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公开(公告)号:US20190177677A1
公开(公告)日:2019-06-13
申请号:US16324535
申请日:2017-08-19
申请人: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BRIGHAM AND WOMEN'S HOSPITAL
摘要: A microfluidic device for processing cells for the intracellular delivery of molecules or other cargo includes a plurality of microchannels disposed in a substrate or chip and fluidically coupled to an inlet configured to receive a solution containing the cells and the molecules or other cargo to be delivered intracellularly to the cells. Each of the plurality of microchannels has one or more constriction regions therein, wherein the constriction regions comprise an omniphobic, superhydrophilic, or superhydrophobic surface. In some embodiments, multiple microfluidic devices operating in parallel are used to process large numbers of cells. The device and method has particularly applicability to delivering gene-editing molecules intracellularly to cells.
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2.
公开(公告)号:US20210346889A1
公开(公告)日:2021-11-11
申请号:US17269985
申请日:2019-08-21
摘要: A microfluidic device is disclosed that is used to process cells for the intracellular delivery of molecules or other cargo. The device includes one or more microchannels disposed in a substrate or chip and is fluidically coupled to an inlet configured to receive a solution containing the cells and the molecules or other cargo to be delivered intracellularly to the cells. Each of the one or more microchannels has one or more constriction regions formed therein, wherein the inner surface(s) of the microchannels and the one or more constriction regions have a lipid bilayer disposed thereon. In some embodiments, multiple microfluidic devices operating in parallel are used to process large numbers of cells. The device and method have particularly applicability to delivering gene-editing molecules intracellularly to cells.
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3.
公开(公告)号:US20200347409A1
公开(公告)日:2020-11-05
申请号:US16962509
申请日:2019-01-29
发明人: Paul S. Weiss , Hsian-Rong Tseng , Xiaobin Xu , Natcha Wattanatorn , Qing Yang , Steven J. Jonas
IPC分类号: C12N15/87 , G01N33/543
摘要: A method of transporting biomolecular cargo intracellularly into cells includes the operations of providing magnetic nanostructures (e.g., nanospears, nanostars, nanorods, and other nanometer-sized structures) carrying the biomolecular cargo thereon and applying an external magnetic field to move the magnetic nanostructures into physical contact with at least some of the cells (or the cells into the magnetic nanostructures). The magnetic nanostructures move into physical contact with a single cell, a subset of cells, or all cells. The external magnetic field may be applied by a moving permanent magnet although an electromagnetic may also be used. The biomolecular cargo may include a molecule, a plurality of molecules, or higher order biological constructs. For example, the biological construct may include DNA plasmids, small interfering RNA, proteins, or targeted nuclease gene-editing cargo such as zinc-finger nucleases, transcription activator-like effector nucleases, Cas9 protein, Cas9 mRNA, and associated guide RNA sequences.
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公开(公告)号:US20200098577A1
公开(公告)日:2020-03-26
申请号:US16583101
申请日:2019-09-25
发明人: Xiaobin Xu , Qing Yang , Natcha Wattanatorn , Chuanzhen Zhao , Logan A. Stewart , Steven J. Jonas , Paul S. Weiss
IPC分类号: H01L21/308 , H01L21/3065
摘要: A robust and general fabrication/manufacturing method is described herein for the fabrication of periodic three-dimensional (3D) hierarchical nanostructures in a highly scalable and tunable manner. This nanofabrication technique exploits the selected and repeated etching of spherical particles that serve as resist material and that can be shaped in parallel for each processing step. The method enables the fabrication of periodic, vertically aligned nanotubes at the wafer scale with nanometer-scale control in three dimensions including outer/inner diameters, heights/hole-depths, and pitches. The method was utilized to construct 3D periodic hierarchical hybrid silicon and hybrid nanostructures such as multi-level solid/hollow nanotowers where the height and diameter of each level of each structure can be configured precisely as well as 3D concentric plasmonic supported metal nanodisk/nanorings with tunable optical properties on a variety of substrates.
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公开(公告)号:US20210308671A1
公开(公告)日:2021-10-07
申请号:US17268955
申请日:2019-08-16
发明人: Leonardo Scarabelli , Gail Vinnacombe , Liv Heidenreich , Naihao Chiang , Yao Gong , Paul S. Weiss , Steven J. Jonas
IPC分类号: B01L3/00 , G01N33/543 , G01N21/65 , G01N21/64 , G01N33/574 , C01G7/00 , G02B21/00 , G02B21/16
摘要: Systems and methods are disclosed that utilize metal nanostructures that are synthesized in situ along the internal surfaces of a microfluidic device. The nanostructures are formed by initial deposition of metallic seeds followed by flowing growth and reducing agent solutions into the capillaries/microfluidic channels to grow the nanostars. The nanostructures may optionally be functionalized with a capture ligand. The capture ligand may be used to selectively bind to certain cells (e.g., circulating tumor cells). The cells may be removed by a beam of light (e.g., laser beam) that induces localized heating at the surface location(s) containing the nanostructures. The plasmonic nature of the nanostructures can be used to heat the nanostructure(s) locally for the selective removal of one or certain cells. The nanostructures may be used to acquire Raman spectra of molecules or other small objects that are bound thereto for identification and quantification.
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公开(公告)号:US11037794B2
公开(公告)日:2021-06-15
申请号:US16583101
申请日:2019-09-25
发明人: Xiaobin Xu , Qing Yang , Natcha Wattanatorn , Chuanzhen Zhao , Logan A. Stewart , Steven J. Jonas , Paul S. Weiss
IPC分类号: H01L21/308 , H01L21/3065 , B81C1/00 , B82Y40/00
摘要: A robust and general fabrication/manufacturing method is described herein for the fabrication of periodic three-dimensional (3D) hierarchical nanostructures in a highly scalable and tunable manner. This nanofabrication technique exploits the selected and repeated etching of spherical particles that serve as resist material and that can be shaped in parallel for each processing step. The method enables the fabrication of periodic, vertically aligned nanotubes at the wafer scale with nanometer-scale control in three dimensions including outer/inner diameters, heights/hole-depths, and pitches. The method was utilized to construct 3D periodic hierarchical hybrid silicon and hybrid nanostructures such as multi-level solid/hollow nanotowers where the height and diameter of each level of each structure can be configured precisely as well as 3D concentric plasmonic supported metal nanodisk/nanorings with tunable optical properties on a variety of substrates.
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7.
公开(公告)号:US20190381507A1
公开(公告)日:2019-12-19
申请号:US16485424
申请日:2018-02-13
发明人: Paul S. Weiss , Steven J. Jonas , Dan Wilkinson , Adam Z. Stieg , Jason Belling
摘要: A microfluidic-based device and system is disclosed for the high-throughput intracellular delivery of biomolecular cargo to cells (eukaryotic or prokaryotic) or enveloped viruses. Cargo integration occurs due to transient membrane permeabilization by exposure to bulk acoustic waves (BAWs) transduced from surface acoustic waves (SAWs) generated by a rapidly oscillating piezoelectric substrate. In this approach, temporary pores are established across the cellular membrane as cells are partially deformed and squeezed or subject to shearing forces as they travel through the vibrational modes created within the microfludic channel(s) of the device.
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