Method for manufacturing a microarray and verifying the same

• US 20040259261A1
• Filed: 06/20/2003
• Published: 12/23/2004
• Est. Priority Date: 06/20/2003
• Status: Abandoned Application

• Current Assignee: Phalanx Biotech Group, Inc.
• Original Assignee: Phalanx Biotech Group, Inc.
• Inventors: Liao, Wen-Yeh, Chiou, Chung-Fan
• Application Number:
  US10/465,588
• Publication Number:
  US 20040259261A1
• Time in Patent Office: Days
• US Class Current: 436/43
• 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 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00574 radioactive
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• 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 35/1016 Control of the volume dispensed or introduced
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

Here discloses a method for manufacturing microarrays and verifying the quality of the produced microarrays at the same time. The method includes (a) providing a plurality of reagents; (b) loading the plurality of reagents on a microdispenser in a predetermined arrangement; (c) dispensing the reagents on a test array through said microdispenser, and identifying the reagents on said test array; (d) dispensing said reagents on a plurality of microarrays; and (e) taking an image through an image-recording device for checking the spots of reagents on the microarrays.

Claims

1. A method of providing a comprehensive quality assurance for a microarray manufacturing process, comprising the following steps:

a. providing a plurality of reagents;

b. loading said reagents on a microdispenser in a predetermined arrangement;

c. dispensing said reagents on a test array, wherein the dispensed pattern of said reagents on said test array is corresponding to said predetermined arrangement of said reagents in said microdispenser;

d. identifying said reagents on said test array, then verifying whether the identities of the said reagents on said test array match the identities of the said reagents loaded into the said microdispenser;

e. dispensing said reagents on a plurality of microarrays;

f. recording the image of an entire surface of said microarray by an image-recording device to inspect the droplets of the said reagents dispensed on the surface of said microarray; and

g. proceeding said microarray to an immobilization process and then a washing process to remove un-attached reagents from said microarray surface.

2. The method as claimed in claim 1, further comprising step h observing the signal intensities of markers from locations occupied by said plurality of reagents on the surface of said microarray to evaluate an amount of the said reagents immobilized on the surface of the said microarray, wherein said markers are labeled on said reagents as they are provided in step a.

3. The method as claimed in claim 1, further comprising step a1, wherein the purity of said plurality of reagents is analyzed.

4. The method as claimed in claim 1, wherein said plurality of reagents contains biological materials.

5. The method as claimed in claim 4, wherein said biological materials are oligonucleotides, peptides or the derivatives thereof.

6. The method as claimed in claim 1, wherein said test array is a multi-well plate, a set of microtubes or a solid support.

7. The method as claimed in claim 1, wherein the order of step b and step c being carried out can be sequential, reversed, or simultaneous.

8. The method as claimed in claim 3, step a1., wherein the analysis of the purity of said provided reagents is based on the difference of molecular weight of said reagents.

9. The method as claimed in claim 8, wherein the molecular weight of said reagents is revealed by electrophoresis, mass spectrum, liquid chromatography, or spectrophotometers.

10. The method as claimed in claim 1 step d., wherein the identities of said reagents on the said test array are verified through sequencing.

11. The method as claimed in claim 10, wherein said reagents on the test array are sequenced through MALDI-TOF MS (matrix assisted laser desorption ionization time of flight mass spectrum).

12. The method as claimed in claim 10, wherein when the identity verification results are satisfactory, said microdispenser is suitable for microarray manufacturing.

13. The method as claimed in claim 1, step f., wherein said image-recording device is a CCD or a CMOS sensor.

14. The method as claimed in claim 13, wherein said image-recording device further comprising a computer equipped with an image analysis software to verify all said reagents dispensed on the surface of said microarray.

15. The method as claimed in claim 2, wherein said markers are chemically or enzymatically active moieties.

16. The method as claimed in claim 2, wherein said markers are radioactive isotopes or fluorescent chromophores.