Electronic sensing of chemical and biological agents using functionalized nanostructures

• US 20030134433A1
• Filed: 01/16/2003
• Published: 07/17/2003
• Est. Priority Date: 01/16/2002
• Status: Abandoned Application

• Current Assignee: Nanomix Incorporated (CJY Holdings Ltd.)
• Original Assignee: Nanomix Incorporated (CJY Holdings Ltd.)
• Inventors: Gruner, George, Gabriel, Jean Christophe, Swanson, Basil, Collins, Philip, Wudl, Fred
• Application Number:
  US10/345,783
• Publication Number:
  US 20030134433A1
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/551 the carrier being inorganic
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y10T 29/49002 Electrical device making

Abstract

This invention provides for an apparatus and a method for detecting the presence of pathogenic agents with sensors containing functionalized nanostructures integrated into circuits on silicon chips. The nanostructures are functionalized with molecular transducers that recognize and bind targeted analytes which are diagnostic of the pathogenic agent of interest. The molecular transducer includes a receptor portion, which binds the analyte, and an anchor portion that attaches to the nanostructure. Upon binding of the analyte, a change in molecular configuration represented by the newly formed receptor-analyte complex creates a force that is transmitted to the nanostructure via the anchor portion of the transducer. The effect of the force transmitted to the nanostructure is to alter its conductivity. The change in conductivity of the nanotube thus represents a signal that indicates the presence of the pathogenic agent of interest.

Claims

1. A nanostructure sensing device for an analyte, including:

a least one nanostructure;

a layer encapsulating at least a portion of the nanostructure, the layer configured to inhibit non-specific interaction between the nanostructure and molecules other than the analyte; and

at least one molecular transducer configured to interact with the analyte, the transducer connected to the nanostructure and extending therefrom into a local environment.

2. The device of claim 1, wherein the analyte is a biomolecule.

3. The device of claim 2, wherein the biomolecule is.diagnostic of a predetermined human pathogenic organism.

4. The device of claim 3, wherein the biomolecule is selected from a group including a peptide, a protein, a glycoprotein, a lipid, a glycolipid, a carbohydrate, a polysaccharide, a polynucleotide sequence, and a molecule of intermediary metabolism.

5. The device of claim 1, wherein the layer includes molecules selected from the group consisting of amphipathic molecules configured into a monolayer;

a bilayer;

a multilayer;

a micellar layer;

or hybrid bilayer;

a self-assembled monolayer of biological materials, a self-assembled monolayer of non-biological materials;

a polymer layer;

or other amphipathic macromolecular assemblies.

6. The device of claim 1, wherein the nanostructure is selected from the group consisting of nanofibers, single-walled nanotubes, multi-walled nanotubes, nanocages, nanococoons, nanohorns, nanotopes, nanotori, nanorods, nanowires, and other fullerene-like molecules.

7. The device of claim 1, wherein the molecular transducer includes:

a receptor molecule configured to bind to the analyte and upon such binding, change in molecular configuration, such change representing a signal; and

an anchor molecule functionally connected to the receptor molecule and configured to modify a conductivity of the nanostructure upon receipt of the signal from the receptor.

8. The devise of claim 1, wherein the nanostructure has a conductivity, the nanostructure configured to change said conductivity upon receipt of a signal from the molecular transducer.

9. The devise of claim 8, further including:

a signal processing unit configured to provide analysis of the changes in conductivity of the nanostructure;

a record keeping device for storage of the analysis of changes in conductivity; and

an alarm configured to respond upon receipt of conductivity changes that exceed a predetermined threshold.

10. The device of claim 7, wherein the receptor molecule is selected from a group that includes an antibody, a portion of an antibody, an enzyme, a portion of an enzyme, a DNA sequence, an RNA sequence, a carbohydrate, a cyclodextrin, a crown ether, or any other molecule capable of specifically recognizing and binding the analyte.

11. The device of claim 7 further including a tether molecule functionally interposed between the receptor molecule and the anchor molecule.

12. An electronic sensing system including:

a substrate;

at least one nanostructure with a layer encapsulating at least a portion thereof, the nanostructure having a conductivity, the encapsulated nanostructure exposed to a local environment;

a first conductive element disposed over the substrate and making a first electrical connection to the nanostructure;

a second conductive element disposed over the substrate and making a second electrical connection to the nanostructure; and

at least one molecular transducer configured to interact with a biomolecular analyte, the transducer attached to the nanostructure and extending therefrom into the local environment;

wherein the molecular transducer is also configured to modify the conductivity of the nanostructure upon interaction with the analyte.

13. A circuit for detecting an analyte diagnostic of a pathogenic agent, including:

an electrical supply;

a meter connected to the electrical supply;

a substrate;

at least one nanostructure disposed over the substrate and exposed to a local environment, the nanostructure having a conductivity;

a layer encapsulating at least a portion of the nanostructure;

a first conductive element disposed over the substrate and making a first electrical connection to the nanostructure;

a second conductive element disposed over the substrate and making a second electrical connection to the nanostructure; and

at least one molecular transducer configured to interact with the analyte, the transducer anchored to the nanostructure and extending therefrom into the local environment;

wherein the molecular transducer is also configured to modify the conductivity of the nanostructure upon interaction with the analyte; and

wherein the first and second conductive elements are in electrical connection with the electrical supply and the meter.

