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31. 发明申请

WO0009307A3 A MOLD FOR MAKING A THREE-DIMENSIONAL COMPLEX STRUCTURE, SAID MOLD COMPRISING AT LEAST THREE MOLD PORTIONS, METHOD OF MAKING SAID MOLD, AND USE OF SAID MOLD FOR MAKING THREE-DIMENSIONAL COMPLEX STRUCTURES 审中-公开
标题翻译：用于制造三维复杂结构的模具，包含至少三个模具部分的模具，制造所述模具的方法以及使用所述模具制造三维复杂结构
公开(公告)号：WO0009307A3
公开(公告)日：2000-06-08
申请号：PCT/US9918209
申请日：1999-08-11
申请人： MOLECULAR GEODESICS INC , INGBER DONALD E , BUTZ DAVID E , ROBERTS ERIC R , CLIFFORD DALE , KUMMAILIL JOHN J
发明人： INGBER DONALD E , BUTZ DAVID E , ROBERTS ERIC R , CLIFFORD DALE , KUMMAILIL JOHN J
IPC分类号： B29C33/00 , B29C33/30 , B29C33/38 , B29C33/42 , B29C33/44 , B29C33/52 , A61L27/00
CPC分类号： B29C33/301 , B29C33/0033 , B29C33/3857 , B29C33/42 , B29C33/448 , B29C33/52
摘要： Molds, methods of forming the molds, and methods of using the molds to form complex unitary three-dimensional structures are provided. The complex unitary three-dimensional structures and its complement have a high degree of interlocking. The molds include at least three mold portions constructed and arranged to include a complement of complex three-dimensional unitary structure when in an assembled configuration, and a portion of the complement when in an unassembled configuration. The structure is not removable from the mold portions without destroying at least a portion of the mold. The method involves providing a mold that includes a complement of the complex unitary three-dimensional structure, introducing a fluid material into the mold, and removing the complex unitary three-dimensional structure from the mold.
摘要翻译：提供了模具，形成模具的方法以及使用模具形成复杂的单一三维结构的方法。复杂的酉三维结构及其互补具有高度的互锁性。模具包括至少三个模具部分，所述模具部分被构造和布置成当处于组装构造时包括复杂的三维一体结构的补充以及处于未组装构造时的补充物的一部分。在不破坏模具的至少一部分的情况下，结构不能从模具部分移除。该方法包括提供包括复杂的单一三维结构的补充的模具，将流体材料引入模具中，并且从模具中移除复杂的单一三维结构。

32. 发明申请

WO0237102A3 METHODS FOR ANALYZING DYNAMIC CHANGES IN CELLULAR INFORMATICS 审中-公开
标题翻译：分析细胞动力学变化的方法
公开(公告)号：WO0237102A3
公开(公告)日：2003-03-20
申请号：PCT/US0143041
申请日：2001-10-19
申请人： CHILDRENS MEDICAL CENTER
发明人： HUANG SUI , INGBER DONALD E
IPC分类号： C12Q1/00 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/12 , G06F19/20 , G01N33/68
CPC分类号： G01N33/5091 , G01N33/5008 , G01N33/502 , G01N33/5023 , G01N33/5038 , G01N33/5088 , G06F19/12 , G06F19/20 , G06Q50/24
摘要： Methods are provided for analyzing dynamic changes in cellular processes and for representing cellular processes as dynamic signatures or phase portraits. Methods of the invention are useful for comparing cellular processes and providing diagnostic and prognostic information. Methods of the invention are also useful for identifying important molecular components of cellular processes, for identifying targets for drug development, and in assays for identifying drug candidates and evaluating frug effectiveness.
摘要翻译：提供了用于分析细胞过程中的动态变化并将蜂窝过程表示为动态签名或相位肖像的方法。本发明的方法可用于比较细胞过程并提供诊断和预后信息。本发明的方法还可用于鉴定细胞过程的重要分子组分，用于鉴定药物开发的靶标，以及用于鉴定候选药物和评估节食效果的测定法。

