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1. 发明授权

US11371988B2 Cell concentration, capture and lysis devices and methods of use thereof 有权
公开(公告)号：US11371988B2
公开(公告)日：2022-06-28
申请号：US14735917
申请日：2015-06-10
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Stephen W Leonard , Robert Maaskant , Tino Alavie
IPC分类号： G01N33/543 , B01L3/00 , C12M3/06 , C12M1/12 , C12M1/00 , C12M1/42 , C12M1/34 , C12N1/06 , C12N11/14 , C12N13/00 , G01N33/50
摘要： The present invention provides a microfluidic devices and methods of use thereof for the concentration and capture of cells. A pulsed non Faradaic electric field is applied relative to a sample under laminar flow, which results to the concentration and capture of charged analyte. Advantageously, pulse timing is selected to avoid problems associated with ionic screening within the channel. At least one of the electrodes within the channel is coated with an insulating layer to prevent a Faradaic current from flowing in the channel. Under pulsed application of a unipolar voltage to the electrodes, charged analyte within the sample is moved towards one of the electrodes via a transient electrophoretic force.

2. 发明申请

US20190177766A1 METHODS OF TARGETED ANTIBIOTIC SUSCEPTIBILITY TESTING 审中-公开
公开(公告)号：US20190177766A1
公开(公告)日：2019-06-13
申请号：US16280842
申请日：2019-02-20
申请人： Qvella Corporation
发明人： Samad Talebpour , Aye Aye Khine , Tino Alavie , Stephen Wesley Leonard
IPC分类号： C12Q1/18 , C12Q1/689
摘要： Methods are provided for performing antibiotic susceptibility testing based on the detection of RNA, such as tmRNA, from microbial cells after exposure to antibiotics. In some embodiments, aliquots are obtained from a sample, one of which contains a selected antibiotic. The aliquots, which include growth media, are incubated under conditions suitable for microbial growth, and the microbial cells in each aliquot are removed and lysed, and the lysate is subjected to reverse transcription and amplification in infer the effect of the selected antibiotic on the microbial cells. In one embodiment, a sample containing microbial cells is incubated in the presence of a selected antibiotic and a stimulus is provided to induce the production of m RNA within the microbial cells. The microbial cells are subsequently lysed without substantial degradation of the m RNA within the lysate, and the m RNA is detected to determine the effect of the antibiotic on the microbial cells.

3. 发明授权

US09574245B2 Methods and devices for electrical sample preparation 有权
标题翻译：电气样品制备的方法和装置
公开(公告)号：US09574245B2
公开(公告)日：2017-02-21
申请号：US13750723
申请日：2013-01-25
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Robert Maaskant , Tino Alavie
IPC分类号： C12Q3/00 , C12M1/42 , C12M1/00 , C12N1/06 , C12N1/08 , C12N13/00 , B01L3/00 , C12Q1/68
CPC分类号： C12Q1/6806 , B01L3/502715 , B01L3/502738 , B01L3/502753 , B01L7/52 , B01L2200/0631 , B01L2200/143 , B01L2300/0645 , B01L2300/0681 , B01L2300/0809 , B01L2300/0858 , B01L2300/087 , B01L2300/0874 , B01L2300/0887 , B01L2300/14 , B01L2300/1833 , B01L2400/0694 , C12M35/02 , C12M47/06 , C12N1/066 , C12N1/08 , C12N13/00 , C12Q1/686 , C12Q3/00
摘要： Devices and methods are provided for electrically lysing cells and releasing macromolecules from the cells. A microfluidic device is provided that includes a planar channel having a thickness on a submillimeter scale, and including electrodes on its upper and lower inner surfaces. After filling the channel with a liquid, such that the channel contains cells within the liquid, a series of voltage pulses of alternating polarity are applied between the channel electrodes, where the amplitude of the voltage pulses and a pulsewidth of the voltage pulses are effective for causing irreversible electroporation of the cells. The channel is configured to possess thermal properties such that the application of the voltage produces a rapid temperature rise as a result of Joule heating for releasing the macromolecules from the electroplated cells. The channel may also include an internal filter for capturing and concentrating the cells prior to electrical processing.
摘要翻译：提供了用于电解裂解细胞并从细胞释放大分子的装置和方法。提供一种微流体装置，其包括具有亚毫米级厚度的平面通道，并且在其上下表面上包括电极。在用液体填充通道之后，使得通道在液体内包含单元，在通道电极之间施加一系列交替极性的电压脉冲，其中电压脉冲的幅度和电压脉冲的脉冲宽度对于引起细胞的不可逆电穿孔。该通道被配置为具有热性质，使得施加电压由于焦耳加热而导致快速升温，以从电镀细胞释放大分子。通道还可以包括内部滤波器，用于在电处理之前捕获和集中单元。

