsa-miR-28-5p, miR-28-5p; SEQ. ID. NO: 2), on somatic cells separated from both an experimental group and a normal control group; and'}{'i': Homo sapiens', 'Homo sapiens, '2) determining the experimental group to be exposed to lower aliphatic saturated aldehydes, if the expression of the micro RNA accession number (miRbase) MIMAT0003258 (hsa-miR-590-5p, miR-590-5p; SEQ. ID. NO: 1), and the micro RNA accession number (miRbase) MIMAT0000085 (hsa-miR-28-5p, miR-28-5p; SEQ. ID. NO: 2) on the somatic cells from the experimental group is up-regulated or down-regulated compared to the expression of the normal control group.'}2. The method for the identification of exposure to lower aliphatic saturated aldehydes according to claim 1 , wherein the lower aliphatic saturated aldehydes are propionaldehyde claim 1 , butylaldehyde claim 1 , valeraldehyde claim 1 , hexanal claim 1 , heptanal claim 1 , octanal claim 1 , and nonanal.3Homo sapiens. ...

DETECTION OF NUCLEIC ACID REACTIONS ON BEAD ARRAYS

The present invention is directed to methods and compositions for the use of micro sphere arrays to detect and quantify a number of nucleic acid reactions. The invention finds use in genotyping, i.e. the determination of the sequence of nucleic acids, particularly alterations such as nucleotide substitutions (mismatches) and single nucleotide polymorphisms (SNPs). Similarly, the invention finds use in the detection and quantification of a nucleic acid target using a variety of amplification techniques, including both signal amplification and target amplification. The methods and compositions of the invention can be used in nucleic acid sequencing reactions as well. All applications can include the use of adapter sequences to allow for universal arrays. 134.-. (canceled)35. A method of detecting a plurality of target nucleic acid sequences , comprising:a) providing a plurality of target sequences that are immobilized to one or more first solid supports;b) hybridizing a plurality of different first primers to first portions of said plurality of target sequences, wherein each of said different first primers comprises an adapter sequence exogenous to said target sequences;c) hybridizing a plurality of different second primers to second portions of said plurality of target sequences;d) extending said first or said second primers, and then ligating said first and second primers together to form a plurality of different modified primers comprising said adapter sequences;e) amplifying said plurality of different modified primers to form amplified products comprising said adapter sequences;f) hybridizing said adapter sequences of said amplified products, or their complements, to an array of capture probes attached to a second solid support, thereby forming hybridized capture probes;g) modifying said hybridized capture probes by polymerase extension to form modified capture probes, andh) detecting said modified capture probes, thereby detecting said plurality of target ...

SYSTEMS AND METHODS FOR IDENTIFYING COSMETIC AGENTS FOR HAIR/SCALP CARE COMPOSITIONS

Provided are methods and systems for determining functional relationships between a cosmetic agent and a hair biology condition of interest. Also provided are methods and systems for identifying cosmetic agents that affect a hair biology condition, as well as the use of agents identified by such methods and systems for the preparation of cosmetic compositions, personal care products, or both. 1. A method for constructing a data architecture for use in identifying connections between perturbagens and genes associated with one or more hair biology conditions , comprising:(a) providing a gene expression profile for a control human fibroblast cell;(b) generating a gene expression profile for a human fibroblast cell exposed to at least one perturbagen;(c) identifying genes differentially expressed in response to the at least one perturbagen by comparing the gene expression profiles of (a) and (b);(d) creating an ordered list comprising identifiers representing the differentially expressed genes, wherein the identifiers are ordered according to the differential expression of the genes;(e) storing the ordered list as a fibroblast instance on at least one computer readable medium; and(f) constructing a data architecture of stored fibroblast instances by repeating (a) through (e), wherein the at least one perturbagen of step (a) is different for each fibroblast instance.2. A method according to claim 1 , comprising using a programmable computer to perform one or more of steps (c) claim 1 , (d) claim 1 , (e) and (f).3. A method according to claim 1 , wherein the ordered list comprises the ordered list of identifiers in association with a numerical ranking for the identifier corresponding to its rank in the ordered list.4. A method according to claim 1 , wherein the step of generating is performed by extracting a biological sample from the treated cell and subjecting the biological sample to microarray analysis.5. A method according to claim 4 , wherein the biological sample ...

