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

• US 9,410,923 B2
• Filed: 06/22/2015
• Issued: 08/09/2016
• 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 R., Van Zeghbroeck, Bart J.
• Primary Examiner(s): Arora, Ajay K
• Application Number:
  US14/745,753
• Publication Number:
  US 20150284790A1
• Time in Patent Office: 414 Days
• Field of Search: 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 detector comprising:

a source region;

a drain region;

a detection region disposed between the source region and the drain region, the detection region defining a distance between the source region and the drain region on the order of the size of a single nucleotide base; and

a channel formed over the source region, the drain region, and the detection region;

wherein a charge on a component of a polymer passing through the channel induces an image charge sufficient to change the conductivity of the detection 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 detection region.

2. The detector of claim 1, wherein the polymer is a nucleic acid strand.

3. The detector of claim 2, wherein the nucleic acid strand is a DNA strand.

4. The detector of claim 2, wherein the component is a nucleotide base of the nucleic acid strand.

5. The detector of claim 1, further comprising an electrode disposed remote from the source region and the drain region.

6. The detector of claim 5, wherein the electrode is to have a potential relative to the source region and the drain region to move the polymer to the channel.

7. The detector of claim 5, further comprising a second electrode disposed remote from the source region and the drain region.

8. The detector of claim 7, the electrode and the second electrode to apply a voltage relative to the source region and the drain region to move the polymer.

9. A detector comprising:

a source region;

a drain region;

a detection region disposed between the source region and the drain region, the detection region defining a distance between the source region and the drain region on the order of the size of a single nucleotide base;

a channel formed over the source region, the drain region, and the detection region; and

an electrode disposed remote from the source region, drain region, and detection region, the electrode to apply a negative voltage relative to the source region and the drain region;

wherein a charge on a nucleotide base of a nucleic acid strand passing through the channel induces an image charge sufficient to change the conductivity of the detection region by an amount related to the charge of the nucleotide base of the nucleic acid strand, the device to detect the nucleotide base of the nucleic acid strand based on the conductivity of the detection region.

10. The detector of claim 9, further comprising a second electrode disposed remote from the source region and the drain region.

11. The detector of claim 10, the electrode and the second electrode to apply a voltage relative to the source region and the drain region to move the polymer.

12. A method of detecting a composition of a polymer, the method comprising:

applying the polymer to a detector comprising;

a source region;

a drain region;

a detection region disposed between the source region and the drain region, the detection region defining a distance between the source region and the drain region on the order of the size of a single nucleotide base; and

a channel formed over the source region, the drain region, and the detection region;

wherein a charge on a component of a polymer passing through the channel induces an image charge sufficient to change the conductivity of the detection region by an amount related to the charge of the component of the polymer;

applying a potential between the source region and the drain region to generate current in the detection region; and

detecting a change in conductivity in the detection region in response to applying the polymer, the change indicative of the component of the polymer.

13. The method of claim 12, wherein the detector further comprises an electrode disposed remote from the source region and the drain region.

14. The method of claim 13, further comprising applying a potential to the electrode relative to the source region and the drain region.

15. The method of claim 13, wherein the detector further includes a second electrode.

16. The method of claim 15, further comprising applying a potential across the electrode and the second electrode relative to the source region and the drain region to move the polymer across the detection region.

17. The method of claim 13, further comprising applying an electrophoretic gel over the channel.

18. The method of claim 12, further comprising identifying the component of the polymer based on the change in conductivity.

19. The method of claim 12, wherein the polymer includes a nucleic acid strand.

20. The method of claim 19, wherein the component is a nucleotide base.