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1. 发明专利

IL272320D0 Methods and devices for detection of anticoagulants in plasma and whole blood 未知
公开(公告)号：IL272320D0
公开(公告)日：2020-03-31
申请号：IL27232020
申请日：2020-01-28
申请人： MASSACHUSETTS INST TECHNOLOGY , MASSACHUSETTS GEN HOSPITAL , FRYDMAN GALIT H , TONER MEHMET , TOMPKINS RONALD G , BENDAPUDI PAVAN
发明人： FRYDMAN GALIT H , TONER MEHMET , TOMPKINS RONALD G , BENDAPUDI PAVAN
IPC分类号： B01L20060101
摘要： Methods and devices for evaluating coagulation are described, including methods and devices for detecting an anticoagulant agent or a coagulation abnormality. In various embodiments, the methods and devices of the invention measure coagulation of a sample in response to a gradient of one or more coagulation factors. These responses can be evaluated to accurately profile coagulation impairments of the sample, including the presence of anticoagulant medication. In various embodiments, the invention provides point-of-care or bedside testing with a convenient, microfluidic device that can be used by minimally trained personnel.

2. 发明申请

WO2018232110A1 HIGH SUBZERO CRYOPRESERVATION 审中-公开
公开(公告)号：WO2018232110A1
公开(公告)日：2018-12-20
申请号：PCT/US2018/037525
申请日：2018-06-14
申请人： THE GENERAL HOSPITAL CORPORATION , TONER, Mehmet , UYGUN, Mustafa Korkut , TESSIER, Shannon N. , STOTT, Shannon L. , WENG, Lindong , DE VRIES, Reinier , PENDEXTER, Casie A , CRONIN, Stephanie EJ
发明人： TONER, Mehmet , UYGUN, Mustafa Korkut , TESSIER, Shannon N. , STOTT, Shannon L. , WENG, Lindong , DE VRIES, Reinier , PENDEXTER, Casie A , CRONIN, Stephanie EJ
IPC分类号： A01N1/00 , A01N1/02
摘要： This disclosure is related to methods of preserving biological samples, organs, and organisms. This disclosure is based, at least in part, on the discovery that in the presence of heterogenous extracellular ice, endothelial cells have improved attachment and viability after preservation, and particularly by uniformly nucleating ice across the microvasculature using ice nucleating agents, the chance of intracelluar ice formation can be significantly reduced.

3. 发明申请

WO2016023008A1 PLATELET-TARGETED MICROFLUIDIC ISOLATION OF CELLS 审中-公开
标题翻译：细胞靶向微流控分离
公开(公告)号：WO2016023008A1
公开(公告)日：2016-02-11
申请号：PCT/US2015/044375
申请日：2015-08-07
申请人： THE GENERAL HOSPITAL CORPORATION , TONER, Mehmet , STOTT, Shannon , REATEGUI, Eduardo
发明人： TONER, Mehmet , STOTT, Shannon , REATEGUI, Eduardo , JIANG, Xiaoncheng
IPC分类号： G01N1/18 , G01N1/40 , G01N33/48 , G01N33/49 , G01N33/543 , G01N33/569 , G01N33/574
CPC分类号： C12N5/0694 , C12N2531/00
摘要： Methods and systems for isolating platelet-associated nucleated target cells, e.g., such as circulating epithelial cells, circulating tumor cells (CTCs), circulating endothelial cells (CECs), circulating stem cells (CSCs), neutrophils, and macrophages, from sample fluids, e.g., biological fluids, such as blood, bone marrow, plural effusions, and ascites fluid, are described. The methods include obtaining a cell capture chamber including a plurality of binding moieties bound to one or more walls of the chamber, wherein the binding moieties specifically bind to platelets; flowing the sample fluid through the cell capture chamber under conditions that allow the binding moieties to bind to any platelet-associated nucleated target cells in the sample to form complexes; and separating and collecting platelet-associated nucleated target cells from the complexes.
摘要翻译：用于从样品流体分离血小板相关的成核靶细胞的方法和系统，例如循环上皮细胞，循环肿瘤细胞（CTC），循环内皮细胞（CEC），循环干细胞（CSCs），嗜中性粒细胞和巨噬细胞，例如生物流体，例如血液，骨髓，多发性积液和腹水。所述方法包括获得细胞捕获室，其包含与所述室的一个或多个壁结合的多个结合部分，其中所述结合部分特异性结合血小板; 在允许结合部分结合样品中与血小板相关的成核靶细胞形成复合物的条件下使样品流体流过细胞捕获室; 并从复合物中分离和收集血小板相关的成核靶细胞。