Methods for Diagnosing Stomach Cancer Using MicroRNAs

Described herein are methods for diagnosing stomach cancer using microRNAs. Also described are methods and compositions for the diagnosis and treatment of solid cancers. Methods of identifying inhibitors of tumorigenesis are also provided.

Nucleic Acid Analysis by Random Mixtures of Non-Overlapping Fragments

The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered. In one aspect, this process is carried out in a hierarchical fashion until the one or more target polynucleotides are characterized, e.g. by their nucleic acid sequences, or by an ordering of sequence segments, or by an ordering of single nucleotide polymorphisms (SNPs), or the like.

Hybridization-based biosensor containing hairpin probes and use thereof

A sensor chip that includes: a fluorescence quenching surface; a nucleic acid probe that contains first and second ends with the first end bound to the fluorescence quenching surface, a first region, and a second region complementary to the first region, the nucleic acid probe having, under appropriate conditions, either a hairpin conformation with the first and second regions hybridized together or a non-hairpin conformation; and a first fluorophore bound to the second end of the first nucleic acid molecule. When the first nucleic acid molecule is in the hairpin conformation, the fluorescence quenching surface substantially quenches fluorescent emissions by the first fluorophore; and when the first nucleic acid molecule is in the non-hairpin conformation, fluorescent emissions by the fluorophore are substantially free of quenching by the fluorescence quenching surface. Methods of making the sensor chip, and their methods of use are also disclosed.

Nucleic Acid Analysis by Random Mixtures of Non-Overlapping Fragments

The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered. In one aspect, this process is carried out in a hierarchical fashion until the one or more target polynucleotides are characterized, e.g. by their nucleic acid sequences, or by an ordering of sequence segments, or by an ordering of single nucleotide polymorphisms (SNPs), or the like.

BIOSENSOR ARRAY FORMED BY JUNCTIONS OF FUNCTIONALIZED ELECTRODES

We provide a sensor array device for the measurement of mixtures of organic compounds comprising an assembly of sensor half elements which have been functionalized through sensor compounds before the assembly. Each individual sensor of the array contains two sensor compounds pounds which are bound at opposite sensor half elements. The molecular recognition is bi-functional. While the amount of sensor compounds increases linearly, the individual sensors increase with the second power. 117-. (canceled)18. A sensor array , comprising:a) a plurality of sensor half elements for measuring a concentration and identifying a plurality of organic target compounds under investigation or related copies thereof within a mixture of organic compounds;b) a plurality of different sensor compounds wherein each sensor half element contains and/or carries one of said sensor compounds, the sensor compounds binding to a specific binding site of said target compounds, respectively;c) wherein each of said sensor compounds is assigned to at least one of said sensor half elements;d) wherein each sensor half element intersects or traverses at least one of the other said sensor half elements in a separate junction area;e) wherein said sensor compounds of two intersecting or traversing sensor half elements are spaced and/or converge and/or touch each other;f) wherein in each junction area an individual sensor is formed with a determined combination of two sensor compounds each said sensor compound being located at one of the intersecting or traversing sensor half elements; andg) the sensor array having at least two junction areas with different combinations of sensor compounds;h) said sensor half elements being aligned in a grid structure, with a plurality of row elements and a plurality of column elements;i) said row elements being formed by a number of sensor half elements and said column elements being formed by the remaining said sensor half elements;j) said row elements being aligned and ...

MANUFACTURING AND PROCESSING POLYMER ARRAYS

The invention provides methods to process multiple microarrays by providing a microarray plate and processing plates. In an embodiment of the invention, methods for assembling microarray plates by using wafers are described for high throughput microarray processing. 122-. (canceled)23. A sensor plate comprising:a substrate comprising a plurality of sensors, each sensor surrounded by a border region that does not comprise any sensors, each sensor comprising an array of probes, wherein the substrate has an active side from which the sensor probes are dipped in a reservoir of a processing plate and an inactive side for attachment to a support plate; anda support plate comprising structural elements;wherein the support plate is fixedly attached to the substrate, with the structural elements of the support plate contacting the inactive side of the substrate within the border regions surrounding the sensors, and wherein the attached substrate protrudes from the support plate to facilitate dipping the active side of the substrate into the reservoir of a processing plate.24. The sensor plate according to claim 23 , wherein the substrate is a wafer section.25. The sensor plate according to claim 23 , wherein each sensor is a microarray and the sensor plate is a microarray plate.26. The sensor plate according to claim 25 , wherein the microarray plate is a microarray strip plate.27. The sensor plate according to claim 23 , wherein the support plate structural elements are ridges or walls.28. The sensor plate according to claim 23 , wherein the support plate further comprises at least one alignment feature that guides the alignment of the substrate with the support plate during manufacturing.29. The sensor plate according to claim 28 , wherein the alignment feature is selected from the group consisting of a hole claim 28 , a post claim 28 , a raised edge claim 28 , and an indentation.30. The sensor plate according to claim 23 , wherein the support plate further comprises at ...

