High density arrays
First Claim
1. A method for generating a microarray, comprising:
- (a) applying at least one reagent solution containing receptor molecules to a solid support to form a first applied spot pattern, wherein spots in the first applied spot pattern have an area and wherein the reagent solution, the receptor molecules, the solid support, or any combination thereof includes at least one photoreactive group;
(b) illuminating the first applied spot pattern to immobilize the receptor molecules to the solid support in a first immobilized spot pattern, wherein spots in the first immobilized spot pattern have an area and wherein the area of the spots in the first immobilized spot pattern is less than the area of the spots in the first applied spot pattern.
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Abstract
The invention provides a method for generating arrays with a variety of densities, in particular, high density arrays. Generally, the method includes a printing step and an illumination step. In the printing step, a predetermined volume of a reagent solution containing receptor molecules is applied to a solid support in a desired pattern. In one embodiment, the receptor molecule is derivatized with a photoreactive agent. In an alternate embodiment, the solid support includes a photoreactive agent. In a preferred embodiment, the receptor molecule is a nucleic acid. In the illumination step, the photoreactive groups are irradiated to immobilize the receptor molecule to the solid support. In one embodiment, a mask having the same center to center distance (e.g., pitch) as the printed spots, but a smaller diameter, is placed over the printed pattern and illuminated. Preferably the mask illuminates a spot having a smaller diameter than the printed spots. Thus, according to the invention, the immobilized reagent spot has a smaller diameter than the original printed spot. In an alternate embodiment, the illumination step can be carried out using mirrored laser technology. If desired, the application and illumination of offset spots can be repeated to form a high density array.
26 Citations
33 Claims
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1. A method for generating a microarray, comprising:
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(a) applying at least one reagent solution containing receptor molecules to a solid support to form a first applied spot pattern, wherein spots in the first applied spot pattern have an area and wherein the reagent solution, the receptor molecules, the solid support, or any combination thereof includes at least one photoreactive group;
(b) illuminating the first applied spot pattern to immobilize the receptor molecules to the solid support in a first immobilized spot pattern, wherein spots in the first immobilized spot pattern have an area and wherein the area of the spots in the first immobilized spot pattern is less than the area of the spots in the first applied spot pattern. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A microarray comprising a solid support having a pattern of nucleic acid spots wherein the spots have a diameter of less than 100 μ
- m and comprise nucleic acids having a sequence of at least 30 bases.
- View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
Specification