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1. 发明公开

US20240310356A1 Nanopore Sensor Having A Fluidic Passage And Transistor Sensing of Local Electrical Potential At The Fluidic Passage 审中-公开
公开(公告)号：US20240310356A1
公开(公告)日：2024-09-19
申请号：US18672910
申请日：2024-05-23
申请人： President and Fellows of Harvard College
发明人： Ping Xie
IPC分类号： G01N33/487 , B01L3/00 , C12Q1/6869 , G01N27/414 , G01N27/416 , G01N27/447
CPC分类号： G01N33/48721 , B01L3/502715 , B01L3/50273 , C12Q1/6869 , G01N27/4145 , G01N27/4146 , G01N27/4163 , G01N27/44726 , G01N27/4473 , G01N27/44791 , B01L2300/0645 , B01L2300/0867 , B01L2300/0896 , B01L2300/12 , B01L2400/0421
摘要： A nanopore sensor includes a nanopore disposed in a support structure with a nanopore diameter and having a nanopore fluidic resistance, RPore. A fluidic passage, is disposed in fluidic connection between a first fluidic reservoir of ionic concentration solution and the nanopore, and includes a passage length having a fluidic passage width, along at least a portion of a fluidic passage length, that is greater than the diameter of the nanopore and less than the fluidic passage length. The fluidic passage has a fluidic passage fluidic resistance, RFP, of at least about 10% of the nanopore fluidic resistance, RPore, and no more than about 10 times the nanopore fluidic resistance, RPore. The nanopore is disposed in fluidic connection between the fluidic passage and a second fluidic reservoir of ionic concentration solution. At least one transistor is operatively connected electrically to sense electrical potential local to the fluidic passage.

2. 发明授权

US10436747B2 Nanopore sensing by local electrical potential measurement 有权
公开(公告)号：US10436747B2
公开(公告)日：2019-10-08
申请号：US15616225
申请日：2017-06-07
申请人： President and Fellows of Harvard College
发明人： Charles M. Lieber , Ping Xie
IPC分类号： G01N27/327 , G01N27/447 , B82Y30/00 , C12Q1/6869 , G01N33/487 , B82Y15/00
摘要： There is provided a method for sensing the translocation of a molecule through a nanopore. In the method, there is directed to an inlet of a nanopore a molecule that is disposed in a first ionic solution of a first ionic concentration. The molecule is caused to translocate through the nanopore from the inlet of the nanopore to an outlet of the nanopore and into a second ionic solution of a second ionic concentration that is different than the first ionic concentration. An electrical potential, local to that ionic solution, of the first and second ionic solutions, which has a lower ionic concentration, is measured while the molecule is caused to translocate through the nanopore.