Methods for Diagnosing Prostate Cancer using MicroRNAs

Described herein are methods for diagnosing prostate cancer using microRNAs. Also described are methods and compositions for the diagnosis and treatment of solid cancers. Methods of identifying inhibitors of tumorigenesis are also provided.

RANDOM ARRAY DNA ANALYSIS BY HYBRIDIZATION

The invention relates to methods and devices for analyzing single molecules, i.e., nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air, and water without separating or enriching individual components. In certain aspects of the invention, the methods and devices are useful in performing nucleic acid sequence analysis by probe hybridization. 123-. (canceled)24. A method for determining sequence information for a polynucleotide , comprising:(a) providing an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;{'sub': x', 'y', 'z, 'claim-text': (i) each N is independently a degenerate base;', '(ii) each B is independently an informative base;', '(iii) x and z are each at least one; and', '(iv) y is 2 to 20;, '(b) contacting the array with a set of informative oligonucleotide probes, wherein each probe comprises a label and a nucleotide sequence comprising the formula NBN, wherein(c) detecting labeled probes once the probes have hybridized to DNA molecules in the array, thereby obtaining data indicating which of the labeled probes are hybridized to each DNA molecule; and(d) processing the data to obtain said sequence information for the polynucleotide.25. The method of claim 24 , wherein each DNA molecule comprises multiple copies of the respective fragment.26. The method of claim 24 , wherein y is 2 to 8.27. The method of claim 24 , wherein the labels are fluorescent labels.28. The method of claim 24 , wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome.29. A method for determining sequence information for a polynucleotide claim 24 , comprising:(a) providing an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;{'sub': x', 'y', 'y', 'z, 'claim-text': (i) each N is independently a degenerate base;', '(ii) each B is independently an informative base;', '(iii) x and z are each at least one; ...

Optimized probe selection method

The present invention provides methods for optimizing oligonucleotide hybridization probes for use in basic and clinical research. Specifically, the invention involves hybridizing serially diluted genomic sample to the oligonucleotide probes on the array, such that a signal intensity is produced for each of the probes; computationally identifying optimized probes which exhibit signal intensities that correspond to the serial dilutions of genomic sample and are reproducibly strong relative to non-optimized probes.

DIAGONSIS AND TREATMENT OF AUTOIMMUNE DISEASES BY TARGETING AUTOIMMUNE-RELATED B CELLS ("ABCS")

The present invention is directed to methods of diagnosis and treatment of autoimmune diseases based on the identification of a novel population of B cells known as Autoimmune- or Age-related B cells (“ABCs”). These cells express the CDI Ic cell surface protein and exhibit a unique gene expression profile. The ABCs increase in numbers in subjects that are prone to developing autoimmune diseases or in healthy individuals, particularly females, as they age. Accordingly, the present invention includes methods and kits for diagnosis of autoimmune diseases based on the detection of the ABCs before overt symptoms of the disease become detectable. The present invention also includes methods of treatment of autoimmune diseases by targeting the ABCs, as well as methods for assessing the efficacy of treatments of autoimmune diseases. 1. A method of diagnosing an autoimmune disease in a subject , comprising:a) obtaining a test sample from the subject andb) detecting the presence of autoimmune-associated B cells (“ABCs”) in the test sample, wherein the ABCs comprise B cells that express the protein CD11c; andwherein the presence of ABCs in the sample at an elevated level as compared to a baseline level established from a control sample, identifies the subject as having or likely to develop the autoimmune disease.2. The method of claim 1 , wherein the ABCs express one or more of the proteins selected from the group consisting of: CD11b claim 1 , B220 claim 1 , CD19 and a cell surface Immunoglobulin Ig.3. The method of claim 2 , wherein the surface Ig is selected from the group consisting of: IgG claim 2 , IgM claim 2 , IgA and IgE.4. The method of claim 1 , wherein the ABCs express one or more of the proteins selected from the group consisting of: CD80 claim 1 , CD86 claim 1 , MHC class 11 claim 1 , CD5 claim 1 , CCL3 claim 1 , CXCL10 claim 1 , CCL19 claim 1 , CXCL9 claim 1 , granzyme A and perforin.5. The method of claim 1 , wherein the ABCs express low levels of CD21 as ...

