Microelectronic device and method for label-free detection and quantification of biological and chemical molecules

• US 6,482,639 B2
• Filed: 06/22/2001
• Issued: 11/19/2002
• Est. Priority Date: 06/23/2000
• Status: Expired due to Fees

• Current Assignee: the united states of america as represented by the secretary of the navy
• Original Assignee: the united states of america as represented by the secretary of the navy
• Inventors: Tender, Leonard M., Peckerar, Martin, Perkins, Frank K., Fertig, Stephanie J., Snow, Eric S.
• Primary Examiner(s): Siew, Jeffrey
• Application Number:
  US09/886,051
• Publication Number:
  US 20020012937A1
• Time in Patent Office: 515 Days
• Field of Search: 435/6, 435/7.1, 435/91.1, 435/91.2, 435/287.2, 536/22.1, 536/23.1, 536/24-- 2, 438/49
• US Class Current: 435/287.2
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: H01L 2924/00 Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/0002 Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00

Abstract

Molecular recognition-based electronic sensor, which is gateless, depletion mode field effect transistor consisting of source and drain diffusions, a depletion-mode implant, and insulating layer chemically modified by immobilized molecular receptors that enables miniaturized label-free molecular detection amenable to high-density array formats. The conductivity of the active channel modulates current flow through the active channel when a voltage is applied between the source and drain diffusions. The conductivity of the active channel is determined by the potential of the sample solution in which the device is immersed and the device-solution interfacial capacitance. The conductivity of the active channel modulates current flow through the active channel when a voltage is applied between the source and drain diffusions. The interfacial capacitance is determined by the extent of occupancy of the immobilized receptor molecules by target molecules. Target molecules can be either charged or uncharged. Change in interfacial capacitance upon target molecule binding results in modulation of an externally supplied current through the channel.

Claims

1. A sensor for detecting target molecules comprising:

a depletion-mode field effect transistor (FET) having a source implant and a drain implant that are spatially arranged within a semiconductor structure, said source and drain being separated by an active channel, said field effect transistor being gateless;

a dielectric layer covering said active channel, said dielectric layer having a bottom surface in contact with the active channel and a top surface in contact with a sample solution, said top surface being surface modified with immobilized molecular receptors, said immobilized molecular receptors being available to bind target molecules present in the sample solution, wherein said FET is imbedded in a substrate with said receptor modified dielectric layer exposed; and

a reference electrode in contact with said sample solution, wherein said substrate is biased with respect to said reference electrode.

2. A sensor as in claim 1 wherein said immobilized molecular receptors are biological receptors.

3. A sensor as in claim 2 wherein said immobilized molecular receptors are selected from the group consisting of single strand DNA, single strand PNA, binding proteins, antibodies, DNA aptamers, PNA aptamers, RNA aptamers, antigens, enzymes, and peptides.

4. A sensor as in claim 1 wherein said immobilized molecular receptors are non-biological receptors.

5. A sensor as in claim 4 wherein said immobilized molecular receptors are selected from the group consisting of chelating molecules, molecular assemblies with chelating functional groups, and reagents for covalent attachment of target molecules.

6. A sensor as in claim 1 wherein said target molecules are charged.

7. A sensor as in claim 1 wherein said target molecules are uncharged.

8. A sensor as in claim 1 wherein said target molecules are biological molecules.

9. A sensor as in claim 8 wherein said target molecules are selected from the group consisting of single strand DNA, proteins, antigens, bacteria, viruses, and biological molecules with functional groups that are covalently bound to reactive species.

10. A sensor as in claim 1 wherein said target molecules are non-biological molecules.

11. A sensor as in claim 10 wherein said target molecules are selected from the group consisting of chemical species for which biological receptors exist, chemical species for which PNA receptors exist, chemical species for which RNA receptors exist, chemical species for which DNA receptors exist, chemical species which are bound by chemical chelators, and metal ions.

12. A sensor array, comprising:

at least two sensors as in claim 1, said sensors being fabricated onto a substrate with each individual said sensor'"'"'s respective said receptor modified dielectric layer exposed to said sample solution, said each individual sensor being individually modified with a molecular receptor, said sensors operating in parallel, each sensor being individually electrically addressable.

13. A method for detecting a target molecule species comprising the steps of:

contacting the sensor of claim 1 with a sample solution wherein an interface between said sample solution and said receptor modified dielectric layer of the sensor is created, wherein an interfacial capacitance exists at said interface between said sample solution and said receptor modified dielectric layer;

placing said reference electrode in contact with said sample solution;

applying a terminal bias between the reference electrode and the substrate;

applying a terminal bias between said source and said drain, wherein said interfacial capacitance is changed by the binding of target molecules to said receptor molecules immobilized on said dielectric layer by displacement of a solution ionic charge, wherein said change of interfacial capacitance changes the conductivity of the active channel, wherein the conductivity of the active channel modulates the externally supplied current flowing through said active channel when said externally supplied current is caused by a terminal bias applied between said source and said drain; and

measuring the change in current between the source and drain.

14. A method for detecting and quantifying at least two target molecule species comprising the steps of:

contacting the sensor array of claim 12 in said sample solution, wherein an interface between said sample solution and each individual sensor'"'"'s receptor-modified dielectric layer is created, wherein an interfacial capacitance exists at said interfaces between said sample solution and said each individual sensor'"'"'s receptor-modified dielectric layer;

placing the reference electrode in contact with said sample solution;

applying a terminal bias between the reference electrode and the substrate;

applying an terminal bias between each individual sensor'"'"'s said source and said drain, wherein said interfacial capacitance is changed by the binding of target molecules to said receptor molecules immobilized on said dielectric layer by displacement of a solution ionic charge, wherein said change of interfacial capacitance changes the conductivity of the active channel, wherein the conductivity of the active channel modulates the externally supplied current flowing though said active channel when said terminal bias is applied between said source and said drain; and

measuring the change in current between each individual sensor'"'"'s source and drain.