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    • 1. 发明申请
    • METHODS AND DEVICES FOR COMPOUND SCREENING
    • 用于化合物筛选的方法和装置
    • WO2005054501A1
    • 2005-06-16
    • PCT/EP2004/013379
    • 2004-11-25
    • PAMGENE BVVAN BEUNINGEN, Marinus, Gerardus, JohannesBLOK, Herman, Jacobus
    • VAN BEUNINGEN, Marinus, Gerardus, JohannesBLOK, Herman, Jacobus
    • C12Q1/68
    • B01J19/0046B01J2219/00378B01J2219/00387B01J2219/00427B01J2219/00641B01J2219/0072B01J2219/00722B01J2219/00725B01J2219/00734B01J2219/0074C40B40/06C40B40/10C40B60/14G01N2500/00
    • The present invention relates methods for screening of compounds for drug candidates comprising: (a) providing a solid porous support having first and second surfaces and at least one area with a plurality of through-going channels wherein said solid porous support comprises compounds within predefined regions of the said support; wherein said compounds within the porous structure are stored in dried condition, wherein said dried condition is obtained after a drying treatment by slow evaporation, vacuum drying or by blowing air or inert gas above and below said solid support; (b) providing a liquid sample comprising at least one molecular target; (c) mixing said dried compounds of step (a) with said liquid sample of step (b) by flow of the sample through said predefined regions of the solid support through the said through-going channels; (d) screening said compounds for drug candidates; said screening is by monitoring in an assay a compound-target interaction by measurement of a signal, said signal indicating interaction between a compound and a molecular target; (e) optionally screening for a compound having a putative effect on a drug candidate identified in step (d). The present invention further relates to the uses of said methods and solid supports and methods for the manufacture of said solid supports for carrying out said methods as well as to the use of a porous support for the preparation of a kit for carrying out said methods.
    • 本发明涉及用于筛选药物候选化合物的方法,包括:(a)提供具有第一和第二表面的固体多孔载体和至少一个具有多个通过通道的区域,其中所述固体多孔载体包含预定区域内的化合物 的支持; 其中所述多孔结构体内的所述化合物在干燥状态下储存,其中所述干燥条件通过缓慢蒸发,真空干燥或通过吹入所述固体支持物上方和下方的空气或惰性气体进行干燥处理后获得; (b)提供包含至少一种分子靶的液体样品; (c)通过样品通过所述通过通道的固体支持物的所述预定区域的流动将步骤(a)的所述干燥的化合物与步骤(b)的所述液体样品混合; (d)筛选所述化合物用于候选药物; 所述筛选是通过在测定中监测化合物 - 靶相互作用,通过测量信号,所述信号指示化合物和分子靶之间的相互作用; (e)任选地筛选对步骤(d)中鉴定的药物候选物具有推定作用的化合物。 本发明还涉及所述方法的用途和用于制备用于实施所述方法的所述固体支持物的固体支持物和方法,以及使用多孔载体来制备用于实施所述方法的试剂盒。
    • 4. 发明申请
    • METHOD FOR DETECTION AND QUANTIFICATION OF TARGET NUCLEIC ACIDS IN A SAMPLE
    • 在样品中检测和定量目标核酸的方法
    • WO2007025594A1
    • 2007-03-08
    • PCT/EP2006/006542
    • 2006-07-05
    • PAMGENE BVWU, YingVAN BEUNINGEN, Marinus, Gerardus, Johannes
    • WU, YingVAN BEUNINGEN, Marinus, Gerardus, Johannes
    • C12Q1/68
    • C12Q1/6837C12Q1/6851C12Q2537/149C12Q2531/137C12Q2531/113
    • The present invention relates to methods for multiplex detection and quantification of target nucleic acid sequences in a sample comprising the steps of: (i) providing a solid support having immobilized thereon an array of detector oligonucleotides, wherein said array of detector oligonucleotides is designed by random selection of non-eukaryotic genomic sequences followed by random selection of oligonucleotide sequences and subsequent conversion of these oligonucleotide sequences such that these are composed of only three types of nucleotides; (ii) providing a sample having added thereto a fixed amount of control nucleic acid of known sequence; (iii) contacting said sample with at least two probes that hybridise to adjacent sites of a target sequence under conditions favouring hybridisation between the sample nucleic acids and the said at least two probes, wherein, a) a first probe is composed of a 5' end sequence part for hybridisation to a PCR primer and a 3' end sequence part for hybridisation to the target nucleic acid; and b) a second probe is composed of a 5' end sequence part for hybridisation to the target nucleic acid, and a 3' end sequence part for hybridisation with a PCR primer; and c) an intermediate sequence is present in between said 5' and 3' end sequence parts of said first or second probe; and d) said second probe is characterized by having a 5' phosphate group allowing ligation with a 3' hydroxyl group at the said first probe forming a ligation-mediated probe; (iv) ligation of the said hybridised first and second probes to form ligation-mediated probes; (v) contacting a set of detectable labelled PCR primers with the ligation-mediated probes allowing amplification thereof; (vi) detection and quantification of sample nucleic acids via hybridisation of the said intermediate parts within the amplified ligation-mediated probes onto the array of detector oligonucleotides provided in The present invention also relates to the use of said methods as well as microarrays and kits for performing said methods.
    • 本发明涉及在样品中多重检测和定量目标核酸序列的方法,其包括以下步骤:(i)提供在其上固定有检测器寡核苷酸阵列的固体支持物,其中所述检测器寡核苷酸阵列通过随机 选择非真核生物基因组序列,然后随机选择寡核苷酸序列,随后转化这些寡核苷酸序列,使得它们仅由三种类型的核苷酸组成; (ii)提供具有已知序列的固定量的对照核酸的样品; (iii)在有利于样品核酸和所述至少两种探针之间的杂交的条件下,使所述样品与至少两种与靶序列的相邻位点杂交的探针接触,其中a)第一探针由5' 用于与PCR引物杂交的末端序列部分和用于与靶核酸杂交的3'末端序列部分; 和b)第二探针由用于与靶核酸杂交的5'末端序列部分和用于与PCR引物杂交的3'末端序列部分组成; 和c)所述第一或第二探针的所述5'和3'末端序列部分之间存在中间序列; 和d)所述第二探针的特征在于具有5'磷酸基,允许在所述第一探针处与3'羟基连接形成连接介导的探针; (iv)连接所述杂交的第一和第二探针以形成连接介导的探针; (v)将一组可检测的标记的PCR引物与连接介导的探针接触,允许其扩增; (vi)通过将扩增的连接介导的探针内的所述中间体部分杂交到本发明提供的检测器寡核苷酸阵列上来检测和定量样品核酸还涉及所述方法以及微阵列和试剂盒的用途 执行所述方法。