AUTOMATED PROCESS LINE

• US 20020009394A1
• Filed: 04/02/1999
• Published: 01/24/2002
• Est. Priority Date: 04/02/1999
• Status: Abandoned Application

• Current Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: YIP, PING, MACDONALD, RICHARD, STEADMAN, JHOBE, REUTER, DIRK, KOSTER, HUBERT
• Application Number:
  US09/285,481
• Publication Number:
  US 20020009394A1
• Time in Patent Office: Days
• US Class Current: 422/65
• 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

A fully automated modular analytical system integrates instrumentation to permit analysis of biopolymer samples. The samples include, but are not limited to, all biopolymers, e.g., nucleic acids, proteins, peptides and carbohydrates. The system integrates analytical methods of detection and analysis, e.g., mass spectrometry, radiolabeling, mass tags, chemical tags, fluorescence chemiluminescence, and the like, with robotic technology and automated chemical reaction systems to provide a high-throughput, accurate Automated Process Line (APL).

Claims

1. A system for high throughput processing of biological samples, the system comprising:

a process line comprising a plurality of processing stations, each of which performs a procedure on a biological sample contained in a reaction vessel;

a robotic system that transports the reaction vessel from processing station to processing station;

a data analysis system that receives test results of the process line and automatically processes the test results to make a determination regarding the biological sample in the reaction vessel; and

a control system that determines when the test at each processing station is complete and, in response, moves the reaction vessel to the next test station, and continuously processes reaction vessels one after another until the control system receives a stop instruction.

2. A system as defined in claim 1, wherein the reaction vessel comprises a multiple-well sample tray.

3. A system as defined in claim 1, wherein one of the processing stations comprises a mass spectrometer.

4. A system as defined in claim 3, further including a mass spectrometer interface that automatically transfers samples into the mass spectrometer for processing.

5. A system as defined in claim 3, wherein the data analysis system processes the test results by receiving test data from the mass spectrometer such that the test data for a biological sample contains one or more peaks, whereupon the data analysis system removes a residual baseline from the test data for a biological sample, curve fits each peak of the biological sample test data to predetermined input parameters, determines a probability that each peak of the biological sample test data is a valid peak, and makes a data typing decision regarding the biological sample in accordance with the determined valid peaks.

6. A system as defined in claim 3, 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.

7. A system as defined in claim 3, wherein the data analysis system receives test run input parameters that determine processing until a different set of input parameters are received.

8. A system as defined in claim 7, 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.

9. A system as defined in claim 3, 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.

10. A system as defined in claim 9, wherein the input parameters specify a range of data over which the baseline will be modeled.

11. A system as defined in claim 10, wherein the baseline is modeled over a peak free region specified by the input parameters.

12. A system as defined in claim 8, wherein the picked peaks graph represents all peaks in the mass spectrometer output that have a height that exceeds the residual baseline corrected data.

13. A system as defined in claim 12, 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.

14. A system as defined in claim 1, wherein the process line includes a contamination-controlled environment and a non-sterile environment, and further includes a taxicab that automatically transports samples between the two environments.

56. The system of claim 1 that occupies two rooms, wherein the components in each room are linked by an automated sample transporter.

57. The system of claim 56, wherein one room is a clean room.

15. A method for high throughput processing of biological samples, the method comprising:

transporting a reaction vessel along a process line having a plurality of processing stations, each of which performs a procedure on one or more biological samples contained in the reaction vessel;

determining when the test procedure at each processing station is complete and, in response, moving the reaction vessel to the next processing station;

receiving test results of the process line and automatically processing the test results to make a data analysis determination regarding the biological samples in the reaction vessel; and

processing reaction vessels continuously one after another until receiving a stop instruction.

16. A method as defined in claim 15, wherein the reaction vessel comprises a multiple-well sample tray.

17. A method as defined in claim 16, wherein one of the processing stations comprises a mass spectrometer.

18. A method as defined in claim 17, wherein the step of transporting includes automatically transferring samples into a mass spectrometer for processing using a robotic mass spectrometer interface.

19. A method as defined in claim 17, wherein the step of receiving test results comprises:

receiving test data from the mass spectrometer such that the test data for a biological sample contains one or more peaks;

removing a residual baseline from the test data 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.

20. A method as defined in claim 17, further including the step of displaying 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.

21. A method as defined in claim 17, wherein the data analysis system receives test run input parameters that determine processing until a different set of input parameters are received.

22. A method as defined in claim 21, wherein the step of displaying comprises displaying 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.

23. A method as defined in claim 17, wherein the step of removing residual baseline from the test data comprises modeling the baseline of the mass spectrometer data with a quadratic equation specified by the input parameters.

24. A method as defined in claim 23, wherein the input parameters specify a range of data over which the baseline will be modeled.

