Waters Technologies Corporation

Waters Investments Limited

Waters Technology Corporation

Geoff C Gerhardt

Keith Fadgen

Joseph D Michienzi

Michael O Fogwill

Martin Gilar

Theodore A Dourdeville

Sylvain Gilles Cormier

James P Murphy

Bernard Bunner

Jeffrey Musacchio

Joseph A Luongo

Thomas S McDonald

Wade P Leveille

Jason F Hill

Richard Wayne Andrews

Peyton C Beals

Bruce J Compton

Rachel Mumma

Jordan Kornfeld

Joseph A Jarrell

Moon Chul Jung

Edouard S P Bouvier

Jacob Nathan Fairchild

Michael John Tomany

Paul D Rainville

Robert Stephen Plumb

Robert Ward Crocker

Kenneth R Plant

Christopher C Benevides

James W Jorgenson

Gary W Bertone

Curt Devlin

Pamela F Caton

Christopher C Charlton

Christopher B Charlton

Thomas Mcdonald

Keith Edward Fadgen

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

Sample preparation and separation can be performed using a sample cartridge (). The cartridge includes a barrel () with a first and second end, a column segment () connected to the second end of the barrel, and a column () containing a sorbent material. The sorbent material includes particles that have antibodies attached to them to selectively retain analytes, proteins attached to them to retain certain classes of antibodies, or enzymes attached to them to perform specific modifications to certain classes of molecules. The column segment can be in thermal communication with a temperature control device in order to control the temperature of the column.

Micro solid phase extraction devices and methods

Methods and devices for the washing, extraction, and separation of a sample in a disposable chromatography cartridge () comprising a barrel () and a column (), and especially including reinforcement to the column permitting high-pressure separation.

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

Thermally modulated variable restrictors used in chromatography systems enable independent control of system pressure and linear velocity of a compressible mobile phase passing through a chromatography column. A method for configuring a chromatography system with independent control of system pressure and mass flow rate of a compressible mobile phase includes determining a type of chromatography separation column to be used in the chromatography system, matching a thermally modulated variable restrictor to the type of chromatography separation column for use together during operation of the chromatography system, and bundling the chromatography column with its matching thermally modulated variable restrictor for distribution as a single package.

Matching thermally modulated variable restrictors to chromatography separation columns

Techniques and apparatus for ion source devices with minimized post-column volumes are described. In one embodiment, for example, an ion source assembly may include a chromatography column in fluid communication with an ion source device, the chromatography column arranged within a minimum distance of the ion source, the minimum distance comprising between about 60 mm and about 150 mm.

Mass spectrometer ion source with integrated column

A method for injecting a diluted sample in a chromatography system includes merging a flow of a sample and a flow of a diluent to form a flow of a diluted sample. A dilution ratio of the diluted sample equals a sum of the volumetric flow rates of the sample and the diluent divided by the volumetric flow rate of the sample. The diluted sample is stored in a holding element before injection into a chromatographic system flow. Sample dilution occurs under low pressure relative to the chromatographic flow thereby allowing lower pressure sample and diluent syringes to be used. Other benefits include reduced compressibility and a reduction in leaks due to the lower pressure operation. The method avoids problems associated with manual techniques which can introduce errors due, for example, to loss of sample, sample precipitation and adsorption of sample to vials.

Method and apparatus for injecting a chromatographic sample

Described are a method and apparatus for diluting a chromatographic sample. The method includes repeating an alternating acquisition of sample fluidic plugs each having an incremental volume of sample and diluent fluidic plugs each having an incremental volume of diluent to obtain a stack of alternating sample and diluent fluidic plugs. The stack is inserted into a flow of a mobile phase in a chromatography system. Alternatively, the method includes repeating the steps of injecting an incremental volume of sample into a chromatographic system flow and providing an incremental volume of mobile phase into the chromatographic system flow. In either implementation, the dilution ratio of the sample equals the sum of the incremental volumes of the sample and the diluent or mobile phase divided by the sum of the incremental volumes of the sample.

A method may include reducing fluid flow between a rotor and a microfluidic device. The method may further include reducing a sealing force between the rotor and the microfluidic device. The method may also include rotating the rotor relative to the microfluidic device, at the reduced sealing force, to change a fluid pathway therebetween. The method may additionally include reestablishing the sealing force to produce a fluid tight seal between the rotor and the microfluidic device. Moreover, the method may include reestablishing the fluid flow between the rotor and the microfluidic device.

