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公开(公告)号：WO2020035514A1
公开(公告)日：2020-02-20
申请号：PCT/EP2019/071769
申请日：2019-08-14
IPC分类号： G06T7/00
摘要： Currently, there is interest in applying machine learning techniques to analyse digital pathology images automatically. Machine learning techniques often rely on training with a ground-truth image input. The quality and amount of training data determines the quality of the detector, as expressed in the rate of true and false positives, and robustness against variations in the appearance of the input images. The present application proposes to obtain image data of the same sample before and after at least one re- staining step (firstly with a structure-revealing stain, and secondly with a bio marker revealing stain). Sections of the first and second image data having a good registration relationship are chosen, along with the probability of detecting a desired candidate object (such as nucleus) and the probability of the bio marker revealing stain being present annotation data suitable for training a machine learning algorithm on the first and/or the second image data is provided.
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公开(公告)号：WO2014177551A1
公开(公告)日：2014-11-06
申请号：PCT/EP2014/058703
申请日：2014-04-29
发明人： PIERIK, Anke , WIMBERGER-FRIEDL, Reinhold , VAN EEMEREN, Johannes Theodorus Wilhelmus Maria , DOBBELAER-BOSBOOM, Irene Johanna Monica , VAN ZELST, Martinus Johannes , MEIJERING, Bernadet Dagmar Marielle
IPC分类号： B01L3/00
CPC分类号： B01L3/502 , B01L3/502738 , B01L3/527 , B01L2200/0647 , B01L2200/10 , B01L2200/16 , B01L2300/123 , B01L2400/0487 , B01L2400/06
摘要： The invention relates to a fluidic system comprising at least one bead chamber (311) containing a lyophilized reagent (LB) and a reaction chamber in a cartridge. In one embodiment, a series of bead chambers with different lyophilized reagents may be provided such that sample fluid can sequentially pass through them. In another embodiment, bead chambers may be located on a movable carrier, for example a rotating carousel, from which they may selectively be connected to a reaction chamber in a cartridge. In still another embodiment, the bead chamber (311) may comprise at least one flexible wall (FW) allowing for a minimization of dead volume associated with the extraction of lyophilized reagent (LB).
摘要翻译： 本发明涉及一种流体系统，其包含至少一个含有冻干试剂（LB）的珠粒室（311）和在筒中的反应室。 在一个实施方案中，可以提供具有不同冻干试剂的一系列珠腔，使得样品流体可以顺序地通过它们。 在另一个实施例中，胎圈室可以位于可移动的载体上，例如旋转的转盘，它们可以从该轮毂选择性地连接到筒中的反应室。 在另一个实施例中，胎圈室（311）可以包括至少一个柔性壁（FW），允许最小化与冻干试剂（LB）的提取相关的死体积。
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公开(公告)号：WO2014122548A3
公开(公告)日：2014-08-14
申请号：PCT/IB2014/058480
申请日：2014-01-23
发明人： VAN DE STOLPE, Anja , FEITSMA, Harma Martine , VAN DER ZAAG, Pieter Jan , WIMBERGER-FRIEDL, Reinhold , DEN TOONDER, Jacob Marinus Jan , PIERIK, Anke , VAN HEMERT, Freek
IPC分类号： G01N27/327 , C12Q1/68 , B82Y15/00
摘要： The invention relates to a method and an apparatus (100) for the processing of nucleotide sequences. An apparatus (100) according to an embodiment of the invention comprises an array of electrodes (120a,120b,...), wherein at least one nanoball (NB) comprising replications of a nucleotide sequence (1,2) of interest is attached to an electrode to which only one nanoball (NB) of that size can be attached at the same time. Thus a unique association of electrodes (120a,120b,...) to nucleotide sequences (1,2) of interest can be achieved. The nanoballs (NB) are preferably produced by rolling circle amplification. Application of attractive and/or repulsive electric potentials to the electrodes (120a,120b,...) can be used to control the attachment of nanoballs (NB). The measurement of changes in the capacitance of electrodes (120a,120b,...) can be used to detect and monitor the incorporation of mono-or oligonucleotides provided sequentially by different solutions (A, T, G, C) into strands that are replicated in a nanoball (NB) at an electrode.
