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1. 发明申请

WO2012030675A1 SYSTEMS, METHODS, AND DEVICES FOR PLASMID GENE TRANSFECTION USING POLYMER-MODIFIED MICROBUBBLES 审中-公开
标题翻译：使用聚合物改性的微生物进行PLASMID基因转移的系统，方法和设备
公开(公告)号：WO2012030675A1
公开(公告)日：2012-03-08
申请号：PCT/US2011/049455
申请日：2011-08-26
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, Andrew , SIRSI, Shashank, Ramesh
发明人： BORDEN, Mark, Andrew , SIRSI, Shashank, Ramesh
IPC分类号： A61B8/00 , A61K49/00
CPC分类号： A61K9/1075 , A61K31/7088 , A61K41/0028 , A61K47/59 , A61K47/60 , A61K47/62 , A61K47/6845 , A61K47/6925 , A61K48/0041 , A61K49/223
摘要： Thiolated polyethylenimine (PEI) polymers can be covalently attached to lipid shell microbubbles. The PEI polymer can be modified with polyethylene glycol (PEG) chains to improve biocompatibility. The covalent attachment of the PEI polymer to the microbubble shell can result from a bond between a free sulfhydryl group (SH) of the thiolated PEI and a free maleimide group on the microbubble shell. DNA can be electrostatically bound to the PEI polymers to form polyplexes. A plurality of the polyplex -microbubble hybrids can be injected into a patient and can be imaged via ultrasound. While circulating in the bloodstream, and in particular, within a region of interest, high-pressure, low-frequency acoustic energy can be applied, thereby causing destruction by cavitation. Such cavitation can transiently increase the permeability of the endothelial vasculature thereby allowing plasmid DNA of the polyplexes carried by the microbubbles to be delivered to targeted cells.
摘要翻译：硫醇化聚乙烯亚胺（PEI）聚合物可以共价连接到脂壳微泡。 PEI聚合物可以用聚乙二醇（PEG）链改性以提高生物相容性。 PEI聚合物与微泡壳的共价连接可以由硫醇化PEI的游离巯基（SH）与微泡壳上的游离的马来酰亚胺基团之间的键形成。 DNA可以静电结合到PEI聚合物上以形成复合物。多个复合微泡混合物可以注射到患者体内并且可以通过超声波成像。虽然在血流中，特别是在感兴趣的区域内循环，但是可以施加高压，低频声能，从而引起空化破坏。这种气蚀可以瞬时地增加内皮脉管系统的通透性，从而允许由微泡承载的复合物的质粒DNA被递送到靶细胞。

2. 发明申请

WO2010030779A1 ISOLATION OF MICROBUBBLES OF SELECTED SIZE RANGE FROM POLYDISPERSE MICROBUBBLES 审中-公开
标题翻译：从多晶硅微球中分离选择尺寸范围的微生物
公开(公告)号：WO2010030779A1
公开(公告)日：2010-03-18
申请号：PCT/US2009/056513
申请日：2009-09-10
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
发明人： BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
IPC分类号： A61B8/00
CPC分类号： A61K49/223
摘要： In one aspect of the disclosed subject matter, a method for isolating target microbubbles having a predetermined size range from polydisperse microbubbles is disclosed. The method includes applying a first centrifugal field having a first field strength to a suspension comprising the polydisperse microbubbles for a first duration of time, thereby forming a first infranatant comprising at least a portion of target microbubbles and a first supernatant cake comprising microbubbles having a greater size than the target microbubbles; removing the first supernatant cake; applying a second centrifugal field having a second field strength to the first infranatant for a second duration of time, the second field strength being greater than the first field strength, thereby forming a second supernatant cake comprising at least a portion of the target microbubbles and second infranatant comprising microbubbles having a smaller size than the target microbubbles; and isolating the second supernatant cake. In another aspect of the disclosed subject matter, a method for performing high frequency ultrasonic imaging using isolated microbubbles is provided.
摘要翻译：在所公开的主题的一个方面，公开了一种从多分散微泡分离具有预定尺寸范围的目标微泡的方法。该方法包括将第一场强度的第一离心场施加到包含多分散微泡的悬浮液的第一持续时间，由此形成包含至少一部分目标微泡的第一细胞悬液，以及包含具有更大的微泡的第一上清液滤饼尺寸比目标微泡; 去除第一上清液滤饼; 在第二持续时间内将具有第二场强的第二离心场施加到所述第一干扰素，所述第二场强大于所述第一场强，从而形成包含所述目标微泡的至少一部分的第二上清液滤饼和第二场强包含具有比目标微泡更小的微泡的微泡; 并分离第二上清液滤饼。在所公开的主题的另一方面，提供了一种使用隔离微泡进行高频超声成像的方法。