G-quadruplex binding assays and compounds therefor

The present invention provides methods for assaying binding of compounds to G-quadruplex structures. Also provided are methods for screening candidate compounds for use as modulators of G-quadruplex activity, and methods for screening candidate compounds for telomerase inhibitory activity. The invention further provides novel compounds useful in the assays of the invention.

INTEGRATED PLASMONIC SENSING DEVICE AND APPARATUS

An integrated plasmonic sensing device is monolithically integrated and provides marker-free detection (eliminating the need to use fluorescent or absorbing markers) and in-situ monitoring of conditions at each detection region. The integrated plasmonic sensing device includes a plasmonic backplane disposed on a monolithically integrated image sensor. One or more plasmonic scattering regions and one or more plasmonic via regions laterally offset from the plasmonic scattering regions are provided in the plasmonic sensing device. Guided plasmonic modes mediate power transfer through the plasmonic backplane to one or more underlying image sensor pixels. 1. A sensor comprising:a plurality of measurement regions supporting changes in surface plasmon excitation in response to incident light at each measurement region,a plurality of photodetectors, with each photodetector connected to one or more measurement regions by plasmon vias capable of supporting guided plasmons, andwherein the plurality of measurement regions and plurality of photodetectors are monolithically integrated and together form an integrated sensor capable of producing electrical signals in response to molecular recognition events at each measurement region.2. A sensor in accordance with wherein the plurality of photodetectors together comprise an image sensor formed in a semiconductor substrate and the plurality of measurement regions form part of a plasmonic backplane located between a fluid chamber and the plurality of photodetectors.3. A sensor in accordance with wherein more than one of the plurality of photodetectors are connected to one of the plurality of measurement regions by one or more plasmon vias.4. A sensor in accordance with wherein more than one of the plurality of measurement regions are connected to one of the plurality of photodetectors by one or more plasmon vias.5. A sensor in accordance with wherein at least some of the plurality of measurement regions are laterally offset from and ...

System and Methods for Massively Parallel Analysis of Nucleic Acids in Single Cells

Methods and systems are provided for massively parallel genetic analysis of single cells in emulsion droplets or reaction containers. Genetic loci of interest are targeted in a single cell using a set of probes, and a fusion complex is formed by molecular linkage and amplification techniques. Methods are provided for high-throughput, massively parallel analysis of the fusion complex in a single cell in a population of at least 10,000 cells. Also provided are methods for tracing genetic information back to a cell using barcode sequences. 1. A method for analyzing at least two nucleic acid sequences in a single cell contained within a population of at least 10 ,000 cells , comprising:providing a first set of nucleic acid probes, the first set comprising a first probe comprising a sequence that is complementary to a first target nucleic acid subsequence, a second probe comprising a sequence that is complementary to a second subsequence of the first target nucleic acid and a second sequence that is complementary to an exogenous sequence, a third probe comprising the exogenous sequence and a sequence that is complementary to a first subsequence of a second target nucleic acid, and a fourth probe comprising a sequence that is complementary to a second subsequence of the second target nucleic acid sequence, wherein the first target nucleic acid or the second target nucleic acid comprises an endogenous sequence;isolating the single cells with at least one set of nucleic acid probes;amplifying the first and second target nucleic acid sequences independently, wherein the first target nucleic acid sequence is amplified using the first probe and the second probe, and wherein the second target nucleic acid sequence is amplified using the third probe and the fourth probe;hybridizing the exogenous sequence to its complement;amplifying the first target nucleic acid sequence, the second target nucleic acid sequence, and the exogenous sequence using the first and fourth probes, ...