3. 发明申请

US20160282303A1 BENT NANOWIRES AND RELATED PROBING OF SPECIES 审中-公开
标题翻译： BENT NANOWIRES和相关物种的探索
公开(公告)号：US20160282303A1
公开(公告)日：2016-09-29
申请号：US15047267
申请日：2016-02-18
申请人： President and Fellows of Harvard College
发明人： Charles M. Lieber , Bozhi Tian , Ping Xie , Thomas J. Kempa , Itzhaq Cohen-Karni , Quan Qing , Xiaojie Duan
IPC分类号： G01N27/414 , H01L51/00 , H01L29/06 , H01L21/02
CPC分类号： G01N27/4146 , B82Y10/00 , B82Y15/00 , G01N33/48728 , H01L21/02603 , H01L29/045 , H01L29/0665 , H01L29/0669 , H01L51/0048
摘要： The present invention generally relates to nanoscale devices and methods, including bent nanowires and other bent nanoscale objects, and in particular, the ability to probe cells with nanoscale objects. In some aspects, nanoscale objects, including nanowires, are provided that facilitate cell probing, e.g. nanowires that are surface modified such that cells can fuse with the nanowires. Devices including nanoscale objects are provided that allow small or large scale (e.g., multiplexed) probing of cells, and related methods of making such nanoscale objects and devices, and methods of investigating cells, are provided by certain embodiments of the invention. In a related set of embodiments, the present invention is generally related to bent nanowires and other bent nanoscale objects. For instance, in one aspect, the present invention is generally related to a semiconductor nanoscale wire having at least one kink. The semiconductor nanoscale wire may be formed out of any suitable semiconductor, e.g., Si, CdS, Ge, or the like. In some embodiments, a kink in the semiconductor nanoscale wire may be at an angle of about 120° or a multiple thereof. Yet other aspects of the invention are generally directed to methods of using such nanoscale wires, kits involving such nanoscale wires, devices involving such nanoscale wires, or the like.
摘要翻译：本发明一般涉及纳米级器件和方法，包括弯曲的纳米线和其他弯曲的纳米尺度物体，特别是涉及用纳米尺度物体探测细胞的能力。在一些方面，提供纳米级物体，包括纳米线，其促进细胞探测，例如，表面改性的纳米线使得电池可以与纳米线熔合。提供包括纳米尺度物体的装置，其通过本发明的某些实施例提供允许细胞的小规模（例如，多路复用）探测，以及制造这种纳米级物体和装置的相关方法以及调查细胞的方法。在相关的一组实施例中，本发明通常涉及弯曲的纳米线和其它弯曲的纳米尺度物体。例如，一方面，本发明通常涉及具有至少一个扭结的半导体纳米级线。半导体纳米线可以由任何合适的半导体形成，例如Si，CdS，Ge等。在一些实施例中，半导体纳米尺度线中的扭结可以是大约120°的角度或其倍数。本发明的其它方面通常涉及使用这种纳米级线材的方法，涉及这种纳米线材的套件，涉及这种纳米级线材的装置等。

4. 发明授权

US11994507B2 Nanopore sensor calibration and operation with a fluidic passage 有权
公开(公告)号：US11994507B2
公开(公告)日：2024-05-28
申请号：US17007290
申请日：2020-08-31
申请人： President and Fellows of Harvard College
发明人： Ping Xie
IPC分类号： G01N27/327 , B01L3/00 , C12Q1/6869 , G01N27/414 , G01N27/416 , G01N27/447 , G01N33/487
CPC分类号： G01N33/48721 , B01L3/502715 , B01L3/50273 , C12Q1/6869 , G01N27/4145 , G01N27/4146 , G01N27/4163 , G01N27/44726 , G01N27/4473 , G01N27/44791 , B01L2300/0645 , B01L2300/0867 , B01L2300/0896 , B01L2300/12 , B01L2400/0421
摘要： A first fluidic solution having a first ionic concentration is provided in a first fluidic reservoir in direct fluidic connection with a nanopore. A second fluidic solution, having a second ionic concentration, is provided in a second fluidic reservoir disposed in fluidic connection with the nanopore through a fluidic passage having at least one fluidic section in which the section length is greater than the section width. The electrical potential local to the fluidic passage is measured, and the resistance of both the fluidic passage the nanopore are determined based on the fluidic passage electrical potential. The fluidic passage resistance is compared with the nanopore resistance and at least one of the first and second ionic concentrations is adjusted based on the comparison. The measuring, determining, comparing, and adjusting steps are conducted until the fluidic passage resistance is between about 0.1 times and about 10 times the nanopore resistance.

5. 发明授权

US11959904B2 Nanopore sensing with a fluidic passage 有权
公开(公告)号：US11959904B2
公开(公告)日：2024-04-16
申请号：US17007114
申请日：2020-08-31
申请人： President and Fellows of Harvard College
发明人： Ping Xie
IPC分类号： G01N27/327 , B01L3/00 , C12Q1/6869 , G01N27/414 , G01N27/416 , G01N27/447 , G01N33/487
CPC分类号： G01N33/48721 , B01L3/502715 , B01L3/50273 , C12Q1/6869 , G01N27/4145 , G01N27/4146 , G01N27/4163 , G01N27/44726 , G01N27/4473 , G01N27/44791 , B01L2300/0645 , B01L2300/0867 , B01L2300/0896 , B01L2300/12 , B01L2400/0421
摘要： In a method for sensing translocation of a molecule through a nanopore, a molecule in a first fluidic solution in a first fluidic reservoir that is in direct fluidic connection with the nanopore is directed to a nanopore inlet and translocated through the nanopore to a nanopore outlet and through a fluidic passage that is in direct fluidic connection with the nanopore outlet, to a second fluidic solution in a second fluidic reservoir disposed in direct fluidic connection with the fluidic passage. The fluidic passage has at least one fluidic section in which a length of the fluidic section is greater than a width of the fluidic section. Translocation of the molecule through the nanopore is sensed by measuring the electrical potential local to the fluidic passage during the translocation of the molecule.