3. 发明申请

WO2012019146A1 SYSTEMS, METHODS, AND DEVICES FOR ULTRASONIC ASSESSMENT OF CANCER AND RESPONSE TO THERAPY 审中-公开
标题翻译：用于癌症超声评估和治疗反应的系统，方法和装置
公开(公告)号：WO2012019146A1
公开(公告)日：2012-02-09
申请号：PCT/US2011/046830
申请日：2011-08-05
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, Andrew , KANDEL, Jessica , SIRSI, Shashank, Ramesh , YAMASHIRO, Darrell
发明人： BORDEN, Mark, Andrew , KANDEL, Jessica , SIRSI, Shashank, Ramesh , YAMASHIRO, Darrell
IPC分类号： A61B17/20
CPC分类号： A61K49/223 , A61B8/085 , A61B8/481 , A61K49/221 , A61N7/02 , A61N2007/0039
摘要： Microbubbles can be injected into the bloodstream of a patient, for example, a cancer patient undergoing a treatment specifically targeting a biological process in a tumor. The injected microbubbles can act as vascular contrast agents, which can be detected in vivo using high-frequency ultrasound imaging. The microbubbles can have a surface chemistry that allows them to bind to molecular targets in the tumor vasculature. After injection, the microbubbles can selectively adhere to endothelia expressing a target receptor. The selective adhesion can be used to quantify the tumor vasculature in vivo. By imaging the adhered microbubbles with ultrasound, an indication of how tumor vasculature is affected by a specific cancer treatment can be obtained. Such techniques can be used in a clinical setting for rapid determination of anti- cancer treatment efficacy for individual patients.
摘要翻译：微泡可以注射到患者的血液中，例如，经历特异性靶向肿瘤中生物过程的治疗的癌症患者。注射的微泡可以作为血管造影剂，其可以使用高频超声成像在体内检测。微泡可以具有允许它们结合肿瘤脉管系统中的分子靶标的表面化学物质。注射后，微泡可以选择性地粘附到表达目标受体的内皮。选择性粘附可用于体内肿瘤脉管系统的定量。通过用超声波对粘附的微泡进行成像，可以获得肿瘤脉管系统如何受特定癌症治疗影响的指示。这样的技术可以用于临床环境中，用于快速测定个体患者的抗癌治疗功效。

4. 发明申请

WO2011028690A1 MICROBUBBLE DEVICES, METHODS AND SYSTEMS 审中-公开
标题翻译：微型设备，方法和系统
公开(公告)号：WO2011028690A1
公开(公告)日：2011-03-10
申请号：PCT/US2010/047263
申请日：2010-08-31
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , BORDEN, Mark, A. , LIMA, Eric, G. , HUNG, Clark, T. , SIRSI, Shashank, Ramesh
发明人： BORDEN, Mark, A. , LIMA, Eric, G. , HUNG, Clark, T. , SIRSI, Shashank, Ramesh
IPC分类号： C12N5/00 , C12N5/02
CPC分类号： C12M41/48 , C12N5/0655 , C12N2533/76
摘要： A hydrogel tissue engineering scaffold having microbubbles dispersed therein is disclosed. Also, a system for cell culturing including a controller and actuator to apply dynamic deformational loading to a hydrogel is disclosed. Also disclosed are methods for producing hydrogels with microbubbles and for culturing cells using hydrogels with microbubbles.
摘要翻译：公开了一种其中分散有微泡的水凝胶组织工程支架。此外，公开了一种用于细胞培养的系统，包括控制器和致动器以对水凝胶施加动态变形负荷。还公开了用微泡制备水凝胶的方法以及使用具有微泡的水凝胶培养细胞的方法。

