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

• US 8,232,582 B2
• Filed: 12/13/2005
• Issued: 07/31/2012
• 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, van Zeghbroeck, Bart
• Primary Examiner(s): ARORA, AJAY
• Application Number:
  US11/301,259
• Publication Number:
  US 20060154399A1
• Time in Patent Office: 2,422 Days
• Field of Search: 438/48, 438/49, 257/266, 257/253, 257/239
• US Class Current: 257/239
• 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-type regions implanted in a p-type semiconductor layer or two p-type regions implanted in an n-type 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 method for manufacturing a device for detecting a polymer, comprising:

providing a semiconductor structure comprising at least one semiconductor layer, creating in said semiconductor structure a detecting region having an opening through which said polymer can pass, said detecting region including an active electronic structure including a source region and a drain region; and

forming an oxide layer on a wall of said semiconductor layer forming said opening wherein said oxide layer separates said source and drain regions from said opening and decreases said cross-section of said opening;

said opening having a cross-sectional dimension of less than about 100 nm and being configured such that while said at least one polymer passes through said opening, a charge of at least a component of said polymer-creates image charges in said detecting region, said image charges being sufficient to increase the conductivity of said detecting region by an amount related to said charge of said component of said polymer.

2. A method as claimed in claim 1, wherein said oxide layer includes at least one silicon nanocrystal.

3. A method as claimed in claim 1, wherein creating said detecting region further includes forming an insulating layer including an oxide.

4. A method for manufacturing a device for detecting a polymer, comprising:

providing a structure comprising an insulating layer and at least one metal layer; and

creating a detecting region in said structure, said detecting region including an active electronic structure;

said detecting region having an opening through which said polymer can pass, wherein said insulating layer separates said at least one metal layer and said detecting region from said opening, said opening having a cross-sectional dimension of less than about 100 nm and being configured such that while said polymer passes through said opening, a charge of at least a component of said polymer creates image charges in said detecting region, said image charges being sufficient to increase the conductivity of said detecting region by an amount related to said charge of said component of said polymer.

5. A method as claimed in claim 4, wherein:

said component includes a base in a nucleic acid strand; and

said creating step creates said detecting region which is adapted to detect said charge representative of said base in said nucleic acid strand.

6. A method as claimed in claim 4, further comprising the step of:

creating an opening in said structure, said opening having a cross-section sufficient to enable a portion of said polymer to pass therethrough, and being positioned in relation to said detecting region such that said detecting region is adapted to detect said charge representative of said component in said opening.

7. A method as claimed in claim 6, wherein:

said opening is non-circular.

8. A method as claimed in claim 4, further comprising a step of:

creating a recess in said structure, positioned in relation to said detecting region such that said detecting region is adapted to detect said charge representative of said component in said recess.

9. A method as claimed in claim 4, wherein:

said detecting region detects said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.

10. A method as claimed in claim 4, wherein:

said detecting region detects a single said charge of said component.

11. A method for manufacturing a device for detecting a polymer, comprising the steps of:

providing a semiconductor structure comprising at least one semiconductor layer; and

creating a detecting region in said semiconductor structure, said detecting region including an active electronic structure;

said detecting region having an opening through which said polymer can pass, said opening having a cross-sectional dimension of less than about 100 nm and being configured such that while said at least one polymer passes through said opening, a charge of at least a component of said polymer creates images charges in said region, said image charges being sufficient to increase the conductivity of said region by an amount related to said charge of said component;

wherein said opening creating step includes the step of forming an oxide layer on a wall of said semiconductor layer forming said opening that separates said detecting region from said opening and decreases said cross-section of said opening, said oxide layer including at least one silicon nanocrystal.