Nanodevices, microdevices and sensors on in-vivo structures and method for the same

An in-vivo method and apparatus is disclosed that comprises at least one sensor for determining changes in a human's an animal's body and reporting said changes outside the body. The sensor may be embedded in a sheath. The apparatus may be used to monitor chemical or physical changes in the body fluids. Alternatively, the apparatus may be used to monitor and regulate chemical or physical levels in humans and animals.

BACKGROUND OF THE INVENTION

1. Technical Field

This invention relates to a method and apparatus for forming devices on substrates and using these devices to provide in-vivo treatment of certain disease conditions in animals and humans. Specifically, the present invention relates to a method and apparatus for nanodevices, microdevices, and sensors on in-vivo structures.

2. Background Art

Typically diagnosis of animal and human diseases or body disfunctions involves testing a person's physical parameters such as blood pressure, temperature and pulse. Additionally, diagnosis commonly requires removing samples of blood and other body fluids and subjecting them to diagnostic tests to determine levels of enzymes, metabolites, toxins or other chemicals essential to life. Medical imaging instruments based on inter alia x-ray, ultrasound or magnetic resonance provide additional information used by the medical profession to diagnose causes of animal and human illness. Once diagnosed, the ailment may commonly be treated inter alia using drugs administered transdermally, orally or by injection.

Diagnosis and treatment by these common techniques may be difficult because physical and chemical testing is not sufficiently specific to the diseased or disfunctional part of the body. Also, drug effectiveness may be reduced because traditional methods of introduction are not specifically directed to the diseased or disfunctional part of the body.

SUMMARY OF THE INVENTION

The present invention overcomes the deficiencies of the related art by providing an apparatus comprising nanodevices, microdevices and sensors on in-vivo structures and method for the same. Also disclosed is a device that is insertable into a body passage or implantable into body tissue, wherein a sensor operatively attached to a device determines changes in body conditions, and wherein the apparatus reports the changes. The biosensors transmit wirelessly outside or within the body.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1depicts a longitudinal cross-section of an in-vivo apparatus10that comprises a tube24having an inner surface13, an outer surface17and a body11. Hereinafter, a “tube” is a portion of an “internal medical device” such as a catheter, stent, endoscope, defibrillator or the like. The catheter, endoscope, or defibrillator may be used for biodetection of infection or patient monitoring, e.g., liver, heart enzymes and blood glucose. Hereinafter, a “stent” is a small, expandable wire mesh tube. The stent may be either a vascular stent or a urinary stent. The defibrillator is an implantable defibrillator such as that disclosed in U.S. Pat. No. 6,358,247 which is hereby incorporated by reference. “Nanodevice(s)” may be any inorganic device on the order of magnitude of 1 nanometer (nm) to 800 nanometers. However, a typical nanodevice will be between 5–100 nm. Examples of nanodevices include nanotubes, nanoparticles (such as lithium particles), buckyballs, and nanowires made from silicon, gallium nitride, zinc oxide and other semiconducting inorganic materials such as oxides of transition metals or semiconducting organic materials.

The body11further comprises conductive contacts12,16,18, and22operatively attached to and coplanar14with the inner surface13of the tube24. Referring toFIG. 1, contact12may be oriented opposite and parallel to contact18, and contact16may be oriented opposite and parallel to contact22. Alternatively, contact12may be oriented opposite and parallel to contact18, and contacts16may be oriented orthogonal to contact22. The body11of the tube24may be made from electrically insulating materials such as polyethylene, polypropylene, silicone elastomer, nylon, or polytetrafluoroethylene. The tube24may also be made from nitinol7, a typical nickel/tin metal alloy. The apparatus10further may include a microchip26that is electrically coupled to conductor23and to conductive contact12and additionally to conductor25and to conductive contact16. The microchip26further comprises an on-chip battery32or like source of electromotive force (EMF). The microchip is capable of passive remote EM interrogation. In addition the microchip26may further comprise a receiver/transmitter device34. The receiver/transmitter34may include an FM receiver having a receiving/transmitting antenna. Microchip26is conductively coupled to the receiving/transmitting antenna. When the body11of the tube24is made from electrical conductors such as metal or metal alloys such as nitinol7, the conductive components of apparatus11must be electrically insulated to prevent malfunction due to shorting. The microchip26, the conductors,23,25,19, and21and conductive contacts12,16,18, and22are encapsulated by insulator15. The insulator15may be made from silica, silicone elastomer, insulating plastics such as Ultem™ from General Electric Co., nylon, acrylic, polypropylene, polyethylene or polytetrafluoroethylene or similar electrically insulating material.

