Methods and apparatus for analyzing samples and collecting sample fractions

• US 8,305,581 B2
• Filed: 12/03/2010
• Issued: 11/06/2012
• Est. Priority Date: 12/05/2007
• Status: Active Grant

• Current Assignee: BÜCHI Labortechnik AG
• Original Assignee: Alltech Associates Incorporated (WR Grace & Company)
• Inventors: Anderson, James, Saari-Nordhaus, Raaidah, Mendoza, Washington, Bystron, Josef, Helgemo, Dirk, McCreary, Dennis
• Primary Examiner(s): Pajoohi Gomez, Tara S
• Application Number:
  US12/960,042
• Publication Number:
  US 20110310390A1
• Time in Patent Office: 704 Days
• Field of Search: 356432-442
• US Class Current: 356/436
• CPC Class Codes: G01N 2030/322 pulse dampers
• CPC Class Codes: G01N 2030/621 signal-to-noise ratio
• CPC Class Codes: G01N 30/28 Control of physical parameters of the fluid carrier
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J
• CPC Class Codes: G01N 30/78 using more than one detector
• CPC Class Codes: G01N 30/82 Automatic means therefor

Abstract

Methods and apparatus for analyzing a sample using at least one detector are disclosed.

Claims

1. A method of detecting and collecting one or more sample components within a sample stream in a chromatography system during a chromatographic run comprising:

generating a first signal during the chromatographic run from at least one destructive detector, including at least one evaporative particle detector;

generating a second signal during the chromatographic run from at least one non-destructive detector,

wherein said non-destructive detector monitors a whole absorbance spectrum or a portion thereof comprising more than one wavelength, and wherein said second signal comprises at least one response value from each of the more than one wavelength; and

collecting the one or more components from the stream in a fraction collector during the chromatographic run in response to a change in at least one of said signals during said chromatographic run.

2. The method of claim 1, wherein each signal comprises:

(i) detector response values for the respective generating detector at a given time,

(ii) the first derivatives of detector response values at a given time,

(iii) the second derivatives of said detector response values at a given time, or

(iv) any combination of (i) to (iii).

3. The method of claim 1, including at least one destructive detector selected from the group consisting of evaporative light scattering detectors (ELSD), mass spectrometers (MS), condensation nucleation light scattering detectors (CNLSD), and corona discharge detectors.

4. The method of claim 1, including at least one non-destructive detector selected from the group consisting of optical absorbance detectors, refractive index detectors (RID), fluorescence detectors (FD), chiral detectors (CD), and conductivity detectors.

5. The method of claim 1, wherein the non-destructive detector comprises at least one optical absorbance detector.

6. The method of claim 5, wherein the optical absorbance detector observes two or more optical wavelengths so as to produce two or more detector response values.

7. The method of claim 1, wherein the evaporative particle detector comprises an evaporative light scattering detector.

8. The method of claim 1, wherein the evaporative particle detector comprises an evaporative light scattering detector and the non-destructive detector comprises at least one optical absorbance detector.

9. The method of claim 1, further comprising:

actively controlling fluid flow to the at least one destructive detector via

a splitter pump;

a shuttle valve;

or

a combination of a splitter pump and a shuttle valve;

wherein the splitter pump, the shuttle valve, or the combination are in fluid communication with the at least one destructive detector.

10. The method of claim 9, wherein said actively controlling step comprises moving an aliquot to said destructive detector at a frequency of at least 1 aliquot every 10 seconds.

11. A non-transitory computer readable medium having stored thereon computer executable instructions for performing the method of claim 1.

12. An apparatus for detecting a sample using the method of claim 1.

13. A chromatographic apparatus for detecting and collecting one or more components within a sample stream during a chromatographic run comprising:

at least one destructive detector, including at least one evaporative particle detector, to generate a response value during a chromatographic run;

at least one non-destructive detector, wherein said non-destructive detector monitors a whole absorbance spectrum or a portion thereof comprising more than one wavelength during a chromatographic run and generates at least one response values from each of the more than one wavelength;

a processor to receive said response values and to generate a first signal from the response value received from said destructive detector and to generate a second signal from the at least one response value received from said non-destructive detector; and

a fraction collector to collect at least one fraction corresponding to one of said components in response to a change in at least one of said signals during said chromatographic run.

14. The apparatus of claim 13, wherein each signal comprises:

(i) detector response values for the respective generating detector at a given time,

(ii) the first derivatives of said detector response values at a given time,

(iii) the second derivatives of said detector response values at a given time, or

(iv) any combination of (i) to (iii).

15. The apparatus of claim 13, including at least one destructive detector selected from the group consisting of evaporative light scattering detectors (ELSD), mass spectrometers (MS), condensation nucleation light scattering detectors (CNLSD), and corona discharge detectors.

16. The apparatus of claim 13, including at least one non-destructive detector selected from the group consisting of optical absorbance detectors, refractive index detectors (RID), fluorescence detectors (FD), chiral detectors (CD), and conductivity detectors.

17. The apparatus of claim 13, wherein the non-destructive detector includes at least one optical absorbance detector.

18. The apparatus of claim 17, wherein the optical absorbance detector is adapted to observe two or more optical wavelengths so as to produce two or more detector response values.

19. The apparatus of claim 13, wherein the evaporative particle detector comprises an evaporative light scattering detector.

20. The apparatus of claim 13, further comprising:

a splitter pump;

a shuttle valve;

or

a combination of a splitter pump and a shuttle valve;

wherein the splitter pump, the shuttle valve, or the combination are in fluid communication with the at least one destructive detector.