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11. 发明申请

WO2011109762A1 MICROFLUIDICS SORTER FOR CELL DETECTION AND ISOLATION 审中-公开
标题翻译：用于细胞检测和分离的微流控分离器
公开(公告)号：WO2011109762A1
公开(公告)日：2011-09-09
申请号：PCT/US2011/027276
申请日：2011-03-04
申请人： NATIONAL UNIVERSITY OF SINGAPORE , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , LIM, Chwee, Teck , HAN, Jongyoon , HOU, Han, Wei , BHAGAT, Ali, Asgar , VAN VLIET, Krystyn, J. , LEE, Wong, Cheng
发明人： LIM, Chwee, Teck , HAN, Jongyoon , HOU, Han, Wei , BHAGAT, Ali, Asgar , VAN VLIET, Krystyn, J. , LEE, Wong, Cheng
IPC分类号： C12M1/34 , C12M3/00
CPC分类号： C12Q1/04 , B01L3/50273 , B01L3/502761 , B01L2200/0636 , B01L2300/0864 , B01L2400/0457 , B01L2400/086 , C12Q1/025 , G01N2015/1415 , G01N2015/149
摘要： A method of detecting one or more diseased blood cells in a blood sample includes introducing a blood sample into at least one inlet of a microfluidic device comprising one or more linear channels wherein each channel has a length and a cross-section of a height and a width defining an aspect ratio adapted to isolate diseased blood cells along at least one portion of the cross-section of the channel based on reduced deformability of diseased blood cells as compared to non-diseased blood cells, wherein diseased blood cells flow along a first portion of the channel to a first outlet and non-diseased blood cells flow along a second portion of the channel to a second outlet. The one or more channels can be adapted to isolate cells along portions of the cross-section of the channel based on cell size. In some embodiments, the one or more channels can be spiral channels.
摘要翻译：一种检测血液样本中的一种或多种患病血细胞的方法包括将血液样品引入到包括一个或多个线性通道的微流体装置的至少一个入口中，其中每个通道具有高度的长度和横截面宽度限定适于根据与非病变血细胞相比减少的患病血细胞的可变形性，沿着所述通道的横截面的至少一部分分离患病血细胞，其中患病血液细胞沿第一部分流动通道的第一出口和非患病血液细胞沿着通道的第二部分流动到第二出口。一个或多个信道可以适于基于小区大小来隔离信道横截面的部分。在一些实施例中，一个或多个通道可以是螺旋通道。

12. 发明授权

EP2542661B1 DETECTION OF CIRCULATING TUMOR CELLS IN A MICROFLUIDIC SORTER 有权
公开(公告)号：EP2542661B1
公开(公告)日：2020-04-22
申请号：EP11751463.8
申请日：2011-03-04
申请人： National University of Singapore , Massachusetts Institute of Technology
发明人： LIM, Chwee, Teck , HAN, Jongyoon , HOU, Han, Wei , BHAGAT, Ali, Asgar , VAN VLIET, Krystyn, J. , LEE, Wong, Cheng
IPC分类号： C12M1/34 , C12M3/00 , B01L3/00

13. 发明公开

EP2897730A1 MICRO-FLUIDIC DEVICE AND USES THEREOF 审中-公开
标题翻译：微流体装置及其应用
公开(公告)号：EP2897730A1
公开(公告)日：2015-07-29
申请号：EP13838795.6
申请日：2013-09-20
申请人： Massachusetts Institute of Technology , National University of Singapore
发明人： HAN, Jongyoon , CHEN, Chao Yu Peter , ONG, Chong Jin , GUAN, Guofeng , BHAGAT, Ali Asgar , WU, Lidan
IPC分类号： B01L3/00
CPC分类号： B01L3/502753 , B01D21/00 , B01D21/0087 , B01D21/265 , B01F5/0606 , B01L3/50273 , B01L2200/0652 , B01L2300/0816 , B01L2300/0864 , B01L2300/0883 , B01L2400/0463 , B01L2400/0478 , B01L2400/0487 , B01L2400/084 , B03B5/62 , C12M47/04
摘要： A micro-fluidic device includes at least one inlet and a curvilinear microchannel having a trapezoidal cross section defined by a radially inner side, a radially outer side, a bottom side, and a top side, the cross section having a) the radially inner side and the radially outer side unequal in height, or b) the radially inner side equal in height to the radially outer side, and wherein the top side has at least two continuous straight sections, each unequal in width to the bottom side.