4. 发明申请

US20160138072A1 METHODS OF TARGETED ANTIBIOTIC SUSCEPTIBILITY TESTING 审中-公开
标题翻译：靶向抗生素耐药性测试方法
公开(公告)号：US20160138072A1
公开(公告)日：2016-05-19
申请号：US14901200
申请日：2014-07-03
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Tino Alavie , Stephen Wesley Leonard
IPC分类号： C12Q1/18 , C12Q1/68
CPC分类号： C12Q1/18 , C12Q1/689 , C12Q2600/106 , C12Q2600/158
摘要： Methods are provided for performing antibotic susceptibility testing based on the detection of RNA, such as tmRNA, from microbial cells after exposure to antibiotics. In some embodiments, aliquots are obtained from a sample, one of which contains a selected antibiotic. The aliquots, which include growth media, are incubated under conditions suitable for microbial growth, and the microbial cells in each aliquot are removed and lysed, and the lysate is subjected to reverse transcription and amplification in infer the effect of the selected antibiotic on the microbial cells. In one embodiment, a sample containing microbial cells is incubated in the pressence of a selected antibiotic and a stimulus is provided to induce the production on m RNA within the microbial cells. The microbial cells are subsequently lysed without substantial degradation of the m RNA within the lysate, and the m RNA is detected to determine the effect of the antibiotic on the microbial cells.
摘要翻译：提供了基于在暴露于抗生素后从微生物细胞中检测RNA（例如tmRNA）进行抗生素敏感性测试的方法。在一些实施方案中，从样品获得等分试样，其中一个样品含有选定的抗生素。包括生长培养基在内的等分试样在适合于微生物生长的条件下孵育，并除去每个等分试样中的微生物细胞并裂解，并将裂解物进行逆转录和扩增，推断所选抗生素对微生物的作用细胞。在一个实施方案中，将含有微生物细胞的样品在所选择的抗生素的压力下孵育，并提供刺激以诱导在微生物细胞内的m RNA上产生。随后裂解微生物细胞，而不会在裂解物中明显降解m RNA，并检测m RNA以确定抗生素对微生物细胞的作用。

5. 发明授权

US08975060B2 Method for pretreatment of microbial samples 有权
标题翻译：微生物样品预处理方法
公开(公告)号：US08975060B2
公开(公告)日：2015-03-10
申请号：US13833872
申请日：2013-03-15
申请人： Qvella Corporation
发明人： Samad Talebpour , Aye Aye Khine , Robert Maaskant , Tino Alavie
IPC分类号： C12N1/00
CPC分类号： C12Q1/6848 , B01L3/5021 , B01L3/50215 , B01L3/5027 , B01L7/52 , B01L2200/026 , B01L2300/046 , B01L2300/0816 , B01L2300/0864 , B01L2300/1833 , C12Q1/02 , C12Q1/6806 , C12Q2523/307 , C12Q2527/125 , C12Q2527/137
摘要： Methods and devices are provided for pretreatment of a sample containing microbial cells. In some embodiments, the pretreatment of the sample is performed via the initial selective lysis, within a sample pretreatment vessel, of non-microbial cells (such as blood cells) and the subsequent centrifugation of the sample to remove the resulting debris and concentrate the microbial cells. An immiscible and dense cushioning liquid may be included, for collecting the microbial cells adjacent to a liquid interface formed by the cushioning liquid, upon centrifugation of the pretreatment vessel. After removal of a substantial quantity of the supernatant, resuspension of the collected microbial cells, and re-establishment of the liquid interface, at least a portion of the remaining suspension may be removed without substantially removing the cushioning liquid. One or more intermediate wash cycles may be performed to prior to extraction of the pretreated sample.
摘要翻译：提供了用于预处理含有微生物细胞的样品的方法和装置。在一些实施方案中，样品的预处理通过在样品预处理容器内，非微生物细胞（例如血细胞）中的初始选择性裂解进行，随后将样品离心以除去所得碎片并浓缩微生物细胞。可以包括不混溶和致密的缓冲液体，用于在预处理容器离心时收集由缓冲液形成的液体界面附近的微生物细胞。在除去大量的上清液后，重新悬浮收集的微生物细胞并重新建立液体界面，可以除去至少一部分剩余的悬浮液，而基本不除去缓冲液体。可以在提取预处理样品之前进行一个或多个中间洗涤循环。

