Innovative nanopore sequencing technology including a self-assembled porous membrane

Patent metadata

Field	Value
Publication number	US-9927397-B1
Application number	US-201414555453-A
Country	US
Kind code	B1
Filing date	Nov 26, 2014
Priority date	Nov 26, 2013
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

First claim

What is claimed is:

1. A method for forming a device for the manipulation of a target long chain molecule comprising:
forming an enclosed nanochannel comprising a base, a porous roof, and sidewalls, wherein the enclosed nanochannel is formed by stacking a plurality of nanoparticles on each other, and wherein the spaces between the stacked plurality of nanoparticles define a plurality of tortuous nanopores that provide extended and convoluted pathways through the porous roof to the enclosed nanochannel;
forming a partially sealed porous roof by depositing a conformal layer over the porous roof using a conformal atomic layer deposition (ALD) by sealing some of the plurality of tortuous nanopores thereby forming a plurality of closed nanopores, wherein the partially sealed porous roof comprises the plurality of closed nanopores and a plurality of tortuous nanopores which are not sealed; and
forming a mesoporous silica network on top of the partially sealed porous roof.

2. The method of claim 1 wherein the mesoporous silica network is formed using silica-surfactant self-assembly.

3. The method of claim 1 further comprising depositing an electromagnetic field enhancing structure on the partially sealed porous roof prior to forming the mesoporous silica network.

4. The method of claim 3 wherein the electromagnetic field enhancing structure is a metal-insulator-metal (MIM) structure.

5. The method of claim 1 further comprising depositing an electromagnetic field enhancing structure on the mesoporous silica network.

6. The method of claim 5 wherein the electromagnetic field enhancing structure is a metal-insulator-metal (MIM) structure.

7. A method for manipulating a target long chain molecule comprising:
a) providing an enclosed nanochannel comprising:
a base, a partially sealed porous roof, and sidewalls,
wherein the enclosed nanochannel is formed by stacking a plurality of nanoparticles on each other,
wherein the spaces between the stacked plurality of nanoparticles define a plurality of tortuous nanopores that provide extended and convoluted pathways through the partially sealed porous rod to the enclosed nanochannel, and
wherein the partially sealed porous roof is formed by depositing a conformal layer over a porous roof using a conformal atomic layer deposition (ALD) sealing some of the plurality of tortuous nanopores thereby forming a plurality of closed nanopores,
the partially sealed porous roof comprises the plurality of dosed nanopores and a plurality of tortuous nanopores which are not sealed; and

a mesoporous silica network positioned over the partially sealed porous roof;

b) introducing a sample comprising the target long chain molecule to the enclosed nanochannel;
c) allowing the target long chain molecule to travel through at least one of the plurality of the tortuous nanopores of the partially sealed porous roof and the mesoporous silica network before and/or after the target long chain molecule travels through the enclosed nanochannel.

8. The method of claim 7 wherein the partially sealed porous roof further comprises an electromagnetic field enhancing structure.

9. The method of claim 8 wherein the electromagnetic field enhancing structure is positioned between the partially sealed porous roof and the mesoporous silica network.

10. The method of claim 8 wherein the electromagnetic field enhancing structure is positioned on top of the mesoporous silica network.

11. The method of claim 8 wherein the electromagnetic field enhancing structure is a metal-insulator-metal (MIM) structure.

12. The method of claim 7 , wherein the step of providing an enclosed nanochannel comprises providing at least one of a plurality of nanochannels and a plurality of multilevel nanochannels.

13. The method of claim 7 , wherein adjacent tortuous nanopores of the plurality of tortuous nanopores are spaced at a distance greater than an optical wavelength used in an optical detection of the target long chain molecule.

14. A method for forming a device for the manipulation of a target long chain molecule comprising:
providing a nanochannel having a porous roof comprising a plurality of tortuous nanopores;
sealing some of the plurality of tortuous nanopores in the porous roof via conformal atomic layer deposition (ALD) to form a partially sealed roof; and
forming a mesoporous silica network on top of the partially sealed roof;
depositing an electromagnetic field enhancing structure on the partially sealed roof prior to forming the mesoporous silica network, wherein the electromagnetic field enhancing structure is a metal-insulator-metal (MIM) structure.

15. The method of claim 12 wherein the mesoporous silica network is formed using silica-surfactant self-assembly.

16. The method of claim 1 , wherein the plurality of tortuous nanopores are spaced at a distance greater than a wavelength used in an optical detection of the target long chain molecule.

17. The method of claim 1 , wherein the plurality of nanoparticles has a dispersion in size.

Assignees

• Brueck Steven R J
• Edwards Jeremy Scott
• Neumann Alexander
• Kuznetsova Yuliya
• Mendoza Edgar A
• Brinker C Jeffrey
• Stc Unm

Inventors

• Brueck Steven R J
• Edwards Jeremy Scott
• Neumann Alexander
• Kuznetsova Yuliya
• Mendoza Edgar A
• Brinker C Jeffrey

Classifications

• B01L2200/0663

  Stretching or orienting elongated molecules or particles · CPC title

• B01L3/50273

  characterised by the means or forces applied to move the fluids · CPC title

• B01L2400/0421

  electrophoretic flow · CPC title

• G01N27/44791 Primary

  Microapparatus (sample containers with integrated microfluidic structures B01L3/5027) · CPC title

• C12Q1/6869

  Methods for sequencing · CPC title