14. 发明申请

WO2021141539A1 A METHOD OF PROFILING A SAMPLE COMPRISING A PLURALITY OF CELLS AND A SYSTEM FOR PERFORMING THE SAME 审中-公开
公开(公告)号：WO2021141539A1
公开(公告)日：2021-07-15
申请号：PCT/SG2021/050011
申请日：2021-01-08
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , NATIONAL UNIVERSITY HOSPITAL (SINGAPORE) PTE. LTD.
发明人： HAN, Jongyoon , KWEK, Kerwin Zeming , KUAN, Win Sen
IPC分类号： G01N33/483 , B01L3/00
摘要： The invention is to provide a method of profiling a sample comprising a plurality of cells, the method comprising: flowing cells from the sample through a first array of pillars to obtain one or more distribution profiles of cells sorted by the first array; flowing cells from the sample through a second array of pillars that is different from the first array of pillars to obtain on one or more distribution profiles of cells sorted by the second array; and deriving a biophysical signature of the sample based on at least the one or more distribution profiles of the cells sorted by the first array and/or the one or more distribution profiles of the cells sorted by the second array. The method further comprises determining a health status of a subject based on the biophysical signature of the sample. The invention is also to provide a sample profiling system. In various embodiments, the distribution profile of cells in the output regions is indicative of one or more biophysical properties of the cells, which may include the size and deformability of the cells. The pillars in the first array and the second array may have a shape selected from the group consisting of a substantially L shape and a substantially inverse L shape, mirror reflections thereof or combinations thereof.

15. 发明申请

WO2016077055A1 SYSTEM AND METHOD FOR MULTIPLEXED AFFINITY PURIFICATION OF PROTEINS AND CELLS 审中-公开
标题翻译：蛋白质和细胞的多重亲和纯化的系统和方法
公开(公告)号：WO2016077055A1
公开(公告)日：2016-05-19
申请号：PCT/US2015/057146
申请日：2015-10-23
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE MASSACHUSETTS GENERAL HOSPITAL
发明人： SARKAR, Aniruddh , HOU, Han, Wei , HAN, Jongyoon , ALTER, Galit
IPC分类号： C12Q1/24
CPC分类号： G01N1/405 , B01L3/502707 , B01L3/502761 , B01L3/502776 , B01L2200/0652 , B01L2300/0816 , B01L2300/0864 , B01L2300/088 , B01L2400/0409 , B01L2400/0487 , C12Q1/24
摘要： In accordance with an embodiment of the invention, there is provided a method for: a) high-throughput, multiplexed, affinity-based separation of proteins - especially low abundance proteins - from complex biological mixtures such as serum; and b) high- throughput, multiplexed, affinity-based separation of cells - especially rare cells - from complex biological mixtures such as blood or blood fractions. The separation of proteins or cells is achieved based on differential binding to affinity-capture beads of different sizes and then sorting the protein-bound or cell-bound beads using the concept of centrifugal-induced Dean migration in a spiral microfluidic device. This method enables continuous-flow, high throughput affinity-separation of milligram-scale protein samples or millions of cells in minutes after binding. This is particularly applicable to the isolation of antigen-specific antibodies from polyclonal sera and antigen-specific immune cells or circulating tumor cells from blood, both of which are otherwise highly labor-intensive and expensive to perform.
摘要翻译：根据本发明的一个实施方案，提供了一种用于：a）从复杂的生物混合物如血清中高通量，多重的，基于亲和力的蛋白质特别是低丰度蛋白质的分离; 和b）来自复杂生物混合物如血液或血液部分的高通量，多重的，基于亲和力的细胞分离 - 特别是稀有细胞。蛋白质或细胞的分离基于与不同大小的亲和力捕获珠粒的差异结合，然后使用在螺旋微流体装置中离心诱导的Dean迁移的概念来分选蛋白质结合或细胞结合的珠粒来实现。该方法能够在结合后的几分钟内实现毫克级蛋白质样品或数百万个细胞的连续流量，高通量亲和力分离。这特别适用于从多克隆血清和抗原特异性免疫细胞或来自血液的循环肿瘤细胞分离抗原特异性抗体，两者都是高度劳动密集型和执行昂贵的。