METHOD AND PRODUCT FOR LOCALIZED OR SPATIAL DETECTION OF NUCLEIC ACID IN A TISSUE SAMPLE

The present invention relates to methods and products for the localized or spatial detection of nucleic acid in a tissue sample and in particular to a method for localized detection of nucleic acid in a tissue sample comprising: (a) providing an array comprising a substrate on which multiple species of capture probes are directly or indirectly immobilized such that each species occupies a distinct position on the array and is oriented to have a free 3′ end to enable said probe to function as a primer for a primer extension or ligation reaction, wherein each species of said capture probe comprises a nucleic acid molecule with 5′ to 3′: (i) a positional domain that corresponds to the position of the capture probe on the array, and (ii) a capture domain; (b) contacting said array with a tissue sample such that the position of a capture probe on the array may be correlated with a position in the tissue sample and allowing nucleic acid of the tissue sample to hybridize to the capture domain in said capture probes; (c) generating DNA molecules from the captured nucleic acid molecules using said capture probes as extension or ligation primers, wherein said extended or ligated DNA molecules are tagged by virtue of the positional domain; (d) optionally generating a complementary strand of said tagged DNA and/or optionally amplifying said tagged DNA; (e) releasing at least part of the tagged DNA molecules and/or their complements or amplicons from the surface of the array, wherein said part includes the positional domain or a complement thereof; and (f) directly or indirectly analyzing the sequence of the released DNA molecules. 1. A method for localized detection of nucleic acid in a tissue sample comprising: (i) a positional domain that corresponds to the position of the capture probe on the array, and', '(ii) a capture domain;, '(a) providing an array comprising a substrate on which multiple species of capture probes are directly or indirectly immobilized such that each ...

Self-Assembled Single Molecule Arrays and Uses Thereof

The present invention provides methods of making and using self-assembled arrays of single polynucleotide molecules for carrying out a variety of large-scale genetic measurements, such as gene expression analysis, gene copy number assessment, and the like. Random arrays used in the invention are “self-assembled” in the sense that they are formed by deposition of polynucleotide molecules onto a surface where they become fixed at random locations. The polynucleotide molecules fixed on the surface are then identified by direct sequence determination of component nucleic acids, such as incorporated probe sequences, or by other decoding schemes. Such identification converts a random array of determinable polynucleotides, and their respective probes into an addressable array of probe sequences.

Rapid Genotyping Analysis and the Method Thereof

The present invention describes methods of performing rapid nucleic acid detection using a flow through process. The methods comprise single-step signal amplification and/or a one-step hybridization protocol. Using the flow through hybridization process, the present invention provides a more efficient, faster and less expensive genotyping method. This invention further provides a Single Nucleotide Polymorphism (SNP)-based DNA fingerprinting method for rapid and accurate genotyping, identification as well as DNA analyses of genetic materials from human beings and other different organisms. In addition this invention also discloses devices for rapid and sensitive analysis of target analysts. 1. A method of performing rapid nucleic acid detection , comprising the steps of: obtaining a sample comprising a target nucleic acid molecule;(a) mixing the target nucleic acid molecule with (i) a first probe that will bind to the nucleic acid molecule, and (ii) a second agent that will bind to the first probe, thereby forming a nucleic acid molecule complex in solution, wherein the nucleic acid molecule complex comprises the first probe and the second agent, the second agent comprising a signal generating labeling tag or an enzyme-linked conjugate;(b) applying in a flow through manner the solution comprising the nucleic acid molecule complex to an array comprising a third probe that will bind to the complex, thereby capturing the nucleic acid molecule complex on the array; and(c) detecting the captured nucleic acid molecule on the array.2. The method of claim 1 , wherein the labeling tag includes colloidal gold claim 1 , fluorescent tag claim 1 , quantum dot or magnetic particle.3. The method of claim 1 , wherein the first probe and the third probe bind to different regions of the target nucleic acid molecule.4. The method of claim 1 , wherein the method further comprises a step of asymmetric amplification to generate single strand copies of the target nucleic acid molecule.5. ...

