Waters Technologies Corporation

Fabrice Gritti

Michael O Fogwill

Joseph D Michienzi

Sylvain Gilles Cormier

Wade P Leveille

Jonathan L Belanger

Jason F Hill

Thomas S McDonald

Daniel Marc Lemire, Jr

Mike Leal

Disclosed herein are chromatography columns with conical or reducing inside dimensions and improved fits for use therewith, along with methods for making the columns and the frits.

Conical columns and low dispersion frits

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.

Dynamically adjusting set points for a heating/cooling element of a chromatography column using available information

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.

Compact liquid chromatography system providing thermal management and detection

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.

Automated semi-preparative gradient recycling liquid chromatography

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.

Reducing thermal gradients in chromatography columns with sub-ambient cooling/super-ambient heating and radial distribution

A mixer arrangement for use in a chromatography system includes a first frequency targeting mixer including a first flow channel coupled between an inlet and an outlet and a second flow channel coupled between the inlet and the outlet, the second flow channel including a volume offset region configured to delay fluid propagation through the second flow channel, wherein the volume offset region is configured to reduce or eliminate fluidic compositional oscillations in a compositional solvent stream that depart from a desired composition at a first target frequency, and a residual noise targeting mixer fluidically connected in series to the frequency targeting mixer, the residual noise targeting mixer configured to dampen aperiodic baseline noise in the compositional solvent stream.

Combination mixer arrangement for noise reduction in liquid chromatography

Described is a mixer for a liquid chromatography system. The mixer includes a flow distributor, a mixing disk and a flow collector. The mixer includes an inlet face, an outlet face and a plurality of channels each having an inlet end at the inlet face and an outlet end at the outlet face. The channels have a flow direction anisotropy between the inlet and outlet faces. A compositional solvent stream received at the flow distributor is distributed across the inlet face of the mixing disk and the flow collector collects the distributed solvent composition stream after passing through the mixing disk. The mixing disk may include a dispersive medium having a random porous structure. A retention time distribution of the mixer may depend on the structure of the channels between the inlet and outlet faces of the mixing disk.

Mixer for liquid chromatography

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.

High resolution and semi-preparative recycling chromatography system for isolation and preparation of unknown trace impurities in pharmaceutical products

Growing community of inventors

Franklin, MA, United States of America

Fabrice Gritti