33. 发明申请

WO2014152122A3 METHODS OF ALTERING VASCULAR PERMEABILITY AND USES THEREOF 审中-公开
标题翻译：改善血管渗透性的方法及其用途
公开(公告)号：WO2014152122A3
公开(公告)日：2014-12-31
申请号：PCT/US2014026975
申请日：2014-03-14
申请人： CHILDRENS MEDICAL CENTER
发明人： INGBER DONALD E , MAMMOTO AKIKO
IPC分类号： A61K48/00 , C12P19/34
CPC分类号： A61K38/10 , A61K31/275 , A61K31/519 , A61K31/713 , A61K38/1841 , A61K38/39 , A61K38/44 , A61K48/005 , A61K2039/505 , A61N5/062 , A61N2005/0661 , C07K16/28 , C07K16/40 , C07K2317/33 , C07K2317/34 , C07K2317/76 , C12N15/1137 , C12N2310/14 , C12Y104/03013
摘要： Provided here are methods of modulating vascular permeability by changing the mechanical properties of extracellular matrices (ECM) and methods of treatment of diseases, conditions and symptoms related to vascular permeability such as pulmonary edema and acute respiratory distress syndrome (ARDS). The modulation can be increasing or decreasing vascular permeability. Vascular leakage can be normalized by increasing or decreasing ECM stiffness depending on the baseline mechanical properties of the tissue or organ. Vascular permeability is altered by changing the mechanical properties of ECM by administering a lysyl oxidase modulating (LOX) agent.
摘要翻译：这里提供了通过改变细胞外基质（ECM）的机械性质和治疗与血管通透性相关的疾病，病症和症状的方法（如肺水肿和急性呼吸窘迫综合征（ARDS））来调节血管通透性的方法。调节可以增加或减少血管通透性。根据组织或器官的基线机械性质，可以通过增加或减少ECM刚度来标准化血管渗漏。通过施用赖氨酰氧化酶调节（LOX）剂来改变ECM的机械性质来改变血管通透性。

34. 发明申请

WO2014209947A3 METHODS AND COMPOSITIONS FOR THE INHIBITION OF TRPV4 审中-公开
标题翻译：用于抑制TRPV4的方法和组合物
公开(公告)号：WO2014209947A3
公开(公告)日：2015-04-02
申请号：PCT/US2014043785
申请日：2014-06-24
申请人： CHILDRENS MEDICAL CENTER
发明人： INGBER DONALD E , KOBAYASHI MARIKO
IPC分类号： A61K38/00 , C07H21/02 , C07H21/04 , G01N33/00
CPC分类号： C07K14/70596 , A61K38/00 , C07K14/705 , C07K2319/10
摘要： TRPV4 activation increases vascular permeability and can be triggered by both chemical and mechanical cues. This activation of TRPV4 can contribute to a number of pathological conditions, e.g., edema, inflammation, hypertension, and/or hyperalgesia. Described herein are methods and compositions relating to inhibition of mechanically-induced TRPV4 activation, e.g., for the treatment of pulmonary edema, edema, inflammation, hypertension, and/or hyperalgesia.
摘要翻译： TRPV4激活增加血管通透性，并可由化学和机械提示触发。 TRPV4的这种激活可以导致许多病理状况，例如水肿，炎症，高血压和/或痛觉过敏。本文描述了与机械诱导的TRPV4活化的抑制有关的方法和组合物，例如用于治疗肺水肿，水肿，炎症，高血压和/或痛觉过敏。

35. 发明申请

WO2016077067A3 MAGNETIC CAPTURE OF A TARGET FROM A FLUID 审中-公开
标题翻译：从流体中捕获一个目标的磁性
公开(公告)号：WO2016077067A3
公开(公告)日：2016-07-28
申请号：PCT/US2015057516
申请日：2015-10-27
申请人： HARVARD COLLEGE
发明人： KANG JOO HUN , INGBER DONALD E , SUPER MICHAEL
IPC分类号： B03C5/00 , B03C1/00
CPC分类号： B03C1/002 , B03C1/01 , B03C1/025 , B03C1/0332 , B03C1/286 , B03C1/288 , B03C2201/18 , B03C2201/26 , C12N1/20
摘要： Disclosed herein is an improved method for magnetic capture of target molecules (e.g., microbes) in a fluid. Kits and solid substrates for carrying the method described herein are also provided. In some embodiments, the methods, kits, and solid substrates described herein are optimized for separation and/or detection of microbes and microbe-associated molecular pattern (MAMP) (including, e.g., but not limited to, a cell component of microbes, lipopolysaccharides (LPS), and/or endotoxin).
摘要翻译：本文公开了用于磁性捕获流体中的靶分子（例如微生物）的改进方法。还提供了用于运载本文所述方法的试剂盒和固体基质。在一些实施方案中，本文所述的方法，试剂盒和固体基质针对微生物和微生物相关分子模式（MAMP）（包括例如但不限于微生物的细胞组分，脂多糖的分离和/ （LPS）和/或内毒素）。

