Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2003-08-26
2004-10-12
Wells, Nikita (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S282000, C250S281000, C250S285000, C250S428000
Reexamination Certificate
active
06803568
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to microfluidic chips for electrospray ionization applications. More particularly, the invention relates to improved electrospray ionization tips for mass spectrometric analysis.
BACKGROUND OF THE INVENTION
Electrospray ionization is used to produce ions for mass spectrometry analysis including ions that are derived from relatively large complex molecules such as proteins and nucleic acid molecules. During the electrospray ionization procedure, a sample solution is exposed to an electrical field that charges the surface of the liquid and emerges from an electrospray tip or needle. A spray of finely dispersed charged droplets is thereby generated that is suitable for analysis by a mass spectrometer. The need for conducting high-throughput analysis of relatively small biological samples has led to the development of microfluidic chip devices for electrospray ionization applications.
Microfluidic chips are often constructed using well known techniques employed in the semiconductor industry such as photolithography, wet chemical etching, and thin film deposition. These devices conveniently support the separation and analysis of sample sizes that are as small as a few nanoliters or less. In general, these chips are formed with a number of microchannels that are connected to a variety of reservoirs containing fluid materials. The fluid materials are driven or displaced within these microchannels throughout the chip using electrokinetic forces, pumps and/or other driving mechanisms. The microfluidic devices available today can conveniently provide mixing, separation, and analysis of fluid samples within an integrated system that is formed on a single chip.
There are numerous design alternatives to choose from when constructing an interface for microfluidic chips and electrospray ionization mass spectrometers. Some electrospray ionization interfaces include microfluidic chips that attempt to spray charged fluid droplets directly from the edge of the chip. But the accompanying solvent is known to wet much of the edge surface of the chip so as not to offer a high-stability spray for many applications. Other attempts to spray ionized particles directly from the edge of a microfluidic chip edge therefore rely on the formation of a hydrophobic surface that can yield improved spray results; however, even that often proves to be insufficiently stable. At the same time, adequate results can be also achieved with other chip devices that incorporate fused silica capillary needles or micromachined or molded tips. In particular, some recent electrospray ionization designs incorporate small silicon etched emitters positioned on the edge of a microfluidic chip. While it is possible to generate a relatively stable ionization spray for mass spectrometric analysis with some of these microfluidic devices today, they generally require apparatus that is relatively impractical and economically unfeasible for mass production.
A high performance electrospray ionization device is therefore needed for mass spectrometry applications that can be economically produced using large scale manufacturing processes.
SUMMARY OF THE INVENTION
The invention provides methods and apparatus related to microfluidic chips and electrospray ionization applications. Various aspects of the invention can be appreciated individually or collectively to provide an effective interface for microfluidic systems and mass spectrometers or other analytical devices.
A preferable embodiment of the invention provides microfluidic chips that are formed with individual fluid channels. These fluid channels extend through the body of the microfluidic chip and converge at a common distal tip region. The distal tip region includes an open-ended distal tip formed along a defined surface of a microfluidic chip body. The microfluidic chip may be constructed from a pair of polymer plates in which the converging channels run through and lead up to the distal tip region. The microfluidic chip can be also formed with multiple but separate channels that supply fluids such as samples and sheath flow solutions to a single common electrospray tip.
In accordance with another embodiment of the invention, a recessed electrospray ionization tip is provided that is formed along a defined edge of a microfluidic chip. The electrospray device may include a separately formed tip constructed from a shaped thin-film that is bonded to and in between a pair of polymer layers. The separately formed tip may be formed with an exposed distal tip region at which multiple fluid channels converge. The tip may further include fluid channels that are respectively aligned with corresponding fluid channels that are embossed or otherwise formed within the microfluidic chip.
The invention further provides single-use disposable microfluidic chips that are reliable, reproducible and easy-to-use. These microfluidic chips may be selected for sample separation and electrospray ionization processes utilizing electrospray emitters that are formed as an integral part of the chip. These embodiments of the invention reflect a chip design that provides an economical and effective solution that can be reproduced on a large scale production. Many microfluidic chips can be fabricated in batch quantities thus reducing the number of time-consuming steps in forming electrospray emitters and tips.
Another aspect of the invention provides methods of manufacturing microfluidic devices with separately formed ESI emitters. The microfluidic devices may be readily manufacturable following a mass production molding process. Many individual fluid devices may be fabricated at the same time using techniques similar to the manufacture of semiconductor chips for microprocessors. A metal-coated thin film polymer may be separately formed and bonded to polymer plates which are later separated into individual microfluidic devices by cutting apparatus. These and other embodiments of the invention provide convenient fabrication methods for economically manufacturing microfluidic devices for electrospray ionization applications.
Other goals and advantages of the invention will be further appreciated and understood when considered in conjunction with the following description and accompanying drawings. While the following description may contain specific details describing particular embodiments of the invention, this should not be construed as limitations to the scope of the invention but rather as an exemplification of preferable embodiments. For each aspect of the invention, many variations are possible as suggested herein that are known to those of ordinary skill in the art. A variety of changes and modifications can be made within the scope of the invention without departing from the spirit thereof.
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Bousse Luc
Stults John T.
Predicant Biosciences, Inc.
Wells Nikita
Wilson Sonsini Goodrich & Rosati
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