16. 发明申请

WO2016044537A1 MICROFLUIDIC SYSTEM AND METHOD FOR PERFUSION BIOREACTOR CELL RETENTION 审中-公开
标题翻译：微流体系统和灌注生物反应器细胞保留的方法
公开(公告)号：WO2016044537A1
公开(公告)日：2016-03-24
申请号：PCT/US2015/050604
申请日：2015-09-17
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , NATIONAL UNIVERSITY OF SINGAPORE
发明人： EBRAHIMI WARKIANI, Majid , HAN, Jongyoon , TAY, Kah Ping, Andy , GUAN, Guofeng
IPC分类号： C12M1/00 , C12M3/00 , C12M3/04 , C12N5/02
CPC分类号： C12M29/10 , B01L3/502753 , B01L3/502761 , B01L2200/0647 , B01L2300/0681 , B01L2300/0848 , B01L2300/0861 , C12M23/02 , C12M23/16 , C12M29/04 , C12M47/02 , C12M47/04
摘要： A microfluidic system for cell retention for a perfusion bioreactor is provided. The system comprises at least one inlet configured to receive a bioreaction mixture to be processed. At least one curvilinear microchannel is in fluid flow connection with the at least one inlet, the at least one curvilinear microchannel being adapted to isolate cells in the bioreaction mixture, based on cell size, along at least one portion of a cross-section of the at least one curvilinear microchannel. At least two outlets are in fluid flow connection with the at least one curvilinear microchannel. At least one outlet of the at least two outlets is configured to flow the isolated cells to be recycled to the perfusion bioreactor.
摘要翻译：提供了用于灌注生物反应器的用于细胞保留的微流体系统。该系统包括至少一个入口，该入口构造成接收待处理的生物反应混合物。至少一个曲线微通道与所述至少一个入口流体流动连接，所述至少一个曲线微通道适于基于细胞尺寸沿着所述生物反应混合物的横截面的至少一部分隔离所述生物反应混合物中的细胞至少一个曲线微通道。至少两个出口与至少一个曲线微通道流体连通。所述至少两个出口的至少一个出口构造成使分离的细胞流动以再循环到灌注生物反应器。

17. 发明申请

WO2015156876A2 INTEGRATED ELECTRICAL PROFILING SYSTEM FOR MEASURING LEUKOCYTES ACTIVATION FROM WHOLE BLOOD 审中-公开
标题翻译：用于测量全血中白细胞激活的集成式电气系统
公开(公告)号：WO2015156876A2
公开(公告)日：2015-10-15
申请号：PCT/US2015/011801
申请日：2015-01-16
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： VOLDMAN, Joel , SU, Hao-Wei , PRIETO, Javier, Lopez , HAN, Jongyoon , WU, Lidan
IPC分类号： H01J49/04
CPC分类号： A61B5/412 , A61B5/14546 , A61B5/1468 , A61B5/1486 , B01L3/502715 , B01L3/502746 , B01L3/502753 , B01L3/502761 , B01L2200/0605 , B01L2200/0647 , B01L2200/0652 , B01L2300/0645 , B01L2300/0816 , B01L2300/088 , G01N15/1031 , G01N15/1404 , G01N15/1459 , G01N15/1463 , G01N15/1484 , G01N33/48735 , G01N2015/0073 , G01N2015/008 , G01N2015/1006 , G01N2015/1486 , G01N2015/149 , G01N2800/7095
摘要： A system includes a microfluidic device configured to isolate one or more particles from a mixture, a flow rate matching device configured to match flow rate of the microfluidic device with flow rate of an electrical measurement device configured to measure an electrical property of the isolated particles, and an electrical measurement device configured to measure an electrical property of the isolated particles.
摘要翻译：系统包括配置成从混合物中分离一个或多个颗粒的微流体装置，配置成匹配微流体装置的流速与配置成测量微流体装置的流量的电测量装置的流速的流速匹配装置分离的颗粒的电性质，以及配置为测量分离的颗粒的电性质的电测量装置。

18. 发明申请

WO2014209669A1 WATER DESALINATION/PURIFICATION AND BIO-AGENT PRECONCENTRATION 审中-公开
标题翻译：水脱盐/净化和生物代谢预处理
公开(公告)号：WO2014209669A1
公开(公告)日：2014-12-31
申请号：PCT/US2014/042655
申请日：2014-06-17
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： KWAK, Rhokyun , HAN, Jongyoon
IPC分类号： B01D61/44 , B01D61/46 , B01D61/54 , C02F1/42 , C02F1/46 , C02F1/469
CPC分类号： C02F1/469 , B01D61/42 , C02F2103/08 , C02F2201/46115
摘要： Between two juxtaposed similar ion exchange membranes (AEMs or CEMs), an ion depletion zone (dde) and ion enrichment zone (den) are generated under an electric field. As cations are selectively transferred through the CEMs, for example, anions are relocated in order to achieve electro-neutrality, resulting in the concentration drop (increase) in ion depletion (enrichment) zone. The concentration drop (i.e. salt removal) is low and spatially gradual at relatively low voltage or current (i.e. Ohmic regime). However, at higher voltage or current (i.e. overlimiting regime), strong electroconvective vortex accelerates cation transport through CEMs, allowing us to "relocate" most salt ions. The flat depletion zone occurs with significantly low ion concentration, and corresponding strong electric field in the zone, and any charged agents cannot penetrate this flat zone. As a result, we can separate and collect the desalted/purified flow from brine flow by bifurcating the channel at the end of the CEMs.
摘要翻译：在两个并置的类似离子交换膜（AEM或CEM）之间，在电场下产生离子耗尽区（dde）和离子富集区（den）。当阳离子选择性地通过CEM转移时，例如，阴离子被重新定位以实现电中性，导致离子耗尽（富集）区域的浓度下降（增加）。在相对低的电压或电流（即欧姆方式）下，浓度下降（即去除盐）是低的并且在空间上逐渐变化。然而，在较高的电压或电流（即覆盖状态）下，强对流涡流加速通过CEMs的阳离子传输，从而允许我们“重新定位”大多数盐离子。平坦耗尽区出现明显低的离子浓度，并且区域中相应的强电场，任何带电剂不能穿透该平坦区域。因此，我们可以通过在CEM结束时分流通道来分离和收集来自盐水流的脱盐/净化流。

