Sample preparation for parallel chromatography

• US 7,074,327 B2
• Filed: 05/07/2004
• Issued: 07/11/2006
• Est. Priority Date: 05/08/2003
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Lee, Mike S., Vajjhala, Surekha, O'Connor, Stephen D., Dantsker, Eugene, Karp, Christoph D.
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US10/841,242
• Publication Number:
  US 20040226884A1
• Time in Patent Office: 795 Days
• Field of Search: 210/635, 210/656, 210/198.2, 210/143, 210/659, 210/502.1, 422/70, 422/100, 422/101
• US Class Current: 210/198.2
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/565 Seals in general F16L
• CPC Class Codes: G01N 2030/085 using absorbing precolumn
• CPC Class Codes: G01N 2030/146 using membranes
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 2030/565 slurry packing
• CPC Class Codes: G01N 2030/8881 Modular construction, specially adapted therefor
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 30/10 : using a splitter
• CPC Class Codes: G01N 30/461 : with serial coupling of separation columns
• CPC Class Codes: G01N 30/466 : with separation columns in parallel
• CPC Class Codes: G01N 30/6043 : in parallel
• CPC Class Codes: G01N 30/6047 : with supporting means; Holders
• CPC Class Codes: G01N 30/606 : with fluid access or exit ports
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/88 : Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86

Abstract

Systems and methods are provided for preparing samples for chromatographic separations and then chromatographically separating the prepared samples, preferably in a high-throughput fashion utilizing multiple parallel first (fluid) processing regions in fluid communication with multiple parallel second (fluid) processing regions wherein the each second processing region includes a chromatography column. One or more common fluid supplies may be utilized in each of the sample preparation and separation steps to minimize the number of requisite fluid connections and external components such as pumps, reservoirs, pulse dampers, flow controllers, and the like.

Claims

1. A microfluidic parallel fluid processing system comprising:

a plurality of parallel separation columns containing stationary phase material;

a sample preparation device defining a plurality of parallel sample preparation elements and a plurality of sample outlet ports in fluid communication with the plurality of sample preparation elements;

a first fluid supply; and

an interface adapted to threadlessly engage at least a portion of the sample preparation device to establish temporary fluid communication between the first fluid supply, at least some sample preparation elements of the plurality of sample preparation elements, and the plurality of separation columns.

2. The system of claim 1 wherein the plurality of sample outlet ports is in fluid communication with the plurality of separation columns.

3. The system of claim 1, further comprising a plurality of fluid conduits disposed between the plurality of sample outlet ports and the plurality of separation columns.

4. The system of claim 1 wherein at least a portion of the interface is moveable.

5. The system of claim 1 wherein the at least a portion of the interface is substantially planar.

6. The system of claim 1 wherein the interface comprises a gasket.

7. The system of claim 1 wherein the interface comprises:

a first interface portion between the first fluid supply and the sample preparation device; and

a second interface portion between the sample preparation device and the plurality of separation columns.

8. The system of claim 1 wherein the first fluid supply comprises a pump and a reservoir.

9. The system of claim 1 further comprising a second fluid supply.

10. The system of claim 1 further comprising a vacuum source in fluid communication with the plurality of sample preparation elements.

11. The system of claim 1 further comprising a voltage source in electrical communication with the plurality of sample preparation elements.

12. The system of claim 1 further comprising a translation element adapted to move the sample preparation device relative to the interface.

13. The system of claim 1 wherein the number of sample preparation elements of the plurality of sample preparation elements exceeds the number of separation columns of the plurality of separation columns.

14. The system of claim 1 wherein each of the plurality of separation columns and the sample preparation device is integrated within a unitary body structure.

15. The system of claim 1 further comprising a plurality of sample injectors adapted to intermittently supply a plurality of samples to a plurality of sample inlet ports.

16. The system of claim 1 wherein each sample preparation element of the plurality of sample preparation elements comprises packed particulate material.

17. The system of claim 1 wherein each sample preparation element of the plurality of sample preparation elements comprises a porous membrane.

18. The system of claim 1 wherein each sample preparation element of the plurality of sample preparation elements comprises a guard column.

19. The system of claim 1 wherein the plurality of sample preparation elements is adapted to perform any of:

size exclusion filtration, chemical affinity filtration, solid phase extraction, liquid phase extraction, protein precipitation, and desalting.

20. The system of claim 1 wherein the plurality of sample preparation elements is adapted to perform any of serial dilution and metering.

21. The system of claim 1 wherein the plurality of sample preparation elements is adapted to perform any of:

permeability assays, solubility assays, bioaffinity assays, sandwich assays, and enzymatic assays.

22. The system of claim 1, further comprising a flow-through detector.

23. The system of claim 22 wherein the flow-through detector is adapted to perform any of:

UV-visible spectroscopy, Raman spectroscopy, fluorescence detection, chemiluminescence, electrochemical detection, capacitive measurement, and conductivity measurement.

24. The system of claim 1, further comprising a consumptive detector.

25. The system of claim 24 wherein the flow-through detector is adapted to perform any of:

mass spectrometry, nuclear magnetic resonance, evaporative light scattering, ion mobility spectrometry, and matrix-assisted laser desorption ionization.