FIG. 2defines a structure30comprising two circuits controlled by the microchip36. In one circuit comprising the microchip26, conductors23and19, the microchip26determines a resistance (R1) between the contacts12and18using Ohm's Law (see formula 1 infra). In a second circuit comprising the microchip26, conductors25and21, the microchip26determines a resistance (R2) between the contact16and22. R1and R2from the microchip26are transmitted through the animal's or human's skin using the transmitter/receiver34. Voltage and current values may be transmitted to the microchip26using the transmitter/receiver34. When the body11of the tube24is made from metal or metal alloy such as nitinol, the inner surface13and the outer surface17of the tube24may be electrically insulated by coating or sheathing (as described inFIGS. 11–13) with silica, silicone elastomer, insulating plastics such as Ultem™ from General Electric Co., nylon, acrylic, polypropylene, polyethylene or polytetrafluoroethylene or similar electrically insulating material to avoid interfering with the determination of R1and R2.
R=V/I.  (1)
(where R=resistance, V=voltage and I=current)
The circuits and field effect transistor (FET) devices in microchip26ofFIG. 2may be formed according to a method of Dr. G. Julius Vansco et al., who demonstrated that self-assembled thin films of organic-organometallic diblock copolymers made up of poly(isoprene) and poly(ferrocenyldimethylsilane)(PFS) are promising candidates for nanolithography. (“Tying Top-Down to bottom Up,”Chemical and Engineering News,27, 28, Feb. 5, 2001. Hereinafter “nanolithography” is a form of lithography that provides resolution for forming electronic structures that have a maximum dimension equal to or greater than about 5 to 10 nanometers. Polymer chemistry can be used to produce nanometer-sized patterns on silicon wafers using one-step lithographic reactive-ion etching procedures. One key enabling tool for nanotechnology includes scanning probe techniques such as electrochemical atomic force microscopy. Another key tool to enable forming devices such as micro-chip26is chemical self-assembly. Hereinafter, “chemical self-assembly” is the self-organization of small molecular components to form complex functional structures.” Hereinafter, “nanotechnology” is the study of forming miniaturized electronic devices that include devices that have a maximum dimension equal to or greater than about 5 to 10 μm.

Conductors23,2519and21illustrated inFIG. 1may be formed according to a method of Christopher E. D. Chidsey et al., who demonstrated electron tunneling through oligophenylenevinylene (OPV) conductors having ferrocene at one end and thiol at the other “is so fast they could make good molecular wires.” Christopher E. D. Chidsey et al., “Promising Lead for Molecular Wires,Chemical and Engineering News,37, Feb. 26, 2001. Using OPV units from about 0.1 to 28 Angstroms (Å) (from about 0.003 to 0.28 μm) having a ferrocene at one end and a gold electrode at the other, John F. Smalley et al. demonstrated no drop in a rate of electron transfer. Id. at 37.

Alternatively, conductors23,2519and21illustrated inFIG. 1may be formed according to a method of Yuji Okawa et al. who used a scanning tunneling microscope (STM) to form electrically conductive polymer nanowires from 10,12-nonacosadiynoic acid shown in formula (2) infra. Y. Okawa et al., “Polymer Nanowires Connected by STM,”Chemical and Engineering
CH3(CH2)15C≡C—C≡C(CH2)8CO2H  (2)
News,38, 38, Mar. 5, 2001. Hereinafter, “polymer nanowire” is a linear polymer chain having a length ranging from about 3 to 300 nm (from about 0.003 to 0.3 μm). Id. at 38. Okawa et al. reported “. . . demonstrating that we can initiate linearly propagating chain polymerization of organic molecules at any predetermined point and terminate it at another predetermined point with a spatial precision on the order of 1 nm. (0.001 μm).” Id.

In an embodiment of the present invention, referring toFIG. 1, the apparatus10comprises a tube24that may be inserted into a body passage that includes body passages that have a maximum diameter greater than or equal to about 5 to 10 μm. Lubricating the outer surface17of the tube24with materials such as petroleum jelly or mineral oil or compressing the tube24adapts the tube24for insertion.FIG. 1illustrates that the body fluid in the vessel travels through the apparatus10in a direction depicted by arrow4. Hereinafter, a “vessel” is any artery, vein, capillary, duct or channel or the like in an animal or human body that carries body fluids. The microchip26supplies sufficient EMF to the circuit comprising contacts12and18and to the circuit comprising contacts16and22to obtain a resistance in the range of about 50 to 310 ohms when the body fluid flows through the tube24in the direction of the arrow4. The microchip26transmits a value of R1and R2. Monitoring the values over time is used to indicate an onset of disease in the animal or human body.

