Microfluidic device with multiple microcoil NMR detectors enabling fluidic series communication

• US 7,141,978 B2
• Filed: 07/14/2005
• Issued: 11/28/2006
• Est. Priority Date: 12/01/2000
• Status: Expired due to Fees

• Current Assignee: Protasis Corp.
• Original Assignee: Protasis Corp.
• Inventors: Olson, Dean, Peck, Tim L., Norcross, Jim, Strand, David, Sweedler, Jonathan
• Primary Examiner(s): Gutierrez, Diego
• Assistant Examiner(s): Fetzner, Tiffany A.
• Application Number:
  US11/181,076
• Publication Number:
  US 20050253587A1
• Time in Patent Office: 502 Days
• Field of Search: None
• US Class Current: 324/321
• CPC Class Codes: G01R 33/302 Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• CPC Class Codes: G01R 33/307 specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer
• CPC Class Codes: G01R 33/34053 Solenoid coils; Toroidal coils
• CPC Class Codes: G01R 33/34092 RF coils specially adapted for NMR spectrometers

Abstract

An NMR system comprises an NMR probe comprising multiple NMR detection sites. Each of the multiple NMR detection sites comprises a sample holding void and an associated NMR microcoil. The NMR system further comprises a controllable fluid router operative to direct fluid sample to the multiple NMR detection sites.

Claims

1. An NMR system comprising

an NMR probe comprising multiple NMR detection sites, each of the multiple NMR detection sites comprising

a sample holding void, and

an associated NMR microcoil;

and

a controllable fluid router operative in response to electrical router control input signals in order to direct a fluid sample to any selected one or more of the multiple NMR detection sites;

wherein

at least a first plurality of the multiple NMR detection sites are arranged in fluidic series communication with each other configured for acquiring NMR spectra correspondingly in series from the fluid sample.

2. The NMR system of claim 1 wherein each of at least a plurality of the multiple NMR detection sites comprises an NMR microcoil detector.

3. The NMR system of claim 1 wherein the multiple NMR detection sites collectively comprise multiple NMR detectors, each of the multiple NMR detectors being operative for signal acquisition independently of others of the NMR detectors.

4. The NMR system of claim 1 wherein the multiple NMR detection sites collectively comprise multiple transceiver NMR spectrometers.

5. The NMR system of claim 1 wherein the multiple NMR detection sites collectively are operative to receive signals from individual ones of the NMR microcoils using time-multiplexed acquisition.

6. The NMR system of claim 1 further comprising a controller, wherein:

at least a first NMR detection site of the multiple NMR detection sites is operative to generate an NMR sample signal to the controller corresponding to an NMR spectra acquired from a fluid sample in the first NMR detection site;

the controller is operative to generate a corresponding router control input signal to the controllable fluid router at least partly in response to an NMR sample signal received from the first NMR detection site; and

the controllable fluid router is operative to route a fluid sample from the first NMR detection site to any of at least a plurality of the multiple NMR detection sites in response to a router control input signal from the controller generated by the controller at least partly in response to an NMR sample signal received from the first NMR detection site corresponding to the router control signal from the first NMR detection site.

7. The NMR system of claim 6 wherein the controller comprises a microprocessor.

8. The NMR system of claim 7 wherein the controller is programmed to respond to at least selected NMR sample signals to direct storage, disposal or movement of a fluid sample from one of the multiple NMR detection sites.

9. The NMR system of claim 8 wherein the controller is operative to direct movement of a fluid sample from one of the multiple NMR detection sites to at least one of:

others of the multiple NMR detection sites, and

another component of the system.

10. The NMR system of claim 8 wherein the controller is operative to direct movement of a fluid sample from one of the multiple NMR detection sites to another site by action comprising at least one of:

causing pumping of sample volume corresponding to a length of a flow path to the other site, and

controlling gates in order to select amongst multiple possible flow paths.

11. The NMR system of claim 8 wherein the controller is operative to recognize NMR sample signals corresponding to at least one selected molecular structure or analyte composition.

12. The NMR system of claim 8 wherein the controller is operative to recognize NMR sample signals by automatic comparison of NMR sample signals to a pre-stored database and to act automatically on at least one selected NMR sample signal.

13. The NMR system of claim 6 wherein the sample holding void of each of the NMR detection sites is in a capillary-scale fluid channel in the probe and the controllable fluid router is operative to cross-route fluid sample from a first capillary-scale fluid channel to a second capillary-scale fluid channel in the probe in response to a router control input signal from the controller.

14. The NMR system of claim 1 wherein the controllable fluid router

is operative to direct a fluid sample in series to at least a plurality of the multiple NMR detection sites, and

is operative to direct a fluid sample in parallel to at least a plurality of the multiple NMR detection sites.

15. The NMR system of claim 1 wherein the multiple NMR detection sites are integrated with each other in a probe module.

16. The NMR system of claim 15 wherein the probe module comprises a substrate and the microcoils are formed at peninsula extensions of the substrate.

17. The NMR system of claim 15 wherein the sample holding void of each of the NMR detection sites is in a capillary-scale fluid channel in the probe module.

18. The NMR system of claim 15 wherein the sample holding void of each of the NMR detection sites is in a micro-scale fluid channel in the probe module.

19. The NMR system of claim 1 further comprising an operative component in communication with the controllable fluid router and operative to communicate signals with the controllable fluid router.

20. The NMR system of claim 19 wherein the multiple NMR detection sites and the operative component are integrated in a probe module.

21. The NMR system of claim 1 further comprising a controller in communication with the controllable fluid router and operative to generate the router control input signals to the controllable fluid router.

22. The NMR system of claim 21 wherein the multiple NMR detection sites and the controller unit are integrated in a probe module.

23. The NMR system of claim 21 wherein the controller is operative to receive information from the multiple NMR detection sites and operative to generate router control input signals to the controllable fluid router based at least in part on information from one or more of the multiple NMR detection sites.

24. The NMR system of claim 21 further comprising an operative component, wherein the controller is operative to receive component information from the operative component and operative to generate the router control input signals to the controllable fluid router based at least in part on component information received from the operative component.

25. The NMR system of claim 24 wherein the operative component, the controller and the multiple NMR detection sites are integrated in a probe module.

26. The NMR system of claim 24 wherein the operative component comprises at least one of:

a heating device,

an IR detector,

a sonication device,

a UV visibility array,

a photodiode array,

a memory module,

a pump, and

a reaction site.

27. The NMR system of claim 1 wherein the sample holding void is in a capillary-scale fluid channel.

28. The NMR system of claim 1 wherein the sample holding void is in a micro-scale fluid channel.

29. The NMR system of claim 1 wherein each of the multiple NMR detection sites is optimized for a different nuclear species.

30. The NMR system of claim 1 wherein at least one of the multiple NMR detection sites is optimized for 1 dimensional NMR study.

31. The NMR system of claim 1 wherein at least one of the multiple NMR detection sites is optimized for 2 dimensional NMR study.

32. The NMR system of claim 1 wherein the NMR probe further comprises an analyte extraction chamber in fluid communication with at least one of the NMR detection sites.

33. The NMR system of claim 32 wherein the analyte extraction chamber is operative to perform at least one of

liquid chromatography,

capillary electrophoresis, and

dynamic field gradient focusing.

34. The NMR system of claim 1 wherein at least a second plurality of the multiple NMR detection sites are arranged in parallel fluidic communication with each other.