5. 发明公开

EP2600777A1 SYSTEMS, METHODS, AND DEVICES FOR ULTRASONIC ASSESSMENT OF CANCER AND RESPONSE TO THERAPY 审中-公开
标题翻译：系统，方法和设备用于癌症超声检查和治疗反对响应
公开(公告)号：EP2600777A1
公开(公告)日：2013-06-12
申请号：EP11815395.6
申请日：2011-08-05
申请人： The Trustees of Columbia University in the City of New York
发明人： BORDEN, Mark, Andrew , KANDEL, Jessica , SIRSI, Shashank, Ramesh , YAMASHIRO, Darrell
IPC分类号： A61B17/20
CPC分类号： A61K49/223 , A61B8/085 , A61B8/481 , A61K49/221 , A61N7/02 , A61N2007/0039
摘要： Microbubbles can be injected into the bloodstream of a patient, for example, a cancer patient undergoing a treatment specifically targeting a biological process in a tumor. The injected microbubbles can act as vascular contrast agents, which can be detected in vivo using high-frequency ultrasound imaging. The microbubbles can have a surface chemistry that allows them to bind to molecular targets in the tumor vasculature. After injection, the microbubbles can selectively adhere to endothelia expressing a target receptor. The selective adhesion can be used to quantify the tumor vasculature in vivo. By imaging the adhered microbubbles with ultrasound, an indication of how tumor vasculature is affected by a specific cancer treatment can be obtained. Such techniques can be used in a clinical setting for rapid determination of anti- cancer treatment efficacy for individual patients.

6. 发明公开

EP2334239A1 ISOLATION OF MICROBUBBLES OF SELECTED SIZE RANGE FROM POLYDISPERSE MICROBUBBLES 审中-公开
标题翻译：多分散微球从一定尺寸范围内分离微球
公开(公告)号：EP2334239A1
公开(公告)日：2011-06-22
申请号：EP09813604.7
申请日：2009-09-10
申请人： The Trustees of Columbia University in the City of New York
发明人： BORDEN, Mark, A. , FESHITAN, Jameel, Adebayo , CHEN, Cherry , SIRSI, Shashank, Ramesh , KWAN, James, Jing
IPC分类号： A61B8/00
CPC分类号： A61K49/223
摘要： In one aspect of the disclosed subject matter, a method for isolating target microbubbles having a predetermined size range from polydisperse microbubbles is disclosed. The method includes applying a first centrifugal field having a first field strength to a suspension comprising the polydisperse microbubbles for a first duration of time, thereby forming a first infranatant comprising at least a portion of target microbubbles and a first supernatant cake comprising microbubbles having a greater size than the target microbubbles; removing the first supernatant cake; applying a second centrifugal field having a second field strength to the first infranatant for a second duration of time, the second field strength being greater than the first field strength, thereby forming a second supernatant cake comprising at least a portion of the target microbubbles and second infranatant comprising microbubbles having a smaller size than the target microbubbles; and isolating the second supernatant cake. In another aspect of the disclosed subject matter, a method for performing high frequency ultrasonic imaging using isolated microbubbles is provided.
摘要翻译：在所公开的主题的一个方面中，公开了用于从多分散微泡分离具有预定尺寸范围的目标微泡的方法。该方法包括将具有第一场强度的第一离心场施加到包含多分散微泡的悬浮液持续第一持续时间，从而形成包含至少一部分目标微泡的第一infranatant和包含具有更大微泡的微泡的第一上清液饼尺寸比目标微泡大; 除去第一上清液滤饼; 将具有第二场强度的第二离心场施加到第一浸润液持续第二持续时间，第二场强大于第一场强度，由此形成包含至少一部分目标微泡的第二上清液块，以及第二时间段包含具有比目标微泡更小尺寸的微泡的infranatant; 并分离第二上清液滤饼。在所公开的主题的另一方面中，提供了一种使用分离的微泡进行高频超声成像的方法。

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