Biodisc microarray and its fabrication, use, and scanning

• US 20070037146A1
• Filed: 04/14/2003
• Published: 02/15/2007
• Est. Priority Date: 04/14/2003
• Status: Abandoned Application

• Current Assignee: Gilbert Hong
• Original Assignee: Gilbert Hong
• Inventors: Hong, Gilbert
• Application Number:
  US10/412,973
• Publication Number:
  US 20070037146A1
• 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 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support

Abstract

A biodisc comprises a CD-type optical disc with small feature oligonucleotide probes disposed on its surfaces. The biodisc'"'"'s probes are either custom-fabricated in-situ with a master-duplicate tandem arrangement of discs that allows one disc and a reading/tracking head to control the probe locations being synthesized pass-by-pass on the duplicate. Or the biodisc is mass-produced in a manufacturing process that includes a spin-on-and-peel (SOAP) method to create a nickel stamper for standardized biodisc oligonucleotide probes. Such biodisc is fabricated with four masks only, and these are shifted between depositions to synthesize particular individual 4-mer+ target nucleotide probes.

Claims

1. A biodisc, comprising:

a round (plastic, metal or glass) disc having a concentric middle hole or hub for a spindle and opposite flat planar sides; and

a number of oligonucleotide (or protein or other biological interesting polymers)probes with different sequences disposed along tracks at known locations on at least one of said opposite flat planar sides.

2. The biodisc of claim 1, further comprising:

a number of servo tracks on a first or second of said opposite flat planar sides and providing for repeatability in addressing of individual ones of the number of oligonucleotide probes disposed on a first or second one of said opposite flat planar sides.

3. A biodisc system, comprising:

a biodisc with a variety of oligonucleotide (or protein or other biopolymers) probes with different sequences disposed on its surfaces at predetermined and addressable locations;

a disc drive for mounting and optical scanning of the biodisc; and

a computer connected to the disc drive and having a-priori information about said predetermined and addressable locations of said oligonucleotide probes disposed on the biodisc, and able to detect any hybridization of particular ones of said oligonucleotide probes when the biodisc is mounted on the disc drive, and further able to thereby identify particular genetic sequences in a sample material that was in contact with the biodisc.

4. An method for manufacturing a in-situ synthesized biodisc, comprising:

coupling together a servo master disc and an in-situ biodisc together on a common spindle;

paralleling a read head for tracking position information on said servo master disc, and a writing head for recording oligonucleotide information on said in-situ biodisc together on a common actuator;

determining a particular oligonucleotide for synthesis at a location on the in-situ biodisc;

addressing each location on said in-situ biodisc indirectly with said read head for tracking position information on said servo master disc;

depending on said common spindle and said common actuator to repeatably address said locations on said in-situ biodisc as said particular oligonucleotide is in the process of being synthesized.

5. A mass-production method for manufacturing a biodisc, comprising:

using only four different masks in shifted angular positions during each of a plurality of masking operations to synthesize oligonucleotide sequences on a biodisc that exceed four-mer.

6. An biodisc, comprising:

a flat planar disc substrate;

a spiral disposed on at least one surface of the disc substrate;

a first oligomer deposited at a first physical address in the spiral and having an affinity during hybridization for a first DNA particle; and

a second oligomer deposited at a second physical address in the spiral and having an affinity during hybridization for a second DNA particle.

7. The biodisc of claim 6, wherein:

the first and second oligomers and the first and second physical addresses occur in a particular sequence.

8. The biodisc of claim 6, further comprising:

a first DNA particle hybridized to the first oligomer and that has been dyed with a fluorescent; and

a second DNA particle hybridized to the second oligomer and that has been dyed with a fluorescent.

9. The biodisc of claim 8, wherein:

the first and second physical addresses occur in a particular sequence and a fluorescent glow from such location is evidence of a hybridization of a DNA fragment with a first DNA particle in sequence with a second DNA particle.

10. A nucleic acid sequencing method, comprising the steps of:

attaching fluorescent-labeled receptors to a target sample or a synthetic-DNA probe, or both;

placing said target sample in a solution;

heating said solution to obtain a single-strand target material;

hybridizing a biodisc in said solution;

washing away any unreacted solution;

reading patterns of hybridization as indicated by said fluorescent-labeled receptors present at particular physical addresses while rotating said biodisc, and scanning radially across with a detector head until an entire longitudinal length of a synthetic-DNA spiral on a surface of said biodisc is read;

using a lookup table to translates a detected physical address into a complementary nucleic acid sequence for a corresponding synthetic DNA-probe; and

computing a target sequence by interpolating data obtained by from said lookup table.

11. A method for fabricating a biodisc that has a spiral line of synthetic-DNA probes, the method comprising the steps of:

depositing a first layer on a biodisc substrate that repeats a oligomer base pattern along an entire length of the spiral line using four oligomer deposition cycles “

A”

, “

G”

, “

C”

, and “

T”

;

depositing a second layer that repeats said oligomer base pattern on top of said spiral line and said first layer, but shifts the oligomer base pattern forward by one probe; and

depositing n-number of layers that repeat said oligomer base pattern on top of said spiral line and a lower layer, but shifts the oligomer base pattern forward by one;

wherein, at least 4ⁿ uniquely sequenced synthetic-DNA probes each with n-base sequences are fabricated on said substrate for hybridization of nucleic acid target samples.

12. A biodisc for hybridization of nucleic acid target samples, comprising:

a flat, round disc substrate for optical scanning in a CD-type disc drive;

a plurality of independent and individually unique synthetic-DNA probes deposited on the disc substrate in a single layer comprising A, T, C, and G affinity oligomers;

wherein, each said synthetic-DNA probe is laid down on its side.

13. The biodisc of claim 12, wherein:

plurality of independent and unique synthetic-DNA probes have at least two subclasses of with different synthetic-DNA probes numbered base sequences.

14. The biodisc of claim 12, wherein:

the flat disc substrate has an outside diameter of at least ten inches; and

the plurality of independent and unique synthetic-DNA probes are deposited in four different masking cycles, one for each of A, T, C, and G.