36. 发明申请

WO2014014613A3 SELF-ASSEMBLING PEPTIDES, PEPTIDE NANOSTRUCTURES AND USES THEREOF 审中-公开
标题翻译：自组装肽，肽类纳米结构及其用途
公开(公告)号：WO2014014613A3
公开(公告)日：2014-05-01
申请号：PCT/US2013046821
申请日：2013-06-20
申请人： HARVARD COLLEGE
发明人： INGBER DONALD E , ROBERTS KENNY
IPC分类号： C07K7/06 , C07K7/08 , C07K14/00
CPC分类号： C07K14/78 , A61K9/1658 , A61K47/48246 , A61K47/64 , C07K14/001
摘要： Provided herein relates to self-assembling peptides and various nanostructures self-assembled from the isolated peptides. In some embodiments, the self-assembling peptides can form a nanostructure, e.g., a nanoparticle or microparticle, for use in various biomedical applications such as drug delivery or tissue engineering. In some embodiments, the nanostructures can comprise an agent, e.g., a biological molecule. The agent can be encapsulated or entrapped in the nanostructures during formation of the nanostructures. Alternatively or additionally, the agent can be integrated directly or indirectly (e.g., via a linker or a conjugation or crosslinking agent) to the self-assembling peptide structure, prior to formation of the nanostructures. In some embodiments where the agent is a peptide-based agent, unitary peptide nanostructures, rather than nanoparticles that are formed and later covalently modified, can be generated.
摘要翻译：本文涉及自组装肽和从分离的肽自组装的各种纳米结构。在一些实施方案中，自组装肽可以形成用于各种生物医学应用如药物递送或组织工程的纳米结构，例如纳米颗粒或微粒。在一些实施方案中，纳米结构可以包含试剂，例如生物分子。在形成纳米结构期间，该试剂可被包封或包埋在纳米结构中。或者或另外，在形成纳米结构之前，可将试剂直接或间接（例如经由接头或共轭或交联剂）整合至自组装肽结构。在其中试剂是基于肽的试剂的一些实施方案中，可以产生单一肽纳米结构，而不是形成和随后共价修饰的纳米颗粒。

37. 发明申请

WO2015102726A3 A MICROFLUIDIC DEVICE FOR REAL-TIME CLINICAL MONITORING AND QUANTITATIVE ASSESSMENT OF WHOLE BLOOD COAGULATION 审中-公开
标题翻译：用于实时临床监测和全血凝固定量评估的微流体装置
公开(公告)号：WO2015102726A3
公开(公告)日：2015-10-29
申请号：PCT/US2014060956
申请日：2014-10-16
申请人： HARVARD COLLEGE
发明人： JAIN ABHISHEK , WATERHOUSE ANNA , SUPER MIKE , INGBER DONALD E , LESLIE DANIEL C
IPC分类号： G01N33/49 , G01N33/86
CPC分类号： B01L3/50273 , B01L3/502746 , B01L2200/146 , B01L2300/0627 , B01L2300/08 , B01L2300/0816 , B01L2300/0861 , B01L2300/0883 , B01L2400/0478 , B01L2400/084 , G01N33/4905 , G01N33/86 , G06F19/24
摘要： In accord with one aspect, a microfluidic coagulation assessment device defining a plurality of microchannels is provided, wherein a blood sample is driven through the microchannels at a substantially constant flow rate and a controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom. In another aspect, the blood sample is driven through the microchannels at a substantially constant pressure and a controller is configured to, in combination with a timer and a flow sensing device make the determination based on flow rate.
摘要翻译：根据一个方面，提供了限定多个微通道的微流体凝固评估装置，其中血液样本以基本恒定的流速被驱动通过微通道，并且控制器被配置为结合定时器和压力感测装置，在流动开始时确定第一压力值（或流量值），其中第二压力值大约是所确定的第一压力值的两倍的第一时间（Tpg），以及第二时间（Tpf）压力值约为所确定的第一压力值的（1 + e）倍，并建立预测通道阻塞的对象凝固模型。在另一方面，血液样本以基本上恒定的压力驱动通过微通道，并且控制器被配置为结合定时器和流量检测装置基于流量进行确定。