6. 发明授权

US11339366B2 Methods of performing nucleic acid stabilization and separation 有权
公开(公告)号：US11339366B2
公开(公告)日：2022-05-24
申请号：US16347658
申请日：2017-11-08
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine
IPC分类号： C12Q1/68 , C07H21/00 , C12N1/06 , C12N15/10 , C12Q1/6806 , C12Q1/6809 , C12Q1/686 , C12Q1/6876
摘要： Methods are provided for the stabilization and separation of nucleic acids from a sample via contact of the sample with a lysis and stabilization reagent that includes a cationic detergent. The cationic detergent lyses cells in the sample and stabilizes the released nucleic acids via the formation of nucleic acid-surfactant (NAS) complexes. The NAS complexes are centrifugally precipitated, washed, the resuspended in an aqueous resuspension liquid, forming a NAS complex suspension. The suspension is thermally processed to disintegrate the NAS complexes, thereby releasing the nucleic acids and forming a nucleic acid solution. In some example embodiments, the aqueous resuspension liquid is selected to be suitable for performing molecular amplification assays, such that the nucleic acid solution may be employed for performing a molecular amplification assay in the absence of further nucleic acid extraction. Examples are provided whereby the present methods are adapted for performing transcriptomic biomarker assays.

7. 发明授权

US10378043B2 Methods and devices for electrical sample preparation 有权
公开(公告)号：US10378043B2
公开(公告)日：2019-08-13
申请号：US15401291
申请日：2017-01-09
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Robert Maaskant , Tino Alavie
IPC分类号： C12Q1/6806 , C12M1/42 , C12M1/00 , C12N1/06 , C12N1/08 , C12N13/00 , B01L3/00 , C12Q3/00 , B01L7/00 , C12Q1/686
摘要： Devices and methods are provided for electrically lysing cells and releasing macromolecules from the cells. A microfluidic device is provided that includes a planar channel having a thickness on a submillimeter scale, and including electrodes on its upper and lower inner surfaces. After filling the channel with a liquid, such that the channel contains cells within the liquid, a series of voltage pulses of alternating polarity are applied between the channel electrodes, where the amplitude of the voltage pulses and a pulsewidth of the voltage pulses are effective for causing irreversible electroporation of the cells. The channel is configured to possess thermal properties such that the application of the voltage produces a rapid temperature rise as a result of Joule heating for releasing the macromolecules from the electroplated cells. The channel may also include an internal filter for capturing and concentrating the cells prior to electrical processing.