25. A method as defined in claim 24, wherein the baseline is modeled over a peak free region specified by the input parameters.

26. A method as defined in claim 22, wherein the picked peaks graph represents all peaks in the mass spectrometer output that have a height that exceeds the residual baseline corrected data.

27. A method as defined in claim 26, 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.

28. A method as defined in claim 15, wherein the process line includes a contamination-controlled environment and a non-sterile environment, and the step of transporting includes automatically transporting samples between the two environments in a sterile taxicab.

29. 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; 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.

30. A data analysis system as defined in claim 29, wherein the reaction vessel comprises a multiple-well sample tray.

31. A data analysis system as defined in claim 29, wherein one of the processing stations comprises a mass spectrometer.

32. A data analysis system as defined in claim 31, wherein the data analysis system processes the test results by receiving test data from the mass spectrometer such that the test data for a biological sample contains one or more peaks, whereupon the data analysis system removes a residual baseline from the test data for a biological sample, curve fits each peak of the biological sample test data to predetermined input parameters, determines a probability that each peak of the biological sample test data is a valid peak, and makes a data typing decision regarding the biological sample in accordance with the determined valid peaks.

33. A data analysis system as defined in claim 29, 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.

34. A data analysis system as defined in claim 29, wherein the data analysis system receives test run input parameters that determine processing until a different set of input parameters are received.

35. A data analysis system as defined in claim 34, 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.

36. A data analysis system as defined in claim 31, 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.

37. A data analysis system as defined in claim 36, wherein the input parameters specify a range of data over which the baseline will be modeled.

38. A data analysis system as defined in claim 37, wherein the baseline is modeled over a peak free region specified by the input parameters.

39. A data analysis system as defined in claim 35, wherein the picked peaks graph represents all peaks in the mass spectrometer output that have a height that exceeds the residual baseline corrected data.

40. A data analysis system as defined in claim 39, 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.

41. A method for high throughput processing of biological samples, the method comprising:

transporting a reaction vessel along a process line having a processing station that performs a mass spectrometer test procedure on one or more biological samples contained in the reaction vessel;

providing the reaction vessel to the mass spectrometer and performing the mass spectrometer test; and

continuously providing reaction vessels to the mass spectrometer and receiving test results of the mass spectrometer and automatically processing the test results to make a determination regarding a characteristic of the biological samples in the reaction vessel, wherein the characteristic is the biological sample genotype.

42. A method as defined in claim 41, wherein the reaction vessel comprises a multiple-well sample tray.

43. A method as defined in claim 42, wherein the step of continuously providing reaction vessels to the mass spectrometer comprises automatically transferring samples into the mass spectrometer for processing using a robotic mass spectrometer interface.

44. A method as defined in claim 41, wherein the step of receiving test results comprises:

receiving test data from the mass spectrometer such that the test data for a biological sample contains one or more peaks;

removing a residual baseline from the test data 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.

45. A method as defined in claim 41, further including the step of displaying 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.

46. A method as defined in claim 41, wherein the data analysis system receives test run input parameters that determine processing until a different set of input parameters are received.

47. A method as defined in claim 46, wherein the step of displaying comprises displaying 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.

48. A method as defined in claim 41, wherein the step of removing 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.

49. A method as defined in claim 48, wherein the input parameters specify a range of data over which the baseline will be modeled.

50. A method as defined in claim 49, wherein the baseline is modeled over a peak free region specified by the input parameters.

51. A method as defined in claim 47, wherein the picked peaks graph represents all peaks in the mass spectrometer output that have a height that exceeds the residual baseline corrected data.

52. A method as defined in claim 51, 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.

53. A method as defined in claim 41, wherein the process line includes a contamination-controlled environment and a non-sterile environment, and the step of transporting includes automatically transporting samples between the two environments in a sterile taxicab.

54. A system for high throughput processing of biological samples, the system comprising:

a process line comprising a plurality of processing stations, each of which performs a procedure on a biological sample contained in a reaction vessel;

a robotic system that transports the reaction vessel from processing station to processing station; and

a control system that determines when the test at each processing station is complete and, in response, moves the reaction vessel to the next test station, and continuously processes reaction vessels one after another until the control system receives a stop instruction;

wherein the process line includes a taxicab that automatically transports samples between the two environments.

55. A system for high throughput processing of biological samples, the system comprising:

a process line comprising a plurality of processing stations, each of which performs a procedure on a biological sample contained in a reaction vessel;

a robotic system that transports the reaction vessel from processing station to processing station; and

a control system that determines when the test at each processing station is complete and, in response, moves the reaction vessel to the next test station, and continuously processes reaction vessels one after another until the control system receives a stop instruction;

further including a mass spectrometer interface that automatically transfers samples into the mass spectrometer for processing.