Surface plasmon resonance imaging of micro-arrays

• US 20030017579A1
• Filed: 07/10/2002
• Published: 01/23/2003
• Est. Priority Date: 07/10/2001
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Lee, Hye Jin, Goodrich, Terry T., Corn, Robert M.
• Granted Patent: US 7,670,556 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/629 being a microfluidic device
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16

Abstract

Disclosed is a method for fabricating 1-dimensional micro-arrays using parallel micro-fluidic channels on chemically-modified metal, carbon, silicon, and/or germanium surfaces; a μL detection volume method that uses 2-dimensional nucleic acid micro-arrays formed by employing the 1-dimensional DNA micro-arrays in conjunction with a second set of parallel micro-fluidic channels for solution delivery, and the 1-dimensional and 2-dimensional arrays used in the methods. The methodology allows the rapid creation of 1- and 2-dimensional arrays for SPR imaging and fluorescence imaging of DNA-DNA, DNA-RNA, DNA-protein, and protein-protein binding events. The invention enables very small volumes necessary for a variety of bioassay applications to be analyzed by SPR. Target solution volumes as small as 200 pL can be analyzed.

Claims

1. A method of fabricating a biomolecule micro-array on a chemically-modified substrate comprising:

(a) in face-to-face orientation, reversibly attaching a thin film having disposed therein one or more micro-grooves to a chemically-modified substrate, thereby defining one or more micro-channels;

then

(b) passing one or more biomolecules through the micro-channels such that the biomolecules bind to the surface of the chemically-modified substrate at points within the micro-channels; and

then

(c) removing the thin film from the chemically-modified substrate, thereby yielding a chemically-modified substrate having deposited thereon an array of biomolecules.

2. The method of claim 1, wherein in step (a), the chemically-modified substrate is selected from the group consisting of chemically-modified gold, silver, platinum, copper, cadmium, aluminum, silicon, germanium, and carbon.

3. The method of claim 1, wherein in step (a), the chemically-modified substrate is chemically-modified gold or silicon.

4. The method of claim 1, wherein in step (a), the thin film is fabricated from PDMS.

5. The method of claim 1, wherein in step (b)a nucleic acid is passed through the micro-channels.

6. The method of claim 1, wherein in step (a), the chemically-modified substrate is SPR-capable.

7. A method of fabricating a micro-fluidic, biomolecule micro-array on a chemically-modified substrate comprising:

(a) in face-to-face orientation, reversibly attaching a first thin film having disposed therein one or more micro-grooves to a chemically-modified substrate, thereby defining one or more micro-channels;

then

(b) passing one or more biomolecules through the micro-channels such that the biomolecules bind to the surface of the chemically-modified substrate at points within the micro-channels; and

then

(c) removing the thin film from the chemically-modified substrate, thereby yielding a chemically-modified substrate having deposited thereon an array of biomolecules;

then

(d) in face-to-face orientation, reversibly attaching a second thin film having disposed therein one or more micro-grooves to the substrate of step (c) in such a fashion that the micro-grooves of the second thin film intersect the array of biomolecules, thereby defining a distinct set of micro-channels through which can be passed reagents that will make contact with the array of biomolecules deposited on the substrate.

8. The method of claim 7, wherein in step (a), the chemically-modified substrate is selected from the group consisting of chemically-modified gold, silver, platinum, copper, cadmium, aluminum, silicon, germanium, and carbon.

9. The method of claim 7, wherein in step (a), the chemically-modified substrate is chemically-modified gold or silicon.

10. The method of claim 7, wherein in steps (a) and (d), the first and second thin films are fabricated from PDMS.

11. The method of claim 7, wherein in step (a), the chemically-modified substrate is SPR-capable.

12. The method of claim 7, wherein in step (b) nucleic acid is passed through the micro-channels.

15. The micro-array of claim 14, wherein the chemically-modified substrate is selected from the group consisting of chemically-modified gold, silver, platinum, copper, cadmium, aluminum, silicon, germanium, and carbon.

16. The micro-array of claim 14, wherein the chemically-modified substrate is chemically-modified gold or silicon.

17. The micro-array of claim 14, wherein the chemically-modified substrate is SPR-capable.

18. The micro-array of claim 14, wherein, the thin film is fabricated from PDMS.

20. The method of claim 19, wherein in step (c), the chemically-modified substrate is analyzed by surface plasmon resonance.

21. The method of claim 19, wherein in step (c), the chemically-modified substrate is analyzed by fluorescence microscopy.

