公开(公告)号：US20140199764A1

公开(公告)日：2014-07-17

申请号：US14116481

申请日：2012-05-08

申请人： Karel Domansky ,  Daniel C. Leslie ,  Geraldine A. Hamilton ,  Anthony Bahinski ,  Donald E. Ingber

发明人： Karel Domansky ,  Daniel C. Leslie ,  Geraldine A. Hamilton ,  Anthony Bahinski ,  Donald E. Ingber

IPC分类号： C12N5/071 ,  B32B37/18

CPC分类号： C12N5/0602 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00833 ,  B01J2219/0084 ,  B01J2219/0086 ,  B01J2219/00907 ,  B01L3/502707 ,  B01L2300/161 ,  B32B37/18 ,  G01N33/54393

摘要： Described herein are microfluidic modules and methods for making the same, wherein the microfluidic modules include a substrate comprising at least one ether-based, aliphatic polyurethane, and at least one fluidic element disposed therein. The ether-based aliphatic polyurethane can be either the substrate of the microfluidic modules or a coating of another substrate material, such that at least a portion of the ether-based, aliphatic polyurethane is in fluid communication. In one embodiment, the ether-based, aliphatic polyurethane includes dicyclohexylmethane-4,4′-diisocyanate. As the ether-based aliphatic polyurethane can decrease absorption of molecules, e.g., hydrophobic molecules, in such microfluidic modules, the microfluidic modules described herein can be used in various applications such as drug screening and fluorescent microscopy.

摘要翻译： 本文描述的是微流体模块和用于制造其的方法，其中微流体模块包括包含至少一种醚基脂族聚氨酯和设置在其中的至少一个流体元件的基材。 醚基脂肪族聚氨酯可以是微流体模块的基材或另一种基材的涂层，使得至少一部分醚基的脂族聚氨酯与流体连通。 在一个实施方案中，醚基脂族聚氨酯包括二环己基甲烷-4,4'-二异氰酸酯。 由于醚类脂族聚氨酯可以在这种微流体模块中减少分子（例如疏水性分子）的吸收，因此本文所述的微流体模块可用于各种应用，例如药物筛选和荧光显微镜。

公开(公告)号：US06383466B1

公开(公告)日：2002-05-07

申请号：US09222569

申请日：1998-12-28

申请人： Karel Domansky ,  Glen E. Fryxell ,  Jun Liu ,  Nathan J. Kohler ,  Suresh Baskaran

发明人： Karel Domansky ,  Glen E. Fryxell ,  Jun Liu ,  Nathan J. Kohler ,  Suresh Baskaran

IPC分类号： C01B33159

CPC分类号： C01B37/02 ,  H01L21/31695

摘要： The present invention is a method of dehydroxylating a silica surface that is hydroxylated having the steps of exposing the silica surface separately to a silicon organic compound and a dehydroxylating gas. Exposure to the silicon organic compound can be in liquid, gas or solution phase, and exposure to a dehydroxylating gas is typically at elevated temperatures. In one embodiment, the improvement of the dehydroxylation procedure is the repetition of the soaking and dehydroxylating gas exposure. In another embodiment, the improvement is the use of an inert gas that is substantially free of hydrogen. In yet another embodiment, the present invention is the combination of the two-step dehydroxylation method with a surfactant templating method of making a mesoporous film.

摘要翻译： 本发明是一种将羟基化的二氧化硅表面脱羟基化的方法，其具有将二氧化硅表面分别暴露于硅有机化合物和脱羟基化气体的步骤。 暴露于硅有机化合物可以是液体，气体或溶液相，并且暴露于脱羟基化气体通常处于升高的温度。 在一个实施方案中，脱羟基化程序的改进是重复浸泡和脱羟基化气体暴露。 在另一个实施方案中，改进是使用基本上不含氢的惰性气体。 在另一个实施方案中，本发明是两步脱羟基化方法与制备介孔膜的表面活性剂模板法的组合。

公开(公告)号：US20050260745A1

公开(公告)日：2005-11-24

申请号：US11133092

申请日：2005-05-19

申请人： Karel Domansky ,  Linda Griffith ,  Steven Tannenbaum ,  Alan Wells

发明人： Karel Domansky ,  Linda Griffith ,  Steven Tannenbaum ,  Alan Wells

IPC分类号： B01L3/00 ,  C12M1/00 ,  C12M1/32 ,  C12M1/34 ,  C12Q1/68

CPC分类号： B01L3/502715 ,  B01J2219/00315 ,  B01J2219/00743 ,  B01L3/50255 ,  B01L3/50273 ,  B01L3/502738 ,  B01L2300/0681 ,  B01L2300/0829 ,  B01L2300/0861 ,  B01L2400/0481 ,  B01L2400/0638 ,  B33Y80/00 ,  C12M23/12 ,  C12M23/40 ,  C12M25/14 ,  C12M29/10

摘要： A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a “multiwell plate” format amenable to high-throughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.

