Process for aligning, adhering and stretching nucleic acid strands on a support surface by passage through a meniscus

• US 5,840,862 A
• Filed: 06/06/1995
• Issued: 11/24/1998
• Est. Priority Date: 02/11/1994
• Status: Expired due to Term

• Current Assignee: Centre National De La Recherche Scientifique, Institut Pasteur
• Original Assignee: Centre National De La Recherche Scientifique, Institut Pasteur
• Inventors: Bensimon, Aaron, Bensimon, David, Heslot, Fran.cedilla.ois
• Primary Examiner(s): Naff, David M.
• Application Number:
  US08/467,535
• Time in Patent Office: 1,267 Days
• Field of Search: 435/6, 435/174, 435/176, 435/180, 435/181, 435/182, 435/172.1, 536/22.1, 536/25.4, 536/124, 536/127, 935/77, 935/78, 935/19
• US Class Current: 536/22.1
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• 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: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/682 Signal amplification
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2565/518 characterised by the immobilisation of the nucleic acid sample or target
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 33/6803 : General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: Y10S 435/969 : Multiple layering of reactants
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 530/81 : Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
• CPC Class Codes: Y10S 530/811 : Peptides or proteins is immobilized on, or in, an inorganic carrier
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/145555 : Hetero-N

Abstract

Macromolecules such as nucleic acid strands are aligned, adhered and stretched on a support surface by passing the strands through a meniscus of a solvent containing the strands. The meniscus may be that of a solvent between two surfaces at an interface of the solvent with air. One end of a nucleic acid strand is attached to one surface which may be a glass surface and another end is free. The meniscus is moved relative to the surface to which the end is attached such as by evaporating the solvent or by moving the surface. As the nucleic acid strand passes through the meniscus, the strand elongates and aligns perpendicular to the meniscus on the surface. This method may be used in assaying, measuring intramolecular distance of and/or separating macromolecules.

Claims

1. A process for aligning a nucleic acid strand on a surface, wherein the process comprises:

(a) providing a solvent for the nucleic acid strand between two surfaces where one surface is an anchoring surface to which one end of the nucleic acid strand is anchored by a bond and another end of the nucleic acid strand is free, and where the solvent forms a meniscus between and perpendicular to the surfaces at an interface of the solvent with air between the surfaces; and

(b) moving the meniscus and solvent between the surfaces so that the nucleic acid strand passes through the meniscus into air at the interface whereby the nucleic acid strand is aligned on the anchoring surface perpendicular to the meniscus without breaking the bond that anchors the end of the nucleic acid strand to the surface.

2. A process for adhering a nucleic acid strand to a support surface, wherein the process comprises:

(A) providing a support comprising a glass surface, which has one end of a nucleic acid strand anchored thereto by a bond;

(B) providing a solvent for the nucleic acid strand between said glass surface and a second surface wherein the solvent forms a meniscus between and perpendicular to the surfaces at an interface of the solvent with air between the surfaces, and wherein the solvent has a pH of about 5 to about 10, and further wherein the nucleic acid strand has another end that is movable in said solvent beyond its anchored end; and

(C) slowly moving the meniscus and solvent between the surfaces so that the nulceic acid strand passes through the meniscus into air at the interface whereby the nucleic acid strand is aligned on the glass surface perpendicular to the meniscus without breaking the bond that anchors the end of the nucleic acid strand, to cause the nucleic acid strand to adhere to the glass surface and to become stationary on said surface after passage of said strand through the meniscus.

3. A nucleic acid strand adhered to a support surface produced by the process of claim 2.

4. A process for aligning a nucleic acid strand on a support surface, wherein the process comprises:

(A) providing a support comprising a glass surface having one end of a nucleic acid strand anchored by a bond to said surface;

(B) providing a solvent for the nucleic acid strand between said glass surface and a second surface wherein the solvent forms a meniscus between and perpendicular to the surfaces at an interface with air between the surfaces, and;

wherein the solvent has a pH of about 5 to about 10, and further wherein the nucleic acid strand has another end that is movable about its anchored end in the solvent; and

(C) moving the meniscus and solvent between the surfaces with minimum hydrodynamic shear so that the nucleic acid strand passes through the meniscus into air at the interface whereby the nucleic acid strand is aligned on the glass surface perpendicular to the meniscus without breaking the bond that anchors the end of the nucleic acid strand, to cause the strand to become substantially linear;

wherein the resulting linear nucleic acid strand adheres to the glass surface and is stationary on said surface after passage of the meniscus.

5. A nucleic acid strand aligned on a support surface produced by process of claim 4.

6. A process for stretching and adhering a nucleic acid strand to a support surface, wherein the process comprises:

(A) providing a support comprising a glass surface, which has one end of a nucleic acid strand anchored thereto by a bond;

(B) providing a solvent for the nucleic acid strand between the glass surface and a second surface wherein the solvent has a pH of about 5 to about 10, and wherein the solvent forms a meniscus between and perpendicular to the glass surface and the second surface at an interface of the solvent with air between the surfaces, and

wherein the nucleic acid strand has another end that is movable in the solvent beyond its anchored end; and

slowly moving the meniscus and solvent between the surfaces so that the nucleic acid strand passes through the meniscus into air at the interface whereby the nucleic acid strand is aligned on the glass surface perpendicular to the meniscus without breaking the bond that anchors the end of the nucleic acid strand to the glass surface, to cause the nucleic acid strand to stretch and to adhere to the glass surface;

wherein the nucleic acid strand remains stretched and is stationary on said support after passage of said strand through the meniscus.

7. A stretched nucleic acid strand adhered to a support surface produced by the process of claim 6.

8. A process for stretching and aligning a nucleic acid strand on a support surface, wherein the process comprises:

(A) providing a support comprising a glass surface having one end of a nucleic acid strand anchored to said surface by a bond;

(B) providing a solvent for the nucleic acid strand between the glass surface and a second surface wherein the solvent has a pH of about 5 to about 10, and wherein the solvent forms a meniscus between and perpendicular to the glass surface and the second surface at an interface of the solvent with air between the surfaces, and

wherein the nucleic acid strand has another end that is movable in the solvent about its anchored end; and

(C) moving the meniscus and solvent between the surfaces with minimum hydrodynamic shear, so that the nucleic acid strand passes through the meniscus into air at the interface whereby the nucleic acid strand is aligned on the glass surface perpendicular to the meniscus without breaking the bond that anchors the end of the nucleic acid strand to the surface, to cause the strand to stretch and to become substantially linear;

wherein the resulting linear nucleic acid strand is stationary on said support and remains stretched after passage of the meniscus.

9. A stretched nucleic acid strand aligned on a support surface produced by the process of claim 8.