Method of Fast Tuberculosis Diagnosis and Efficacy Test

A method is provided for fast diagnosis of tubercle bacillus (TB). The method can be used for efficacy test at the same time. 13 specific TB genes and 6 drug-resistance genes are selected. Those genes are formed into a construction for diagnosing tuberculosis and testing drug resistance simultaneously. 1. A method of fast tuberculosis diagnosis and efficacy test , comprising steps of:(a) obtaining a sputum specimen and extracting messenger ribonucleic acids (mRNAs) in said sputum specimen to synthesize a required amount of complementary deoxyribonucleic acids (cDNAs) through reverse transcription;(b) labeling said cDNAs with Biotin to obtain a plurality of bioprobes;(c) synthesizing tubercle bacillus (TB) genes and drug-resistance genes in vitro into a specific gene cluster of TB and a drug-resistance gene cluster and obtaining a chip array construction through crosslinking by dotting said specific gene cluster of TB, said drug-resistance gene cluster, positive controls, negative controls and blank controls into array on a nylon membrane,wherein said specific gene cluster of TB is specified through a specific oligonucleotide design; andwherein said chip array construction is formed into a plurality of gene-testing points on said nylon membrane;(d) hybridizing said gene-testing points of said chip array construction with biomolecules of said bioprobes and washing out un-hybridized bioprobes; and(e) blocking said bioprobes obtained after hybridization of said chip array construction to form crosslinks with Streptavidin-HRP accompanied with a washing process afterwards and, then, adding a coloring agent to process color development to analyze and interpret an image thus obtained.2. The method according to claim 1 , wherein said specific gene cluster of TB comprises 13 specific TB genes; wherein said 13 specific TB genes comprises hsp65 claim 1 , Rv0577 claim 1 , Rv3120 claim 1 , Rv2073c claim 1 , Rv1970 claim 1 , Rv3875 claim 1 , Rv3347c claim 1 , Rv1510 claim 1 , ...

METHOD FOR SEPARATION AND DETECTION OF DNA FRAGMENTS

A method of detecting nucleic acid fragments is provided. The method includes providing a plurality of chambers, each chamber separated from the other chambers of the plurality, each chamber having at least one set of probes disposed therein, each set of probes being capable of binding to a different target nucleic acid sequence relative to the other sets of probes. The method also includes providing a sample comprising a plurality of sets of nucleic acid fragments, placing at least a portion of the sample into each of the plurality of chambers and causing the at least one set of probes in each chamber to bind with complementary nucleic acid fragments of the sample, and detecting the binding of the nucleic acid fragments to the sets of probes in each chamber. 1. A method of detecting nucleic acid fragments , the method comprising:providing a plurality of chambers, each chamber separated from the other chambers of the plurality, each chamber having at least one set of probes disposed therein, each set of probes being capable of binding to a different target nucleic acid sequence relative to the other sets of probes;providing a sample comprising a plurality of sets of nucleic acid fragments;placing at least a portion of the sample into each of the plurality of chambers and causing the at least one set of probes in each chamber to bind with complementary nucleic acid fragments of the sample; anddetecting the binding of the nucleic acid fragments to the sets of probes in each chamber.2. The method of claim 1 , wherein the placing the at least a portion of the sample into each of the plurality of chambers comprises flowing the portions of the sample through a first chamber of the plurality of chambers claim 1 , the chambers being fluidically coupled in series.3. The method of claim 1 , wherein the placing the at least a portion of the sample into each of the plurality of chambers comprises flowing the portions of the sample into the plurality of chambers claim 1 , the ...

ENHANCED METHOD FOR PROBE BASED DETECTION OF NUCLEIC ACIDS

A method of detecting nucleic acid fragments is provided. The method includes providing a plurality of sets of probes, each set of probes having a nucleic acid sequence. A first portion of the sequence is complementary to a target nucleic acid sequence, which differs for each set of probes relative to the other sets of probes. A second portion of the sequence is a specified sequence, which is the same for each set of probes. Each probe has a fluorescent label joined to the second portion of the sequence. The first portion of the sequence binds with nucleic acid fragments of a sample having a sequence complementary to said first portion. A quenching compound that has a quenching moiety and a nucleic acid sequence complementary to the specified sequence of the second portion of the sets of probes quenches the fluorescence. 1. A method of detecting nucleic acid fragments , the method comprising: a first portion of the sequence being complementary to a target nucleic acid sequence, the target nucleic acid sequence differing for each set of probes relative to the other sets of probes,', 'a second portion of the sequence being a specified sequence, the second portion of the sequence being the same for each set of probes, and', 'each probe having a fluorescent label joined to the second portion of the sequence;, 'providing a plurality of sets of probes, each set of probes having a nucleic acid sequence,'}providing a sample comprising a plurality of sets of nucleic acid fragments;causing the first portion of the sequence of at least one set of probes to bind with nucleic acid fragments of the sample having a sequence complementary to said first portion;providing a quenching compound that has a quenching moiety and a nucleic acid sequence that is complementary to the specified sequence of the second portion of the sets of probes;causing the quenching compound to bind to the second portions of the sequences of the sets of probes which are not bound to nucleic acid fragments ...

