Parallel fluid processing systems and methods

• US 7,178,386 B1
• Filed: 04/09/2004
• Issued: 02/20/2007
• Est. Priority Date: 04/10/2003
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Gamble, Ronald C., Osechinskiy, Sergey I.
• Primary Examiner(s): LARKIN, DANIEL SEAN
• Application Number:
  US10/821,567
• Time in Patent Office: 1,047 Days
• Field of Search: 73/10.1, 73/615.2, 73/615.5, 73/615.6, 73/615.7, 73/615.8, 210/198.2
• US Class Current: 73/61.57
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/8665 for calibrating the measuring apparatus
• CPC Class Codes: G01N 30/8668 using retention times

Abstract

A parallel fluid processing system including multiple fluid process regions containing solid material in fluid communication with a common first fluid source may be used to conduct analyses and/or synthesis in parallel. A parallel fluid processing data correction method includes supplying and processing a calibrant in each fluid process region, measuring a first physical parameter and deriving at least one correction factor based on the parameter, supplying and processing at least one second fluid in each fluid process region, and then applying the correction factor to yield corrected process data. Retention time correction, peak area correction, and other useful data corrections may be performed. Parallel fluid processing may be performed with microfluidic devices and systems. A system for correcting retention times in parallel liquid chromatography is further provided.

Claims

1. A multi-column liquid chromatography data correction methods comprising the steps of:

providing a plurality of liquid chromatography columns in fluid communication with a common mobile phase source, each column of the plurality of columns containing a stationary phase material, wherein the mobile phase source supplies a mobile phase to the plurality of columns at a selected mobile phase source output flow rate;

providing at least one detector in sensory communication with the plurality of columns;

supplying a calibrant having at least a first component to each column of the plurality of columns;

eluting the at least a first component of the calibrant in each column of the plurality columns according to a first mobile phase source output flow rate and a first mobile phase composition profile;

measuring, for each column of the plurality of columns, a first physical parameter using the at least one detector;

deriving, for each column of the plurality of columns, at least one correction factor based on the first physical parameter;

supplying, to each column of the plurality of columns, at least one sample containing a plurality of sample components;

eluting at least two components of the plurality of sample components of the at least one sample in each column of the plurality of columns to obtain raw chromatographic data; and

applying, for each column of the plurality of columns, the at least one correction factor to the raw chromatographic data to yield corrected chromatographic output data.

2. The method of claim 1 wherein the corrected chromatographic output data includes any of:

corrected retention times, corrected peak areas, corrected baselines, corrected mass throughput, and corrected multiple wavelength correction.

3. The method of claim 1 wherein the at least a first component of the calibrant includes two components having different retention characteristics relative to the stationary phase material.

4. The method of claim 1 wherein the sample elution step is performed according to the first mobile phase source output flow rate and the first mobile phase composition profile.

5. The method of claim 1 wherein the measuring step is performed inferentially.

6. The method of claim 1 wherein the measuring step is performed substantially downstream of each column of the plurality of columns.

7. The method of claim 1 wherein the first physical parameter comprises any of absorbance, fluorescence, optical scattering, evaporative light scattering, temperature profile, voltage profile, current profile, molecular weight, molecular composition, elemental composition, flow, and pressure.

8. The method of claim 1, further comprising the step of recording, for each column of the plurality of columns, the first physical parameter as a function of time.

9. The method of claim 1 wherein the mobile phase comprises a first mobile phase fluid and a second mobile phase fluid, the method further comprising the step of mixing the first mobile phase fluid and the second mobile phase fluid, wherein the composition of the mobile phase changes during each of the calibrant elution step and the sample elution step.

10. The method of claim 1, further comprising the step of flushing the plurality of columns between the calibrant elution step and the sample elution step.

11. The method of claim 1 wherein the common mobile phase source comprises a plurality of pumps and a plurality of fluid reservoirs.

12. The method of claim 1 wherein the sample supplying step includes supplying a different sample of the at least one sample to each column of the plurality of columns.

13. The method of claim 1 wherein each column of the plurality of columns is microfluidic.

14. The method of claim 1 wherein the at least one detector includes a plurality of detector channels, wherein each detector channel of the plurality of detector channels is in indirect sensory communication with a different fluid process region of the plurality of fluid process regions.

15. The method of claim 1 wherein each column of the plurality of columns contains stationary phase material of substantially the same composition.

