Microarray fabrication techniques and apparatus

• US 20030143725A1
• Filed: 01/23/2003
• Published: 07/31/2003
• Est. Priority Date: 02/22/2000
• Status: Abandoned Application

• Current Assignee: Shiping Chen, Yuling Luo
• Original Assignee: Shiping Chen, Yuling Luo
• Inventors: Luo, Yuling, Chen, Shiping
• Application Number:
  US10/351,163
• Publication Number:
  US 20030143725A1
• 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 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00673 Slice arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 2200/021 : Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 : Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/022 : droplet contacts the surface of the receptacle
• CPC Class Codes: B01L 2400/027 : electrostatic forces between substrate and tip
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• 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 3/563 : Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2021/6484 : Optical fibres
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array

Abstract

Disclosed is a microarray printing system and methods of printing probe microarrays. The system has a print head formed of one or more bundles of individual capillaries, such as light-guiding capillaries. The bundles may especially be random bundles of capillaries that provide a large number of probes on the surface of a substrate. Methods of registering or correlating the distal and proximal ends of the capillaries are also provided. Further, the invention provides methods and equipment for identifying defective microarrays that are missing one or more probes from the surface of the microarray.

Claims

1. A capillary bundle comprising a plurality of individual capillaries having proximal and distal ends, each of said capillaries having a channel extending from the proximal end to the distal end of the capillary and having a channel-facing wall, wherein said proximal ends of the individual capillaries are secured to one another in a solid mass such that the proximal ends of said capillaries are substantially coplanar in a static array in a facet of the solid mass.

2. A capillary bundle according to claim 1, wherein each proximal end of said plurality of capillaries has a vertical height above a reference plane and at least one of said capillaries has a minimum vertical height and at least one of said capillaries has a maximum vertical height, and the difference between the minimum vertical height and the maximum vertical height is no more than about 100 micron.

3. A capillary bundle according to claim 1 or 2, wherein said plurality of capillaries comprises light-conducting capillaries.

4. A capillary bundle comprising a plurality of capillaries having proximal and distal ends, each of said capillaries having a channel extending from the proximal end to the distal end of the capillary and having a channel-facing wall, wherein said proximal ends of the individual capillaries are secured to one another such that the proximal ends of said capillaries are substantially coplanar in a static array in a facet and wherein said plurality of capillaries are secured to one another to form a random bundle so that the distal ends of the capillaries are grouped in a first arrangement, the proximal ends are grouped in a second arrangement, and the first arrangement is not identical to the second arrangement, and wherein the bundle has a print density of at least about 500 probes per cm².

5. A capillary bundle according to claim 4, wherein said plurality of capillaries comprises light-conducting capillaries.

6. A method of printing a microarray comprising providing a capillary bundle comprising a plurality of individual capillaries having proximal and distal ends, each of said capillaries having a channel extending from the proximal end to the distal end of the capillary and having a channel-facing wall, wherein said proximal ends of the individual capillaries are secured to one another in a solid mass such that the proximal ends of said capillaries are substantially coplanar in a static array in a facet of the solid mass, passing a probe-containing fluid through a capillary of said capillary bundle, and printing said microarray on a substrate.

7. A method of printing according to claim 6, wherein said plurality of capillaries comprises light-conducting capillaries.

8. A method according to claim 6, wherein said plurality of capillaries are secured to one another to form a random bundle so that the distal ends of the capillaries are grouped in a first arrangement, the proximal ends are grouped in a second arrangement, and the first arrangement is not identical to the second arrangement.

9. A method of making a capillary bundle suitable for printing a probe microarray on a substrate, said method comprising

a) forming a random bundle of a plurality of capillaries having distal and proximal ends;

and

b) securing the proximal ends of the capillaries to form a solid mass containing the proximal ends of said capillaries, said solid mass having a facet and said proximal ends being substantially coplanar at said facet.

10. A method according to claim 9 wherein said capillaries are light-conducting capillaries.

11. A method according to claims 10 wherein said method further comprises registering the proximal ends of the capillaries to the distal ends of the capillaries.

12. A method according to claim 11, wherein the act of registering the proximal ends to the distal ends comprises launching light into a distal end of a first capillary, observing the light exiting a proximal end of the first capillary, and recording information that correlates the distal end of the first capillary to the proximal end of the first capillary.

13. A probe microarray comprising no less than 500 non-identical probes in a honeycomb pattern in an area of no more than 1 cm² on a substrate.

15. A probe microarray according to claim 13 or 14, wherein said probes are selected from the group consisting of oligonucleotides, polypeptides, cells, and compounds.

16. A probe microarray according to claim 13 or 14, where said microarray comprises at least about 10,000 probes.

14. A probe microarray comprising a random arrangement of no less than 500 non-identical probes in an area of no more than 1 cm² on a substrate.

17. A light-conducting capillary that transports both light and a fluid from a distal end to a proximal end of said capillary, wherein said light-conducting capillary is formed of a material that has a refractive index selected so that said capillary transports said light.

18. A light-conducting capillary according to claim 17, wherein said capillary is configured to transport both said light and said fluid simultaneously, and wherein the refractive index is selected so that the light transmits from the distal end to the proximal end of the capillary as said fluid travels through said capillary.

21. A capillary according to claim 17 or 19, wherein the outer diameter of said capillary is less than about 300 micron.

22. A capillary according to claim 17 or 19, wherein the outer diameter is less than about 100 micron.

19. A light-conducting capillary, said capillary having a first portion having a first refractive index and a second portion having a second refractive index, said second refractive index being greater than said first refractive index, said capillary further having a proximal end, a distal end, an axis, an inner wall defining a channel through the capillary, and an outer wall, said inner wall extending coaxially with the axis of the capillary, said outer wall extending coaxially with the axis of the capillary;

wherein the first portion and the second portion are configured such that a light beam launched into the proximal end is transmitted along the capillary and exits the capillary at the distal end;

said channel having a cross-sectional area, and wherein the cross-sectional area of the channel is sufficiently large that a fluid entering the channel at the proximal end of the capillary discharges at the distal end of the capillary.

20. A capillary according to claim 19, wherein the second portion comprises silica doped with an impurity that increases the refractive index of silica, and wherein the first portion comprises silica having a lower refractive index than said second portion.