Managing fluidic connections to microfluidic devices

A method for detecting an analyte in a chromatography system includes performing a separation using a mobile phase that includes an organic component. The separation is performed with a primary separation module such as a chromatographic column. A first effluent, from the primary separation module, is modulated so that a fluidic plug containing an amount of the organic component and an analyte is provided to a secondary separation module where a secondary separation is performed. A second effluent, from the secondary separation module, includes temporally-resolved organic component and analyte peaks due to selective retention of the analyte. The second effluent is provided to a flame-based detector which is disabled when the organic modifier peak is received and enabled at least during the time when the analyte peak is received. Thus the analyte can be detected without interference from any response of the detector to the organic component peak.

Method and apparatus for flame ionization detection for chromatography

A microfluidic device, for use in separation systems, includes a substrate having a fluidic channel. One or more heaters made of a thick film material are integrated with the substrate and in thermal communication with the fluidic channel of the substrate. The one or more heaters produce a thermal gradient within the fluidic channel in response to a current flowing through the one or more heaters. A plurality of electrically conductive taps can be in electrically conductive contact with the one or more heaters. The plurality of electrically conductive taps provides an electrically conductive path to the one or more heaters by which an electrical supply can produce the current flowing through the one or more heaters. Alternatively, the thick film material can be ferromagnetic, and the electrical supply can use induction to cause the current to flow through the one or more heaters.

Apparatus and methods for creating a static and traversing thermal gradient on a microfluidic device

An apparatus for use in a chromatography system includes a microfluidic substrate having a fluidic channel configured as an analytical chromatographic column and a fluidic port on one side of the microfluidic substrate. The fluidic port opens at a head end of the analytical chromatographic column. A dried blood spot (DBS) collection device holds one or more dried biological samples. The DBS collection device is directly coupled to the microfluidic substrate whereby one of the biological samples is placed into fluidic communication with the fluidic channel of the microfluidic substrate and an extraction of that biological sample flows toward the head end of the analytical chromatographic column. A diluent source fluidically coupled to the fluidic port supplies a solvent to the head end of the analytical column to dilute the extracted biological sample before the biological sample flows into the analytical chromatographic column.

Analysis of dried blood spot samples in a microfluidic system with dilution of extracted samples

Flow through pressure sensors for use in fluid chromatography systems include a planar device formed from diffusion bonding of a plurality of metallic sheets and at least one sensing element. The planar device has a top surface, a bottom surface and a flow through channel. A diaphragm formed from a portion of one of the top or bottom surfaces is located adjacent to a sensing region of the flow through channel and is attached to the sensing element. The diaphragm is sized to deflect a distance in response to fluid pressure in the sensing region, which has an internal volume of less than about 25 microliters. The diaphragm and attached sensing element form a pressure sensor that measures strain or deflection of the diaphragm to calculate a pressure within the sensing region.

Pressure sensing and flow control in diffusion-bonded planar devices for fluid chromatography

Provided are systems and methods for adapting to volume variations in microfluidic chromatography columns. A column is calibrated by comparing a parameter of the column with a same parameter of a reference column and generating, by a processor, an adjustment factor in response to the comparison between the parameter of the column with a same parameter of the reference column. Volume differences between the calibrated column and the reference column are compensated for by integrating the generated adjustment factor into a sample separation involving the calibrated column.

Systems and methods of compensation for chromatography column volume variations

The invention provides interfaces between analytical instruments, e.g., between chromatography systems and mass spectrometers. In an exemplary embodiment, an ion source is provided for connecting a carbon dioxide-based chromatograph device to a mass spectrometer. The ion source includes a first conduit for receiving eluent from the chromatography device, a heater for heating at least a portion of said first conduit, a second conduit in fluid communication with the first conduit, an inlet for receiving eluent from said second conduit and introducing the eluent into an ion source region to form a plume of gas and/or liquid in the ion source region, and an ionization promoting inlet for injecting an ionization promoting fluid into the ion source region to interact with the plume to promote ionization of at least some of the plume.

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Millbury, MA, United States of America

Geoff C Gerhardt