8. 发明申请

US20150276727A1 CELL CONCENTRATION, CAPTURE AND LYSIS DEVICES AND METHODS OF USE THEREOF 审中-公开
标题翻译：细胞浓度，捕获和检测装置及其使用方法
公开(公告)号：US20150276727A1
公开(公告)日：2015-10-01
申请号：US14735917
申请日：2015-06-10
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Stephen W. Leonard , Robert Maaskant , Tino Alavie
IPC分类号： G01N33/543 , B01L3/00
CPC分类号： G01N33/5438 , B01L3/502715 , B01L3/502753 , B01L3/502761 , B01L2200/0647 , B01L2300/0645 , B01L2300/0809 , C12M23/16 , C12M25/00 , C12M25/04 , C12M29/10 , C12M35/02 , C12M41/38 , C12N1/066 , C12N11/14 , C12N13/00 , G01N33/5005
摘要： The present invention provides a microfluidic devices and methods of use thereof for the concentration and capture of cells. A pulsed non-Faradaic electric field is applied relative to a sample under laminar flow, which results to the concentration and capture of charged analyte. Advantageously, pulse timing is selected to avoid problems associated with ionic screening within the channel. At least one of the electrodes within the channel is coated with an insulating layer to prevent a Faradaic current from flowing in the channel. Under pulsed application of a unipolar voltage to the electrodes, charged analyte within the sample is moved towards one of the electrodes via a transient electrophoretic force.
摘要翻译：本发明提供一种微流体装置及其用于浓缩和捕获细胞的方法。在层流下相对于样品施加脉冲非法拉第电场，这导致带电分析物的浓度和捕获。有利地，选择脉冲定时以避免与通道内的离子屏蔽相关的问题。通道内的至少一个电极涂有绝缘层，以防止法拉第电流在通道中流动。在脉冲施加单极电压给电极的情况下，样品内的带电分析物经由瞬时电泳力朝向其中一个电极移动。

9. 发明授权

US11788114B2 Methods and devices for electrical sample preparation 有权
公开(公告)号：US11788114B2
公开(公告)日：2023-10-17
申请号：US16510253
申请日：2019-07-12
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Robert Maaskant , Tino Alavie
IPC分类号： C12M1/42 , C12M1/00 , C12N1/06 , C12N1/08 , C12N13/00 , C12Q1/6806 , C12Q3/00 , C12Q1/686 , B01L3/00 , B01L7/00
CPC分类号： C12Q1/6806 , B01L3/502715 , B01L3/502738 , B01L3/502753 , B01L7/52 , C12M35/02 , C12M47/06 , C12N1/066 , C12N1/08 , C12N13/00 , C12Q1/686 , C12Q3/00 , B01L2200/0631 , B01L2200/143 , B01L2300/0645 , B01L2300/0681 , B01L2300/087 , B01L2300/0809 , B01L2300/0858 , B01L2300/0874 , B01L2300/0887 , B01L2300/14 , B01L2300/1833 , B01L2400/0694
摘要： Devices and methods are provided for electrically lysing cells and releasing macromolecules from the cells. A microfluidic device is provided that includes a planar channel having a thickness on a submillimeter scale, and including electrodes on its upper and lower inner surfaces. After filling the channel with a liquid, such that the channel contains cells within the liquid, a series of voltage pulses of alternating polarity are applied between the channel electrodes, where the amplitude of the voltage pulses and a pulse width of the voltage pulses are effective for causing irreversible electroporation of the cells. The channel is configured to possess thermal properties such that the application of the voltage produces a rapid temperature rise as a result of Joule heating for releasing the macromolecules from the electroplated cells. The channel may also include an internal filter for capturing and concentrating the cells prior to electrical processing.

10. 发明授权

US11702647B2 Method for pretreatment of microbial cells 有权
公开(公告)号：US11702647B2
公开(公告)日：2023-07-18
申请号：US16881479
申请日：2020-05-22
申请人： QVELLA CORPORATION
发明人： Samad Talebpour , Aye Aye Khine , Robert Maaskant , Tino Alavie
IPC分类号： C12N15/10 , B01L3/00 , C12Q1/6806 , C12Q1/24 , C08F220/28
CPC分类号： C12N15/1003 , B01L3/5021 , B01L3/5027 , C08F220/286 , C12Q1/24 , C12Q1/6806 , C08G2261/1452
摘要： Methods and devices are provided for pretreatment of a sample containing microbial cells. In some embodiments, the pretreatment of the sample is performed via the initial selective lysis, within a sample pretreatment vessel, of non-microbial cells (such as blood cells) and the subsequent centrifugal separation of the sample to remove the resulting debris and concentrate the microbial cells. An immiscible and dense cushioning liquid may be included for collecting the microbial cells adjacent to the liquid interface formed by the cushioning liquid upon centrifugation of the pretreatment vessel. After removal of a substantial quantity of the supernatant, resuspension of the collected microbial cells, and re-establishment of the cushioning liquid interface, at least a portion of the remaining suspension may be removed without substantially removing the cushioning liquid. One or more intermediate wash cycles may be performed prior to extraction of the remaining suspension, which provides a “pretreated” sample.

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