公开(公告)号：US20060040377A1

公开(公告)日：2006-02-23

申请号：US10921073

申请日：2004-08-17

申请人： Pavel Tsinberg

发明人： Pavel Tsinberg

IPC分类号： C12M1/34

CPC分类号： G01N33/54386

摘要： Methods for making a microarray having minimal background binding of proteins by appropriately coating a substrate surface which is initially derivatized with organic functional groups. A protein-resistant polymeric coating is applied which has hydrophilic backbone polymers that are crosslinked to a substantial degree via polyfunctional isocyanate moieties. Three dimensional hydrogel microspots containing capture agents are affixed at distinct spatial locations across an array region of the surface to form a microarray. The microspots are affixed either to the substrate or to the coating. The polymeric coating preferably comprises isocyanate-capped PEG crosslinked with a polyfunctional isocyanate to form urethane polymers.

摘要翻译： 通过适当地涂覆最初用有机官能团衍生的底物表面，制备具有最小背景结合蛋白质的微阵列的方法。 应用蛋白质抗性聚合物涂层，其具有通过多官能异氰酸酯部分大量交联的亲水性主链聚合物。 含有捕获剂的三维水凝胶微滴被固定在跨越表面的阵列区域的不同空间位置以形成微阵列。 将微孔固定在基底或涂层上。 聚合物涂层优选包含与多官能异氰酸酯交联以形成氨基甲酸酯聚合物的异氰酸酯封端的PEG。

公开(公告)号：US09212977B2

公开(公告)日：2015-12-15

申请号：US13525225

申请日：2012-06-15

申请人： Zhongliang Tang ,  Pavel Tsinberg ,  Ram S. Bhatt

发明人： Zhongliang Tang ,  Pavel Tsinberg ,  Ram S. Bhatt

IPC分类号： G01N1/34 ,  B01F5/10 ,  B01F13/00 ,  B01L3/00 ,  G01N1/40 ,  G01N33/543

CPC分类号： G01N1/34 ,  B01F5/102 ,  B01F13/0059 ,  B01L3/502753 ,  B01L3/502761 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/088 ,  B01L2400/0481 ,  B01L2400/0487 ,  B01L2400/0655 ,  B01L2400/086 ,  G01N1/40 ,  G01N1/405 ,  G01N33/54366

摘要： A micro flow device (11, 71) for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts (23, 81). The posts are spaced across the width of an expanded collection chamber region (17, 75) in the flow path, extending between the upper and lower surfaces thereof; they have rectilinear surfaces, being curved in cross-sections, e.g. circular or tear-drop shaped, and are randomly arranged so as to disrupt streamlined flow. The device is oriented so that its lower surface is aligned at about 45° to the horizontal. Sequestering agents, such as Abs, which are attached to surfaces of the collection region via a hydrophilic coating, preferably a permeable hydrogel containing isocyanate moieties, are highly effective in capturing cells or other targeted biomolecules while the remainder of the liquid sample exits horizontally.

摘要翻译： 用于从体液或其他液体样品中分离或分离细胞的微流量装置（11,71）使用流线，其中直线流被横向柱（23,81）的图案中断。 所述柱在所述流动路径中的扩张的收集室区域（17,75）的宽度上间隔开，并在其上表面和下表面之间延伸; 它们具有弯曲的横截面的直线表面，例如。 圆形或泪滴形，并且随机布置以便破坏流线型流。 该装置被定向成使得其下表面与水平面成约45°对准。 通过亲水涂层，优选含有异氰酸酯部分的渗透性水凝胶连接到收集区域的表面上的螯合剂如Abs在捕获细胞或其它靶向生物分子中而其余液体样品水平离开时是非常有效的。

公开(公告)号：US07439062B2

公开(公告)日：2008-10-21

申请号：US11021304

申请日：2004-12-23

申请人： Ram S. Bhatt ,  Pavel Tsinberg

发明人： Ram S. Bhatt ,  Pavel Tsinberg

IPC分类号： C12N5/00 ,  C12N11/02 ,  C12N11/08 ,  C12N11/06 ,  C12Q1/02

CPC分类号： A61K9/1641 ,  C12N2533/30

摘要： Spheroidal beads present an exterior surface of a hydrophilic hydrogel, which is an isocyanate-functional polymer that is polymerized by urethane bonds and cross-linked by urethane and urea bonds. Sequestering agents present at the surface are covalently bound to isocyanate groups or to intermediate linkers that are so bound. These beads allow sequestering agents to retain their native three-dimensional configuration, and as a result of such surface characteristics and hydrophilicity, they achieve highly effective capture of very small subpopulations of rare cells from bodily fluids or the like and very effectively deter nonspecific binding of other biomaterials present in such bodily fluid. They may be all-hydrogel spheroids or hydrogel-coated substrates.