Devices and methods for efficient capture of nucleic acids

The present invention relates a device for the efficient binding of nucleic acids on a microarray, comprising a reaction zone comprising a microarray, and a capture zone comprising a porous membrane substrate, wherein the capture zone is capable of specifically capturing sense strands of target molecules, whereas complementary antisense strands are captured in the reaction zone, or vice versa. The invention further envisages temperature regulating units in the device allowing to bring or keep the capture at a temperature not allowing hybridizing or binding of nucleic acid(s) to the capture molecules or to a temperature suitable for nucleic acid hybridization. The invention also relates to a method of efficiently binding nucleic acids on a microarray, comprising introducing a medium containing one or more target molecules in denatured form into a capture zone of a device of the present invention, performing an interaction reaction between the target molecules and immobilized capture molecules in said capture zone, and transporting not bound target molecule strands to a reaction zone comprising a microarray, thereby allowing an interaction between the target molecule strands and immobilized capture molecules on the microarray. In a further aspect the invention relates to the use of such a device for enriching target molecules, specifically selecting a target molecules, expression analysis, comparative genomic hybridization, the detection of SNPs, or for microarray-based genomic selection-based sequencing.

Methods, compositions and systems for sample deposition

Methods, compositions, systems, apparatus, and kits are provided for depositing samples onto surfaces. The samples can include one or more particles, and the surface can include one or more reaction chambers. In some embodiments, the depositing can include the use of companion particles in combination with sample particles.

PROCESSES FOR DETECTING OR QUANTIFYING MORE THAN ONE NUCLEIC ACID IN A LIBRARY

This invention provides novel compositions and processes for analyte detection, quantification and amplification. Nucleic acid arrays and libraries of analytes are usefully incorporated into such compositions and processes. Universal detection elements, signaling entities and the like are employed to detect and if necessary or desirable, to quantify analytes. Amplification of target analytes are also provided by the compositions and processes of this invention. 1695-. (canceled)696. A process for detecting or quantifying more than one nucleic acid of interest in a library comprising the steps of: (i) an array of fixed or immobilized nucleic acids identical or complementary in part or whole to sequences of said nucleic acids of interest;', '(ii) a library of nucleic acid analytes which may contain the nucleic acids of interest sought to be detected or quantified; and', '(iii) polymerizing means for synthesizing nucleic acid copies of said nucleic acid analytes, said polymerizing means comprising a first set of primers, a second set of primers and a third set of primers, wherein said first set of primers are fixed or immobilized to a solid support, and wherein said third set comprises at least one production center; and, 'a) providingb) contacting said library of nucleic acid analytes with said first set of primers to form more than one first bound entity;c) extending said bound first set of primers by means of template sequences provided by said nucleic acid analytes to form first copies of said analytes;d) contacting said extended first copies with said second set of primers to form more than one second bound entity;e) extending said bound second set of primers by means of template sequences provided by said extended first copies to form an extended second set of primers;f) separating said extended second set of primers obtained in step e);g) contacting said extended second set of primers with said third set of primers to form more than one third bound entity;h) ...

DETECTION OF NUCLEIC ACID SEQUENCE DIFFERENCES USING THE LIGASE DETECTION REACTION WITH ADDRESSABLE ARRAYS

The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support. 1. A method comprising:providing a collection of oligonucleotides wherein each type of oligonucleotide is greater than 16 nucleotides and differs in nucleotide sequence, when aligned to another type of oligonucleotide in the collection, by at least 25%;providing a sample comprising a plurality of composite oligonucleotides, each composite oligonucleotide comprising (i) a zip-code portion, and (ii) one or more further nucleotide sequences;contacting the sample comprising the plurality of composite oligonucleotides with the collection of oligonucleotides under conditions effective to hybridize the zip-code portion of each composite oligonucleotide to its complementary oligonucleotide in the collection; anddetecting the one or more of the plurality of composite oligonucleotides hybridized to their complementary oligonucleotides in the collection.2. The method according to claim 1 , wherein each oligonucleotide in the collection comprises 20-25 nucleotides.3. The ...