16. A method for correcting retention times in multi-column liquid chromatography, the method comprising the steps of:

providing a plurality of liquid chromatography columns in fluid communication with a common mobile phase source, each column of the plurality of columns containing a stationary phase material and having an associated detection region, wherein the mobile phase source supplies a mobile phase to the plurality of columns at a selected mobile phase source output flow rate;

providing, for the detection region associated with each column of the plurality of columns, a detector in sensory communication with the detection region;

supplying a first calibrant to each column of the plurality of columns, wherein the first calibrant contains at least a first component and a second component, with each of the first component and second component having different retention characteristics relative to the stationary phase material;

eluting the at least first component and second component in each column of the plurality of columns according to a first mobile phase source output flow rate and a first mobile phase composition profile;

measuring, for each column of the plurality of columns, a first time for the first component to reach the associated detection region and a second time for the second component to reach the associated detection region;

deriving, for each column of the plurality of columns, at least one correction factor based on at least one of the first time and the second time;

supplying, to each column of the plurality of columns, at least one sample containing a plurality of sample components;

eluting at least two components of the plurality of sample components of the sample in each column of the plurality of columns to obtain raw chromatographic data; and

applying, for each column of the plurality of columns, the at least one correction factor to the raw chromatographic data to yield corrected chromatographic data with corrected retention times.

17. The method of claim 16, further comprising the step of cleaning the plurality of columns between the first elution step and the second elution step.

18. The method of claim 17 wherein the cleaning step includes maintaining a first mobile phase composition profile of at least seventy percent organic solvent.

19. The method of claim 16 wherein each column of the plurality of liquid chromatography columns is microfluidic.

20. The method of claim 19 wherein each column of the plurality of liquid chromatography columns is integrated into a single microfluidic device.

21. The method of claim 16 wherein the stationary phase material includes packed particulate matter.

22. The method of claim 16 wherein the mobile phase includes a first solvent, and the first mobile phase composition profile includes a substantially constant concentration of the first solvent.

23. The method of claim 16 wherein the mobile phase includes a plurality of solvents, and the mobile phase composition profile includes a variation in the weight percent of at least one solvent.

24. The method of claim 23, further comprising the step of mixing the plurality of solvents.

25. The method of claim 16 wherein the mobile phase includes a solute, and the mobile phase composition profile includes a variation in solute concentration.

26. The method of claim 16 wherein the mobile phase source includes at least one pump.

27. The method of claim 16 wherein the mobile phase source includes at least two fluid reservoirs.

28. The method of claim 16 wherein the elution of the at least two components of the plurality of sample components of the sample is performed according to the first mobile phase source output flow rate and the first mobile phase composition profile.

29. The method of claim 16 wherein the step of supplying at least one sample includes supplying a different sample to each column of the plurality of columns.

30. The method of claim 16 wherein the step of supplying at least one sample includes supplying substantially the same sample to at least two columns of the plurality of columns.

31. The method of claim 16 wherein the deriving step utilizes a least square fit method.

32. The method of claim 16 wherein any of the measuring, deriving, and applying steps are automated.

33. A multi-column chromatography system for performing the method of claim 16.

34. A system for correcting retention times in multi-column liquid chromatography, the system comprising:

a plurality of liquid chromatography columns for performing pressure-driven chromatographic separations;

a common mobile phase source in fluid communication with the plurality of columns;

a plurality of detection regions associated with the plurality of separation columns;

at least one detector in sensory communication with the plurality of detection regions;

a data storage device for receiving and storing data obtained from the at least one detector; and

a microprocessor for executing instructions to derive correction factors based on data obtained from the at least one detector, and to apply the correction factors to generate corrected chromatographic data with corrected retention times.

35. The system of claim 34 wherein the data storage device is integrated with the microprocessor.

36. The system of claim 34 wherein each column of the plurality of liquid chromatography columns is microfluidic.

37. The system of claim 34 wherein the plurality of chromatography columns is integrated within a substantially planar microfluidic device.

38. The system of claim 37 wherein the plurality of detection regions comprises a plurality of substantially optically transmissive regions within the microfluidic device.

39. The system of claim 37 wherein the plurality of detection regions is disposed within a multi-channel flow cell.

40. The system of claim 34 wherein the common mobile phase source includes a plurality of pumps.

41. The system of claim 34, further comprising a degasser in fluid communication with the common mobile phase source.

42. The system of claim 40, further comprising a mixer disposed between the plurality of pumps and the plurality of liquid chromatography columns.

43. The system of claim 34 wherein the detector comprises an electromagnetic source and electromagnetic receiver.

44. The system of claim 34 wherein the detector comprises a plurality of fiber optic conduits.