In June, 1995, remarks of Dr. Alexander Wood were reported in which he stated a use of measurement of resistance of blood in humans. Dr. Wood reported “the ideal resistance of venous blood should be between 180 to 210 ohms.” See “Fungal/Mycotoxin Conference: Excerpts From Dr. Wood's Presentation; Sept. 30 to Oct. 2, 1994,”Alt Healthwatch,143, 9–10 (1995). Dr. Wood further reported “. . . 1) [h]igh resistivity level, between 210 and 300 Ohms, indicates that there are not enough trace elements needed by the enymes to digest food; 2) low resistivity level, dropping below 180 Ohms, indicates that the organs, such as the liver and the pancreas are beginning to show stress. Low resistivity also indicates the presence of a toxic load in the digestive system.” See Id., supra. Dr. Wood also reported “the ideal resistivity of saliva is about the same as for blood.” See Id., supra. In addition, according to Dr. Wood, “the ideal resistivity of urine is 30 Ohms. . . . The resistivity of the urine will rise dramatically to between 60 and 120 Ohms, a clear indication that the body's ability to eliminate waste is being compromised.” See Id., supra.

Referring toFIG. 1, when the tube24in an internal medical device or an apparatus10is a stent, the apparatus10may function as a typical stent in a post-angioplasty medical procedure. Throughout the specification, where a stent is referred to it is also understood that the stent may be any internal medical device as hereinbefore defined. With respect to a stent, it was first performed in the mid-1980s, and first approved by the FDA in the mid-1990s, stenting is a catheter-based procedure in which a stent (a small, expandable wire mesh tube) is inserted into a diseased artery to hold it open. Although stenting reduces a risk of a newly opened artery re-closing (restenosis), there is a need to monitor for restenosis. Hereinafter, “restenosis” is a proliferation of cell growth that causes inter alia varying degree of re-closing of the arterey. The microchip26includes software that controls the function of the microchip26that includes accessing calibration files for correlating resistance to restenosis. The software on microchip26further controls transmitting R1and R2through the animal's or human's skin using the receiver/transmitter34. Since resistivity varies directly as a function of a diameter of the artery, comparison of a value of R1and R2over time indicates if a portion of the stent24has narrowed over time. Substantially similar reduction in the value of R1and R2over time anticipates collapse of the stent24.

Referring toFIG. 1, collapse of the stent24may cause a disease condition. Use of the alternative embodiment of apparatus10, described supra, wherein contact12may be oriented opposite and parallel to contact18, and contact16may be oriented orthogonal to contact22enables distinguishing between collapse of the stent24and restenosis. Biosensors would detect the vascular diameter and arrive at a given resistance for a given diameter. As diameter in the stent changes, so would the resistance. In the case of collapse of the stent24, resistance would remain constant across contacts orthogonal to one another, but resistance would decrease across opposite and parallel contacts. The change in diameter may be determined by either one pair of biosensors or a plurality of biosensors.

In addition to the embodiment of the present invention using the apparatus10to monitor R1and R2in the animal's or human's body fluids, an alternative embodiment of the present invention is apparatus10further comprising a drug delivery system depicted inFIG. 10and described in associated text infra, to monitor and deliver a disease treatment agent such as rapamycin into the animal's or human's body fluid to retard or halt restenosis. Referring toFIG. 1, more than one apparatus10further comprising the drug delivery system depicted inFIG. 10infra may be used to detect restenosis or other disease condition resulting in change in the resistance between conductive contacts12and18or16and22. The microchip26of apparatus10includes software to network in-vivo between the stents. Hereinafter, “network” is a cross-functional communication between microchips to monitor R1and R2and provide a coordinated delivery of disease treatment agent.

