IP Library Granted Patent US 9,725,315
Granted Patent B2
US 9,725,315 · App. 13/498,846 · Granted Aug 8, 2017

Nanochannel arrays and near-field illumination devices for polymer analysis and related methods

Inventors: Michael Austin (Philadelphia, PA); Parikshit A. Deshpande (Princeton, NJ); Alexey Sharonov (Drexel Hill, PA); Valeriy Bogdanov (Philadelphia, PA)
Assignee: BIONANO GENOMICS, INC.
B82Y30/00G01N21/645G01N33/558
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Quick Facts
Patent No.
US 9,725,315
App. No.
13/498,846
Granted
Aug 8, 2017
Kind
B2
Abstract

Provided are devices and methods for polymer analysis, in which labeled polymers are translocated along nanochannels that have illuminated detection regions within. As a labeled polymer translocates along the nanochannel and the labels pass over the illuminated detection regions, the labels become detectable (e.g., where different labels fluoresce in response to different wavelengths present at different illumination regions), and the user generates a spatial map of the location of the various labels along the length of the polymer. The location of the labels is then correlated to one or more structural characteristics of the polymer.

Claims (45)

1. An analysis device, comprising:

a plurality of nanochannels running along a surface of a first substrate,

each nanochannel defined by side walls and a floor; and

at least two nanoslits being disposed in a second substrate, the nanoslits being disposed such that electromagnetic radiation of at least a first wavelength passing through each nanoslit defines, within the at least one nanochannel, an illumination region having a cross-sectional dimension smaller than the first wavelength of the electromagnetic radiation, whereby the illumination region has a spatial resolution less than a diffraction limit of said electromagnetic radiation.

2. The analysis device of claim 1 , wherein the first substrate comprises silica, silicon, dielectrics, insulators, glass, borofloat glass, sodalime glass, silicon oxynitride, SiO x N y , hydrogenated silicon dioxide, hydrogenated silicon nitride, hydrogenated silicon oxynitride, high K dielectrics, compounds comprising titanium: TiSiO, TiO, TiN, titanium oxides, hydrogenated titanium oxides, titanium nitrides, hydrogenated titanium nitrides, TaO, TaSiO, TaO x N y , Ta 2 O 5 , TaCN, tantalum oxides, hydrogenated tantalum oxides, tantalum nitrides, hydrogenated tantalum nitrides, compounds containing hafnium: HfO 2 , HfSiO 2 , HfZrO x , HfN, HfON, HfSiN, HfSiON, hafnium oxides, hydrogenated hafnium oxides, hafnium nitrides, hydrogenated hafnium nitrides, ZrO 2 , ZrSiO 2 , ZrN, ZrSiN, ZrON, ZrSiON, zirconium oxides, hydrogenated zirconium oxides, zirconium nitrides, hydrogenated zirconium nitrides, Al 2 O 3 , AlN, TiAlN, TaAlN, WAlN, aluminum oxides, hydrogenated aluminum oxides, aluminum nitrides, hydrogenated aluminum nitrides, SiN, WN, low K dielectrics, fluorine doped silicon dioxide, carbon doped silicon dioxide, porous silicon dioxide, porous carbon doped silicon dioxide, spin-on organic polymeric dielectrics, graphite, graphene, carbon nano-tubes, plastics, polymer, co-polymer, block copolymer, Polydimethylsiloxane (PDMS), polycarbonate (PC), Poly (methyl methacrylate) (PMMA), Cyclic Olefin Copolymer (COC), a stoichiometric variation of any of the foregoing, or any combination thereof.

3. The analysis device of claim 1 , wherein at least one nanochannel is characterized as comprising a width between side walls in the range of from about 10 nm to about 1000 nm.

4. The analysis device of claim 1 , wherein at least one nanochannel is characterized as comprising a depth from the top of a side wall to the floor of the nanochannel in the range of from about 10 nm to about 1000 nm.

5. The analysis device of claim 1 , wherein each nanoslit is disposed in a second substrate opaque to the electromagnetic radiation of at least a first wavelength.

6. The analysis device of claim 5 , wherein the first and second substrates are bonded to one another.

7. The analysis device of claim 1 , wherein each nanoslit comprises an aperture characterized as having a cross-sectional dimension less than that of the first wavelength.

8. The analysis device of claim 1 , wherein each nanoslit comprises an aperture characterized as having a cross-sectional dimension in the range of from about 1 nm to about 300 nm.

