Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2002-04-30
2003-09-16
Nguyen, Kiet T. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
Reexamination Certificate
active
06621076
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to the transport of sample fluids into a mass spectrometer. More particularly, the invention relates to devices and methods that use a flexible fluid-transporting assembly to deliver sample fluids from a well plate through a mass spectrometer interface directly into an inlet opening of a mass spectrometer.
BACKGROUND
Mass spectrometry is an important analytical technique for the identification of chemical or biochemical compounds. By ionizing sample molecules and sorting the ionized molecules according to their mass-to-charge ratios, mass spectrometry has demonstrated its usefulness in the identification of a wide variety of molecules, such as small organic compounds synthesized in large libraries, biological compounds, such as peptides, proteins, and carbohydrates, and a wide variety of naturally occurring compounds. For example, mass spectrometry may employ electrospray technology that allows ions to be produced from a sample fluid containing sample molecules in a carrier liquid. Typically, electrospray technology produces an ionized aerosol by passing a sample fluid through a rigid capillary extending in a horizontal direction and subjecting the outlet terminus of the capillary to an electric field. The electric field is usually generated by placing a source of electrical potential, e.g., an electrode, near the outlet terminus of the capillary, wherein the electrode is held at a voltage potential difference with respect to the outlet terminus. As the sample fluid exits the capillary from the outlet terminus, droplets having a net charge are formed. When the carrier liquid is evaporated from the droplets, ionized sample molecules are produced. In some instances, a plurality of capillaries may be employed to deliver ions from multiple sample fluids to a mass spectrometer. See, e.g., U.S. Pat. No. 6,191,418 to Hindsgaul et al. The ionized sample molecules are then sorted in a vacuum according to mass-to-charge ratio. When all sample molecules carry the same charge, e.g., are singly charged, sorting the ionized sample molecules according to mass-to-charge ratio is equivalent to sorting the sample molecules according to mass.
Microfluidic devices have also been proposed for use to carry out chemical analysis and processing. Their small size allows for the analysis and processing of minute quantities of a sample fluid, which is an advantage when the sample is expensive or difficult to obtain. See, e.g, U.S. Pat. No. 5,500,071 to Kaltenbach et al., U.S. Pat. No. 5,571,410 to Swedberg et al., and U.S. Pat. No. 5,645,702 to Witt et al. Typically, microfluidic devices are formed from substantially planar structures comprised of glass, silicon, or other rigid materials and employed in conjunction with internal or external motive means to move fluids therein for analysis and/or processing. Microfluidic devices represent a potentially inexpensive or disposable means that integrates sample preparation, separation, and detection functionality in a single tool. In addition, microfluidic devices are well suited to process and/or analyze small quantities of sample fluids with little or no sample waste.
A number of patents and applications have described the incorporation of electrospray technology in microfluidic devices. For example, U.S. Pat. No. 5,994,694 to Tai et al. describes a micromachined electrospray nozzle for mass spectrometry. Instead of using a glass capillary to delivery sample fluid for electrospray ionization, an overhanging silicon nitride microchannel serves as an electrospray ionization nozzle. The microchannel is located within a rigid silicon support substrate.
In addition, commonly owned U.S. Ser. No. 09/324,344 (“Miniaturized Device for Sample Processing and Mass Spectroscopic Detection of Liquid Phase Samples”), inventors Yin, Chakel, and Swedberg (claiming priority to Provisional Patent Application No. 60/089,033), describes a miniaturized device for sample processing and mass spectroscopic detection of liquid phase samples. The described device comprises a substrate having a feature on a surface in combination with a cover plate. Together, a protrusion on the substrate and a corresponding protrusion on the cover plate may form an on-device mass spectrometer delivery means. On-device features such as microchannels and apertures may be formed through laser ablation or other techniques. Other commonly owned applications include: U.S. Ser. No. 09/711,804, which describes a similar microfluidic device having a protruding electrospray emitter; and U.S. Ser. No. 09/820,321, which describes a microfluidic device that includes a means for nebulizing a sample fluid from an outlet of the microfluidic device for delivery into an ionization chamber.
There is a current need in the pharmaceutical industry to quickly screen, identify, and/or process a large number and/or variety of samples. For instance, the samples may represent a collection or library of organic and/or biological compounds. Such compounds may originate from a number of sources and may be, for example, extracted from naturally occurring plants and animals or synthesized as a result of combinatorial techniques. In particular, there is a need to screen biological compounds, such as peptides, proteins, and carbohydrates. Thus, microfluidic devices may contain multiplexed features of multiple inlets and multiple spray tips. For example, U.S. Pat. No. 6,245,227 to Moon et al. describes an integrated monolithic microfabricated electrospray nozzle and liquid chromatography system. This patent also proposes that 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.
Well plates are often used to store a large number of samples for screening and/or processing. Well plates are typically single piece items that comprise a plurality of wells, wherein each well is adapted to contain a sample fluid. Each well of the well plate has a small interior volume, defined in part by an interior surface extending downwardly from an opening at an upper surface of the well plate. Such well plates are commercially available in standardized sizes and may contain, for example, 96, 384, or 1536 wells per well plate.
To bring these samples from their containers to the mass spectrometer, with or without intermediate processing is currently a cumbersome task, requiring excessive fluid volume and time. Pipettes are typically employed to convey sample fluid from the wells of a well plate into an inlet of an analytical and/or processing device. While robotic and/or automated systems using pipette technology may be configured to handle a large number of sample fluids, pipettes suffer from a number of intrinsic drawbacks. For example, pipettes are incapable of performing continuous fluid transfer from a well to the inlet. In addition, many pipettes are typically incapable of dispensing fluids in a horizontal direction into an analytical and/or processing device. Thus, there is a need for a fluid-transporting device that overcomes the drawbacks of pipettes.
Although microfluidic devices often comprise motive means that are well suited for effecting controlled fluid flow, such devices are generally unsuitable for transporting sample fluids directly from a sample well to a mass spectrometer. As discussed above, most microfluidic devices are made from glass, silicon, or other rigid structures. While it is possible to place such devices directly over a well plate in an attempt to transport fluids directly from the sample well for processing before introduction into a mass spectrometer, typical microfluidic device construction would require the device to be positioned vertically on its edge, which would adversely affect control over fluid flow. In addition, when electrospray nozzles are an integral part of a rigid microfluidic device, it may be difficult to achieve the proper alignment needed to carry out mass spectrometry. That is, the relative positions of the well plate, microfluidic d
Killeen Kevin Patrick
van de Goor Tom A.
LandOfFree
Flexible assembly for transporting sample fluids into a mass... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Flexible assembly for transporting sample fluids into a mass..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Flexible assembly for transporting sample fluids into a mass... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3022244