公开(公告)号：WO2021258223A1

公开(公告)日：2021-12-30

申请号：PCT/CA2021/050884

申请日：2021-06-25

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  KHIMCHENKO, Anna ,  ASADISHEKARI, Maryam ,  LEONARD, Stephen Wesley

IPC: C12Q1/04 ,  C12M1/00 ,  C12M1/34 ,  C12N1/00 ,  C12N1/24 ,  G02B21/36 ,  C12M41/36

Abstract: Systems and methods are provided for classifying microbial cells according to morphological features of microcolonies. A dark-field objective is employed to acquire a dark-field image of a microcolony during a microcolony growth phase that is characterized by phenotypic expression of microcolony morphological features which evolve with time and are differentiated among classes of microbial cell types. The dark-field image is processed to classify the microcolony according to two or more microbial cell types, such as Gram status and/or speciation. The dark-field objective may have a numerical aperture selected to facilitate the imaging of microcolony morphological features, residing, for example, between 0.15 and 0.35. A set of dark-field images of a microcolony may be collected during the microcolony growth phase and processed to classify the microcolony. Classification may be performed according to a temporal ordering of the dark-field images, for example, using a recurrent neural network.

公开(公告)号：WO2015172255A1

公开(公告)日：2015-11-19

申请号：PCT/CA2015/050449

申请日：2015-05-19

Applicant: QVELLA CORPORATION

Inventor： MAASKANT, Robert ,  YASOTHARAN, Sanjesh ,  TALEBPOUR, Samad ,  LEONARD, Stephen W. ,  ETEMAD-MOGHADAM, Cyrus ,  ZAHN, Alexandre

IPC: B04B7/12 ,  B01D17/038 ,  B04B15/00 ,  F16K7/00

CPC classification number: B01L3/502753 ,  B01D17/0217 ,  B01D19/0052 ,  B01D21/262 ,  B01L3/5021 ,  B01L3/502715 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/027 ,  B01L2200/0684 ,  B01L2200/10 ,  B01L2300/0816 ,  B01L2300/0887 ,  B01L2300/1822 ,  B01L2300/1827 ,  B01L2300/1844 ,  B01L2400/0409 ,  B01L2400/0487 ,  B01L2400/0655 ,  B04B5/0407 ,  B04B5/0421 ,  B04B13/00 ,  C12N15/1003 ,  F16K7/00 ,  F16K99/0015 ,  F16K2099/0084

Abstract: Systems, methods and devices are provided for the automated centrifugal processing of samples. In some embodiments, an integrated fluidic processing cartridge is provided, in which a centrifugation chamber is fluidically interfaced, through a lateral surface thereof, with a microfluidic device, and wherein the integrated fluidic processing cartridge is configured to be inserted into a centrifuge for centrifugation. A cartridge interfacing assembly may be employed to interface with the integrated fluidic processing cartridge for performing various fluidic processing steps, such as controlling the flow of fluids into and out of the centrifugation chamber, and controlling the flow of fluids into the microfluidic device, and optionally for the further fluidic processing of fluids extracted to the microfluidic device. The integrated fluidic processing cartridge may include a supernatant chamber the extraction of a supernatant thereto, and a diluent chamber for diluting a suspension collected in the centrifugation chamber.

Abstract translation: 提供了用于样品的自动离心处理的系统，方法和装置。 在一些实施例中，提供了一种集成流体处理盒，其中离心室通过其侧表面与微流体装置流体连接，并且其中集成流体处理盒被配置为插入到离心机中用于离心。 可以使用药筒接口组件与集成流体处理药筒接合，以执行各种流体处理步骤，例如控制流入和离开离心室的流动，以及控制流体进入微流体装置的流动，以及任选地 用于进一步流体处理提取到微流体装置的流体。 集成流体处理盒可以包括上清液的上清液，以及用于稀释收集在离心室中的悬浮液的稀释剂室。

公开(公告)号：WO2013013304A1

公开(公告)日：2013-01-31

申请号：PCT/CA2012/000698

申请日：2012-07-25

Applicant: QVELLA CORPORATION ,  TALEBPOUR, Samad ,  KHINE, Aye Aye ,  MAASKANT, Robert ,  ALAVIE, Tino

Inventor： TALEBPOUR, Samad ,  KHINE, Aye Aye ,  MAASKANT, Robert ,  ALAVIE, Tino

IPC: C12M1/42 ,  B81B1/00 ,  B81B7/02 ,  C12M1/33 ,  C12N1/06 ,  C12N13/00 ,  C12N15/10 ,  C12Q1/68

CPC classification number: 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

Abstract: 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.

