Chemistry: analytical and immunological testing – Nuclear magnetic resonance – electron spin resonance or other...
Reexamination Certificate
1999-03-25
2002-02-26
Soderquist, Arlen (Department: 1743)
Chemistry: analytical and immunological testing
Nuclear magnetic resonance, electron spin resonance or other...
C250S285000, C250S288000, C422S068100, C422S105000, C436S161000, C436S174000, C436S177000, C436S180000, C436S183000
Reexamination Certificate
active
06350617
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to liquid delivery devices, and more particularly, the invention relates to devices for delivery of multiple liquid sample streams to a mass spectrometer for analysis of compound libraries.
2. Brief Description of the Related Art
In recent years, a large number of combinatorial chemistry techniques have been developed which permit vast libraries of diverse chemical compounds to be rapidly synthesized. In combinatory chemistry, a series of chemical reactions is conducted, typically employing a plurality of reagents at each step, to generate a library of compounds. Such techniques have the potential to greatly accelerate the discovery of new compounds having biologically useful properties by providing large collections of diverse chemical compounds for biological screening.
Mass spectrometry is emerging as an important tool for the interrogation of combinatorial libraries. To date, mass spectrometry has been used to assess library quality and, when coupled with molecular recognition technologies, has allowed for some success in the isolation and characterization of active library compounds. Applications of mass spectrometry have become increasingly important in combinatory chemistry and biological research.
Mass spectrometry obtains molecular weight and structural information on chemical compounds by ionizing the molecules and measuring either their time-off-light or the response of the molecular trajectories to electric and/or magnetic fields. The electrospray process is one of the most promising techniques for producing gas phase molecular ions for a wide range of molecular entities.
Mass spectrometry is also being increasingly relied on for the analysis of large numbers of samples. In particular, biomolecule sequencing (proteins, DNA) as well as the emerging field of proteomics require the mass spectral profiling of a large number of chromatographic fractions. For example, a two-dimensional electrophoretic separation such as SDS-PAGE (sodium docecyl sulfatepolyacrylamide gel electrophoresis) can lead to the separation of several thousand proteins from a cell extract, where each fraction requires mass spectral characterization.
According to a conventional electrospray process, a sample solution containing molecules of interest and a suitable solvent is pumped or drawn through an electrospray needle into an electrospray chamber. A potential of up to several kilovolts may be applied to the needle to generate a fine spray of charged droplets. Conversely, the needle may be held at ground and the solution sprayed into an externally generated electric field. The droplets are typically sprayed into the chamber at atmospheric pressure. Optionally, this chamber houses gas lines (e.g., N
2
) to aid in the nebulization of the solvent stream and the disolvation or evaporation of solvent. The ions generated by the electrospray process are then guided into the mass spectrometer by appropriate electric field gradients. This typically requires multiple stages of pumping for the removal of excess neutrals, such as solvent vapor.
With this conventional electrospray apparatus, the electrospray needle is connected to a single sample stream and delivers the molecules contained therein by the electrospray process to the mass spectrometer for analysis. When multiple sample streams are prepared, it is time consuming to switch between successive sample streams. This is due to the fact that the available electrospray mass spectrometers are marketed with a single electrospray needle. Therefore, switching streams involves physically breaking the connection between the needle and one sample stream, and re-establishing a connection with the next stream. Aside from the time involved in switching streams, the possibility exists for cross-contamination of the various streams.
It would be desirable to permit multiple sample streams from multiple chromatography columns or from other sample sources to be easily connected to the electrospray apparatus of a mass spectrometer for intermittent analysis of the sample streams from multiple columns. It would also be desirable to automatically move from analysis of one sample stream to another to analyze a plurality of sample streams in as short a period of time as possible.
SUMMARY OF THE INVENTION
The present invention relates to electrospray devices employing multiple electrospray needles mounted to sequentially deliver multiple sample streams to a mass spectrometer for analysis.
In accordance with one aspect of the invention, an electrospray device for a mass spectrometer includes an electrospray chamber, a plurality of electrospray needles mounted on a support in a substantially circular arrangement, a rotatable member, and a charger. The electrospray needles are connectable to a plurality of sample streams for delivery of droplets of the sample streams to a mass spectrometer orifice. The rotatable member rotates to direct droplets of one of the sample streams at a time to the mass spectrometer orifice. The charger applies a charge to the droplets of the sample stream in the electrospray chamber and causes the droplets to be focused into a beam passing through the orifice into the mass spectrometer.
In accordance with another aspect of the present invention, a method is provided for delivering a plurality of sample streams to a mass spectrometer for analysis. The method includes the steps of: providing a plurality of sample streams to a plurality of electrospray needles mounted on a support; continuously spraying the sample streams with the electrospray needles; and sequentially providing an outlet of each of the electrospray needles at a delivery position for a predetermined dwell time by rotating and stopping a rotatable member to deliver the sample streams to the mass spectrometer.
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Hindsgaul Ole
Schriemer David C.
Burns Doane , Swecker, Mathis LLP
Soderquist Arlen
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