9. The analysis device of claim 1 , wherein the second substrate comprises silica, silicon, dielectrics, insulators, glass, borofloat glass, sodalime glass, silicon oxynitride, SiO x N y , hydrogenated silicon dioxide, hydrogenated silicon nitride, hydrogenated silicon oxynitride, high K dielectrics, compounds comprising titanium: TiSiO, TiO, TiN, titanium oxides, hydrogenated titanium oxides, titanium nitrides, hydrogenated titanium nitrides, TaO, TaSiO, TaO x N y , Ta 2 O 5 , TaCN, tantalum oxides, hydrogenated tantalum oxides, tantalum nitrides, hydrogenated tantalum nitrides, HfO 2 , HfSiO 2 , HfZrO x , HfN, HfON, HfSiN, HfSiON, hafnium oxides, hydrogenated hafnium oxides, hafnium nitrides, hydrogenated hafnium nitrides, ZrO 2 , ZrSiO 2 , ZrN, ZrSiN, ZrON, ZrSiON, zirconium oxides, hydrogenated zirconium oxides, zirconium nitrides, hydrogenated zirconium nitrides, Al 2 O 3 , AlN, TiAlN, TaAlN, WAlN, aluminum oxides, hydrogenated aluminum oxides, aluminum nitrides, hydrogenated aluminum nitrides, SiN, WN, low K dielectrics, fluorine doped silicon dioxide, carbon doped silicon dioxide, porous silicon dioxide, porous carbon doped silicon dioxide, spin-on organic polymeric dielectrics, graphite, graphene, carbon nano-tubes, plastics, polymer, co-polymer, block co-polymer, Polydimethylsiloxane (PDMS), polycarbonate (PC), Poly (methyl methacrylate) (PMMA), Cyclic Olefin Copolymer (COC), a stoichiometric variation of any of the foregoing, or any combination thereof.

10. The analysis device of claim 1 , further comprising a source capable of emitting the electromagnetic radiation of at least a first wavelength.

11. The analysis device of claim 10 , wherein the source comprises a laser.

12. The analysis device of claim 10 , wherein the source comprises a device capable of emitting electromagnetic radiation having at least one frequency component in the range of from about 100 nm to about 20,000 nm.

13. An analysis device, comprising:

a plurality of nanochannels running along a surface of a first substrate,

each nanochannel being defined by side walls and a floor; and

a phase-shift mask disposed in at least one of the nanochannels such that electromagnetic radiation of at least a first wavelength passing through the phase-shift mask defines, within the at least one of the nanochannels, an illumination region, wherein the illumination region has a cross-sectional dimension smaller than the first wavelength of the electromagnetic radiation, whereby the illumination region has a spatial resolution less than a diffraction limit of said electromagnetic radiation.

14. The analysis device of claim 13 , wherein the substrate comprises silica, silicon, dielectrics, insulators, glass, borofloat glass, sodalime glass, silicon oxynitride, SiO x N y , hydrogenated silicon dioxide, hydrogenated silicon nitride, hydrogenated silicon oxynitride, high K dielectrics, compounds comprising titanium: TiSiO, TiO, TiN, titanium oxides, hydrogenated titanium oxides, titanium nitrides, hydrogenated titanium nitrides, TaO, TaSiO, TaO x N y , Ta 2 O 5 , TaCN, tantalum oxides, hydrogenated tantalum oxides, tantalum nitrides, hydrogenated tantalum nitrides, HfO 2 , HfSiO 2 , HfZrO x , HfN, HfON, HfSiN, HfSiON, hafnium oxides, hydrogenated hafnium oxides, hafnium nitrides, hydrogenated hafnium nitrides, ZrO 2 , ZrSiO 2 , ZrN, ZrSiN, ZrON, ZrSiON, zirconium oxides, hydrogenated zirconium oxides, zirconium nitrides, hydrogenated zirconium nitrides, Al 2 O 3 , AlN, TiAlN, TaAlN, WAlN, aluminum oxides, hydrogenated aluminum oxides, aluminum nitrides, hydrogenated aluminum nitrides, SiN, WAlN, low K dielectrics, fluorine doped silicon dioxide, carbon doped silicon dioxide, porous silicon dioxide, porous carbon doped silicon dioxide, spin-on organic polymeric dielectrics, graphite, graphene, carbon nano-tubes, plastics, polymer, co-polymer, block co-polymer, Polydimethylsiloxane (PDMS), polycarbonate (PC), Poly (methyl methacrylate) (PMMA), Cyclic Olefin Copolymer (COC), a stoichiometric variation of any of the foregoing, or any combination thereof.

15. The analysis device of claim 13 , wherein at least one nanochannel is characterized as comprising a width between side walls in the range of from about 10 nm to about 300 nm.

16. The analysis device of claim 13 , wherein at least one nanochannel is characterized as comprising a depth from the top of a side wall to the floor of the nanochannel in the range of from about 10 nm to about 1000 nm.

17. The analysis device of claim 13 , wherein the phase-shift mask comprises a material essentially transparent to the electromagnetic radiation of at least a first wavelength.

18. The analysis device of claim 13 , further comprising a source capable of emitting electromagnetic radiation of at least a first wavelength.