Abstract translation: 提供了用于电裂解细胞并从细胞释放大分子的装置和方法。 提供了一种微流体装置，其包括具有亚毫米级厚度的平面通道，并且在其上内表面和下内表面上包括电极。 在用液体填充通道之后，使得通道包含液体内的单元，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，以从电镀单元释放大分子。 通道还可以包括用于在电处理之前捕获和集中电池的内部滤波器。

公开(公告)号：WO2020124271A1

公开(公告)日：2020-06-25

申请号：PCT/CA2019/051895

申请日：2019-12-20

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  MAASKANT, Robert ,  KHINE, Aye Aye ,  LEONARD, Stephen Wesley ,  PARMAR, Vilcy ,  KHIMCHENKO, Anna ,  ASADISHEKARI, Maryam ,  MANKU, Sukhdev ,  YASOTHARAN, Sanjesh ,  ALAVIE, Tino ,  SAMIEI, Alaleh

IPC: C12Q1/24 ,  C12M1/00 ,  C12M1/26 ,  C12M1/34 ,  C12N1/00 ,  C12N5/00 ,  C12Q1/00 ,  C12Q1/02 ,  C12Q1/04 ,  G01N1/28 ,  G01N1/40 ,  G01N33/483 ,  G01N33/52

Abstract: An integrated fluidic device is employed to perform microbial cell separation, in situ microcolony growth, and optional identification and antimicrobial susceptibility testing. While the integrated fluidic device is maintained in a closed state, microbial cell separation is performed to provide a microbial cell suspension that is contacted with a solid phase growth medium. A liquid component of the suspension is removed, thereby retaining microbial cells on the growth medium for incubation, growth, and subsequent harvesting and characterization. In some embodiments, antimicrobial susceptibility testing is performed by contacting growth media with a solid support having an antimicrobial agent provided thereon, such that the antimicrobial agent diffuses into a subregion of the growth medium that is accessible through an aperture surrounded, at least in part, by the solid support. Microbial cells retained on the surface of the subregion may be assessed for growth or inhibition in the presence of the antimicrobial agent.

公开(公告)号：WO2015000079A1

公开(公告)日：2015-01-08

申请号：PCT/CA2014/050634

申请日：2014-07-03

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  KHINE, Aye Aye ,  ALAVIE, Tino ,  LEONARD, Stephen Wesley

IPC: C12Q1/68 ,  C12Q1/18 ,  C40B30/06

CPC classification number: C12Q1/18 ,  C12Q1/689 ,  C12Q2600/106 ,  C12Q2600/158

Abstract: 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.

Abstract translation: 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。 将包含生长培养基的等分试样在适于微生物生长的条件下培养，并且将各等分试样中的微生物细胞除去并裂解，并将裂解物进行逆转录和扩增，推断所选择的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选择的抗生素存在下孵育并提供刺激以诱导在微生物细胞内产生m RNA。 随后将微生物细胞裂解，而不会在裂解物中显着降解m RNA，并检测m RNA以确定抗生素对微生物细胞的作用。

公开(公告)号：WO2019222862A1

公开(公告)日：2019-11-28

申请号：PCT/CA2019/050716

申请日：2019-05-24

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  KHINE, Aye Aye ,  PARMAR, Vilcy ,  MANKU, Sukhdev ,  SAMIEI, Alaleh

IPC: G01N1/34 ,  G01N33/48

Abstract: Methods and compositions are provided for the selective lysis of eukaryotic cells and the separation of microbial cells. Blood cells and/or other eukaryotic cells in a sample, may be selectively lysed by adding, to the sample, a blood lysis reagent including saponin and an alkaline buffer, and optionally sodium polyanethole sulfonate and a non-ionic surfactant, thereby forming a mixture, and agitating the mixture. Microbial cells in the mixture may then be separated, for example, using a separation method such as centrifugation or filtration, and optionally detected or cultured in growth media. Blood lysis reagent compositions are provided that are suitable for preserving the intactness of microbial cells upon mixing with the sample. In example embodiments in which the sample is a blood sample, the blood lysis reagent composition may be selected to avoid or reduce the presence of visible blood debris upon centrifugation or filtration.

公开(公告)号：WO2018085928A1

公开(公告)日：2018-05-17

申请号：PCT/CA2017/051329

申请日：2017-11-08

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  KHINE, Aye Aye

IPC: C12Q1/68 ,  C12Q1/6806 ,  C12N1/06 ,  C12N15/10 ,  C12Q1/6809 ,  C12Q1/6844

Abstract: 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.

Abstract translation: 提供了通过使样品与包含阳离子去污剂的裂解和稳定化试剂接触来稳定和分离样品中核酸的方法。 阳离子洗涤剂溶解样品中的细胞并通过形成核酸 - 表面活性剂（NAS）复合物稳定释放的核酸。 将NAS复合物离心沉淀，洗涤，重新悬浮于水性再悬浮液中，形成NAS复合物悬浮液。 对悬浮液进行热处理以分解NAS复合物，由此释放核酸并形成核酸溶液。 在一些示例性实施方案中，水性再悬浮液被选择为适于进行分子扩增测定，使得核酸溶液可用于在不存在进一步核酸提取的情况下进行分子扩增测定。 提供了实施例，由此本方法适用于进行转录组生物标志物测定。

公开(公告)号：WO2014082160A1

公开(公告)日：2014-06-05

申请号：PCT/CA2013/000992

申请日：2013-11-26

Applicant: QVELLA CORPORATION

Inventor： TALEBPOUR, Samad ,  KHINE, Aye Aye ,  MAASKANT, Robert ,  ALAVIE, Tino

IPC: C12Q1/68 ,  C12M1/00 ,  C12M1/42 ,  C12N1/00 ,  C12N1/06 ,  C12N13/00 ,  C12Q1/00 ,  C12Q1/24 ,  G01N1/28 ,  G01N33/48 ,  C12N15/10 ,  C12N5/078

CPC classification number: 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

Abstract: 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.

Abstract translation: 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，随后离心分离样品以除去所得碎片并将其浓缩 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体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缓冲液体界面，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。 在提取剩余悬浮液之前可以进行一个或多个中间洗涤循环，其提供“预处理”样品。