公开(公告)号：US20220357304A1

公开(公告)日：2022-11-10

申请号：US17736371

申请日：2022-05-04

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Fabrice Gritti

IPC: G01N30/46 ,  G01N30/20 ,  G01N30/72

Abstract: The exemplary embodiments may provide liquid chromatography systems that are smaller in size and with reduced extra-column volume than conventional liquid chromatography systems. The exemplary embodiments may reduce the size of the liquid chromatography systems enough that the liquid chromatography systems of the exemplary embodiments may be deployed adjacent to automated sample preparation robotics, adjacent to a process stream, or adjacent to the inlet of a mass spectrometer. In addition, the exemplary embodiments may reduce the extra-column volume of the liquid chromatography system by eliminating many of the connection tubes found in conventional liquid chromatography systems and by situating components of the liquid chromatography system in closer proximity.

公开(公告)号：US11285403B2

公开(公告)日：2022-03-29

申请号：US16426320

申请日：2019-05-30

Applicant: Waters Technologies Corporation

Inventor： Fabrice Gritti ,  Sylvain Cormier

IPC: B01D15/16 ,  B01D15/18 ,  B01D15/40 ,  G01N30/44 ,  G01N30/46 ,  G01N30/88

Abstract: The disclosure relates to a recycling chromatography method that includes injecting a sample into a mobile phase flow stream of a chromatography system to create a combined flow stream. The sample includes an API and at least one impurity. The chromatography system includes a first column and a column in series, a first valve in fluid communication with the first and second chromatographic columns, a heater in communication with the first and second chromatographic columns, a fraction collector in fluid communication with the first and second chromatographic columns, and a second valve positioned before the fraction collector. The combined flow stream is recycled from the first chromatographic column to the second chromatographic column and vice versa by switching the first valve until a baseline resolution is achieved to separate the at least one impurity from the API. The at least one impurity is collected in the fraction collector.

公开(公告)号：US12203906B2

公开(公告)日：2025-01-21

申请号：US17230325

申请日：2021-04-14

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Jason F. Hill ,  Fabrice Gritti

IPC: G01N30/30 ,  G01N30/32 ,  G01N30/60

Abstract: The exemplary embodiments may determine a temperature set point for an outlet heater or cooler based on available information without requiring user input or requiring only minimal user input. The exemplary embodiments may estimate the temperature set point of the outlet heater based on available information, such as pressure delta along the column, temperature at the inlet of the chromatography column, and volumetric flow rate. In some instances, the estimate may be normalized for column dimensions, such as length and diameter. Tailing factor may also be used in determining the estimate. The estimate is not computationally burdensome and can be recalculated as the chromatography column is in use.

公开(公告)号：US20210389284A1

公开(公告)日：2021-12-16

申请号：US17347807

申请日：2021-06-15

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Wade P. Leveille ,  Joseph D. Michienzi ,  Fabrice Gritti

IPC: G01N30/30

Abstract: Exemplary embodiments may compensate for expected frictional heating or Joule-Thomson cooling in chromatography columns. Frictional heating or Joule Thomson cooling are the same thing for a fluid decompressing along a porous material. Either heat is absorbed from or released to the external environment. The exemplary embodiments may cool the mobile phase to a sub-ambient temperature before the mobile phase passes through a chromatography column to compensate for the frictional heating or heat the mobile phase to a super-ambient temperature to compensate for Joule-Thomson cooling. The amount of temperature increase expected from the frictional heating or the amount of temperature decrease expected from the Joule-Thomson cooling may be calculated or estimated. Based on the amount of temperature increase or decrease expected, the set point for the heater/cooler may be determined and applied to the mobile phase. The analyte may be injected solely into a central portion of the chromatography column to further compensate for thermal gradients.

公开(公告)号：US20210318273A1

公开(公告)日：2021-10-14

申请号：US17230325

申请日：2021-04-14

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Jason F. Hill ,  Fabrice Gritti

IPC: G01N30/30 ,  G01N30/60 ,  G01N30/32

Abstract: The exemplary embodiments may determine a temperature set point for an outlet heater or cooler based on available information without requiring user input or requiring only minimal user input. The exemplary embodiments may estimate the temperature set point of the outlet heater based on available information, such as pressure delta along the column, temperature at the inlet of the chromatography column, and volumetric flow rate. In some instances, the estimate may be normalized for column dimensions, such as length and diameter. Tailing factor may also be used in determining the estimate. The estimate is not computationally burdensome and can be recalculated as the chromatography column is in use.

