Implantable biosensor from stratified nanostructured membranes

• US 20040023317A1
• Filed: 03/31/2003
• Published: 02/05/2004
• Est. Priority Date: 03/29/2002
• Status: Active Grant

• Current Assignee: Board of Regents of Oklahoma State University
• Original Assignee: Oklahoma State University, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kotov, Nicholas A., Motamedi, Massoud, Esenaliev, Rinat, Wicksted, James P.
• Granted Patent: US 7,863,038 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A new class of biosensors and methods for making and using same are disclosed. The biosensors are multi-layered membrane composites, where at least one layer is prepared by the layer-by-layer process and at least one layer is responsive to changes is a property of a biological system such as changes in the concentration of an atom, ion, molecule or molecular assembly. Because the biosensors are multi-layered, a single biosensor is capable monitor a number of different properties of a biological system simultaneously. The biosensors are monitored by systems that impinge an excitation waveform on the biosensors and analyze a reflected and/or a transmitted resultant waveform. Additionally, the biosensors can be associated with field activated electronic components so that implantable, self-contained analytical devices can be constructed and monitored by field generators, where data is transmitted to an analyzer after field activation.

Claims

1. A biosensor apparatus comprising at least one LBL layer and at least one responsive layer, where the responsive layer undergoes a change in a detectable property in response to a change in a target physical and/or chemical characteristic of a biological system and where the LBL layer improves detection of the detectable property.

2. The apparatus of claim 1, wherein the LBL layer including at least one positively charged layer and at least one negatively charged layer.

3. The apparatus of claim 1, wherein the responsive layer comprises a material that changes physical dimension in response to a change in concentration of target agent associated with the biological system or includes a marker that undergoes a property change in response to a change in concentration of target agent associated with the biological system, where the marker is selected from the group consisting of dyes, fluorescent dyes, fluorescent donon-acceptor pairs, dyes capable of undergoing FRET, and mixtures or combinations thereof..

4. The apparatus of claim 3, wherein the target agent is selected from the group an atom, ion, molecule and molecular assembly.

5. The apparatus of claim 4, wherein the agent is glucose and the responsive layer is a polymer characterized by undergoing a change in physical dimension or biochemical structure in response to a change in glucose concentration, where the change is detectable via an electromagnetic detection system, an acoustic detection system, a spectroscopic detection system.

6. The apparatus of claim 1, wherein the apparatus is implantable or designed to be placed in contact with the biological system.

7. The apparatus of claim 1, wherein the biological system is a tissue, an organ, a cell culture, a tissue culture, or a mixture or combination thereof.

16. A method of measuring levels of a physiological, biochemical or morphological state of an animal including a human comprising the steps of

implanting in or contacting with a biological system a biosensor of claims 1-7;

generating an input waveform;

directing the input waveform at the biosensor;

detecting an output waveform produced from the interaction of the input waveform and the biosensor; and

analyzing the output waveform to produce a value of the target characteristic of the biological system.

17. The method of claim 16, wherein the biological system is a tissue, an organ, a cell culture, a tissue culture, or a mixture or combination thereof.

18. The method of claim 16, the LBL layer including at least one positively charged layer and at least one negatively charged layer

8. A biosensor/detector apparatus comprising an excitation electronic component, a biosensor component including at least one LBL layer and at least one responsive layer, and a detection electronic component, where the excitation electronic component generates an input waveform that propagates through the biosensor producing an output waveform which enters the detector component and the responsive layer undergoes a change in a detectable property in response to a change in a physical and/or chemical characteristic of a biological system and where the LBL layer improves detection of the detectable property

9. The apparatus of claim 8, wherein the apparatus is implantable or designed to be placed in contact with the biological system and the electronic components are field activated components and the detector component includes a transmitter for transmitted data corresponding to the output waveform to a receiver external to the biological system.

10. The apparatus of claim 9, wherein the LBL layer including at least one positively charged layer and at least one negatively charged layer

11. The apparatus of claim 9, wherein the responsive layer comprises a material that changes physical, chemical, biochemical, and/or molecular properties or characteristics in response to a change in concentration of target agent associated with the biological system, where the change is detectable.

12. The apparatus of claim 11, wherein the target agent is selected from the group an atom, ion, molecule and molecular assembly.

13. The apparatus of claim 12, wherein the agent is glucose and the responsive layer is a polymer characterized by undergoing a change in physical dimension or biochemical structure in response to a change in glucose concentration, where the change is detectable.

14. The apparatus of claim 9, wherein the apparatus is implantable or designed to be placed in contact with the biological system.

15. The apparatus of claim 9, wherein the biological system is a tissue, an organ, a cell culture, a tissue culture, or a mixture or combination thereof.

19. A method of measuring levels of a physiological, biochemical or morphological state of an animal including a human comprising the steps of

implanting in or contacting with a biological system a biosensor/detector of claims 9-15;

generating a field via a field-generator/receiver/analyzer,

producing an input waveform in the excitation component after field activation,

directing the input waveform into and through the biosensor;

detecting a transmitted output waveform, a reflected output waveform or both a transmitted and reflected waveforms produced from the interaction of the input waveform and the biosensor in the detector component after field activation;

transmitting data corresponding to the output waveforms to the external field-generator/receiver/analyzer, and

analyzing the data in order to produce a value of the target characteristic of the biological system.

20. The method of claim 19, wherein the biological system is a tissue, an organ, a cell culture, a tissue culture, or a mixture or combination thereof.