38. 发明申请

WO2016191332A3 METHODS, SYSTEMS, AND COMPOSITIONS FOR DETERMINING BLOOD CLOT FORMATION, AND USES THEREOF 审中-公开
标题翻译：用于确定血液成型的方法，系统和组合物及其用途
公开(公告)号：WO2016191332A3
公开(公告)日：2017-03-16
申请号：PCT/US2016033686
申请日：2016-05-22
申请人： HARVARD COLLEGE , CHILDREN'S MEDICAL CENTER CORP
发明人： INGBER DONALD E , JAIN ABHISHEK , VAN DER MEER ANDRIES D , MICHELSON ALAN DAVID , FRELINGER III ANDREW L
IPC分类号： C12Q1/56 , A61K35/19 , G01N33/48 , G06F19/12
CPC分类号： G01N33/86 , B01L3/5027 , G01N33/5064 , G01N2800/226
摘要： A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.
摘要翻译：一种方法涉及确定血栓形成功能，并且包括使流体样品在具有固定的内皮细胞单层的表面上流动。该方法还包括刺激固定的内皮细胞单层以诱导凝块的形成，凝块通过固定的内皮细胞单层和流体样品之间的相互作用而形成。响应于凝块形成，该方法还包括确定与流体样品和固定内皮细胞单层相关的血栓形成功能。

39. 发明申请

WO2015109220A8 PLATELET DECOYS AND USE THEREOF 审中-公开
标题翻译： PLATELET DECOYS及其使用
公开(公告)号：WO2015109220A8
公开(公告)日：2016-03-10
申请号：PCT/US2015011805
申请日：2015-01-16
申请人： HARVARD COLLEGE
发明人： INGBER DONALD E , PAPA ANNE-LAURE
IPC分类号： A61P7/02
CPC分类号： A61K35/19 , A61K31/122 , A61K31/337 , A61K31/37 , A61K31/4365 , A61K31/4439 , A61K31/4545 , A61K31/5377 , A61K31/64 , A61K31/704 , A61K31/7068 , A61K38/49 , C12N5/0644 , A61K2300/00
摘要： The invention provides platelet decoys and mimics that can bind to platelet receptor substrate but do not undergo platelet activation. The invention also provides methods of using the platelet decoys for treating, preventing or inhibiting a disease or disorder in subject when platelet activation, aggregation and/or adhesion contributes to the pathology or symptomology of the disease.
摘要翻译：本发明提供血小板诱饵和可以结合血小板受体底物但不经历血小板活化的模拟物。本发明还提供了当血小板活化，聚集和/或粘附有助于疾病的病理学或症状学时，使用血小板诱饵来治疗，预防或抑制受试者的疾病或病症的方法。

40. 发明申请

WO2014210364A3 INTERCONNECT ADAPTOR 审中-公开
标题翻译：互连适配器
公开(公告)号：WO2014210364A3
公开(公告)日：2015-10-29
申请号：PCT/US2014044417
申请日：2014-06-26
申请人： HARVARD COLLEGE
发明人： INGBER DONALD E , HINOJOSA CHRISTOPHER DAVID , LEVNER DANIEL , RESNIKOFF JOSH ISAAC NIELSEN , THOMPSON III GUY
IPC分类号： G01N1/00 , B01J4/00
CPC分类号： B01L3/563 , B01J19/0093 , B01J2219/00813 , B01J2219/00988 , B01L3/502715 , B01L2200/025 , B01L2200/027 , B01L2200/04 , B01L2200/0684 , B01L2200/0689 , B01L2200/10 , B01L2200/141 , B01L2300/047 , B01L2300/069 , B01L2300/0861 , B01L2300/0864 , B01L2300/0887 , B01L2300/089 , B01L2300/12 , B01L2300/123 , B01L2300/16 , C12M23/16 , C12M23/40 , C12M29/00
摘要： An interconnect adaptor for connecting a microfluidic device to a fluidic system. The interconnect adapter includes a base substrate and a nozzle array. The base substrate includes a first side and a second side. The nozzle array includes two or more nozzles extending away from the base substrate. Each nozzle includes an opening with a channel extending therefrom. The channels are configured to transport fluid between the microfluidic device and the fluidic system. Each of the nozzles is configured to be inserted into a respective hole in the microfluidic device. In some embodiments, the insertion forms a radially sealed connection between each nozzle and respective hole when the nozzles are inserted a predetermined distance into the respective holes.
摘要翻译：用于将微流体装置连接到流体系统的互连适配器。互连适配器包括基底基板和喷嘴阵列。基底基板包括第一面和第二面。喷嘴阵列包括远离基底基板延伸的两个或更多个喷嘴。每个喷嘴包括具有从其延伸的通道的开口。通道构造成在微流体装置和流体系统之间输送流体。每个喷嘴构造成插入到微流体装置中的相应孔中。在一些实施例中，当喷嘴在相应的孔中插入预定距离时，插入件在每个喷嘴和相应的孔之间形成径向密封的连接。

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