Biochip and Manufacturing Method Thereof

• US 20080220989A1
• Filed: 09/28/2007
• Published: 09/11/2008
• Est. Priority Date: 03/07/2007
• Status: Active Grant

• Current Assignee: National Tsing Hua University
• Original Assignee: National Tsing Hua University
• Inventors: Tseng, Fan Gang, Hsieh, Hsin Yi, Wu, Chun Lung
• Granted Patent: US 8,802,024 B2
• Time in Patent Office: Days
• US Class Current: 506/38
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• 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 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: C40B 80/00 Linkers or spacers specially adapted for combinatorial chemistry or libraries, e.g. traceless linkers or safety-catch linkers

Abstract

A method for manufacturing a biochip is provided. First, a first self-assembled monolayer is coated on a substrate. Next, a plurality of first biomedical molecular dots are formed on the first self-assembled monolayer by micro-titration technique. After the bonding reaction between the first biomedical molecular point and the first self-assembled monolayer, a second self-assembled monolayer is deposited on the surface of the first self-assembled monolayer by evaporation. The second self-assembled monolayer attached on the plurality of first biomedical molecular dots and the first self-assembled monolayer not bonded to the substrate are removed, so that the first biomedical molecular dots immobilized on the first self-assembled monolayer are exposed. Finally, a second biomedical molecular layer is immobilized on the exposed portions of the first biomedical molecular dots.

Claims

1. A method for manufacturing a biochip, comprising:

coating a first self-assembled monolayer on a surface of a substrate;

forming a plurality of first biomedical molecular dots on the first self-assembled monolayer;

vaporously depositing a second self-assembled monolayer on the first self-assembled monolayer; and

removing the second self-assembled monolayer adhered to the plurality of first biomedical molecular dots.

2. The method for manufacturing a biochip of claim 1, wherein the second self-assembled monolayer is a non-biological self-assembled monolayer.

3. The method for manufacturing a biochip of claim 1, wherein the second self-assembled monolayer is a film of organosilicon derivatives containing silicon (Si), carbon (C), and hydrogen (H).

4. The method for manufacturing a biochip of claim 3, wherein the film of organosilicon derivatives containing Si, C, and H is a trichloro(1H, 1H,2H,2H-perfluorooctyl)silane film, and trichloro(1H,1H,2H,2H-perfluorooctyl)silane has a molecular formula of CF₃(CF₂)₅CH₂CH₂SiCl₃.

5. The method for manufacturing a biochip of claim 1, wherein the material of the second self-assembled monolayer is selected from organic thiols, organosilicon derivatives, alcohols, amines, and carboxylic acids.

6. The method for manufacturing a biochip of claim 1, further comprising a step of immobilizing second biomedical molecules on the first biomedical molecular dots, wherein the first biomedical molecule dots and the second biomedical molecules are proteins, genes, cells, or tissues.

7. The method for manufacturing a biochip of claim 1, further comprising a step of removing non-bonded parts of the second self-assembled monolayers on the plurality of first biomedical molecular dots.

8. The method for manufacturing a biochip of claim 1, wherein the first self-assembled monolayer is a (3-aminopropyl)trimethoxysilane film, and (3-aminopropyl)trimethoxysilane has a molecular formula of C₆H₁₇NO₃Si.

9. The method for manufacturing a biochip of claim 1, wherein the first self-assembled monolayer is formed on the substrate surface by soakage or evaporation.

10. The method for manufacturing a biochip of claim 1, wherein the second self-assembled monolayer is deposited on the first self-assembled monolayer by evaporation.

11. A biochip, comprising

a substrate;

a self-assembled monolayer coated or bonded on the substrate;

a plurality of first biomedical molecular layers arranged in the form of dot arrays and adsorbed or bonded on the self-assembled monolayer; and

a non-biological self-assembled monolayer disposed on the self-assembled monolayer.

12. The biochip of claim 11, wherein the non-biological self-assembled monolayer is a layer of organosilicon derivatives containing Si, C, and H.

13. The biochip of claim 12, wherein the layer of organosilicon derivatives containing Si, C, and H is a trichloro(1H,1H,2H,2H-perfluorooctyl)silane layer, and trichloro(1H,1H,2H,2H-perfluorooctyl)silane has a molecular formula of CF₃(CF₂)₅CH₂CH₂SiCl₃.

14. The biochip of claim 11, wherein the material of the non-biological self-assembled monolayer is selected from a group consisting of organic thiols, organosilicon derivatives, alcohols, amines, and carboxylic acids.

15. The biochip of claim 11, wherein the self-assembled monolayer is a (3-aminopropyl)trimethoxysilane film, and (3-aminopropyl)trimethoxysilane has a molecular formula of C₆H₁₇NO₃Si.

16. The biochip of claim 11, wherein the non-biological self-assembled monolayer and the self-assembled monolayer are adsorbed or bonded with each other without reacting with the first biomedical molecular layer.

17. The biochip of claim 11, further comprising a second biomedical molecular layer adsorbed or bonded on the first biomedical molecular layer.

18. The biochip of claim 17, wherein the first biomedical molecular layer and the second biomedical molecular layer are proteins, genes, cells, or tissues.