Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
1999-04-13
2001-10-02
Warden, Jill (Department: 1743)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S450000, C204S600000, C204S603000, C436S172000, C250S458100, C250S459100, C250S461100, C356S344000
Reexamination Certificate
active
06296749
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to systems and methods applicable to chromatography and electrophoresis, and more particularly to a system and method for chromatography and electrophoresis using circular optical scanning.
2. Discussion of Background Art
Chromatography is a technique for separating molecules based on how they tend to cling to or dissolve in various solids, liquids and gases. Electrophoresis is also a technique for separating large molecules (such as DNA fragments or proteins) from a mixture of similar molecules. However, in electrophoresis, an electric current is passed through a medium containing the molecules. Each type of molecule travels through the medium at a different rate, depending on its electrical charge and size, which creates a series of identifying bands.
Many chromatography and electrophoresis systems, having multiple analysis columns within a microchannel plate, use scanning optical detection systems based on Laser Induced Fluorescence (LIF) or UV absorbence to detect the presence of analytes as they travel past the scan path of an optical detection beam. These scanning detection systems typically include a high intensity light source (e.g. laser), one or more optical detectors (e.g. Photo-Multiplier Tubes (PMTs) or Charge Coupled Devices (CCDs), various electronic circuits (e.g. amplifiers, filters, A-to-D converters), and a computer for control, data collection, and storage.
FIG. 1
is a block diagram of a prior art
100
system using “linear” optical scanning. The prior art optical scanning systems
100
use linear scan motors to move the light source back and forth in a straight line
102
across the analysis columns in the microchannel plate so as to periodically excite and detect the presence of analyte molecules. The number of analysis columns that can be detected in these linear scanned systems is limited principally by the width of the array of columns, the velocity of the analytes as they move past the detecting light beam, the intensity of the illuminating light beam on the analyte, and the spatial resolution, accuracy, and maximum speed with which the linear scan stage can be driven (usually via an electric motor). High resolution, accuracy and low vibration requirements limit current stepper motors and servo motors limit the maximum velocities of linear scan stages to approximately 30 cm/sec and therefore, limit the number of analysis columns that can be detected to approximately 100 analysis columns maximum. This is because for wider microchannel plates, some of the analyte molecules on one end of the microchannel plate may pass through the linear detection area before the linear detector can return to the analysis columns in which they are contained.
Recently, efforts are being made to sequence all the molecules in the human genome as soon as possible. Due to this and other growing needs for even faster chromatography and electrophoresis systems, linear systems limited to only 100 analysis columns are too constricting.
In response to the concerns discussed above, what is needed is a system and method for chromatography and electrophoresis that overcomes the problems of the prior art.
SUMMARY OF THE INVENTION
The present invention is a system and method for chromatography and electrophoresis using circular optical scanning. Within the system of the present invention there are either one or more rectangular microchannel plates or radial microchannel plates. Each microchannel plate has a set of analysis channels for insertion of molecular samples for analysis. One or more scanning devices repeatedly pass over the analysis channels in one direction at a predetermined rotational velocity and with a predetermined rotational radius. Radial microchannel plates are built from a substrate whose first analysis channel has a first longitudinal axis, and whose next analysis channel has another longitudinal axis disposed at a non-parallel angle with respect to the first longitudinal axis.
In another aspect of the invention, each microchannel plate could have hundreds or thousands of analysis channels to increase system throughput.
In another aspect of the invention, the rotational radius may be dynamically varied so as to monitor the molecular sample at various positions along a analysis channel. Sample loading robots may also be used to input molecular samples into the analysis channels within one or more microchannel plates.
The method of the present invention includes the steps of accessing a microchannel plate, having a set of analysis channels, and passing a scanning device repeatedly over the analysis channels in a constant direction.
In another aspect of the invention, the method further includes the steps of, selecting a second microchannel plate, having analysis channels, and passing the scanning device repeatedly from the first microchannel plate to the second microchannel plate is a constant direction. Alternatively, the accessing steps are replaced with the step of accessing a radial microchannel plate, having neighboring analysis channels positioned at non-parallel angle with respect to each other.
In another aspect of the invention, the method further includes the step of, passing the scanning device over the analysis channels at a dynamically varying distance from a centerpoint of the scanning device.
In another aspect of the invention, the method further includes the step of, loading molecular samples into the analysis channels with a robot.
The system and method of the present invention are particularly advantageous over the prior art because a circular scanned optical detection system is disclosed that enables efficient detection of material samples being analyzed by multiple chromatography or electrophoresis units each containing a set of analysis channels. This system enables at least a quadrupling of a number of chromatography or electrophoresis sample analysis channels that can be detected by a single optical detection system and can result in a significant cost savings, simpler scanning hardware, and reduced laboratory space needed for high volume material analysis systems based on chromatography or electrophoresis. Also disclosed is a concept for building electrophoresis instrument modules or clusters that have thousand of electrophoresis analysis channels and efficiently share a limited number of circular scanning devices and sample loading robots.
Furthermore, the present invention is applicable to chromatography and electrophoresis material analysis applications involving optical detection, including those which analyze organic and inorganic materials. Well recognized applications include DNA fragment sizing, DNA sequencing, analysis of biological materials for drug discovery effects, and genetic disease susceptibility diagnostics and studies.
These and other aspects of the invention will be recognized by those skilled in the art upon review of the detailed description, drawings, and claims set forth below.
REFERENCES:
patent: 5483075 (1996-01-01), Smith et al.
patent: 6100535 (2000-08-01), Mathies et al.
patent: WO 00/62043 (2000-10-01), None
Balch Joseph W.
Brewer Laurence R.
Davidson James C.
Kimbrough Joseph R.
Scott Eddie E.
Starsiak Jr. John S.
The Regents of the University of California
Thompson Alan H.
Warden Jill
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