Parallel detection chromatography systems

• US 6,976,384 B2
• Filed: 10/30/2003
• Issued: 12/20/2005
• Est. Priority Date: 10/31/2002
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Duong, Hau H., Hobbs, Steven E.
• Primary Examiner(s): CYGAN, MICHAEL T
• Application Number:
  US10/699,533
• Publication Number:
  US 20040089057A1
• Time in Patent Office: 782 Days
• Field of Search: 73/615.8, 73/615.2, 73/615.3, 73/615.5, 73/615.6, 73/615.7
• US Class Current: 73/61.58
• CPC Class Codes: G01N 2030/746 detecting along the line of flow, e.g. axial
• CPC Class Codes: G01N 2030/8881 Modular construction, specially adapted therefor
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/6026 Fluid seals
• CPC Class Codes: G01N 30/6047 with supporting means; Holders
• CPC Class Codes: G01N 30/6091 Cartridges
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J

Abstract

High throughput liquid chromatography systems include multiple separation columns and multiple flow-through detection regions in sensory communication with a common radiation source and a multi-channel detector. Preferred detector types include a multi-anode photomultiplier tube, a charge-coupled device detector, a diode array, and a photodiode array. In certain embodiments, separation columns are microfluidic and integrated into a unitary microfluidic device. The optical path through a detection region is preferably coaxial with the path of eluate flow along a flow axis through a detection region. On-board or off-board detection regions may be provided.

Claims

1. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions includes an internal cavity having a flow axis;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions substantially coaxially with the flow axis of each detection region of the plurality of detection regions;

a wavelength selection element disposed between the common radiation source and the plurality of detection regions;

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions; and

a plurality of fiber optic conduits disposed between the wavelength selection element and the plurality of detection regions for transmitting radiation emitted from the radiation source to the plurality of detection regions, wherein each fiber optic conduit of the plurality of fiber optic conduits has a first end that bounds a portion of the cavity of a different flow-through detection region of the plurality of detection regions.

2. The system of claim 1, further comprising a plurality of flow cells, wherein each detection region of the plurality of detection regions is disposed within a different flow cell of the plurality of flow cells.

3. The system of claim 2, further comprising a plurality of capillary conduits disposed between, and in fluid communication with, the plurality of separation columns and the plurality of flow cells.

4. The system of claim 1 wherein:

each detection region of the plurality of detection regions includes a fluid flow channel along the flow axis;

each fluid flow channel has a length and a width; and

the length is greater than the width.

5. The system of claim 1 wherein each detection region of the plurality of detection regions includes a fluid flow channel along the flow axis, and each fluid flow channel has a length of at least about two millimeters.

6. The system of claim 1 wherein the radiation source comprises a broadband emission UV source.

7. The system of claim 6 wherein the broadband emission UV source comprises a deuterium lamp or an arc lamp.

8. The system of claim 1 wherein the plurality of separation columns includes at least ten separation columns, the plurality of detection regions includes at least ten detection regions, and the multi-channel detector includes at least ten channels.

9. The system of claim 1 wherein each separation column of the plurality of separation columns is microfluidic.

10. The system of claim 9, further comprising:

a common source of pressurized mobile phase; and

a fluidic distribution network in fluid communication with the mobile phase source and with each separation column of the plurality of separation columns.

11. The system of claim 1 wherein the plurality of microfluidic separation columns is integrated into a unitary device.

12. The system of claim 11 wherein the plurality of detection regions is disposed within the unitary device.

13. The system of claim 11 wherein the unitary device comprises a plurality of substantially planar device layers.

14. The system of claim 12 wherein the plurality of substantially planar device layers includes a plurality of stencil layers.

15. The system of claim 12 wherein the plurality of device layers comprises adhesiveless polymer layers that are interpenetrably bound together.

16. The system of claim 15 wherein the polymer comprises a polyolefin.

17. The system of claim 1 wherein the plurality of separation columns includes at least ten separation columns, the plurality of detection regions includes at least ten detection regions, and the multi-channel detector includes at least ten channels.

18. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions has a flow axis;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions substantially coaxially with the flow axis of each detection region of the plurality of detection regions;

a wavelength selection element comprising a plurality of monochromators disposed between the common radiation source and the plurality of detection regions; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions.

19. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromarographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions has a flow axis;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions substantially coaxially with the flow axis of each detection region of the plurality of detection regions;

a wavelength selection element comprising a plurality of wavelength dispersion elements disposed between the common radiation source and the plurality of detection regions; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions.

20. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions has a flow axis;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions substantially coaxially with the flow axis of each detection region of the plurality of detection regions;

a wavelength selection element disposed between the common radiation source and the plurality of detection regions;

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions; and

a photomask disposed between the wavelength selection element and the multi-channel detector.

21. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions has a flow axis;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions substantially coaxially with the flow axis of each detection region of the plurality of detection regions;

a wavelength selection element disposed between the common radiation source and the plurality of detection regions; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions, wherein the multi-channel detector includes a reference channel used to correct signals received from at least one other channel of the multi-channel detector.

22. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, wherein each detection region of the plurality of detection regions includes an internal cavity having a flow axis;

a common radiation source;

a first plurality of fiber optic conduits optically coupled to the radiation source and to the plurality of detection regions, wherein each fiber optic conduit of the plurality of first fiber optic conduits is associated with a different detection region of the plurality of detection regions, has a first end bounding a portion of the cavity of its associated detection region, and transmits radiation to its associated detection region along the flow axis; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions.

23. The system of claim 22, further comprising a second plurality of fiber optic conduits optically coupled to the plurality of detection regions and the multi-channel detector, wherein each fiber optic conduit of the plurality of second fiber optic conduits is associated with a different detection region of the plurality of detection regions, has a second end bounding a portion of the cavity of its associated detection region, and is associated with a different detector channel of the multi-channel detector.

24. A high throughput liquid chromatography system comprising:

a plurality of separation colunms containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, each detection region of the plurality of detection regions having a flow axis;

a common radiation source;

a plurality of optical conduits coupled to the radiation source and the plurality of detection regions, each optical conduit of the plurality of optical conduits being associated with a different detection region of the plurality of detection regions and transmitting radiation to its associated detection region along the flow axis;

a wavelength selection element comprising a plurality of wavelength dispersion elements disposed between the common radiation source and the plurality of optical conduits; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions.

25. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, each detection region of the plurality of detection regions having a flow axis;

a common radiation source;

a plurality of optical conduits coupled to the radiation source and the plurality of detection regions, each optical conduit of the plurality of optical conduits being associated with a different detection region of the plurality of detection regions and transmitting radiation to its associated detection region along the flow axis;

a wavelength selection element comprising a plurality of monochromators disposed between the common radiation source and the plurality of optical conduits; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions.

26. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, each detection region of the plurality of detection regions having a flow axis;

a common radiation source;

a plurality of optical conduits coupled to the radiation source and the plurality of detection regions, each optical conduit of the plurality of optical conduits being associated with a different detection region of the plurality of detection regions and transmitting radiation to its associated detection region along the flow axis;

a wavelength selection element disposed between the common radiation source and the plurality of optical conduits;

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions; and

a photomask disposed between the wavelength selection element and the multi-channel detector.

27. A high throughput liquid chromatography system comprising:

a plurality of separation columns containing stationary phase material and adapted to perform a plurality of parallel chromatographic separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation columns, each detection region of the plurality of detection regions having a flow axis;

a common radiation source;

a plurality of optical conduits coupled to the radiation source and the plurality of detection regions, each optical conduit of the plurality of optical conduits being associated with a different detection region of the plurality of detection regions and transmitting radiation to its associated detection region along the flow axis;

a wavelength selection element disposed between the common radiation source and the plurality of optical conduits; and

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions, wherein the multi-channel detector includes a reference channel used to correct signals received from at least one other channel of the multi-channel detector.

28. A high throughput liquid analytical separation system comprising:

a plurality of separation channels adapted to perform a plurality of parallel analytical separations;

a plurality of flow-through detection regions in fluid communication with the plurality of separation channels, wherein each detection region of the plurality of detection regions includes an internal cavity;

a common radiation source for emitting radiation, wherein at least a portion of the radiation is transmitted into each detection region of the plurality of detection regions;

a multi-channel detector in sensory communication with each detection region of the plurality of detection regions; and

a first plurality of fiber optic conduits optically coupling the radiation source and the plurality of detection regions, wherein each fiber optic conduit of the first plurality of fiber optic conduits is associated with a different detection region of the plurality of detection regions, and has a first end bounding a portion of the cavity of its associated detection region.

29. The system of claim 28, further comprising a second plurality of fiber optic conduits optically coupling the plurality of detection regions and the multi-channel detector, wherein each fiber optic conduit of the second plurality of fiber optic conduits is associated with a different detection region of the plurality of detection regions, has a second end bounding a portion of the cavity of its associated detection region, and is associated with a different channel of the multi-channel detector.

30. The system of claim 28 wherein the plurality of microfluidic separation channels is integrated into a unitary device.

31. The system of claim 30 wherein the plurality of detection regions is disposed within the unitary device.