Multi-transduction mechanism based microfluidic analyte sensors

• US 7,935,309 B2
• Filed: 04/14/2006
• Issued: 05/03/2011
• Est. Priority Date: 04/15/2005
• Status: Expired due to Fees

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG), Worcester Polytechnic Institute
• Original Assignee: Worcester Polytechnic Institute
• Inventors: Lambert, Christopher R., McGimpsey, W. Grant, Benco, John S., Thalladi, Venkat R.
• Primary Examiner(s): Jung; Unsu
• Application Number:
  US11/404,319
• Publication Number:
  US 20070042450A1
• Time in Patent Office: 1,845 Days
• Field of Search: None
• US Class Current: 422/82.08
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

In various aspects are provided a microfluidic and/or nanofluidic sensor that can provide an indication of the reliability of its measurement of the presence of an analyte in a sample under investigation, an analyte concentration in the sample under investigation, or both. The provided sensors, microfluidic devices, and methods of analyte detection, utilize two transduction mechanisms from the same molecule to determine analyte presence, analyte concentration, or both. An analyte sensing molecule is used that can provide both an optical signal and electrochemical signal when an analyte is recognized by an analyte binding portion of the sensing molecule.

Claims

1. An analyte sensor comprising:

a substrate having a surface;

an electrically conductive material covering at least a portion of the surface;

an analyte sensor layer covering at least a portion of the electrically conductive material;

the analyte sensor layer comprising analyte sensing molecules, the analyte sensing molecule comprising;

an analyte binding portion for a first signal of at least two signal transduction mechanisms, said analyte binding portion comprising an aza crown calixarene;

a fluorophore portion for a second signal of the at least two signal transduction mechanisms; and

a linker portion connecting the analyte sensing molecule to the electrically conductive material.

2. The analyte sensor of claim 1, wherein the analyte sensor layer is a substantially monolayer thick film.

3. The analyte sensor of claim 1, wherein the substrate comprises a material substantially transparent to one or more of an excitation wavelength and a fluorescence wavelength of the fluorophore portion.

4. The analyte sensor of claim 1, wherein the substrate comprises a silicon dioxide glass material.

5. The analyte sensor of claim 1, wherein the electrically conductive material comprises a material substantially transparent to one or more of an excitation wavelength and a fluorescence wavelength of the fluorophore portion.

6. The analyte sensor of claim 1, wherein the electrically conductive material comprises an electrically conductive oxide layer.

7. The analyte sensor of claim 1, wherein the electrically conductive material comprises one or more of indium tin oxide, tin oxide, fluorine-doped tin oxide, tin oxide, and zinc oxide.

8. The analyte sensor of claim 1, wherein the analyte binding portion is an ionophore.

9. The analyte sensor of claim 8, wherein the ionophore is an ionophore for a monovalent cation selected from the group consisting of:

lithium, sodium, potassium and cesium ions.

10. The analyte sensor of claim 1, wherein the fluorophore portion comprises anthracene.

11. The analyte sensor of claim 1, wherein the linker portion comprises a C₁-C₂₀ alkyl group.

12. The analyte sensor of claim 1, wherein the first signal comprises an electrochemical signal.

13. The analyte sensor of claim 12, wherein the electrochemical signal comprises impedance or capacitance measurement.

14. The analyte sensor of claim 1, wherein the second signal comprises an optical signal.

15. An microfluidic device comprising:

a substrate having a surface;

an electrically conductive material covering at least a portion of the surface;

an analyte sensor layer covering at least a portion of the electrically conductive material;

the analyte sensor layer comprising a substantially monolayer thick film of an analyte sensing molecule, the analyte sensing molecule comprising;

an analyte binding portion for a first signal of at least two signal transduction mechanisms, said analyte binding portion comprising an aza crown calixarene;

a fluorophore portion for a second signal of the at least two signal transduction mechanisms; and

a linker portion connecting the analyte sensing molecule to the electrically conductive material;

a reference electrode in electrical contact with the analyte sensor layer; and

a counter electrode in electrical contact with the analyte sensor layer.

16. The microfluidic device of claim 15, wherein the linker portion comprises a C₁-C₂₀ alkyl group.