公开(公告)号：US20250027911A1

公开(公告)日：2025-01-23

申请号：US18777771

申请日：2024-07-19

Applicant: Waters Technologies Corporation

Inventor： Wade P. Leveille ,  Fabrice Gritti ,  Jason F. Hill ,  Sornanathan Meyyappan ,  Joseph D. Michienzi

IPC: G01N30/60 ,  G01N30/02

Abstract: A frit and a chromatography column that includes the frit are described. The frit is formed as a disk having a porosity, a radius and a thickness. The disk has a variation in porosity, thickness, or both porosity and thickness along a radial direction. A flow of a liquid through an outer region of the disk is advanced at an outlet end of the disk relative to a flow of the liquid through an inner region of the disk. The frit is configured to be disposed at one end of a column bed of a liquid chromatography column where the advance in the flow in the outer region relative to the flow in the inner region is predetermined to at least partially compensate for a radial variation in the linear velocity of the flow through the column bed.

公开(公告)号：US20220308020A1

公开(公告)日：2022-09-29

申请号：US17699775

申请日：2022-03-21

Applicant: Waters Technologies Corporation

Inventor： Fabrice Gritti

IPC: G01N30/46 ,  G01N30/82

Abstract: The disclosure relates to a gradient twin column recycling chromatography method that is used to separate a mixture containing closely eluting compounds. In one embodiment, a sample includes a primary organic compound and one or more impurities that closely elute with the primary organic compound. A gradient mobile phase is initially used to remove unwanted early eluting and late eluting impurities from the sample. After the gradient removal of some of the impurities is complete, the remaining mixture of the primary organic compound and the closely eluting impurities are separated using recycle chromatography methodology with an isocratic mobile phase.

公开(公告)号：US20180224404A1

公开(公告)日：2018-08-09

申请号：US15891463

申请日：2018-02-08

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Martin Gilar ,  Fabrice Gritti ,  Joseph D. Michienzi

IPC: G01N30/30

CPC classification number: G01N30/30 ,  G01N30/34 ,  G01N30/6095 ,  G01N2030/027 ,  G01N2030/3015 ,  G01N2030/3038 ,  G01N2030/3046 ,  G01N2030/3053

Abstract: A method of performing a chromatographic separation includes generating a spatial temperature gradient along a length of a chromatographic column in a liquid chromatography system. A sample is injected into a flow of a mobile phase to the column and a flow of a mobile phase having a composition gradient is provided to the column after the sample is received at the column. The spatial temperature gradient is moved along the length of the column from the column inlet to the column outlet during the time that the composition gradient traverses the column. This coordination of the composition gradient with the movement of the spatial thermal gradient yields a significant increase in peak capacity per unit time compared with conventional separation techniques performed in a conventional isothermal column environment.

公开(公告)号：US20250060342A1

公开(公告)日：2025-02-20

申请号：US18938818

申请日：2024-11-06

Applicant: Waters Technologies Corporation

Inventor： Michael O. Fogwill ,  Fabrice Gritti

IPC: G01N30/30 ,  G01N30/20 ,  G01N30/46 ,  G01N30/72

Abstract: Liquid chromatography systems described herein are smaller in size and with a reduced extra-column volume due to direct connection of a liquid chromatography column and/or detector to an injector valve and due to eliminating the need for a column oven by relying on heating of the liquid chromatography column and detector by a preheater. The size of the liquid chromatography systems are enough that the liquid chromatography systems may be deployed adjacent to automated sample preparation robotics, adjacent to a process stream, or adjacent to the inlet of a mass spectrometer. In addition, the extra-column volume of the liquid chromatography systems may be reduced by eliminating many of the connection tubes and by situating components of the liquid chromatography system in closer proximity.

公开(公告)号：US12078621B2

公开(公告)日：2024-09-03

申请号：US17699775

申请日：2022-03-21

Applicant: Waters Technologies Corporation

Inventor： Fabrice Gritti

IPC: G01N30/46 ,  G01N30/02 ,  G01N30/32 ,  G01N30/82 ,  G01N30/30

CPC classification number: G01N30/461 ,  G01N30/82 ,  G01N2030/027 ,  G01N2030/3007 ,  G01N2030/326 ,  G01N2030/328

Abstract: The disclosure relates to a gradient twin column recycling chromatography method that is used to separate a mixture containing closely eluting compounds. In one embodiment, a sample includes a primary organic compound and one or more impurities that closely elute with the primary organic compound. A gradient mobile phase is initially used to remove unwanted early eluting and late eluting impurities from the sample. After the gradient removal of some of the impurities is complete, the remaining mixture of the primary organic compound and the closely eluting impurities are separated using recycle chromatography methodology with an isocratic mobile phase.