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公开(公告)号：WO2019166611A1
公开(公告)日：2019-09-06
申请号：PCT/EP2019/055107
申请日：2019-03-01
摘要： Disclosed is a device for controlling a volume of an analysis chamber of a micro chamber arrangement to which a region of interest of an object is exposed. The volume is controlled using a volume reducing element which is deposited on a surface of the micro chamber arrangement. The device comprises a deposition unit configured to determine a positon and an extent of the volume reducing element depending on (a) the region of interest and further depending on (b) a predetermined level by which a volume of the analysis chamber is reduced using the volume reducing structure. The deposition unit is further configured to deposit the volume reducing element depending on the determined position and extent.
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公开(公告)号：WO2017009450A1
公开(公告)日：2017-01-19
申请号：PCT/EP2016/066884
申请日：2016-07-15
发明人： BOAMFA, Marius Iosif , PIERIK, Anke , WIMBERGER-FRIEDL, Reinhold , VAN LEEUWEN, Marinus Bastiaan (Rien)
CPC分类号： G02B21/367 , G01N1/30 , G02B21/0068 , G02B21/12 , G02B21/34
摘要： The present invention relates to digital pathology. In order to improve the workflow in the process of selecting a region of interest of an unstained sample to be removed for molecular diagnostic, a method (100) is provided for selecting a sample removing area of an unstained sample to be removed for molecular diagnostic. The method comprises the following steps: In a first step 102, also referred to as step a), a reference removing area is selected in a reference image of a reference slice of an object, wherein biological material in the reference slice is stained. In a second step 104, also referred to as step b), a digital sample image of a sample slice of the object is obtained under an imaging setting. The biological material in the sample slice is unstained. The sample slice is received on a sample slide and positioned in an optical path between a light source and an image detector. In the optical path between the light source and the image detector, it is further provided a contrast enhancing arrangement for improving contrast between the unstained biological material and background. Light is provided passing through the sample slice to be received by the image detector. In a third step 106, also referred to as step c), the digital sample image is registered with the reference image for translating the reference removing area in the reference image to the digital sample image. In a fourth step 108, also referred to as step d), a sample removing area is identified in the digital sample image based on the translated reference removing area.
摘要翻译： 本发明涉及数字病理学。 为了提高选择待分离诊断的未染色样品的感兴趣区域的过程中的工作流程，提供了用于选择要去除的未染色样品的样品去除区域用于分子诊断的方法（100）。 该方法包括以下步骤：在第一步骤102中，也称为步骤a），在对象的参考切片的参考图像中选择参考去除区域，其中参考切片中的生物材料被染色。 在第二步骤104中，也称为步骤b），在成像设置下获得对象的样本片段的数字样本图像。 样品切片中的生物材料未染色。 样品片被接收在样品载玻片上并且定位在光源和图像检测器之间的光路中。 在光源和图像检测器之间的光路中，还提供了用于改善未染色的生物材料和背景之间的对比度的对比度增强装置。 光被提供通过样本切片以由图像检测器接收。 在也称为步骤c）的第三步骤106中，将数字样本图像与参考图像一起登记，用于将参考图像中的参考去除区域转换为数字样本图像。 在第四步骤108中，也称为步骤d），基于经翻译的参考去除区域，在数字样本图像中识别样本去除区域。
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公开(公告)号：WO2017009337A1
公开(公告)日：2017-01-19
申请号：PCT/EP2016/066540
申请日：2016-07-12
发明人： VINK, Jelte Peter , VLUTTERS, Ruud , PIERIK, Anke , HULSKEN, Bas , WIMBERGER-FRIEDL, Reinhold , NEERKEN, Sieglinde
CPC分类号： G06T11/00 , G06T7/0012 , G06T7/30 , G06T2200/24 , G06T2207/30024
摘要： The present invention relates to an illustration of an annotation (22) at a sample slide (14). It is the intention for the invention to copy the annotation (22) provided at a reference slide (12) to the sample slide (14). Typically, a reference image (26) of the reference slide (12) is provided, in particular by scanning the reference slide (12). The reference image (26) therefore has the information about a reference slice (16) which is carried by the reference slide (12). Furthermore, the reference slide (12) has been marked with a region of interest (20) and the annotation (22), which can be associated with the region of interest (20). If such reference slide (12) is scanned, the respective reference image (26) comprises the information about the marked region of interest (20) as well as the annotation (22), too. Furthermore, the sample slide (14) carrying a sample slice (18) can be scanned, in order to provide a sample image (28). The sample slice (18) and the reference slice (16) are cut from the same object (10) of a biological material. In particular, the sample slice (16) has been cut directly after a cut of a material block has been preformed to provide the reference slice (18). Since the reference slice (16) and the sample slice (18) are from the same object (10), their features are very likely that the reference image (26) and the sample image (28) are very similar. Due to this similarity, the annotation (22) of the reference slide (12) is copied on a basis of an image recognition between reference image (26) and the sample image (28) to the sample slide (14).