6. 发明申请

US20220260522A1 Method For Nanopore Sensing With Local Electrical Potential Measurement 有权
公开(公告)号：US20220260522A1
公开(公告)日：2022-08-18
申请号：US17732990
申请日：2022-04-29
申请人： President and Fellows of Harvard College
发明人： Ping Xie , Charles M. Lieber
IPC分类号： G01N27/447 , B82Y30/00 , C12Q1/6869 , G01N33/487
摘要： To sense the translocation of a molecule through a nanopore, there is directed to an inlet of the nanopore, having a nanopore fluidic resistance, RP, a molecule disposed in a cis fluidic ionic solution having a cis fluidic access resistance, RC. The molecule is caused to translocate through the nanopore from the inlet of the nanopore to an outlet of the nanopore and to a trans fluidic ionic solution having a trans fluidic access resistance, RT. The trans fluidic access resistance, RT, is of the same order of magnitude as the nanopore fluidic resistance, RP, and both RT and RP are at least an order of magnitude greater than the cis fluidic access resistance, RC. An indication of local electrical potential is produced at a site within the nanopore sensor that is on the trans fluidic ionic solution-side of the nanopore, to sense translocation of the molecule through the nanopore.

7. 发明申请

US20150137794A1 NANOSCALE SENSORS FOR INTRACELLULAR AND OTHER APPLICATIONS 有权
标题翻译：纳米级传感器用于细胞和其他应用
公开(公告)号：US20150137794A1
公开(公告)日：2015-05-21
申请号：US14396542
申请日：2013-05-02
申请人： President and Fellows of Harvard College
发明人： Charles M. Lieber , Ruixuan Gao , Steffen Strehle , Xiaojie Duan , Bozhi Tian , Itzhaq Cohen-Karni , Ping Xie , Quan Qing
IPC分类号： G01R1/30 , G01R3/00 , H01L29/772 , H01L21/283 , H01L29/423 , B82Y99/00 , B82Y40/00 , G01R1/067 , H01L29/41
CPC分类号： G01R1/30 , B82Y40/00 , B82Y99/00 , G01N27/4146 , G01N33/48728 , G01R1/06705 , G01R1/06755 , G01R3/00 , H01L21/283 , H01L29/413 , H01L29/42316 , H01L29/772
摘要： The present invention generally relates to nanoscale wires for use in sensors and other applications. In various embodiments, a probe comprising a nanotube (or other nanoscale wire) is provided that can be directly inserted into a cell to determine a property of the cell, e.g., an electrical property. In some cases, only the tip of the nanoscale wire is inserted into the cell; this tip may be very small relative to the cell, allowing for very precise study. In some aspects, the tip of the probe is held by a holding member positioned on a substrate, e.g., at an angle, which makes it easier for the probe to be inserted into the cell. The nanoscale wire may also be connected to electrodes and/or form part of a transistor, such that a property of the nanoscale wire, and thus of the cell, may be determined. Such probes may also be useful for studying other samples besides cells. Other aspects of the invention are generally directed to methods of making or using such probes, kits involving such probes, devices involving such probes, or the like.
摘要翻译：本发明一般涉及用于传感器和其它应用的纳米尺度线。在各种实施例中，提供了包括纳米管（或其他纳米线）的探针，其可以直接插入细胞中以确定细胞的性质，例如电性质。在某些情况下，只有纳米线的尖端插入电池中; 该尖端相对于细胞可能非常小，允许非常精确的研究。在一些方面，探针的尖端由例如以一定角度定位在基底上的保持构件保持，这使得探针更容易插入细胞中。纳米尺寸的导线也可以连接到电极和/或形成晶体管的一部分，使得可以确定纳米线的性质，从而确定电池的性质。这种探针也可用于研究细胞外的其它样品。本发明的其他方面通常涉及制造或使用这种探针，涉及这种探针的试剂盒，涉及这种探针的装置等的方法。

