Spotting device for manufacturing DNA microarray and spotting method using the same

• US 20050158755A1
• Filed: 12/10/2004
• Published: 07/21/2005
• Est. Priority Date: 12/24/2003
• Status: Active Grant

• Current Assignee: Samsung Electronics Co. Ltd. (Samsung Group)
• Original Assignee: Samsung Electronics Co. Ltd. (Samsung Group)
• Inventors: Lee, Jeong-gun, Lee, Hun-joo
• Granted Patent: US 7,416,705 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00529 DNA chips
• 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 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• 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 2219/00729 Peptide nucleic acids [PNA]
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/02 Drop detachment mechanisms of single droplets from nozzles or pins
• CPC Class Codes: B01L 2400/0475 specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 3/0248 : Prongs, quill pen type dispenser
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A spotting device for manufacturing a DNA microarray and a spotting method using the same are provided. The spotting device for dropping and immobilizing a solution of biomolecules, for example nucleic acids such as probe DNA, mRNA, and peptide nucleic acid (PNA), and proteins on a DNA microarray surface to manufacture a DNA microarray, includes a first microchannel with a tube shape; a supplying unit supplying the solution of biomolecules to the first microchannel; a biomolecule solution droplet forming unit cross-linked to the first microchannel and forming biomolecule solution droplets with a predetermined size by periodically jetting a gas toward the biomolecule solution flowing in the first microchannel; a second microchannel linked to the first microchannel and having a greater diameter than the first microchannel; a cooling unit surrounding at least a part of the second microchannel to freeze the biomolecule solution droplets which pass through the second microchannel; and a spotting unit thawing the frozen biomolecule solution droplets and dropping the thawed biomolecule solution droplets on a surface of the DNA microarray. The spotting device can form spots with uniform shape, minimize an effect of temperature on biomolecules, and easily manipulate biomolecules when manufacturing a DNA microarray.

Claims

1. A spotting device for dropping and immobilizing a solution of biomolecules, for example, nucleic acids such as probe DNA, mRNA, and peptide nucleic acid (PNA), and proteins on a DNA microarray surface to manufacture a DNA microarray, the spotting device including:

a first microchannel with a tube shape;

a supplying unit supplying the solution of biomolecules to the first microchannel;

a biomolecule solution droplet forming unit cross-linked to the first microchannel and forming biomolecule solution droplets with a predetermined size by periodically jetting a gas toward the biomolecule solution flowing in the first microchannel;

a second microchannel linked to the first microchannel and having a greater diameter than the first microchannel;

a cooling unit surrounding at least a part of the second microchannel to freeze the biomolecule solution droplets which pass through the second microchannel; and

a spotting unit to thaw the biomolecule solution droplets and dropping the thawed biomolecule solution droplets on a surface of the DNA microarray.

2. The spotting device of claim 1, wherein the spotting unit includes:

a third microchannel having a microvalve opening and closing a path which the frozen biomolecule solution droplets pass through, and storing the frozen biomolecule solution droplets at a sub-zero temperature;

a discharger coupled to the third microchannel and opening the microvalve to discharge the frozen biomolecule solution droplets from the third microchannel; and

a fourth microchannel linked to the third microchannel and heated to a predetermined temperature by a heater to thaw the biomolecule solution droplets which have been discharged from the third microchannel.

3. The spotting device of claim 2, wherein the predetermined temperature is 20 to 200°

C., the sub-zero temperature is −

5 to −

30°

C., and an adiabatic channel is installed between the third microchannel and the fourth microchannel so as to prevent heat from being conducted from the fourth microchannel to the third microchannel.

4. The spotting device of claim 2, wherein the discharger is a microactuator installed over the third microchannel and a plurality of the spotting units are regularly arranged.

5. The spotting device of claim 1, wherein the supplying unit includes:

a solution reservoir linked to the first microchannel and storing the biomolecule solution; and

a first micropump to pump the biomolecule solution stored in the solution reservoir into the first microchannel.

6. The spotting device of claim 1, wherein the gas is air and the biomolecule solution droplet forming unit includes:

an air reservoir storing air; and

a second micropump periodically jetting the air stored in the air reservoir toward the biomolecule solution flowing in the first microchannel.

7. The spotting device of claim 1, wherein the predetermined size of the biomolecule solution droplet is a diameter of 2000 μ

m to 1 nm.

8. The spotting device of claim 1, wherein the cooling unit further includes a frozen biomolecule solution droplet reservoir which stores the frozen biomolecule solution droplets.

9. A spotting method for dropping and immobilizing a solution of biomolecules, for example, nucleic acids such as probe DNA, mRNA, and peptide nucleic acid (PNA), and proteins on a DNA microarray surface to manufacture a DNA microarray, the spotting method including:

(a) allowing the biomolecule solution to flow in a first microchannel with a tube shape;

(b) periodically jetting a gas toward the biomolecule solution flowing in the first microchannel to form biomolecule solution droplets with a predetermined size;

(c) freezing the biomolecule solution droplets passing through a second microchannel linked to the first microchannel and having a greater diameter than the first microchannel and storing the frozen biomolecule solution droplets; and

(d) thawing the biomolecule solution droplets and dropping the thawed biomolecule solution droplets on the DNA microarray surface.

10. The spotting method of claim 9, wherein in the operation (c), the storage of the frozen biomolecule solution droplets is accomplished in a third microchannel maintained at −

5 to −

30°

C.

11. The spotting method of claim 10, wherein in the operation (d), the frozen biomolecule solution droplets is thawed while being passed through a fourth microchannel maintained at a temperature of 20 to 200°

C. by a heater and linked to the third microchannel.

12. The spotting method of claim 9, wherein in the operation (b), the gas is air and the predetermined size is a diameter of 2000 μ

m to 1 nm.

13. The spotting method of claim 9, wherein in the operation (d), the frozen biomolecule solution droplets are simultaneously discharged by a plurality of the spotting units regularly arranged.