Microfluidic devices for liquid chromatography-mass spectrometry and microscopic imaging

• US 10,203,307 B2
• Filed: 06/03/2015
• Issued: 02/12/2019
• Est. Priority Date: 12/11/2012
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Wang, Daojing, Mao, Pan, Gomez-Sjoberg, Rafael, Wang, Hung-Ta, Yang, Peidong
• Primary Examiner(s): Patel, Harshad R
• Assistant Examiner(s): Tran, Tran M
• Application Number:
  US14/729,999
• Publication Number:
  US 20150293063A1
• Time in Patent Office: 1,350 Days
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• 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: G01N 2030/8813 biological materials
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/7233 interfaced to liquid or supercritical fluid chromatograph interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray
• CPC Class Codes: H01J 49/0431 for liquid samples interfaces to liquid chromatographs G01N30/7233

Abstract

Systems, methods, and apparatus provide integration of microscopic imaging and liquid chromatography-mass spectrometry on a microfluidic device. In one aspect, an apparatus includes a first wafer, a second wafer, and an emitter. The emitter is disposed between the first wafer and the second wafer. The first wafer defines a sample input hole. The first wafer and the second wafer define a first channel, the first channel including a first end and a second end. The first end of the first channel is proximate the sample input hole. The first channel is configured to contain separation media. The second end of the first channel is proximate the emitter.

Claims

1. An apparatus comprising:

a first wafer;

a second wafer, the first and second wafers comprising silicon wafers and defining a sample input hole, the second wafer defining a first portion of a first channel, the first channel including a first end and a second end, the first end of the first channel proximate to and fluidly coupled to the sample input hole, the first channel configured to contain separation media;

an emitter, the emitter being disposed between the first wafer and the second wafer, the second end of the first channel proximate to and fluidly coupled to the emitter; and

a transparent wafer being an optically transparent glass wafer configured to define a second portion of the first channel, the transparent wafer being bonded to a bottom surface of the second wafer, wherein the bond is an anodic silicon-glass bond, and wherein the first wafer, the second wafer, and the transparent wafer are monolithically integrated,

the transparent wafer being further configured to be transparent along the second portion of the first channel to provide an imaging window of an entirety of the separation media included in the first channel, wherein the second wafer is disposed between the first wafer and the transparent wafer.

2. The apparatus of claim 1, wherein the second end of the first channel includes a frit configured to retain separation media in the first channel.

3. The apparatus of claim 1, further comprising:

separation media disposed in the first channel, wherein the separation media includes a coating configured for separation of the sample into specific molecules.

4. The apparatus of claim 1, further comprising:

separation media disposed in the first channel, wherein the separation media includes beads, and wherein the beads are substantially spherical and have a diameter of about 1 micron to 50 microns.

5. The apparatus of claim 1, further comprising:

one or more channels, in addition to the first channel, forming a plurality of channels.

6. The apparatus of claim 5, wherein the first wafer and the second wafer are each substantially circular, and wherein the plurality of channels are arranged about an axis of the first wafer and the second wafer.

7. The apparatus of claim 5, wherein the one or more channels have a plurality of channel dimensions that are the same as the first channel.

8. The apparatus of claim 1, wherein the first channel has a cross-section of about 100 microns to 300 microns by about 100 microns to 300 microns.

9. The apparatus of claim 1, wherein the first channel has a length of about 3 centimeters to 15 centimeters.

10. The apparatus of claim 1, wherein the first wafer and the second wafer include through vias configured to allow fastening hardware to pass through the first wafer and the second wafer.

11. The apparatus of claim 1, wherein the sample input hole has dimensions of about 500 microns to 1.5 millimeters.

12. The apparatus of claim 1, wherein the sample input hole is a through via in the first wafer.

13. An apparatus comprising:

an emitter;

a first wafer;

a second wafer, the first and second wafers comprising silicon wafers, the first wafer and the second wafer defining a sample input hole, the first wafer and the second wafer defining a first exit channel having a first end and a second end, the emitter being disposed between the first wafer and the second wafer, the second end of the first exit channel proximate to and fluidly coupled to the emitter; and

a transparent wafer being an optically transparent glass wafer, the second wafer and the transparent wafer defining a first channel having a first end and a second end, the first end of the first channel proximate to and fluidly coupled to the sample input hole, the second end of the first channel proximate to and fluidly coupled to the first end of the first exit channel, the first channel being configured to contain separation media,

wherein the transparent wafer is bonded to a bottom surface of the second wafer, wherein the bond is an anodic silicon-glass bond, wherein the first wafer, the second wafer, and the transparent wafer are monolithically integrated,

wherein the transparent wafer is configured to be transparent along the first channel to provide an imaging window of an entirety of the separation media included in the first channel, and wherein the second wafer is disposed between the first wafer and the transparent wafer.

14. The apparatus of claim 13, further comprising:

one or more channels and exit channels, in addition to the first channel and the first exit channel, forming a plurality of channels and exit channels.

15. The apparatus of claim 14, wherein the first wafer, the second wafer, and the transparent wafer are each substantially circular, and wherein the plurality of channels and exit channels are arranged about an axis of the first wafer, the second wafer, and the transparent wafer.

16. The apparatus of claim 14, wherein the one or more additional channels and exit channels have a plurality of dimensions that are the same as the first channel and the first exit channel.