Advion Biosciences, Inc.

Other

Kionix, Inc.

Advanced Bioanalytical Services, Inc.

Advion Bioscience, Inc.

Advion Inc.

Advion Biosystems, Inc.

Thomas N Corso

Gary A Schultz

Timothy J Davis

Gregory J Galvin

James E Moon

Stephen Lowes

Simon Prosser

Xian Huang

Sheng Zhang

Jie Li

Colleen K Van Pelt

Simon J Prosser

A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths in its microchannels is disclosed. The polymer monoliths are liquid-permeable and serve as microcolumns for liquid chromatography, which are prepared by in situ radical polymerization of a mixture containing vinyl monomers and solvents (porogen) in the microchannels. A method and system are disclosed to generate one or more electrospray plumes from one or more nozzles that provide an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analyses contained within the fluid. A plurality of electrospray devices can be used in the form of an array of miniaturized separate electrospray devices for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid for analysis. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods. The silicon chip having the packed microchannels disclosed herein finds application in coupling with mass spectrometry for sample analysis. Also disclosed is a separation block having multiple through-substrate channels filled with a separation material such as polymer monolith which can be stacked in multiple blocks for sequential two-dimensional chromatographic separation and integrated with the electrospray device.

Separation media, multiple electrospray nozzle system and method

A dielectric film is provided which includes a base layer and a capping layer, preferably silicon oxynitride, wherein the film is an effective moisture and ion barrier when disposed between a conductive substrate and a liquid having an electrical potential different than the electrical potential of the substrate.

Dielectric film

An electrospray nozzle system is disclosed. The electrospray portion of the device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The nozzle system may be utilized alone or as part of a liquid chromatography system.

Electrospray nozzle and monolithic substrate

An electrospray device is disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray.

Microfabricated electrospray device

A method for fabricating a nozzle of microchip-based electrospray device is disclosed. The method includes using a primary mask to accurately define the nozzle feature including the annulus and the through hole of the electrospray device. A secondary masking step is conducted to pattern the through channel (typical the photoresist would serve as the secondary mask), followed by the defining and etching of the primary mask containing the full nozzle feature. The secondary mask serves to selectively mask given areas of the primary mask for subsequent etching. The through hole feature of the secondary mask aligns over the already patterned primary mask through channel, except that the secondary mask contains a slightly larger through channel diameter. This serves to mask off the annulus, but allowing the silicon through channel to be exposed for etching.

Fabrication of a microchip-based electrospray device

A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate droplets or an electrospray. A plurality of these electrospray devices can be used in the form of an array of miniaturized nozzles. The liquid chromatography-electrospray device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow. A cover substrate is bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate. The exit orifice of the liquid chromatography device is homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. Procedures for fabrication of the electrospray devices of the present invention are also disclosed.

Integrated monolithic microfabricated dispensing nozzle and liquid chromatography-electrospray system and method

A microchip-based electrospray ionization device and column with affinity adsorbents is disclosed. The invention includes a microchip array and a capillary tube or alone or attached in combination. At least a portion of the device or column has immobilized affinity adsorbents. Methods for using the device are provided as well for affinity capture of biomolecules to meet the needs for the modem life sciences such as proteomics and drug discover.

Microchip electrospray device and column with affinity adsorbents and use of the same

A microchip-based electrospray ionization device and column with affinity adsorbents is disclosed. The invention includes a microchip array and a capillary tube or alone or attached in combination. At least a portion of the device or column has immobilized affinity adsorbents. Methods for using the device are provided as well for affinity capture of biomolecules to meet the needs for the modern life sciences such as proteomics and drug discover.

An electrospray device, a liquid chromatography device and an electrosprayliquid chromatography system are disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The liquid chromatography device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow; a cover substrate bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate; and, optionally, electrode(s) for application of a electric potential to the fluid. The exit orifice of the liquid chromatography device may be homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. An array of multiple systems may be fabricated in a single monolithic chip for rapid sequential fluid processing and generation of electrospray for subsequent analysis, such as by positioning the exit orifices of the electrospray devices near the sampling orifice of a mass spectrometer.

Integrated monolithic microfabricated electrospray and liquid chromatography system and method

An electrospray device, a liquid chromatography device and an electrospray-liquid chromatography system are disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The liquid chromatography device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow; a cover substrate bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate; and, optionally, electrode(s) for application of a electric potential to the fluid. The exit orifice of the liquid chromatography device may be homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. An array of multiple systems may be fabricated in a single monolithic chip for rapid sequential fluid processing and generation of electrospray for subsequent analysis, such as by positioning the exit orifices of the electrospray devices near the sampling orifice of a mass spectrometer.

A microchip-based electrospray device, system, and method of fabrication thereof are disclosed. The electrospray device includes a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electric field generating source for application of an electric potential to the substrate to optimize and generate an electrospray. A method and system are disclosed to generate multiple electrospray plumes from a single fluid stream that provides an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analytes contained within the fluid. A plurality of electrospray nozzle devices can be used in the form of an array of miniaturized nozzles for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid stream. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods.

Growing community of inventors

Lansing, NY, United States of America

Thomas N Corso