DEVICES AND METHODS FOR MICROARRAY SELECTION

• US 20120165219A1
• Filed: 08/26/2010
• Published: 06/28/2012
• Est. Priority Date: 09/01/2009
• Status: Active Grant

• Current Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Van Der Zaag, Pieter Jan, Den Toonder, Jacob Marinus Jan, Wimberger-Friedl, Reinhold, Feitsma, Harma
• Granted Patent: US 9,493,822 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2527/107 Temperature of melting, i.e. Tm
• CPC Class Codes: C12Q 2537/149 Sequential reactions

Abstract

The present invention relates to a device for the specific selection of target molecules, comprising: (a) at least one reaction zone comprising a microarray, wherein the microarray comprises a substrate, on which one or more species of capture molecules are immobilized, comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone; (b) at least one non-reaction zone comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone, which is in fluid connection with the reaction zone; and (c) at least one transportation means capable of generating and/or regulating a fluid flow between said reaction zone (a) and said non-reaction zone comprising one or more temperature control and/or regulating units (b). The present invention further relates to a device for the specific selection of target molecules wherein the immobilized capture molecules are organized in the microarray in the form of spots, elongated spots and/or lines. In a further aspect the present invention relates to a method of specifically selecting target molecules, comprising the introducing a medium to such a device, performing interaction reactions in a reaction zone, transporting not interacted or not bound target molecules to a zone allowing reactivation of the target molecules and performing additional interaction reactions with the reactivated target molecules at the reaction zone, as well as the use of such a device for specifically selecting target molecules, e.g. for target enrichment also referred to as microarray based genome selection (MGS) in the literature.

Claims

1. A device for the specific selection of target molecules, comprising:

(a) at least one reaction zone comprising a microarray, wherein the microarray comprises a substrate, on which one or more species of capture molecules are immobilized, the reaction zone further comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the reaction zone;

(b) at least one non-reaction zone comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the non-reaction zone, which is in fluid connection with the reaction zone; and

(c) at least one transportation means capable of generating and/or regulating a fluid flow between said reaction zone (a) and said non-reaction zone comprising one or more temperature control and/or regulating units (b).

2. The device of claim 1, wherein said unit for controlling and/or regulating the temperature within the non-reaction zone is integrated in said non-reaction zone.

3. The device of claim 1, wherein said reaction zone (a), said non-reaction zone (b), and said transportation means (c) are arranged in a closed loop.

4. The device of claim 3, wherein said closed loop allows a continuous exchange of fluid between said reaction zone (a) and said non-reaction zone.

5. The device of claim 1, wherein said device additionally comprises mixing means, preferably in regions of fluid connection between the zones.

6. The device of claim 1, wherein said device comprises a meandering flow path.

7. The device of claim 1, wherein said a reaction zone (a) is a hybridizing zone capable of allowing hybridization of nucleic acids to said capture molecules.

8. The device of claim 1, wherein said non-reaction zone comprising a temperature control and/or regulating unit (b) is a denaturation zone capable of mediating denaturation of nucleic acids.

9. The device of claim 1, wherein said immobilized capture molecules are organized in the microarray in the form of spots, elongated spots and/or lines.

11. The device of claim 9, wherein said lines have a width of between about 300 nm and 30 μ

m and/or are arranged in an inter-line distance of about 500 nm to 100 μ

m.

12. The device of claim 1, wherein said capture molecules are molecules selected from the group comprising nucleic acids, peptides, proteins, antigens, antibodies, carbohydrates and/or analogs thereof.

13. A method of specifically selecting target molecules, comprising the steps of:

(a) introducing a medium containing one or more target molecules into a zone of a device as defined in claim 1;

(b) performing an interaction reaction between said target molecules and immobilized capture molecules in a reaction zone;

(c) transporting not interacted or not bound target molecules to a non-reaction zone comprising one or more temperature control and/or regulating units;

(d) reactivating, said target molecule in said zone comprising one or more temperature control and/or regulating units; and

(e) transporting reactivated target molecules to the reaction zone, thus allowing further interaction between said target molecule and immobilized capture molecules according to step (b).

14. The method of claim 13, wherein steps (b) to (e) are repeated at least 2 times.

15. Use of a device as defined in claim 1 for specifically selecting target molecules.

10. The device of claim 10, wherein said lines are arranged in an angle of between about 20°

and 90 with respect to the flow path.