摘要翻译： 球形珠呈现亲水性水凝胶的外表面，其是通过氨基甲酸酯键聚合并通过氨基甲酸酯和脲键交联的异氰酸酯官能聚合物。 存在于表面的螯合剂共价结合到异氰酸酯基团或与其结合的中间接头。 这些珠子允许螯合剂保留其天然三维构型，并且由于这些表面特性和亲水性，它们实现了非常有效地捕获来自体液等的非常小的稀有细胞亚群，并且非常有效地阻止非特异性结合 存在于这种体液中的其它生物材料。 它们可以是全水凝胶球状体或水凝胶涂覆的基底。

公开(公告)号：US20070161051A1

公开(公告)日：2007-07-12

申请号：US11331988

申请日：2006-01-12

申请人： Pavel Tsinberg ,  Zhongliang Tang

发明人： Pavel Tsinberg ,  Zhongliang Tang

IPC分类号： G01N33/567 ,  C12M1/34

CPC分类号： G01N1/40 ,  B01L3/5027 ,  G01N1/2813

摘要： A microflow device for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts which are arranged across the width of a collection region in an irregular or set random pattern so as to disrupt streamlined flow. Sequestering agents, such as Abs, are attached to all surfaces in the collection region via a hydrophilic permeable hydrogel coating. The collection region is formed as a cavity in a body molded from PDMS, which flexible body is sandwiched between a glass slide or comparable flat plate and a rigid top cap plate, both of which are pressed into abutting relation with the PDMS body by a heat-shrunk polymeric sleeve. Following cell separation and washing, cells can be released from the sequestering agents and the device centrifuged to force said cells to collect adjacent the hydrogel-coated slide or plate. Slitting the polymeric sleeve allows the body to then be peeled from the slide or plate, using an integral tab, to expose the separated cells on the top surface thereof for ready microscopic examination.

摘要翻译： 用于从体液或其他液体样品中分离或分离细胞的微流装置使用流动路径，其中直线流被横向柱的图案中断，所述横向柱横跨收集区域的宽度以不规则或设置的随机图案 以便破坏流线型流程。 螯合剂如Abs通过亲水可渗透的水凝胶涂层附着在收集区域中的所有表面上。 收集区域形成为由PDMS模制的主体中的空腔，该柔性体被夹在玻璃滑块或类似的平板和刚性顶盖板之间，两者均通过热量与PDMS体压接成邻接关系 -shrunk聚合物套管。 细胞分离和洗涤后，细胞可以从多价螯合剂中释放出来，离心的装置迫使细胞收集在水凝胶涂层的载玻片或板附近。 分开聚合物套筒可以使用整体制表片将身体从滑块或板上剥离，以暴露其顶部表面上的分离的细胞，以进行显微镜检查。

公开(公告)号：US20060252087A1

公开(公告)日：2006-11-09

申请号：US11458668

申请日：2006-07-19

申请人： Zhongliang Tang ,  Ram Bhatt ,  Pavel Tsinberg

发明人： Zhongliang Tang ,  Ram Bhatt ,  Pavel Tsinberg

IPC分类号： C12Q1/68 ,  G01N33/574 ,  C12M1/34

CPC分类号： G01N1/40 ,  B01L3/502738 ,  B01L3/502746 ,  B01L3/502753 ,  B01L2300/0816 ,  B01L2400/0487 ,  B01L2400/086 ,  C12M47/04 ,  G01N1/405 ,  G01N33/53 ,  G01N33/574

摘要： A microflow apparatus for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts. The posts are spaced across the width of a collection region in the flow path, extending between the upper and lower surfaces thereof; they have rectilinear surfaces, have arcuate cross-sections, and are randomly arranged so as to disrupt streamlined flow. Sequestering agents, such as Abs, are attached to all surfaces in the collection region via a hydrophilic coating, preferably a hydrogel containing isocyanate moieties or a PEG or polyglycine of substantial length, and are highly effective in capturing cells or other targeted biomolecules as a result of such streamlined flow disruption.

摘要翻译： 用于从体液或其他液体样品中分离或分离细胞的微流装置使用流线，其中直线流被横向柱的图案中断。 柱在流动路径中的收集区域的宽度上间隔开，并在其上表面和下表面之间延伸; 它们具有直线表面，具有弧形横截面，并且被随机排列以便破坏流线型流动。 螯合剂如Abs通过亲水涂层，优选含有非常长的异氰酸酯部分或PEG或聚甘氨酸的水凝胶附着在收集区域中的所有表面上，因此在捕获细胞或其它靶向生物分子中是非常有效的 这种流线型流动中断。

公开(公告)号：US20060160243A1

公开(公告)日：2006-07-20

申请号：US11038920

申请日：2005-01-18

申请人： Zhongliang Tang ,  Ram Bhatt ,  Pavel Tsinberg

发明人： Zhongliang Tang ,  Ram Bhatt ,  Pavel Tsinberg

IPC分类号： G01N1/00

CPC分类号： G01N1/40 ,  G01N1/405 ,  Y10T436/25375

摘要： A microflow apparatus for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts. The posts are spaced across the width of a collection region in the flow path, extending between the upper and lower surfaces thereof; they have rectilinear surfaces, have arcuate cross-sections, and are randomly arranged so as to disrupt streamlined flow. Sequestering agents, such as Abs, are attached to all surfaces in the collection region via a hydrophilic coating, preferably a hydrogel containing isocyanate moieties or a PEG or polyglycine of substantial length, and are highly effective in capturing cells or other targeted biomolecules as a result of such streamlined flow disruption.