Chemistry: electrical and wave energy – Apparatus – Electrophoretic or electro-osmotic apparatus
Reexamination Certificate
2000-07-21
2001-05-15
Warden, Jill (Department: 1743)
Chemistry: electrical and wave energy
Apparatus
Electrophoretic or electro-osmotic apparatus
C204S451000, C422S105000, C422S105000
Reexamination Certificate
active
06231739
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to apparatus and methods useful for biochemical analysis. More specifically, this invention relates to a highly automated capillary electrophoresis apparatus for the simultaneous analysis of multiple samples, and methods for using such apparatus.
BACKGROUND
Capillary electrophoresis (CE) is a powerful analytical separation technique that brings speed, quantitation, reproducibility and automation to the inherently highly resolving but typically labor intensive methods of electrophoresis (e.g.,
Capillary Electrophoresis Theory and Practice
, Grossman and Colburn, eds., Academic Press (1992)). While early capillary electrophoresis systems utilized only a single capillary tube, multi-capillary systems have been developed to provide increased throughput (e.g., Mathies et al., U.S. Pat. No. 5,247,240; Dovichi and Zhang, U.S. Pat. No. 5,439,578; Kambara, U.S. Pat. No. 5,516,406; Takahashi, et al.,
Anal. Chem.,
66: 1021-1026 (1994)). Such multi-capillary CE systems are particularly attractive for use in large scale DNA sequencing projects.
However, existing multi-channel capillary electrophoresis systems have several significant shortcomings that limit their utility, particularly for applications requiring a high degree of automation, throughput, detection sensitivity and reliability. For example, existing systems do not provide for a sheath-flow detection cuvette wherein a capillary array may be replaced by a user without extensive disassembly of the cuvette. In addition, existing systems do not provide for a sheath-flow detection cuvette wherein fresh separation media and/or capillary wash solutions may be introduced into outlets of the capillary tubes under high pressure. Thus, there remains a continuing need for an automated multi-channel capillary electrophoresis device including these features.
SUMMARY
The present invention is directed towards our discovery of a multi-channel capillary electrophoresis device including a sheath-flow detection cuvette wherein a capillary array is easily replaceable by a user, and wherein fresh separation media and/or capillary wash solutions may be introduced into outlets of the capillary tubes under high pressure.
In a first aspect, the invention comprises a multi-channel capillary electrophoresis apparatus. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having an outlet, and an outlet support for supporting the capillary outlets. In addition, the apparatus includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot of the cuvette is adapted to removably receive the outlet support. When the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. The apparatus further includes a plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.
These and other features and advantages of the present invention will become better understood with reference to the following description, drawings, and appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1
shows a perspective view of a preferred capillary array assembly with an outlet support in the foreground.
FIG. 2
shows a perspective view of a preferred capillary array assembly with an inlet support in the foreground.
FIG. 3
shows a cross-section of a preferred capillary tube.
FIG. 4
shows a perspective view of a preferred inlet support.
FIG. 5
shows a perspective view of a preferred inlet support wherein the inlet support is registered with respect to a frame member.
FIG. 6
shows a side view of a preferred inlet support.
FIG. 7
shows a perspective view of a preferred outlet support.
FIGS. 8
a
,
8
b
and
8
c
show an expanded perspective view of a platform portion of a preferred outlet support.
FIGS. 9
a
and
9
b
show a side view of a platform portion of a preferred outlet support.
FIG. 10
shows a side view of an alternative platform portion of a preferred outlet support.
FIG. 11
shows a perspective view of a preferred cuvette with a receiving slot in the foreground.
FIG. 12
shows a side view of a preferred cuvette.
FIG. 13
shows a perspective view of a preferred cuvette with a gap region in the foreground.
FIG. 14
shows a front view of a preferred cuvette located in a clamping block of the present invention.
FIG. 15
shows a perspective view of a preferred front plumbing block.
FIG. 16
shows a cutaway view of a preferred front plumbing block and a cuvette located behind the front plumbing block.
FIG. 17
shows a cross-section of a preferred operational combination of an outlet support, front plumbing block, and cuvette.
FIG. 18
shows a cross-section through the front plumbing block of FIG.
17
.
FIG. 19
shows a cross-section through the cuvette and platform portion of the outlet support of FIG.
17
.
FIG. 20
shows a see-through view of a preferred rear plumbing block.
REFERENCES:
patent: 4811218 (1989-03-01), Hunkapiller et al.
patent: 5274240 (1993-12-01), Mathies et al.
patent: 5439578 (1995-08-01), Dovichi et al.
patent: 5516409 (1996-05-01), Kambara
patent: 5667656 (1997-09-01), Kambara
patent: 6054032 (2000-04-01), Haddad et al.
patent: 0723149 (1996-07-01), None
patent: WO9938005 (1999-07-01), None
Cheng et al.,Science,vol. 242, Oct. 28, 1988, pp. 562-564.
Cheng Y F et al., “Interaction of Capillary Zone electrophoresis with a Sheath Flow Cuvette Detector,”Analytical Chemistry,US, American Chemical Society, Columbus, vol. 62, No. 5, Mar. 1, 1990, pp. 496-503.
K. Ueno et al.,Analytical Chemistry,vol. 66, No. 9, May 1, 1994, pp. 1424-1431.
Woolley et al., “High-Speed DNA Genotyping Using Microfabricated Capillary Array Electrophoresis Chips,”Anal. Chem.69(11):2181-2186 (Jun. 1, 1997).
Carrillo Albert L.
Demorest David M.
Nordman Eric S.
Shigeura John
Wunderle Philip J.
Grossman Paul D.
Starsiak Jr. John S.
The Perkin-Elmer Corporation
Warden Jill
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