摘要翻译： 已经构建了通过正常人体组织重现毛细血管床特征的系统。 该系统有助于在毛细血管床的长度尺度上灌注三维（3D）细胞单一培养物和异型细胞共培养物。 一个主要特征是该系统可以在“多孔板”格式中使用，适合与药物开发中通常使用的机器人类型相容的高通量测定。 该系统提供了进行毒理学和代谢测定的手段，并作为人类疾病（如肝脏疾病，包括肝炎，暴露相关病理和癌症）的模型。 癌症应用包括原发性肝癌以及转移瘤。 该系统还可用作测试基因治疗方法的手段，用于治疗疾病和先天性遗传缺陷。

公开(公告)号：US06197575B1

公开(公告)日：2001-03-06

申请号：US09272227

申请日：1999-03-18

申请人： Linda G. Griffith ,  Steven Tannenbaum ,  Mark J. Powers ,  Karel Domansky ,  Charles D. Thompson

发明人： Linda G. Griffith ,  Steven Tannenbaum ,  Mark J. Powers ,  Karel Domansky ,  Charles D. Thompson

IPC分类号： C12M134

CPC分类号： G01N33/5038 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00308 ,  B01J2219/00313 ,  B01J2219/00317 ,  B01J2219/00319 ,  B01J2219/00351 ,  B01J2219/00376 ,  B01J2219/00416 ,  B01J2219/00585 ,  B01J2219/00659 ,  B01J2219/0072 ,  B33Y10/00 ,  B33Y80/00 ,  B82Y30/00 ,  C12M21/08 ,  C12M23/12 ,  C12M41/46 ,  C40B60/14 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5058 ,  G01N33/5064 ,  G01N33/5073

摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form “blood vessels”, and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.

摘要翻译： 系统包括（1）微阵列和灌注组件，其适合于接种和附着基质内的细胞，并将种子细胞的形态发生转化为复杂的分层组织或器官结构，其中所述基质包括通道或血管，培养基，氧气或 可以灌注其他营养液或体液，同时在整个灌注路径中独立于灌注速率控制营养物质和外源代谢物的梯度，以及（2）用于检测基质内的任何细胞或暴露于细胞的材料中的变化的传感器装置， 发达。 制造微阵列的方法包括微加工，微型成型，压花，激光钻孔和电沉积加工。 细胞可以是一种或多种，​​分化或未分化。 在优选的实施方案中，用包含内皮细胞的细胞混合物接种基质，所述内皮细胞将通道形成“血管”，以及至少一种类型的实质细胞，例如肝细胞，胰腺细胞或其它器官细胞。 该系统可以用于筛选对细胞的影响的材料，用于细胞对材料的影响（例如，以与药物的组织代谢相当的方式），或测试生物上必需的材料 首先感染细胞或组织，如病毒。 该装置还可用于提供用于扩大干细胞的生理环境，或用于在体外实现基因治疗。

公开(公告)号：US20140158233A1

公开(公告)日：2014-06-12

申请号：US14116477

申请日：2012-05-09

申请人： Daniel Christopher Leslie ,  Karel Domansky ,  Geraldine A. Hamilton ,  Anthony Bahinski ,  Donald E. Ingber

发明人： Daniel Christopher Leslie ,  Karel Domansky ,  Geraldine A. Hamilton ,  Anthony Bahinski ,  Donald E. Ingber

IPC分类号： B05B15/00

摘要： The present invention is directed to systems and methods for delivering aerosolized micro-droplets into microfluidic devices. In some embodiments, the microfluidic devices are designed for the culture of living cells at an air interface. In some embodiments, the systems and methods described herein can be used to deliver aerosolized micro-droplet into detection systems and small animals, tissues, organs and organisms.

