Ultra-fast nucleic acid sequencing device and a method for making and using the same

• US 9,063,081 B2
• Filed: 10/30/2007
• Issued: 06/23/2015
• Est. Priority Date: 04/24/2000
• Status: Expired due to Fees

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Sauer, Jon Robert, Van Zeghbroeck, Bart
• Primary Examiner(s): ARORA, AJAY
• Application Number:
  US11/929,794
• Publication Number:
  US 20080119366A1
• Time in Patent Office: 2,793 Days
• Field of Search: 257/253, 257/239
• US Class Current: 1/1
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68

Abstract

A system and method employing at least one semiconductor device, or an arrangement of insulating and metal layers, having at least one detecting region which can include, for example, a recess or opening therein, for detecting a charge representative of a component of a polymer, such as a nucleic acid strand proximate to the detecting region, and a method for manufacturing such a semiconductor device. The system and method can thus be used for sequencing individual nucleotides or bases of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). The semiconductor device includes at least two doped regions, such as two n-typed regions implanted in a p-typed semiconductor layer or two p-typed regions implanted in an n-typed semiconductor layer. The detecting region permits a current to pass between the two doped regions in response to the presence of the component of the polymer, such as a base of a DNA or RNA strand. The current has characteristics representative of the component of the polymer, such as characteristics representative of the detected base of the DNA or RNA strand.

Claims

1. A field effect transistor type detector, comprising:

a silicon substrate including a device, the device comprising;

a source region;

a drain region; and

at least one detecting region between the source and drain regions, the at least one detecting region having a recess or an opening; and

an insulator disposed about the recess or opening separating a polymer from the device when the polymer passes through the recess or opening;

wherein a charge on a component of the polymer passing through the recess or opening induces an image charge sufficient to increase the conductivity of the detecting region by an amount related to the charge of the component of the polymer, the device to detect the component of the polymer based on the conductivity of the detecting region.

2. The detector of claim 1, wherein the source and drain regions are doped regions.

3. The detector of claim 2, wherein the doped regions comprise a p-type or an n-type doping.

4. The detector of claim 2, wherein the device comprises a plurality of doped regions and a detecting region associated with a pair of each doped regions.

5. The detector of claim 1, wherein the detecting region is adapted to generate a signal representative of a component of the polymer.

6. The detector of claim 1, wherein the device includes a plurality of detecting regions.

7. The detector of claim 1, wherein the detecting region passes a current between the source and drain regions in response to the presence of the component of the polymer proximate to the detecting region.

8. The detector of claim 1, wherein the polymer is DNA or RNA.

9. The detector of claim 1, wherein the source and drain regions are partially covered by the insulator at locations remote from the recess or opening.

10. The detector of claim 1, wherein the source and drain regions are coupled to contacts at locations remote from the recess or opening.

11. An array comprising:

multiple detecting devices, each of the detecting devices comprising a;

a source region;

a drain region; and

at least one detecting region between the source and drain regions, the at least one detecting region having a recess or opening;

each of the detecting devices associated with an insulator disposed about the recess or opening and separating a polymer from each of the detecting devices when the polymer is in the recess or opening;

wherein a charge on a component of the polymer passing through the recess or opening induces an image charge sufficient to increase the conductivity of the at least one detecting region by an amount related to the charge of the component of the polymer, each of the detecting devices to detect the component of the polymer based on the conductivity of the detecting region.

12. The array of claim 11, wherein the detecting devices comprise a plurality of detecting regions.

13. The array of claim 11, wherein the detecting regions comprise an opening or a recess.

14. The array of claim 11, wherein the polymer is DNA or RNA.

15. A method for detecting at least one polymer comprising:

providing at least one detector comprising;

a silicon substrate including a device, the device comprising;

a source region;

a drain region; and

at least one detecting region between the source and drain regions, the at least one detecting region having a recess or an opening; and

an insulator disposed about the recess or opening separating a polymer from the device when the polymer passes through the recess or opening;

wherein a charge on a component of the polymer passing through the recess or opening induces an image charge sufficient to increase the conductivity of the detecting region by an amount related to the charge of the component of the polymer; and

detecting with the at least one detector the charge of the component of the polymer based on the conductivity of the at least one detecting region.

16. The method of claim 15, further comprising identifying the component based on the detected charge.

17. The method of claim 15, wherein the semiconductor substrate comprises a plurality of detecting regions.

18. The method of claim 15, wherein the detecting region is adapted to generate a signal representative of a component of the polymer.

19. The method of claim 15, wherein the silicon substrate further includes at least two doped regions such that the detecting region can pass a current between the doped regions in response to the presence of the component of the polymer.

20. The method of claim 15, further including the step of generating a signal at the detecting region representative of a charge of the component of the polymer.

21. The method of claim 15, wherein the polymer is DNA or RNA.