In another embodiment of the present invention,FIG. 3depicts a longitudinal cross-section of an in-vivo apparatus31, comprising a tube8, that may be inserted into a body passage cavity or attached to an organ that includes vessels. The tube8may be adapted for insertion into the body vessel as described supra forFIG. 1and associated text.FIG. 3illustrates that the body fluid in the vessel travels through the apparatus31in a direction depicted by arrow35. The tube8that includes catheters and stents further comprises an inner surface28, an outer surface29and a body9. The body9further comprises light emitting diodes or lasers33, and38and light sensors37and a39operatively attached to and coplanar6with the inner surface28of the tube8. Referring toFIG. 3, light emitting diode or laser38may be oriented opposite and parallel to light sensor39, and light emitting diode or laser33may be oriented opposite and parallel to light sensor37. Alternatively, light emitting diode or laser33and light sensor37may be oriented in a non-opposite and non-parallel orientation to optimize a signal to noise ratio (S/N). Hereinafter, a “signal” is a response from a sensor due to absorption, transmission or fluorescence of light from a light emitting diode or laser by a chemical analyte or by a solid state photoreceptor such as that developed by Foveon, Inc. Hereinafter, “noise” is a response from sensor due to response of a sensor to light scattering of the light from a light emitting diode or laser. A test that a signal is real instead of noise is that the signal to noise ratio (S/N) is greater than 2.0. Hereinafter, a “chemical analyte” is an enzyme, metabolite, toxin or chemical essential to life. The body9of the tube8may be made from electrically insulating materials such as polyethylene, polypropylene, silicone elastomer, nylon, or polytetrafluoroethylene. The tube8may also be made from nitinol7, a typical nickeltin metal alloy. The apparatus31further comprises a microchip36that is electrically coupled to conductor1and to light emitting diode or laser33and additionally to conductor2and to light emitting diode or laser38. In addition, the microchip36may be electrically coupled to conductor3and light sensor37and additionally to conductor5and light sensor39. The microchip36may further comprise an on-chip battery24or like source of electromotive force (EMF). In addition the microchip36may further include a receiver/transmitter device27. The microchip36, the conductors,1,2,3and5and light emitting diodes or lasers33, and38and light sensors37and39are encapsulated by electrical insulator15when the body9of the tube8is made from electrical conductors such as metal or metal alloys such as nitinol to prevent malfunction due to shorting. The insulator15may be made from silica, silicone elastomer, insulating plastics such as Ultem™ from General Electric Co., nylon, acrylic, polypropylene, polyethylene or polytetrafluoroethylene or similar electrically insulating material.

Referring toFIG. 3, when the tube8in apparatus31is a stent, the apparatus31may function as a typical stent in a post-angioplasty medical procedure. As described supra forFIG. 1and associated text, there is a need to monitor the stent8for restenosis. Formula3depicts an inverse square law relating light energy, luminescence (intensity) and distance between the source of the light, such as light emitting diodes33or38and a sensor of the light, such as a light sensors37or39.
Light Energy=Intensity/distance2(3)
If X is the energy detected by a sensor of light when the source and the sensor are separated by 1 meter, 0.25×will be the energy detected by the sensor of light when the same source and sensor are separated by 2 meters. Light sensors37and39respond to a light energy from light emitting diodes or lasers33and38over time and the response from light sensor37is electrically conducted to microchip36through conductor3and the response from light sensor39is electrically conducted to microchip36through conductor5over time. Hereinafter, the combined circuit comprising the light sensors37and39, light emitting diodes33and38, the microchip36and associated conductors1,2,3and5comprises a “monitoring circuit” . Microchip36determines the light energy change over time using formula (3), and transmits the light energy change from light sensors37and39outside the animal's or human's body using the receiver/transmitter27. Monitoring the light energy from light sensors37and39over time is used to test for vascular patency in the animal or human body. Hereinafter, “vascular patency” is the state of an artery or vessel being open. Occlusion of the vessel by either collapse or blockage (e.g., clot formation) will alter light transmittance. Characteristics of light transmittance is a function of Diameter of the stent and the presence of serum and vascular cells (erythrocytes, leukocytes, and platelets).

In an alternative embodiment,FIG. 4depicts a transmission spectrum for hemoglobin having no oxygen, 50% oxygenated hemoglobin, 90% oxygenated hemoglobin and 100% oxygenaged hemoglobin.FIG. 5depicts a hemoglobin transmission (Log) spectrum illustrating that the greatest variability in spectra from hemoglobin having the aforementioned levels of oxygen is in a range between about 600 nm and 800 nm.