14. The circuit of claim 13, wherein the substrate is configured to function as a gate electrode within the circuit.

15. A sensing device for a biomolecular analyte, including:

a substrate;

a least one nanostructure disposed over the substrate, the nanostructure having a conductivity;

a layer encapsulating at least a portion of the nanostructure;

an electrical circuit connected to the nanostructure, configured to detect changes in conductivity; and

at least one molecular transducer configured to interact with the analyte, the transducer attached to the nanostructure and extending therefrom into a local environment;

wherein the molecular transducer is also configured to modify the conductivity of the nanostructure upon interaction with the analyte.

16. The sensing device of claim 15, wherein the nanostructure is selected from the group consisting of nanofibers, single-walled nanotubes, multi-walled nanotubes, nanocages, nanococoons, nanohorns, nanotopes, nanotori, nanorods, nanowires, and other fullerene-like molecules.

17. The sensing device of claim 15, wherein the layer is selected from the group consisting of amphipathic molecules configured into a monolayer;

a bilayer;

a multilayer;

a micellar layer;

or hybrid bilayer;

a self-assembled monolayer of biological materials, a self-assembled monolayer of non-biological materials;

a polymer layer;

or other amphipathic macromolecular assemblies.

18. The sensing device of claim 17, wherein the layer includes polyethylene glycol.

19. The sensing device of claim 15, wherein the molecular transducer includes:

a receptor molecule configured to bind to the analyte and upon binding, to change in molecular configuration;

an anchor molecule configured to modify the conductivity of the nanostructure upon the change in molecular configuration of the receptor molecule; and

a tether molecule connecting the receptor molecule and the anchor molecule.

20. A biomolecular analyte sensing device, including:

a substrate;

a plurality of nanostructures disposed over the substrate, each nanostructure having a conductivity;

a first conductive element disposed over the substrate and connected to each nanostructure;

a second conductive element disposed over the substrate and connected to each nanostructure;

a layer encapsulating at least a portion of each of the nanostructures; and

a plurality of molecular transducers configured to interact with a biomolecular analyte, the transducers attached to the nanostructures and extending therefrom through the layer and into a local environment;

wherein, the molecular transducers, upon interaction with the analyte in the local environment, are configured to modify the conductivity of the nanostructure to which they are attached.

21. The sensing device of claim 21, wherein the plurality of molecular transducers includes more than one type of transducer, the transducers types being different by being configured to interact with different analytes.

22. An electronic circuit for detecting a biomolecular analyte, including:

at least one nanostructure disposed over a substrate;

the nanostructure having a conductivity;

a layer encapsulating at least a portion of the nanostructure;

at least one molecular transducer attached to the nanostructure and extending therefrom through the layer;

the transducer configured both to bind a biomolecular analyte and to attach to the nanostructure, the transducer further configured to undergo a change in molecular configuration upon binding of the analyte;

.

at least two electrodes electrically connected to the nanostructure;

a power supply configured to apply a voltage to the electrodes; and

an electrical meter configured to measure the current conducted across the circuit upon application of voltage.

23. A method of making a nanostructure sensing device for a biomolecular analyte, including the steps of:

disposing at least one nanostructure over a substrate, the nanostructure have a conductivity;

encapsulating at least a portion of the nanostructure with a coating;

attaching a molecular transducer to the nanostructure, the transducer configured to bind the biomolecular analyte and further configured to modify the conductivity of the nanostructure upon binding of the analyte;

forming a first conductive element connected to the nanostructure; and

forming a second conductive element connected to the nanostructure.

24. A method of sensing a biomolecular analyte with a nanostructure sensing device, including the steps of:

binding the analyte to a receptor, thereby inducing a change in molecular configuration of the receptor;

transmitting a force generated by the change in the configuration of the receptor to an anchor molecule, the anchor molecule connected both to the receptor and a nanostructure;

modifying the interaction between the anchor molecule and the nanostructure as a consequence of the force exerted upon it by the change in the configuration of the receptor molecule; and

changing the conductivity of the nanostructure as a consequence of the modifying of the interaction between the anchor molecule and the nanostructure.

25. The method of claim 24, where the modified interaction between the anchor molecule and the nanostructure includes a structural deformation of the nanostructure.

26. The method of claim 24, wherein the modified interaction between the anchor molecule and the nanostructure includes electrical modifications of a type selected from a group including charge transfer, change in the local electric field, change in the distortion of bonds, and change in the π

-bond overlaps.

27. A method of sensing an analyte diagnostic of a pathogenic agent, including the steps of:

providing a nanostructure sensing device having at least one nanostructure in contact with at least two electrodes;

the nanostructure having a conductivity, the nanostructure having a molecular transducer attached to it, the nanostructure further being at least partially covered with a coating;

measuring a first electrical signal under control conditions, in the absence of the analyte;

binding the analyte to a receptor, thereby inducing a change in molecular configuration of the receptor;

transmitting a force generated by the change in the configuration of the receptor to an anchor molecule, the anchor molecule connected both to the receptor and the nanostructure;

modifying the interaction between the anchor molecule and the nanostructure as a consequence of the force exerted upon it by the change in the configuration of the receptor molecule;

changing the conductivity of the nanostructure as a consequence of the modifying of the interaction between the anchor molecule and the nanostructure;

measuring a second electrical signal after exposing the device to a test sample, possibly containing the analyte; and

correlating a change between the first electrical signal and the second electrical signal to the sensing of the analyte.