4. 发明申请

WO2015010019A1 SELECTIVE CAPTURE AND RELEASE OF RARE MAMMALIAN CELLS USING PHOTODEGRADABLE HYDROGELS IN A MICROFLUIDIC PLATFORM 审中-公开
标题翻译：选择性捕获和释放使用可溶性水凝胶在微流感平台中的稀有马马里亚细胞
公开(公告)号：WO2015010019A1
公开(公告)日：2015-01-22
申请号：PCT/US2014/047195
申请日：2014-07-18
申请人： THE GENERAL HOSPITAL CORPORATION , TIBBITT, Mark, W. , ANSETH, Kristi, S. , KLOXIN, April, M. , TONER, Mehmet , OAKEY, John , SHAH, Ajay
发明人： TIBBITT, Mark, W. , ANSETH, Kristi, S. , KLOXIN, April, M. , TONER, Mehmet , OAKEY, John , SHAH, Ajay
IPC分类号： A61K41/00 , C08G73/00 , A61K47/34 , C12M1/34
CPC分类号： G01N33/57492 , A61K41/0028 , A61K47/34 , B01L3/502761 , B01L2200/0647 , B01L2300/16 , C08F222/22 , C12M47/02 , C12M47/04 , G01N33/531 , G01N33/54366 , G01N33/56966
摘要： Disclosed herein are photodegradable hydrogels and associated kits for selectively capturing and releasing cells. The hydrogels result from cross linking in the presence of a photoinitiator (1) a macromer having a polymeric backbone structure, a photo labile moiety, and a first linking moiety, and (2) a cell-binding moiety having a second linking moiety. These two components are cross-linked by a polymerization reaction of the linking moieties to form a photodegradable hydrogel incorporating the cell-binding moiety within the hydrogel. Also disclosed are methods of making the hydrogels, and methods of using the hydrogels for selectively capturing and releasing cells and for detecting cells in a fluid. Such methods can be used to detect the presence and quantity of certain rare cell types in a biological fluid.
摘要翻译：本文公开了可降解水凝胶和用于选择性捕获和释放细胞的相关试剂盒。水凝胶由光引发剂（1）具有聚合物主链结构的大分子单体，光不稳定部分和第一连接部分的存在下交联而产生，和（2）具有第二连接部分的细胞结合部分。这两个组分通过连接部分的聚合反应交联以形成在水凝胶内掺入细胞结合部分的可光降解的水凝胶。还公开了制备水凝胶的方法，以及使用水凝胶选择性捕获和释放细胞并检测流体中的细胞的方法。这种方法可用于检测生物流体中某些稀有细胞类型的存在和数量。

5. 发明申请

WO2013028848A1 BOUNDARY LAYER SUCTION FOR CELL CAPTURE 审中-公开
标题翻译：细胞捕获的边界层吸收
公开(公告)号：WO2013028848A1
公开(公告)日：2013-02-28
申请号：PCT/US2012/052041
申请日：2012-08-23
申请人： THE GENERAL HOSPITAL CORPORATION , MITTAL, Sukant , TONER, Mehmet
发明人： MITTAL, Sukant , TONER, Mehmet
IPC分类号： C12Q1/00 , A61B6/02 , C12M3/00
CPC分类号： G01N1/34 , B01L3/502753 , G01N33/54366
摘要： Capturing particles includes introducing a fluid sample, which includes particles of a first type, into a first channel of a microfluidic device and flowing the fluid sample past a porous or partially porous membrane. The pores fluidly connect the first channel to a second channel, and the device further includes multiple binding moieties on a first side of the porous membrane adjacent to the first channel. The binding moieties are capable of binding to the first type of particles. Capturing particles also includes creating a pressure difference between the first and second channels to enable the fluid sample to flow from the first channel through the porous membrane into the second channel and to direct the particles toward the binding moieties, thereby capturing the first type of particles. In addition, by creating a modified capture surface that is impermeable near the walls of the channels, capture efficiencies and throughput can be increased.
摘要翻译：捕获颗粒包括将包括第一类型的颗粒的流体样品引入微流体装置的第一通道并使流体样品流过多孔或部分多孔的膜。孔隙将第一通道流体地连接到第二通道，并且该装置还包括在与第一通道相邻的多孔膜的第一侧上的多个结合部分。结合部分能够结合第一类型的颗粒。捕获颗粒还包括在第一和第二通道之间产生压差，使得流体样品能够从第一通道流过多孔膜进入第二通道并将颗粒引向结合部分，从而捕获第一类型的颗粒。此外，通过创建在通道壁附近不可透过的改进的捕获表面，可以提高捕获效率和产量。

