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

• US 7,001,792 B2
• Filed: 04/24/2001
• Issued: 02/21/2006
• Est. Priority Date: 04/24/2000
• Status: Expired due to Term

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Eagle Research & Development LLC
• Inventors: Sauer, Jon R., van Zeghbroeck, Bart J.
• Primary Examiner(s): CHEN, JACK S J
• Application Number:
  US10/258,439
• Publication Number:
  US 20030211502A1
• Time in Patent Office: 1,764 Days
• Field of Search: 438/49, 257/253, 422/82.01, 422/82.02, 435/6, 435/287.2, 435/287.3, 435/285.2, 436/89, 436/151
• US Class Current: 438/49
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/414 Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
• 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 system for detecting at least one polymer, comprising:

at least one semiconductor device having at least one 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 image 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;

said detecting region including a region of said semiconductor device including an insulating layer defining an opening in said semiconductor device having a cross-section sufficient to enable said polymer to enter said opening, such that said detecting region is adapted to detect said charge of said component in said opening, wherein said region of said detecting region includes an oxide layer defining said opening, said oxide layer including at least one silicon nanocrystal.

2. A system as claimed in claim 1, wherein:

said opening is non-circular.

3. A system for detecting at least one polymer, comprising:

a plurality of semiconductor detecting devices, each having at least one 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 image 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, such that said detecting region is adapted to detect said charge of said component in said opening, wherein said detecting region includes an oxide layer defining said opening, said oxide layer including at least one silicon nanocrystal; and

a reader, adapted to selectably obtain a respective reading from each of said semiconductor detecting devices, said respective readings representing respective charges detected by said semiconductor detecting devices.

4. A system as claimed in claim 3, wherein:

said semiconductor detecting devices are each adapted to passively detect said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.

5. A system for detecting at least one polymer, comprising:

at least one semiconductor device having at least one 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 image 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, such that said detecting region is adapted to detect said charge of said component in said opening, wherein said detecting region includes an oxide layer defining said opening, said oxide layer including at least one silicon nanocrystal.