摘要翻译： 本发明涉及用于将雾化的微滴输送到微流体装置中的系统和方法。 在一些实施例中，微流体装置被设计用于在空气界面处培养活细胞。 在一些实施方案中，本文所述的系统和方法可用于将雾化的微滴输送到检测系统和小动物，组织，器官和生物中。

公开(公告)号：US20130157283A1

公开(公告)日：2013-06-20

申请号：US13522800

申请日：2011-01-19

申请人： Chong Wing Yung ,  Donald E. Ingber ,  Ryan Mcomber Cooper ,  Frank Vollmer ,  Karel Domansky ,  Daniel Christopher Leslie ,  Michael Super

发明人： Chong Wing Yung ,  Donald E. Ingber ,  Ryan Mcomber Cooper ,  Frank Vollmer ,  Karel Domansky ,  Daniel Christopher Leslie ,  Michael Super

IPC分类号： C12Q1/04

CPC分类号： C12Q1/04 ,  B01L3/502761 ,  B01L2200/0668 ,  B01L2300/0816 ,  B01L2400/043 ,  G01N33/54306 ,  G01N33/54333 ,  G01N33/54366 ,  G01N35/0098

摘要： A microfluidic device of a diagnostic and detection system includes an inlet port connected by one or more microchannels to an outlet port and includes a capture and visualization chamber (CVC) connected to at least one microchannel. A fluid to be analyzed can be mixed with magnetic microbeads that have an affinity to become bound to target components, such as pathogens in the fluid. The fluid including the magnetically bound target components can be injected through the microfluidic device. Magnetic field gradient, such as provided by permanent or electro-magnets, can be applied to the fluid and the magnetically bound target components flowing through the microfluidic device to cause the magnetically bound target components to migrate into the (CVC) and become separated from the fluid. The magnetically bound target components can be analyzed and tested using various techniques to detect the presence of specific organic and inorganic materials, such as pathogens in bio-fluids and contamination in liquid food sources (e.g. water). The device and method provide a system for rapidly detecting pathogens and contamination in relatively small fluid samples.

摘要翻译： 诊断和检测系统的微流体装置包括通过一个或多个微通道连接到出口的入口端口，并且包括连接到至少一个微通道的捕获和可视化室（CVC）。 要分析的流体可以与具有亲和性的磁性微珠混合，以结合到目标组分，例如流体中的病原体。 包括磁结合的靶组分的流体可以通过微流体装置注入。 磁场梯度，例如由永磁体或电磁铁提供的磁场梯度可以被施加到流过微流体装置的流体和磁结合的目标组分，以使磁结合的靶组分迁移到（CVC）中并与 流体。 可以使用各种技术来分析和测试磁结合的靶组分，以检测特定有机和无机材料（例如生物流体中的病原体和液体食物来源（例如水））中的污染物的存在。 该装置和方法提供用于在相对小的流体样品中快速检测病原体和污染物的系统。

公开(公告)号：US08318479B2

公开(公告)日：2012-11-27

申请号：US11133092

申请日：2005-05-19

申请人： Karel Domansky ,  Linda G. Griffith ,  Steven R. Tannenbaum ,  Alan Wells ,  Samuel Walker Inman

发明人： Karel Domansky ,  Linda G. Griffith ,  Steven R. Tannenbaum ,  Alan Wells ,  Samuel Walker Inman

IPC分类号： C12M1/22 ,  C12M3/00 ,  C12M1/34

CPC分类号： B01L3/502715 ,  B01J2219/00315 ,  B01J2219/00743 ,  B01L3/50255 ,  B01L3/50273 ,  B01L3/502738 ,  B01L2300/0681 ,  B01L2300/0829 ,  B01L2300/0861 ,  B01L2400/0481 ,  B01L2400/0638 ,  B33Y80/00 ,  C12M23/12 ,  C12M23/40 ,  C12M25/14 ,  C12M29/10

摘要： A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a “multiwell plate” format amenable to high-throughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.

摘要翻译： 已经构建了通过正常人体组织重现毛细血管床特征的系统。 该系统有助于在毛细血管床的长度尺度上灌注三维（3D）细胞单一培养物和异型细胞共培养物。 主要特征是该系统可以在多孔板格式中使用，适合与药物开发中通常使用的机器人类型兼容的高通量测定。 该系统提供了进行毒理学和代谢测定的手段，并作为人类疾病（如肝脏疾病，包括肝炎，暴露相关病理和癌症）的模型。 癌症应用包括原发性肝癌以及转移瘤。 该系统还可用作测试基因治疗方法的手段，用于治疗疾病和先天性遗传缺陷。

公开(公告)号：US20140220617A1

公开(公告)日：2014-08-07

申请号：US14007738

申请日：2012-04-02

申请人： Chong Wing Yung ,  Karel Domansky ,  Richard Terry ,  David Kalish ,  Alexa Schulte ,  Joo Hun Kang ,  Donald E. Ingber ,  Michael Super ,  Ryan M. Cooper

发明人： Chong Wing Yung ,  Karel Domansky ,  Richard Terry ,  David Kalish ,  Alexa Schulte ,  Joo Hun Kang ,  Donald E. Ingber ,  Michael Super ,  Ryan M. Cooper

