Microfluidic system (MS)

• US 6,653,625 B2
• Filed: 03/19/2001
• Issued: 11/25/2003
• Est. Priority Date: 03/19/2001
• Status: Expired due to Term

• Current Assignee: Gyros Patent AB (Mesa Laboratories Inc.)
• Original Assignee: Gyros AB (Mesa Laboratories Inc.)
• Inventors: Andersson, Per, Derand, Helene, Palm, Anders, Gustafsson, Magnus, Wallenborg, Susanne
• Primary Examiner(s): Wells, Nikita
• Application Number:
  US09/811,741
• Publication Number:
  US 20020158195A1
• Time in Patent Office: 981 Days
• Field of Search: 250/288, 250/281, 250/282, 422/70, 422/68.1, 422/100
• US Class Current: 250/288
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• 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 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0806 Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 2035/00504 combined with carousels
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/7266 : by electric field, e.g. electrospray
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk

Abstract

The present invention relates to a method for presenting an analyte of a liquid sample as an MS-analyte to a mass spectrometer. More particularly, the method comprises the steps of applying a liquid sample containing the analyte to a sample inlet port of a microchannel structure of a microfluidic device, said structure also comprising an outlet port (MS-port) that is capable of being interfaced with a mass spectrometer, passing the analyte to the MS-port thereby transforming it to an MS-analyte, and presenting the MS-analyte to mass spectrometer via the MS-port.

Claims

1. A method for presenting an analyte of a liquid sample as an MS-analyte to a mass spectrometer, characterized

(a) in comprising the steps of:

(i) applying a liquid sample containing the analyte to a sample inlet port of a microchannel structure of a microfluidic device, said structure also comprising an outlet port (MS-port) that is capable of being interfaced with a mass spectrometer,

(ii) passing the analyte to the MS-port thereby transforming it to an MS-analyte, and

(iii) presenting the MS-analyte to the mass spectrometer via the MS-port, and

(b) centrifugal force being used for liquid transportation within at least a part of said microchannel structure.

2. The method of claim 1, characterized by the use of capillary action, hydrodynamic pressure, or electrokinetics to transport liquid within at least a part of said microchannel structure.

3. The method of claim 1, characterized in that

(a) the device is a planar, preferably circular, substrate (plate, disc), and contains the microchannel structure which extends radially in the plane of the plate with the MS-port being located at an outer position and an inlet port at an inner position, and

(b) said planar substrate after or simultaneously with the application of the sample is spinned around its central axis which is perpendicular to said plane thereby forcing liquids present in the microchannel structure to move outwards, e.g. in the direction of the MS-port.

4. The method of claims 1 or 3, characterized in that there are two or more, preferably a plurality of microchannel structures.

5. The method of claim 4, characterized in that there is a plurality of microchannel structures that are annularly arranged around the central axis.

6. The method of claim 1, characterized in that the MS-port comprises an electrospray arrangement, with preference for all of the MS-ports comprising this arrangement.

7. The method of claim 1, characterized in that the MS-port comprises an EDI arrangement with an EDI area, for instance an IDI arrangement such as an LDI arrangement.

8. The method of claim 7, characterized in that each EDI area comprises a conducting layer (layer I), for instance a metal layer, with a conductive connection.

9. The method of claim 8, characterized in that there are two or more EDI areas on the device and that layer I in at least two of said EDI areas, preferably all of them, are present in a common continuous conducting layer comprising the connection for electricity.

10. The method of claim 8 or 9, characterized in that there is a layer (II) of non-conducting material on top of layer (I) in an EDI area, preferably in each of them.

11. The method of claim 10, characterized in that the layer (I) or layer (II) is exposed on the surface of an EDI area, preferably in each of them.

12. The method of claim 7, characterized in the microfluidic device comprises

(a) a planar substrate having in the surface of one side at least a part of said microchannel structure, and

(b) a matching lid which on one side comprises the remaining parts, if any, of the microchannel structure so that said microchannel structure is completed when said two sides mate to each other, the part of the MS-port comprising the EDI area being present either in the substrate or in the lid.

13. The method of claim 12, characterized in that said substrate and said lid are separable from each other.

14. The method of claim 1, characterized in that said MS-port comprises an opening permitting release of the MS-analytes into the mass spectrometer.

15. The method of claim 1, characterized

(a) in that the microchannel structure comprises a zone downstream the inlet port and upstream the MS-port, which zone comprises a separation medium which is capable of selectively capturing the analyte or possibly an analyte-derived entity when a liquid containing one of these components is allowed to pass through the zone, and

(b) in that the analyte or the analyte-derived entity is captured in the zone and then released by application of a releasing liquid to an inlet port that may be different from the sample inlet port and transported, preferably by inertia force, to the MS-port where the analyte or the analyte-derived entity is collected, and subsequently released as an MS-analyte to the mass spectrometer.

16. The method of claim 15, characterized in that the separation medium comprises ligand structures that are capable of binding to the analyte or an analyte derived entity by affinity or reversible covalent bonds.

17. The method of claim 16, characterized in that the outlet port contains an EDI area, and that an EDI matrix (a) is included in the releasing liquid either before or after passing the separation medium, or in the MALDI area before release of the analyte or the analyte-derived entity, or (b) applied to the MALDI area after the analyte or the analyte-derived entity has been collected thereon.

18. The method of claim 1, characterized in that said sample inlet port and said MS-port coincide, and that the transport of liquid is out from the combined port via the microchannel structure of the device.

19. The method of claim 18, characterized in that said combined port comprises a separation medium selectively binding to the analyte under the condition provided by the liquid sample and that the analyte or possibly an analyte-derived form thereof is released as the MS-analyte to the mass spectrometer.

20. A microfluidic device as defined claims 3 or 12.