6. 发明申请

WO2011119962A3 MICROFLUIDIC ENRICHMENT OF SELECTED CELL POPULATIONS 审中-公开
标题翻译：选择细胞群体的微流感增殖
公开(公告)号：WO2011119962A3
公开(公告)日：2012-01-12
申请号：PCT/US2011029999
申请日：2011-03-25
申请人： GEN HOSPITAL CORP , TONER MEHMET , FISHMAN ALAN , TOMPKINS RONALD G , KAPUR RAVI
发明人： TONER MEHMET , FISHMAN ALAN , TOMPKINS RONALD G , KAPUR RAVI
IPC分类号： G01N33/96 , G01N33/53 , G01N35/08
CPC分类号： B01L3/502753 , B01L2200/0652 , B01L2300/0816 , B01L2400/086 , G01N33/5094
摘要： Methods, devices, and systems for microfluidic enrichment of selected cell populations are described. Methods of labeling white blood cells include obtaining whole blood drawn from a patient, separating the white blood cells from the whole blood by flowing the whole blood through a microfluidic device that includes one or more arrays of obstacles configured to deflect the white blood cells in a direction away from a direction of remaining components of the whole blood, and collecting the separated white blood cells. A buffer containing a labeling agent with an affinity for white blood cells is mixed with the white blood cells either before or after separating the white blood cells from the whole blood resulting in labeled white blood cells.
摘要翻译：描述了所选细胞群体微流体富集的方法，装置和系统。标记白细胞的方法包括获得从患者抽取的全血，通过使全血流过包括一个或多个障碍物阵列的微流体装置将白细胞从全血中分离出来，所述微流体装置被配置为使白细胞偏转方向远离全血的剩余组分的方向，并收集分离的白细胞。在从全血分离白细胞之前或之后，将含有对白细胞亲和力的标记试剂的缓冲液与白细胞混合，得到标记的白细胞。

7. 发明申请

WO2011063416A3 MICROFLUIDIC DEVICES FOR THE CAPTURE OF BIOLOGICAL SAMPLE COMPONENTS 审中-公开
公开(公告)号：WO2011063416A3
公开(公告)日：2011-05-26
申请号：PCT/US2010/057894
申请日：2010-11-23
申请人： THE GENERAL HOSPITAL CORPORATION , BARBER, Thomas A. , SHAH, Ajay , WALSH, John , TONER, Mehmet , KAPUR, Ravi
发明人： BARBER, Thomas A. , SHAH, Ajay , WALSH, John , TONER, Mehmet , KAPUR, Ravi
IPC分类号： G01N35/08 , G01N33/53 , G01N33/574 , G01N33/48 , G01N1/28
摘要： Methods and systems for selectively capturing analytes, such as cells, e.g., circulating tumor cells (CTCs), from fluid samples are disclosed. The methods include contacting the sample with an analyte binding moiety that selectively binds to the analytes; optionally separating first components of the sample including a majority of the analytes bound to the binding moieties from second components of the sample using size-based separation, e.g., in a microfluidic channel; adding to the first components of the sample a plurality of binding agents under conditions that enable a plurality of the binding agents to be linked to the analyte binding moieties to form multivalent tagging agents bound to the analyte; passing the first components of the sample past a surface to which is attached a plurality of capture agents that selectively bind to the binding agents; and capturing the analytes by providing conditions that enable the multivalent tagging agents bound to the analytes to bind to one or more of the capture agents.