19. 发明申请

WO2013181615A1 SEPARATION OF BINDING MOLECULES 审中-公开
标题翻译：结合分子的分离
公开(公告)号：WO2013181615A1
公开(公告)日：2013-12-05
申请号：PCT/US2013/043732
申请日：2013-05-31
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： BIRCH, Christina, Marie , HOU, Han, Wei , HAN, Jongyoon , NILES, Jacquin, C.
IPC分类号： C12M3/06
CPC分类号： C12N15/1048 , B01L3/502746 , B01L3/502753 , B01L2200/0636 , B01L2300/0816 , B01L2300/0864 , B01L2300/088 , C12N15/1003
摘要： A method of separating one or more binding molecules that are specifically bound to one or more binding targets from a mixture of bound and unbound molecules includes introducing the mixture into at least one inlet of a microfluidic device at a sample flow rate. The microfluidic device includes at least one curved channel, wherein each curved channel has a length, a radius, and a cross-section of a height and a width defining an aspect ratio adapted to isolate the one or more molecules bound to the binding target along portions of the cross-section of the channel based on size. Bound molecules flow along a radially innermost portion of the channel to a first outlet, and unbound molecules flow along one or more other portions of the channel to at least one other outlet, thereby separating the one or more binding molecules that are specifically bound to the one or more binding targets from the mixture of bound and unbound molecules.
摘要翻译：分离从结合和未结合分子的混合物特异性结合一个或多个结合靶的一个或多个结合分子的方法包括以样品流速将混合物引入至少一个微流体装置的入口。微流体装置包括至少一个弯曲通道，其中每个弯曲通道具有长度，半径和横截面，其高度和宽度限定了适于隔离结合到结合靶的一个或多个分子的纵横比基于尺寸的通道的横截面的部分。结合的分子沿着通道的径向最内部分流动到第一出口，未结合的分子沿着通道的一个或多个其它部分流动到至少一个其它出口，从而将一个或多个特异性结合到来自结合和未结合分子的混合物的一种或多种结合靶。

20. 发明申请

WO2011112803A1 METHOD FOR BUILDING MASSIVELY-PARALLEL PRECONCENTRATION DEVICE FOR MULTIPLEXED, HIGH-THROUGHPUT APPLICATIONS 审中-公开
标题翻译：用于建立用于多路复用，高通量应用的大规模并行预处理器件的方法
公开(公告)号：WO2011112803A1
公开(公告)日：2011-09-15
申请号：PCT/US2011/027883
申请日：2011-03-10
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , KO, Sung, Hee , KIM, Sung, Jae , HAN, Jongyoon
发明人： KO, Sung, Hee , KIM, Sung, Jae , HAN, Jongyoon
IPC分类号： G01N27/447 , B01L3/00
CPC分类号： G01N27/44791 , B01L3/502753 , B01L3/502761 , B01L3/502784 , B01L2300/0645 , B01L2300/0681 , B01L2300/0803 , B01L2300/0829 , B01L2300/0864 , B01L2300/0867 , B01L2300/0883 , B01L2300/0896 , B01L2300/161 , B01L2400/0415 , B01L2400/0487 , Y10T137/2224
摘要： A multiplexed concentration interface that can connect with a plurality of microchannels, conventional 96 well plates or other microarrays is disclosed. The interface can be used in biosensing platforms and can be designed to detect single or multiple targets such as DNA/RNA, proteins and carbohydrates/oligosaccharides. The multiplexed concentration device will provide a set of volume-matched sample preparation and detection strategies directly applicable by ordinary researchers. Furthermore, a multiplexed microfluidic concentrator without buffer channels is disclosed.
摘要翻译：公开了可与多个微通道连接的多路复用浓度界面，常规96孔板或其它微阵列。界面可用于生物传感平台，可设计用于检测单个或多个靶标，如DNA / RNA，蛋白质和碳水化合物/寡糖。复合浓缩装置将提供一套直接适用于普通研究者的体积匹配样品制备和检测策略。此外，公开了一种没有缓冲通道的复用微流控集中器。

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