Automated process line

• US 6,730,517 B1
• Filed: 10/05/2000
• Issued: 05/04/2004
• Est. Priority Date: 04/02/1999
• Status: Expired due to Term

• Current Assignee: Agena Bioscience Inc. (Mesa Laboratories Inc.)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: Yip, Ping, Köster, Hubert, Steadman, Jhobe, MacDonald, Richard, Reuter, Dirk
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): CROSS, LATOYA I
• Application Number:
  US09/680,581
• Time in Patent Office: 1,307 Days
• Field of Search: 422/63, 422/65, 422/67, 422/102, 436/43, 436/47, 436/173, 436/131, 250/251, 250/282, 250/287, 250/288, 700/266
• US Class Current: 436/47
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/203332 Hydroxyl containing
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25875 Gaseous sample or with change of physical state

Abstract

Fully automated modular analytical systems with integrated instrumentation for analysis of biopolymer samples, such as nucleic acids, proteins, peptides and carbohydrates, are provided. Analytical methods of detection and analysis, such as mass spectrometry, radiolabeling, mass tags, chemical tags and fluorescence chemiluminescence, are integrated with robotic technology and automated chemical reaction systems to provide a high-throughput, accurate Automated Process Line (APL).

Claims

1. A data analysis system comprising:

a computer having an operating environment that executes a data analysis program for processing test results from a process line having a plurality of processing stations, each of which performs a procedure on a biological sample contained in a reaction vessel, wherein one of the processing stations comprises a mass spectrometer;

a data analysis program for processing the test results by receiving test results from one or more of the processing stations;

removing a residual baseline from the test data from the mass spectrometer for a biological sample;

curve fitting each peak of the biological sample test data to predetermined input parameters;

determining a probability that each peak of the biological sample test data is a valid peak; and

making a data typing decision regarding the biological sample in accordance with the determined valid peaks; and

a computer interface that receives the test results from the process line and provides the test results to the data analysis program, wherein the data analysis program automatically processes the test results to make a determination regarding the biological sample in the reaction vessel, and continuously performs such processing for biological samples until a stop instruction is received.

2. A data analysis system of claim 1, wherein the reaction vessel comprises a multiple-well plate.

3. A data analysis system of claim 1, wherein the data analysis system displays exemplary test spectra for data types to be determined by the data analysis system, along with a graph of test data picked peaks and a graph of smoothed test spectra data for a biological sample.

4. A data analysis system of claim 1, wherein the data analysis system receives test run input parameters that determine processing until a different set of input parameters are received.

5. A data analysis system of claim 4, wherein the data analysis system displays exemplary test spectra for data types to be determined by the data analysis system, along with a graph of test data picked peaks and a graph of smoothed test spectra data for a biological sample, and the input parameters specify display parameters.

6. A data analysis system of claim 1, wherein the data analysis system removes the residual baseline from the test data by modeling the baseline of the mass spectrometer data with a quadratic equation specified by the input parameters.

7. A data analysis system of claim 6, wherein the input parameters specify a range of data over which the baseline will be modeled.

8. A data analysis system as defined in claim 7, wherein the baseline is modeled over a peak, free region specified by the input parameters.

9. A data analysis system as defined in claim 5, wherein the picked peaks graph represents all peaks in the mass spectrometer output that have a height that exceeds the residual baseline corrected data.

10. A data analysis system as defined in claim 9, wherein the data analysis system validates a peak after comparing a probability density function for the peak free region with a probability density function for a fitted peak if the comparison shows that the respective probability density functions overlap by a predetermined amount.

11. The system of claim 1, wherein the mass spectrometric format is matrix assisted laser desorption time-of-flight analysis (MALDI-TOF).

12. A data analysis system of claim 1, wherein the data typing decision is a genotype.

13. A data analysis system of claim 1, wherein the predetermined input parameters serve as landmarks to identify output shifting.

14. A data analysis system of claim 1, further comprising an operator interface.