Waters Technologies Corporation

Michael O Fogwill

Joseph D Michienzi

James P Murphy

Wade P Leveille

Sylvain Gilles Cormier

Geoff C Gerhardt

Abhijit Tarafder

Jason F Hill

Joshua A Shreve

Jeffrey Musacchio

Theodore A Dourdeville

Thomas S McDonald

Martin Gilar

Fabrice Gritti

Joseph A Jarrell

Keith Fadgen

Kevin Daniel Wyndham

Matthew A Lauber

Jonathan L Belanger

Edouard S P Bouvier

Joshua A Burnett

Jacob Nathan Fairchild

Joseph D Antocci

Stephen J Shiner

Gary W Bertone

Curt Devlin

Mark Basile

Emily J Berg

Michael Eggertson

Scott Kelley

Francis Patrick Tracey

Thomas Swann

Cheryl Boissel

Sebastien Besner

Isabelle François

Fabrice Gilles Ernest Gritti

Edouard SP Bouvier

Syvlain Gilles Cormier

The exemplary embodiments control solvent pumps so that system flow is constant. One or more controllers may control the flow rate produced by the pumps over time. The one or more controllers control a first pump so that, as the first pump is refilling, a second pump maintains a sufficient flow rate to compensate for the lost flow due to the refilling event. In some exemplary embodiments, the one or more controllers control the timing of the refilling event for the first event such that the refilling event overlaps with the equilibrating of the chromatography column with solvent(s) from the second pump. Similarly, the one or more controllers control the timing of the refilling event for the second pump such that the refilling event overlaps with the equilibrating of the chromatography column.

Solvent delivery with a reduced volume single stroke pumping arrangement providing continuous solvent flow

Exemplary embodiments integrate a tee or valve into an outlet end fitting of a liquid chromatography column. The tee or valve is suitable for providing additional fluidic flow paths to ports of the end fitting and eliminates the need for post-column fluidic conduits connecting to tees or valves to insert fluidic inputs or divert flow to outputs. This integration decreases the distance that eluent from the liquid chromatography column has to travel to reach a detector relative to systems that use external tees or valves while providing tee/valve functionality and reducing the fluidic volume post-column. As a result, the exemplary embodiments help decrease sample dispersion.

Ported end fitting for a liquid chromatography column with an integrated valve/tee having additional input and/or output

Exemplary embodiments eliminate the need for column ovens in serial column chromatography arrangements and systems by using insulated sleeves. The insulated sleeves may encase individual chromatography columns or clusters of chromatography columns. The use of the insulated sleeves allows the chromatography columns to be positioned in close proximity to each other. This may decrease the overall size of a serial column chromatography arrangement and may reduce costs by not requiring the column ovens.

Insulated serial column chromatography arrangements and systems

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

The exemplary embodiments provide chromatography column positioning assemblies that can ensure that the distance between face seals or other sealing surfaces/mechanisms at the respective ends of a liquid chromatography column is a desired distance (i.e., the length of the liquid chromatography column). The exemplary embodiments can adjust the separation between the face seals to accommodate different length liquid chromatography columns. For example, a chromatography column positioning assembly of an exemplary embodiment can set the distance between face seals to accommodate a 25 mm column, a 50 mm column or a 100 mm column.

Chromatography column positioning assemblies

A chromatographic device including a coated metallic frit is disclosed. The coating is provided over the fluid exposed surfaces of the frit, thereby covering metallic surfaces to prevent interaction with an analyte in the flowstream. This technology relates to the use of a vapor deposition coated frit together with an uncoated frit in a liquid flow path for improved chromatography. More specifically, this technology relates to liquid chromatographic devices for separating analytes in a sample having a single coated frit within an uncoated metallic fluidic flow path (i.e., the column tube or channel is formed of stainless steel, titanium (pure or alloyed), or some mixture of stainless steel and titanium) and does not include the coating applied to the frit.

Use of vapor deposition coated flow paths for improved chromatography of metal interacting analytes

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 exemplary embodiments may provide a collective insulating sleeve for a plurality of chromatography columns or may provide separate insulating sleeve for each of the chromatography columns in a plurality. As a result, column ovens are not needed, and pre-heaters may not be required for each chromatography column in some exemplary embodiments. Thus, parallel column arrangements in the exemplary embodiments may be more compact than conventional arrangements.

Parallel insulated chromatography columns

Exemplary embodiments may deploy a valve that introduces a sample of a calibrant coaxially with flow exiting a source of a mobile phase flow, such as a liquid chromatography (LC) column, on a path to an ion source for the mass spectrometer (MS). The valve may be positioned remotely on a branch that has a junction with the path leading form the source of the mobile phase flow to the ion source. Alternatively, the valve may be positioned in line on the flow path from the source of the mobile phase flow to the ion source of the MS. A novel five port valve design may be employed. With this valve design, a first position of the valve allows a sample loop for the calibrant to be filled. In a second position, the calibrant is added coaxially to the flow from the source of the mobile phase to the MS. In a third position of the valve, diversion of or infusion to a post-source flow is enabled.

Coaxial introduction of calibrant in a flow path with analyte to an ion source

The present disclosure relates to methodologies, systems, and apparatus for controlling fluid flow within a chromatography system. The chromatography system includes a mobile phase pump configured to pump a liquid mobile phase through a column and a restrictor positioned downstream of the column and upstream of a detector. The system also includes a valve configured to operate in at least two positions. In a first position, the valve is configured to direct the output of the column to bypass the valve and reach the detector, while in the second position the valve directs the output of the column to waste.

System and method for controlling fluid flow within a liquid chromatography system

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

Techniques and apparatus for thermally controlled interfaces for separation devices and optical flow cell devices with minimized post-column volumes are described. In one embodiment, for example, a column-optical cell assembly may include an insulating device, a chromatography column arranged within the insulating device, and an optical flow cell in fluid communication with the chromatography column, the chromatography column arranged within a minimum distance of the optical flow cell.

Techniques for temperature control of separation devices and optical detection devices of mass analysis systems

Described are apparatuses, devices, and systems implementing seals for separation devices. An apparatus for a separation device may include an end nut shaped to be positioned on one of an inlet side and an outlet side of the separation device. The end nut may be further shaped to mate with a connecting fitting. The apparatus may further include a face seal having a device side and a fitting side. The face seal may be positioned, at least in part, in the end nut on the device side of the face seal. The face seal may be positioned to interface with the connecting fitting on the fitting side of the face seal upon the end nut being mated with the connecting fitting. The apparatus may also include a face seal bore of the face seal being axially alignable with at least one of an inlet and an outlet of the separation device.

Seal for separation device

Multidimensional liquid chromatography (MDLC) systems include valve configurations that enable a flow containing analytes in the eluent of a first dimension liquid chromatography system to be modulated such that the analytes can be captured in fluidic loops and subsequently provided to a second dimension liquid chromatography system. Optionally, a single detector is used for both first and second dimensions. In addition, the systems can enable dilution of the analytes and enable incompatible mobile phases and mobile phase flow rates to be used in the first and second dimensions.

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South Grafton, MA, United States of America

Michael O Fogwill