Micro fabricated fountain pen apparatus and method for ultra high density biological arrays

• US 20030148539A1
• Filed: 11/04/2002
• Published: 08/07/2003
• Est. Priority Date: 11/05/2001
• Status: Abandoned Application

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Reese, Matthew O., Scherer, Axel, Quake, Stephen R., van Dam, R. Michael
• Application Number:
  US10/288,248
• Publication Number:
  US 20030148539A1
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0248 Prongs, quill pen type dispenser
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 2035/1037 Using surface tension, e.g. pins or wires
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A fluid dispensing system for at least biological applications, e.g., oligonucleotides, peptide nucleic acids (“PNA”), proteins, polysaccharides, polypeptides, inorganic solutions, microelectromechanical systems (MEMS), optical sensors, and other applications. The dispensing system includes a fluid dispensing apparatus for applying selected fluids in a predetermined manner to form a plurality of spots based upon one or more of the selected fluids on a surface of a substrate. The apparatus comprises an elongated member having at least a tip portion, which extends from the elongated member. The apparatus also has an etched trench extending along a portion of a length of the elongated member to the tip to form an opening defined on the tip portion and coupled to the etched trench. A flexible region is defined within the elongated member to allow the tip to adjust in position upon contact with the surface of the substrate. A fluid is disposed within the etched trench. The fluid is output through the opening on the tip to form more than one spots on the surface of the substrate.

Claims

1. A fluid dispensing system for biological applications, the dispensing system including a fluid dispensing apparatus for applying selected fluids in a predetermined manner to form a plurality of spots based upon one or more of the selected fluids on a surface of a substrate, the apparatus comprising;

an elongated member having at least a tip portion, the tip portion extending from the elongated member;

an etched trench extending along a portion of a length of the elongated member to the tip to form an opening defined on the tip portion and coupled to the etched trench;

a flexible region defined within the elongated member to allow the tip to adjust in position upon contact with the surface of the substrate; and

a fluid disposed within the etched trench, the fluid being output through the opening on the tip to form one or more than one spots on the surface of the substrate.

2. The apparatus of claim 1 wherein the etched trench has a width of 30 microns and less.

3. The apparatus of claim 1 wherein the elongated member comprises stainless steel to allow the tip to adjust in position upon contact with the surface of the substrate.

4. The apparatus of claim 1 wherein the depth of the trench is about 6 microns and less and the elongated member has a thickness of less than 13 microns from an upper region to a lower region.

5. The apparatus of claim 1 wherein the etched trench comprises a hydrophilic coating overlying exposed surfaces of the etched trench to enhance capillary action.

6. The apparatus of claim 1 wherein the etched trench comprises an overlying layer of urethane.

7. The apparatus of claim 1 wherein the tip being a continuous region with a positive annular region to form the opening.

8. The apparatus of claim 1 further comprising an upper region extending from the trench region, the upper region having a larger volume than a volume of the trench region to store the fluid.

9. The apparatus of claim 1 wherein the flexible region is free from movement before contact with the surface of the substrate.

10. The apparatus of claim 1 wherein the fluid comprises a salt, a surfactant, and a biological material.

11. The apparatus of claim 1 wherein the etched trench includes an overlying hydrophobic layer in contact with the fluid.

12. The apparatus of claim 1 wherein the tip flexes and moves in a lateral manner on the surface of the substrate to adjust in position to form substantial continuous contact with the surface having a surface roughness of at least ten microns when force has been applied to the tip toward the surface of the substrate.

13. A method for forming a high density array of spots on a substrate for biological applications, the method comprising:

providing a dispensing apparatus, the dispensing apparatus comprising an elongated member having at least a trench region that extends from a first portion of the elongated member to an opening on a tip portion;

applying the tip to a surface of the substrate at an angle whereupon the angle ranges from a position normal to the surface of the substrate; and

dispensing fluid through the trench region that extends from the first portion of the elongated member to the opening at the tip to form a fluid region having a size of a dimension substantially equal to a width of the opening of the trench.

14. The method of claim 13 wherein the angle ranges from about 20 to 30 degrees from the position normal to the surface of the substrate.

15. The method of claim 13 further comprising lifting the tip from the surface of the substrate;

moving the tip to another spatial region of the substrate; and

applying the tip at an angle to the substrate to form another fluid region having a spot size similar in dimension to the first spot size whereupon a distance between the fluid region and the other fluid region defines a pitch between the fluid region and the other fluid region.

16. The method of claim 13 wherein the pitch is 75 micron and less in at least one dimension.

17. The method of claim 13 wherein the size is 30 microns and less in at least one dimension.

18. The method of claim 13 further comprising repeating the applying and dispensing to form one or more other spots on other spatial surface regions of the substrate.

19. A method for manufacturing a fountain pen dispenser for biological applications, the method comprising:

providing a substrate, the substrate having an upper surface, a bottom surface, and a thickness defined there between;

forming a trench region within the substrate from the upper surface, the trench region having a length and a width;

patterning at least the bottom surface of the substrate to define an elongated member from the substrate, the elongated member having the trench region defined therein, whereupon the trench region extends from an upper portion to a lower portion of the elongated member along a length of the elongated member;

etching to free the tip and substantially define the elongated member; and

coating a portion of the trench region including the opening with a hydrophilic material.

20. The method of claim 19 wherein the etching is isotropic.

21. The method of claim 19 wherein the etching is wet etching.

22. The method of claim 19 wherein the trench includes rounded edges.

23. The method of claim 19 wherein the etching is dry etching.

24. The method of claim 19 wherein the patterning includes simultaneously patterning the upper surface to form the elongated member.

25. The method of claim 19 wherein the substrate includes a plurality of elongated members.

26. The method of claim 19 wherein the plurality of elongated members are coupled to each other along a side.

27. The method of claim 19 further comprising releasing the elongated member by removing at least the support structure.

28. A biological array of spots having a quantity to map a complete genome on a single substrate, the biological array comprising:

a substrate including a surface and a thickness, the surface having a hydrophilic surface, the surface having a surface dimension variation from a first end to a second end;

at least 30,000 spots provided on a surface of the substrate, each of the spots being placed in a spatial manner based upon a predetermined order;

wherein the complete human genome is provided on the single substrate to reduce a possibility of variation between the substrate and another substrate.

29. The array of claim 28 wherein substrate is 1 by 3 inch slide.

30. The array of claim 28 wherein the array of spots are provided 18 by 72 millimeters.

31. The array of claim 28 wherein the single substrate is a conventional glass side or a plurality of glass slides.

32. The array of claim 28 wherein the spot density is 5000 genes per square centimeter or greater.

33. A method for manufacturing a fountain pen dispenser, the method comprising:

providing a substrate, the substrate having a top surface, a bottom surface, and a thickness defined between the top surface and bottom surface;

patterning the top surface of the substrate to define a trench region having a length and width; and

forming an elongated member having the trench region defined therein from the substrate, the elongated member having a tip portion coupled to an opening of the trench region.

34. The method of claim 33 further comprising coating a portion of the trench region with a hydrophilic material.

35. The method of claim 33 wherein the forming comprises patterning the top surface and the bottom surface of the substrate simultaneously.

36. The method of claim 33 wherein the forming comprises patterning only the top surface.

37. The method of claim 33 wherein the forming comprises patterning only the bottom surface.