8. 发明申请

WO2010132795A3 SYSTEMS, DEVICES, AND METHODS FOR SPECIFIC CAPTURE AND RELEASE OF BIOLOGICAL SAMPLE COMPONENTS 审中-公开
标题翻译：用于特定捕获和释放生物样品成分的系统，设备和方法
公开(公告)号：WO2010132795A3
公开(公告)日：2011-03-24
申请号：PCT/US2010034943
申请日：2010-05-14
申请人： GEN HOSPITAL CORP , MASSACHUSETTS INST TECHNOLOGY , SHAH AJAY , KOTZ KENNETH T , TONER MEHMET
发明人： SHAH AJAY , KOTZ KENNETH T , TONER MEHMET
IPC分类号： C12Q1/24 , C12N11/04 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/54393 , C12N11/04 , G01N33/54353
摘要： Living cells can be selectively and reversibly bound to functionalized dissolvable material (e.g., cross-linked hydrogel compositions) and subsequently released from the composition as viable cells. In some examples, the cells are released by reducing the degree of cross-linking within a functionalized hydrogel composition and/or dissolving the functionalized hydrogel composition bound to the cells. The functionalized hydrogel compositions can be adhered to silicon- and silicon-oxide containing surfaces, such as glass and aminated silicon. The living cells can be isolated from biological samples, such as blood, by selectively binding certain cells from the sample to the functionalized hydrogel, removing unbound cells and later releasing viable bound cells from the functionalized hydrogel.
摘要翻译：活性细胞可以选择性地和可逆地结合到官能化的可溶解材料（例如，交联的水凝胶组合物）上，随后从组合物中释放为活细胞。在一些实例中，通过降低功能化水凝胶组合物内的交联度和/或溶解与细胞结合的官能化水凝胶组合物来释放细胞。官能化水凝胶组合物可以粘附到含硅和氧化硅的表面，例如玻璃和胺化硅。可以通过选择性地将样品中的某些细胞与功能化的水凝胶结合，去除未结合的细胞并随后从功能化的水凝胶中释放活的结合细胞，从而将活细胞与生物样品例如血液分离。

9. 发明申请

WO2010042943A1 TUNABLE HYDROGEL MICROPARTICLES 审中-公开
公开(公告)号：WO2010042943A1
公开(公告)日：2010-04-15
申请号：PCT/US2009/060515
申请日：2009-10-13
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE GENERAL HOSPITAL CORPORATION , HAGHGOOIE, Ramin , DOYLE, Patrick Seamus , TONER, Mehmet , PREGIBON, Daniel Colin
发明人： HAGHGOOIE, Ramin , DOYLE, Patrick Seamus , TONER, Mehmet , PREGIBON, Daniel Colin
IPC分类号： C12Q1/00
CPC分类号： C08J3/075 , A61K47/68 , A61K47/6921 , C08J2371/02 , C08L2205/14 , C09D7/20 , C09D7/70 , Y10T428/2982
摘要： Techniques are provided to produce and use non-spherical colloidal particles with independently tuned size, shape, flexibility, and chemical properties. A pre-polymer mixture for forming hydrogel particles includes a percentage of PEGDA selected to impart a target stiffness to the particles and includes, a percentage of acrylic acid selected to impart an independent target chemical function to the particles. The mixture also includes a percentage of photo-initiator to polymerize PEGDA upon exposure to a light source to impart an independently selected target size or shape or both to the particles.
摘要翻译：提供技术来生产和使用具有独立调整的尺寸，形状，柔性和化学性质的非球形胶体颗粒。用于形成水凝胶颗粒的预聚物混合物包括选择用于赋予颗粒目标硬度的百分比的PEGDA，并且包括一定百分比的丙烯酸，其被选择以赋予颗粒独立的目标化学功能。混合物还包括一定百分比的光引发剂，以在暴露于光源时聚合PEGDA以赋予颗粒独立选择的靶尺寸或形状或两者。

10. 发明申请

WO2007106598A2 DEVICES AND METHODS FOR DETECTING CELLS AND OTHER ANALYTES 审中-公开
标题翻译：用于检测细胞和其他分析物的装置和方法
公开(公告)号：WO2007106598A2
公开(公告)日：2007-09-20
申请号：PCT/US2007/006791
申请日：2007-03-15
申请人： THE GENERAL HOSPITAL CORPORATION , IRIMIA, Daniel , CHENG, Xuanhong , TONER, Mehmet , DEMIRCI, Utkan , RODRIGUEZ, William
发明人： IRIMIA, Daniel , CHENG, Xuanhong , TONER, Mehmet , DEMIRCI, Utkan , RODRIGUEZ, William
IPC分类号： G01N33/574
CPC分类号： G01N33/56972 , G01N33/56966 , Y10S436/824
摘要： The invention features methods, devices, and kits for the isolation of analytes (e.g., a cell). A sample containing a desired analyte is introduced into a microfluidic device containing moieties that bind the desired analyte. A shear stress is applied that is great enough to prevent binding of undesired analytes and low enough to allow binding of the analyte of interest. Once bound, the desired analytes can be analyzed (e.g., counted). The invention also features methods for determining a shear stress for isolating a desired analyte.
摘要翻译：本发明的特征在于用于分离分析物（例如，细胞）的方法，装置和试剂盒。将含有所需分析物的样品引入含有结合所需分析物的部分的微流体装置中。施加的剪切应力足够大以防止不需要的分析物的结合，并且足够低以允许感兴趣的分析物的结合。一旦结合，可以分析所需的分析物（例如，计数）。本发明还具有确定用于分离所需分析物的剪切应力的方法。

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