Title: On-line DNA analysis system with rapid thermal cycling

Abstract

An apparatus particularly suited for subjecting biological samples to any necessary sample preparation tasks, subjecting the sample to rapid thermal cycling, and then subjecting the sample to subsequent on-line analysis using one or more of a number of analytical techniques. The apparatus includes a chromatography device including an injection means, a chromatography pump, and a chromatography column. In addition, the apparatus also contains a capillary electrophoresis device consisting of a capillary electrophoresis column with an inlet and outlet end, a means of injection, and means of applying a high voltage to cause the differential migration of species of interest through the capillary column. Effluent from the liquid chromatography column passes over the inlet end of the capillary electrophoresis column through a tee structure and when the loading of the capillary electrophoresis column is desired, a voltage supply is activated at a precise voltage and polarity over a specific duration to cause sample species to be diverted from the flowing stream to the capillary electrophoresis column. A laser induced fluorescence detector preferably is used to analyze the products separated while in the electrophoresis column.

Inventors:

Swerdlow, Harold P ^[1]; Wittwer, Carl T ^[1]

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+ Show Inventor Affiliations

1. Salt Lake City, UT

Issue Date:

Fri Jan 01 00:00:00 EST 1999

Research Org.:

Oak Ridge Associated Universities (ORAU), Oak Ridge, TN (United States)

OSTI Identifier:

872436

Patent Number(s):

5935522

Assignee:

University of Utah Research Foundation (Salt Lake City, UT)

Patent Classifications (CPCs):

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01D - SEPARATION

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01L - CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

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B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01D - SEPARATION

B01D15/34 - Size selective separation, e.g. size exclusion chromatography, gel filtration, permeation

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01L - CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

B01L2400/0644 - rotary valves
B01L7/52 - {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples

G - PHYSICS G01 - MEASURING G01N - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES

G01N2030/027 - {Liquid chromatography}
G01N27/447 - using electrophoresis {
G01N30/02 - Column chromatography
G01N30/06 - Preparation
G01N30/463 - {for multidimensional chromatography}
G01N30/466 - {with separation columns in parallel}

Y - NEW / CROSS SECTIONAL TECHNOLOGIES Y10 - TECHNICAL SUBJECTS COVERED BY FORMER USPC Y10S - TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

Y10S436/807 - Apparatus included in process claim, e.g. physical support structures

Y - NEW / CROSS SECTIONAL TECHNOLOGIES Y10 - TECHNICAL SUBJECTS COVERED BY FORMER USPC Y10T - TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

Y10T436/11 - Automated chemical analysis
Y10T436/118339 - with formation of a segmented stream
Y10T436/25 - including sample preparation
Y10T436/25375 - Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
Y10T436/255 - including use of a solid sorbent, semipermeable membrane, or liquid extraction

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DOE Contract Number:  

AC05-76OR00033

Resource Type:

Patent

Country of Publication:

United States

Language:

English

Subject:

on-line; dna; analysis; rapid; thermal; cycling; apparatus; particularly; suited; subjecting; biological; samples; sample; preparation; tasks; subsequent; analytical; techniques; chromatography; device; including; injection; means; pump; column; addition; contains; capillary; electrophoresis; consisting; inlet; outlet; applying; voltage; differential; migration; species; effluent; liquid; passes; tee; structure; loading; desired; supply; activated; precise; polarity; specific; duration; diverted; flowing; stream; laser; induced; fluorescence; detector; preferably; analyze; products; separated; biological samples; liquid chromatograph; sample preparation; capillary column; voltage supply; particularly suited; capillary electrophoresis; thermal cycling; device including; liquid chromatography; laser induced; rapid thermal; chromatography column; flowing stream; analytical techniques; injection means; fluorescence detector; induced fluorescence; biological sample; electrophoresis device; analytical technique; /422/73/204/210/435/436/