19. The analysis device of claim 18 , wherein the source comprises a laser.

20. The analysis device of claim 18 , wherein the source comprises a device capable of emitting electromagnetic radiation having at least one frequency component of from about 100 nm to about 20,000 nm.

21. The analysis device of claim 13 , wherein the phase-shift mask comprises a near-field holography mask.

22. The analysis device of claim 13 , wherein the phase-shift mask is bonded to the first substrate.

23. The analysis device of claim 13 , wherein the cross-sectional dimension of the illumination region is smaller than ⅓ of the first wavelength of the electromagnetic radiation.

24. A method of analysis, comprising:

providing an analysis device comprising:

a plurality of nanochannels running along a surface of a first substrate, each nanochannel defined by side walls and a floor; and

at least two nanoslits being disposed in a second substrate, the nanoslits being disposed such that electromagnetic radiation of at least a first wavelength passing through each nanoslit defines, within the at least one nanochannel, an illumination region having a cross-sectional dimension smaller than the first wavelength of the electromagnetic radiation, whereby the illumination region has a spatial resolution less than a diffraction limit of said electromagnetic radiation;

translocating a macromolecule comprising two or more labels through two or more illumination regions along one or more nanochannels;

exciting the labels within the illumination regions with electromagnetic radiation to give rise to one or more signals;

detecting the one or more signals from the illumination regions; and

correlating the one or more detected signals to the relative positions of the labels along the macromolecule.

25. The method of claim 24 , wherein the labels are excited using electromagnetic radiation transmitted through a radiation restrictor.

26. The method of claim 24 , wherein a label comprises a fluorescent dye.

27. The method of claim 24 , wherein one or more labels are complementary to a specific region of one or more macromolecules.

28. The method of claim 24 , wherein two or more labels are excited by electromagnetic radiation of the same wavelength.

29. The method of claim 24 , wherein two or more labels are excited by electromagnetic radiation of different wavelengths.

30. The method of claim 29 , wherein the two or more labels are excited at different excitation regions.

31. The method of claim 24 , further comprising correlating signals from two or more labels on two or more macromolecules.

32. The method of claim 24 , further comprising correlating the relative positions of the one or more labels to a physiological state, a disease state, or any combination thereof.

Assignments (10)
RELEASE OF SECURITY INTEREST Recorded May 24, 2024
From: HIGH TRAIL SPECIAL SITUATIONS LLC, AS COLLATERAL AGENT
To: BIONANO GENOMICS, INC.
Reel/Frame 067529/0193 →
SECURITY INTEREST Recorded May 24, 2024
From: BIONANO GENOMICS, INC.; BIODISCOVERY, LLC; LINEAGEN, INC.; PURIGEN BIOSYSTEMS, INC.
To: JGB COLLATERAL, LLC
Reel/Frame 067529/0286 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Oct 16, 2023
From: BIONANO GENOMICS, INC.
To: HIGH TRAIL SPECIAL SITUATIONS LLC
Reel/Frame 065241/0844 →
RELEASE OF SECURITY INTEREST Recorded May 26, 2021
From: INNOVATUS LIFE SCIENCES LENDING FUND I, LP
To: BIONANO GENOMICS, INC.
Reel/Frame 056356/0009 →
SECURITY INTEREST Recorded Mar 22, 2019
From: BIONANO GENOMICS, INC.
To: INNOVATUS LIFE SCIENCES LENDING FUND I, LP
Reel/Frame 048670/0582 →
RELEASE OF SECURITY INTEREST Recorded Mar 22, 2019
From: MIDCAP FINANCIAL TRUST, AS AGENT
To: BIONANO GENOMICS, INC.
Reel/Frame 048674/0556 →
REASSIGNMENT AND RELEASE OF SECURITY INTEREST Recorded Jul 3, 2018
From: WESTERN ALLIANCE BANK
To: BIONANO GENOMICS, INC.
Reel/Frame 046472/0387 →
SECURITY INTEREST Recorded Jul 3, 2018
From: BIONANO GENOMICS, INC.; THE TRUSTEES OF PRINCETON UNIVERSITY
To: MIDCAP FINANCIAL TRUST, AS AGENT
Reel/Frame 046472/0643 →
SECURITY INTEREST Recorded Feb 9, 2018
From: BIONANO GENOMICS, INC.
To: WESTERN ALLIANCE BANK
Reel/Frame 044882/0059 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2012
From: AUSTIN, MICHAEL; SHARONOV, ALEXEY; BOGDANOV, VALERIY; DESHPANDE, PARIKSHIT A.
To: BIONANO GENOMICS, INC.
Reel/Frame 028350/0859 →
Continuity (2)
Provisional Application 61246251 · Sep 28, 2009
Related Publication 20120244635A1 · Sep 27, 2012