摘要翻译： 本发明涉及在样本滑块（14）处的注释（22）的图示。 本发明的意图是将在参考滑块（12）处提供的注释（22）复制到样本滑块（14）。 通常，提供参考滑块（12）的参考图像（26），特别是通过扫描参考滑块（12）。 因此，参考图像（26）具有关于由参考滑块（12）承载的参考切片（16）的信息。 此外，参考幻灯片（12）已经被标记有可以与感兴趣区域（20）相关联的感兴趣区域（20）和注释（22）。 如果扫描这种参考幻灯片（12），则相应的参考图像（26）也包括关于所标记的感兴趣区域（20）的信息以及注释（22）。 此外，可以扫描携带样品切片（18）的样品载玻片（14），以便提供样品图像（28）。 从生物材料的相同对象（10）切割样品切片（18）和参考切片（16）。 特别地，样品切片（16）已经在材料块的切割已被预成型之后被直接切割以提供参考切片（18）。 由于参考片（16）和样本片（18）来自相同的对象（10），所以它们的特征很可能是参考图像（26）和样本图像（28）非常相似。 由于这种相似性，基于参考图像（26）和样本图像（28）之间的图像识别到样本载片（14），参考幻灯片（12）的注释（22）被复制。
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7.发明申请
公开(公告)号：WO2016169745A1
公开(公告)日：2016-10-27
申请号：PCT/EP2016/057178
申请日：2016-04-01
发明人： PIERIK, Anke , WIMBERGER-FRIEDL, Reinhold , CLOUT, Danielle Elisa Willemine , ZUO, Fei , VLUTTERS, Ruud
CPC分类号： B41J2/04508 , B41J2/04586 , G01N1/2813 , G01N2001/282
摘要： The invention relates to a printing control device (10) to control printing of a cover layer on a tissue or cell sample to be examined, a system (1) for printing of a cover layer (1) on a tissue or cell sample to be examined, a method to control printing of a cover layer on a tissue or cell sample to be examined, a computer program element for controlling such device or system for performing such method and a computer readable medium having stored such computer program element. The printing control device (10) comprises an imaging unit (11) and a printing control unit (12). The imaging unit (11) is configured to provide image data of the sample, and to determine a local image parameter from the image data. The local image parameter relates to local tissue porosity and/or a local capillary force of the sample. The printing control unit (12) is configured to control a printing parameter for printing the cover layer on the sample based on the local image parameter.