13. A micro-fluidic driven, biomolecule micro-array on a chemically-modified substrate produced by a series of steps comprising:

(a) in face-to-face orientation, reversibly attaching a first thin film having disposed therein one or more micro-grooves to a chemically-modified substrate, thereby defining one or more micro-channels;

then

(b) passing one or more biomolecules through the micro-channels such that the biomolecules bind to the surface of the chemically-modified substrate at points within the micro-channels; and

then

(c) removing the thin film from the chemically-modified substrate, thereby yielding a chemically-modified substrate having deposited thereon an array of biomolecules;

then

(d) in face-to-face orientation, reversibly attaching a second thin film having disposed therein one or more micro-grooves to the substrate of step (c) in such a fashion that the micro-grooves of the second thin film intersect the array of biomolecules, thereby defining a distinct set of micro-channels through which can be passed reagents that will make contact with the array of biomolecules deposited on the substrate.

14. A micro-fluidic, biomolecule micro-array on a chemically-modified substrate comprising:

a chemically-modified substrate having defined thereon an array of biomolecules;

a thin film having disposed therein one or more micro-grooves, the thin film reversibly attached in face-to-face orientation to the chemically-modified substrate in such a fashion that the micro-grooves of the thin film intersect the array of biomolecules, thereby defining a set of micro-channels through which can be passed reagents that will make contact with the array of biomolecules deposited on the substrate.

19. A method of analyzing interactions between biomolecules comprising:

(a) providing a micro-fluidic, biomolecule micro-array on a chemically-modified substrate comprising;

a chemically-modified substrate having defined thereon an array of biomolecules;

a thin film having disposed therein one or more micro-grooves, the thin film reversibly attached in face-to-face orientation to the chemically-modified substrate in such a fashion that the micro-grooves of the thin film intersect the array of biomolecules, thereby defining a set of micro-channels through which can be passed reagents that will make contact with the array of biomolecules deposited on the substrate; and

(b) passing through the micro-channels one or more solutions suspected of containing molecules capable of interacting with the array of biomolecules bound to the chemically-modified substrate; and

then

(c) analyzing the chemically-modified substrate of step (b) to determine if any interaction has occurred.

22. A biomolecule array on a chemically-modified substrate, the array produced by a series of steps comprising:

(a) in face-to-face orientation, reversibly attaching a thin film having disposed therein one or more micro-grooves to a chemically-modified substrate, thereby defining one or more micro-channels;

then

(b) passing one or more biomolecules through the micro-channels such that the biomolecules bind to the surface of the chemically-modified substrate at points within the micro-channels; and

then

(c) removing the thin film from the chemically-modified substrate, thereby yielding a chemically-modified substrate having deposited thereon an array of biomolecules.

23. The biomolecule array of claim 22, wherein in step (a), the chemically-modified substrate is selected from the group consisting of chemically-modified gold, silver, platinum, copper, cadmium, aluminum, silicon, germanium, and carbon.

24. The biomolecule array of claim 22, wherein in step (a), the chemically-modified substrate is chemically-modified gold or silicon.

25. The biomolecule array of claim 22, wherein in step (a), the thin film is fabricated from PDMS.

26. The biomolecule array of claim 22, wherein in step (b) nucleic acid is passed through the micro-channels.

28. The biomolecule array of claim 27, wherein in step (a), the chemically-modified substrate is selected from the group consisting of chemically-modified gold, silver, platinum, copper, cadmium, aluminum, silicon, germanium, and carbon.

29. The biomolecule array of claim 27, wherein in step (a), the chemically-modified substrate is chemically-modified gold or silicon.

30. The biomolecule array of claim 27, wherein in steps (a) and (d), the first and second thin films are fabricated from PDMS.

31. The biomolecule array of claim 27, wherein in step (b) nucleic acid is passed through the micro-channels.

27. A biomolecule array on a chemically-modified substrate, the array produced by a series of steps comprising:

(a) in face-to-face orientation, reversibly attaching a first thin film having disposed therein one or more micro-grooves to a chemically-modified substrate, thereby defining one or more micro-channels;

then

(b) passing one or more biomolecules through the micro-channels such that the biomolecules bind to the surface of the chemically-modified substrate at points within the micro-channels; and

then

(c) removing the thin film from the chemically-modified substrate, thereby yielding a chemically-modified substrate having deposited thereon an array of biomolecules;

then

(d) in face-to-face orientation, reversibly attaching a second thin film having disposed therein one or more micro-grooves to the substrate of step (c) in such a fashion that the micro-grooves of the second thin film intersect the array of biomolecules, thereby defining a distinct set of micro-channels through which can be passed reagents that will make contact with the array of biomolecules deposited on the substrate.