IPC分类号： C12Q1/04 ,  B03C1/00 ,  B01L3/00

CPC分类号： C12Q1/04 ,  A61M1/36 ,  A61M1/3618 ,  B01L3/502715 ,  B01L3/50273 ,  B01L3/502761 ,  B01L3/56 ,  B01L2200/0652 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/0887 ,  B01L2400/043 ,  B01L2400/0487 ,  B03C1/002 ,  B03C1/01 ,  B03C1/0332 ,  B03C1/0335 ,  B03C1/288 ,  B03C2201/26

摘要： A dialysis like therapeutic (DLT) device is provided. The DLT device includes at least one source channel connected at least one collection channels by one or more transfer channels. Fluid contacting surface of the channels can be an anti-fouling surface such as slippery liquid-infused porous surface (SLIPS). Fluids can be flown at high flow rates through the channels. The target components of the source fluid can be magnetic or bound to magnetic particles using an affinity molecule. A source fluid containing magnetically bound target components can be pumped through the source channel of the microfluidic device. A magnetic field gradient can be applied to the source fluid in the source channel causing the magnetically bound target components to migrate through the transfer channel into the collection channel. The collection channel can include a collection fluid to flush the target components out of the collection channel. The target components can be subsequently analyzed for detection and diagnosis. The source channel and the collection channels of the microfluidic device are analogous to the splenic arterioles and venules, respectively; the transfer channels mimic the vascular sinusoids of the spleen where opsonized particles are retained. Thus, the device acts as a dialysis like therapeutic device by combining fluidics and magnetics.

摘要翻译： 提供透析治疗（DLT）装置。 DLT设备包括通过一个或多个传输信道连接至少一个收集信道的至少一个源信道。 通道的流体接触表面可以是防污表面，例如滑动的液体注入的多孔表面（SLIPS）。 流体可以通过通道以高流速流动。 源流体的目标组分可以是磁性的或使用亲和分子结合到磁性颗粒。 含有磁结合的靶组分的源流体可以泵送通过微流体装置的源通道。 磁场梯度可以施加到源通道中的源流体，使得磁结合的目标分量通过传输通道迁移到收集通道中。 收集通道可以包括收集流体以将目标组分冲洗出收集通道。 随后分析目标成分进行检测和诊断。 微流体装置的源通道和收集通道分别类似于脾小动脉和小静脉; 转移通道模拟脾脏的血管窦状，其中保留调理颗粒。 因此，通过组合流体学和磁性，该装置作为透析像治疗装置。

公开(公告)号：US06329017B1

公开(公告)日：2001-12-11

申请号：US09413062

申请日：1999-10-04

申请人： Jun Liu ,  Karel Domansky ,  Xiaohong Li ,  Glen E. Fryxell ,  Suresh Baskaran ,  Nathan J. Kohler ,  Suntharampillai Thevuthasan ,  Christopher A. Coyle ,  Jerome C. Birnbaum

发明人： Jun Liu ,  Karel Domansky ,  Xiaohong Li ,  Glen E. Fryxell ,  Suresh Baskaran ,  Nathan J. Kohler ,  Suntharampillai Thevuthasan ,  Christopher A. Coyle ,  Jerome C. Birnbaum

IPC分类号： B05D312

CPC分类号： C01B37/02 ,  H01L21/31695 ,  Y10T428/249969 ,  Y10T428/249972

摘要： The present invention is a mesoporous silica film having a low dielectric constant and method of making having the steps of combining a surfactant in a silica precursor solution, spin-coating a film from this solution mixture, forming a partially hydroxylated mesoporous film, and dehydroxylating the hydroxylated film to obtain the mesoporous film. It is advantageous that the small polyoxyethylene ether surfactants used in spin-coated films as described in the present invention will result in fine pores smaller on average than about 20 nm. The resulting mesoporous film has a dielectric constant less than 3, which is stable in moist air with a specific humidity. The present invention provides a method for superior control of film thickness and thickness uniformity over a coated wafer, and films with low dielectric constant.

摘要翻译： 本发明是具有低介电常数的介孔二氧化硅薄膜及其制造方法，其具有以下步骤：在二氧化硅前体溶液中混合表面活性剂，从该溶液混合物中旋涂薄膜，形成部分羟基化介孔薄膜，并使 羟基化膜得到介孔膜。 在本发明中所述的旋转涂膜中使用的小聚氧乙烯醚表面活性剂的优点是平均产生比20nm小的细孔。 得到的介孔膜的介电常数小于3，在湿度相对湿度的空气中稳定。 本发明提供了一种用于在涂覆的晶片上优良控制膜厚度和厚度均匀性的方法以及具有低介电常数的膜。