摘要翻译： 本发明涉及一种用于控制待检查的组织或细胞样品上的覆盖层的印刷的印刷控制装置（10），用于在组织或细胞样品上印刷覆盖层（1）的系统（1） 检查了用于控制要检查的组织或细胞样品上的覆盖层的印刷的方法，用于控制这种用于执行这种方法的装置或系统的计算机程序元件和具有存储这样的计算机程序元件的计算机可读介质。 打印控制装置（10）包括成像单元（11）和打印控制单元（12）。 成像单元（11）被配置为提供样本的图像数据，并且从图像数据确定局部图像参数。 局部图像参数涉及样品的局部组织孔隙度和/或局部毛细管力。 打印控制单元（12）被配置为基于本地图像参数来控制用于在样本上打印覆盖层的打印参数。
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公开(公告)号：WO2016166128A1
公开(公告)日：2016-10-20
申请号：PCT/EP2016/058067
申请日：2016-04-13
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6841 , C12Q1/6837 , C12Q1/6844 , C12Q1/6869 , C12Q2535/10 , C12Q2543/101 , C12Q2535/122 , C12Q2563/179 , C12Q2565/519
摘要： A method is presented that enables the spatial mapping of nucleic acids of tissue samples with high resolution and without sacrificing the degree of multiplexing that is available from next-generation sequencing. The method is based on the application of patterns of barcoded oligonucleotides probes onto predefined locations in a region of interest in a tissue sample. Every nucleic acid analyzed can be allocated to a certain position inside the sample based on the barcode. Various printing technologies can be used and different ways of patterning can be employed, like a regular array with a certain pitch or alternatively an object-based patterning with defined regions of interest without shape constraints.
摘要翻译： 提出了一种能够以高分辨率对组织样品的核酸进行空间映射并且不牺牲下一代测序可获得的复用度的方法。 该方法基于将条形码寡核苷酸探针的模式应用于组织样本中感兴趣区域中的预定位置。 分析的每个核酸可以基于条形码分配到样品内的某个位置。 可以使用各种打印技术，可以采用不同的图案形式，例如具有一定间距的规则阵列，或者替代地，具有限定的感兴趣区域的基于物体的图案，而没有形状限制。
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公开(公告)号：WO2018104254A1
公开(公告)日：2018-06-14
申请号：PCT/EP2017/081425
申请日：2017-12-05
摘要： A device for identifying a region of interest to be dissected from a biological tissue sample is presented. The device comprises an image analyzing unit which iteratively grows the region of interest from an initial size to a final size as long as a target parameter which is based on the two detected densities D 1 and D 2 and which describes the region of interest, is above a predefined target value. Preferably, the target parameter is the density ratio D 1 /D 2 of the region of interest and the first type of detected cells are tumor cells whereas the second type of cells are non-tumor cells. Furthermore, optimization or cost functions can be applied which take into account the percentage of number of cells of the first cell type and the total number of cells of the first cell type in the respective region of interest.
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公开(公告)号：WO2015078755A1
公开(公告)日：2015-06-04
申请号：PCT/EP2014/075067
申请日：2014-11-20
CPC分类号： C12Q1/6874 , B01J19/0046 , B01J2219/00286 , B01J2219/00454 , B01J2219/00495 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00711 , G01N21/6428 , G01N21/6452 , G01N21/648 , G01N2021/6439 , G01N2201/061
摘要： The present invention relates to a device(100) and a method for optically controlling a chemical reaction in a reaction chamber(149) comprising a reagent fluid (114). In a preferred embodiment, the chemical reaction comprises a nucleic acid sequencing on a wiregrid. Based on strong optical confinement of excitation light (110) and of cleavage light (112), the sequencing reaction can be read-out. Stepwise sequencing is achieved by using nucleotides with optically cleavable blocking moieties. After read-out the built in nucleotide is deblocked by cleavage light through the same substrate. This ensures that only bound nucleotides will be unblocked. In order to avoid overheating by cleavage light, the reagent fluid is circulated along the surface of the substrate (101).
摘要翻译： 本发明涉及一种装置（100）和用于光学控制包括反应液（114）的反应室（149）中的化学反应的方法。 在优选的实施方案中，化学反应包括在丝网上的核酸测序。 基于激发光（110）和裂解光（112）的强光学约束，可以读出测序反应。 通过使用具有可光学切割阻断部分的核苷酸来实现逐步测序。 读出后，内置的核苷酸通过裂解光通过相同的底物解封。 这确保仅结合的核苷酸将被解除封闭。 为了避免裂解光过热，试剂液体沿着基板（101）的表面循环。
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