8. 发明授权

US11946925B2 Nanopore sensor having a fluidic passage for local electrical potential measurement 有权
公开(公告)号：US11946925B2
公开(公告)日：2024-04-02
申请号：US17718619
申请日：2022-04-12
申请人： President and Fellows of Harvard College
发明人： Ping Xie
IPC分类号： G01N27/453 , B01L3/00 , C12Q1/6869 , G01N27/414 , G01N27/416 , G01N27/447 , G01N33/487
CPC分类号： G01N33/48721 , B01L3/502715 , B01L3/50273 , C12Q1/6869 , G01N27/4145 , G01N27/4146 , G01N27/4163 , G01N27/44726 , G01N27/4473 , G01N27/44791 , B01L2300/0645 , B01L2300/0867 , B01L2300/0896 , B01L2300/12 , B01L2400/0421
摘要： In a nanopore sensor, a nanopore disposed in a support structure has a nanopore diameter and nanopore resistance, RPore. A fluidic passage, disposed in fluidic connection between a first fluidic reservoir and the nanopore, has a cross-sectional extent, along at least a portion of the fluidic passage length, that is greater than the diameter of the nanopore and that is less than the fluidic passage length. The fluidic passage has a fluidic passage resistance, RFP, of at least about 10% of the nanopore resistance, RPore, and no more than about 10 times the nanopore resistance, RPore. The nanopore is disposed in fluidic connection between the fluidic passage and a second fluidic reservoir. At least one electrical transduction element is disposed at the fluidic passage and electrically connected to produce an indication of electrical potential local to the fluidic passage.

9. 发明申请

US20220236251A1 Nanopore Sensor Having A Fluidic Passage For Local Electrical Potential Measurement 有权
公开(公告)号：US20220236251A1
公开(公告)日：2022-07-28
申请号：US17718619
申请日：2022-04-12
申请人： President and Fellows of Harvard College
发明人： Ping Xie
IPC分类号： G01N33/487 , B01L3/00 , C12Q1/6869 , G01N27/414 , G01N27/416 , G01N27/447
摘要： In a nanopore sensor, a nanopore disposed in a support structure has a nanopore diameter and nanopore resistance, RPore. A fluidic passage, disposed in fluidic connection between a first fluidic reservoir and the nanopore, has a cross-sectional extent, along at least a portion of the fluidic passage length, that is greater than the diameter of the nanopore and that is less than the fluidic passage length. The fluidic passage has a fluidic passage resistance, RFP, of at least about 10% of the nanopore resistance, RPore, and no more than about 10 times the nanopore resistance, RPore. The nanopore is disposed in fluidic connection between the fluidic passage and a second fluidic reservoir. At least one electrical transduction element is disposed at the fluidic passage and electrically connected to produce an indication of electrical potential local to the fluidic passage.

10. 发明授权

US11067534B2 Multi-channel nanopore sensing by local electrical potential measurement 有权
公开(公告)号：US11067534B2
公开(公告)日：2021-07-20
申请号：US16554753
申请日：2019-08-29
申请人： President and Fellows of Harvard College
发明人： Charles M. Lieber , Ping Xie
IPC分类号： G01N27/447 , B82Y30/00 , C12Q1/6869 , G01N33/487 , B82Y15/00
摘要： There is provided a multi-channel nanopore sensor having a plurality of independent nanopore sensors. Each independent nanopore sensor includes a nanopore disposed in a support structure. A fluidic connection is between a first fluidic reservoir, common to all of the independent nanopore sensors, and an inlet to the nanopore, with a first ionic solution of a first ionic concentration disposed in the first fluidic reservoir. A fluidic connection is between a second fluidic reservoir, common to all of the independent nanopore sensors, and an outlet from the nanopore, with a second ionic solution of a second ionic concentration, different than the first ionic concentration, disposed in the second fluidic reservoir. An electrical transduction element, disposed in contact with that ionic solution having a lower ionic concentration, is arranged at a site that produces an electrical signal indicative of electrical potential local to that ionic solution having a lower ionic concentration.

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