FIG. 6depicts a transmission of bright red light emitting diode through hemoglobin having no oxygen, 50% oxygenated hemoglobin, 90% oxygenated hemoglobin and 100% oxygenaged hemoglobin. A single photodiode would see the total integrated power of the product of the diode response and the hemoglobin transmission. The integrated power would be highest for the non-oxygenated blood and lowest for the 100% oxygenated hemoglobin.FIG. 7depicts an integrated bright red light emitting diode and hemoglobin transmission through hemoglobin having no oxygen, 50% oxygenated hemoglobin, 90% oxygenated hemoglobin and 100% oxygenated hemoglobin.

FIG. 8depicts a transmission of bright green light emitting diode through hemoglobin having no oxygen, 50% oxygenated hemoglobin, 90% oxygenated hemoglobin and 100% oxygenated hemoglobin. The transmission of the bright green light emitting diode was insensitive to the oxygen percentage, since the transmission only diminished from 0–10% in the range from about non-oxygenated hemoglobin to 100% oxygenated hemoglobin. Since the bright green light emitting diode transmission was insensitive to the hemoglobin oxygen percentage, the bright green light emitting diode could act a reference that would correct for overall transmission changes due to physical light path length changes and fluid density changes.FIG. 9depicts a range of transmission wavelengths for light emitting diodes. As depicted inFIG. 5and described in associated text, a single bright red light emitting diode would see the total integrated power of the product of the diode response and the hemoglobin transmission.

Referring toFIG. 3, microchip36is used to process a response from the light sensor37from transmission using bright red light emitting diode33through hemoglobin, wherein the processing produces a signal, S1, that is transmitted through the animal's or human's skin. Microchip36is further used to process a response from the light sensor39from transmission using bright green light emitting diode38through hemoglobin, wherein the processing produces a signal, S2, that is also transmitted through the animal's or human's skin using receiver/transmitter27. Subtraction of S2from S1using commercially available computer software yields a corrected transmission signal, wherein the corrected transmission signal is proportional to a correct oxygenation level of the hemoglobin flowing through the apparatus35.

Another embodiment of the present invention is depicted inFIG. 10, comprising the apparatus50that may include delivering a disease treatment agent into the animal's or human's body fluid and monitoring for a disease condition.FIG. 10depictsFIG. 3, further comprising: a disease treatment agent reservoir55that is oriented coplanar6with the inner surface28of the tube8; a microchip52operatively coupled to a drug delivery circuit57that controls a rate of delivery of a disease treatment agent from the disease treatment agent reservoir55to the animal's or human's body fluid. The microchip52is also operatively coupled to the monitoring circuit depicted inFIG. 3supra and described in associated text.

Referring toFIG. 10, the animal's or human's body fluid flows through the apparatus50in a direction depicted by arrow35. If the tube8is a stent, thrombolytics such as those listed in Table 1 infra may be delivered by the apparatus50as the disease treatment agent. The disease treatment reservoir may be made from electroresponsive polymers such as poly(dimethylaminopropylacrylamide (PDMAPAA) poly(methacrylic acid), poly(acrylic acid), alginic acid get, poly(allylamine) or from magnetically enhanced drug release polymer such as ethylene vinyl acetate copolymer (EVAc). Hereinafter, “electroresponsive polymers” are polymers which become permeable to disease treatment agents when electric current is passed through. Hereinafter, “magnetically enhanced drug release polymers” are polymers which become permeable to disease treatment agents when subjected to a magnetic field. The reservoir55may be comprised of a plurality of smaller, individually addressable reservoirs, each containing a minimum desired dose.

Referring toFIG. 10, more than one apparatus50may be used to detect a disease condition detected by monitoring chemical analytes in the animal's or human's body fluids. The microchip52of apparatus50includes software to network in-vivo between the stents. Hereinafter, “network” is a cross-functional communication between microchips to monitor R1and R2and provide a coordinated delivery of disease treatment agent. Alternatively, the networking between microchips52in 2 or more stents8in the animal's or human's body fluid may be controlled by software located in a computer or other data processing device outside the body.

Referring toFIG. 10, the apparatus50may include one or more enzyme, sound, pressure pulse, pH and viral, bacterial or biochemical or other biochemical sensors to detect a disease condition. Hereinafter “disease condition” is pre-heart failure condition or abnormal heart beating through pressure/pulse detection and comparison to history. When the sensor detects sound, the determination of the disease condition may involve the Doppler effect. Hereinafter, “bio-chemical sensor” is a detector of a chemical substance or a vital process occurring in living organisms.

Disease treatment agents of the present invention, a dosage and a standard reconstitution volume required are listed in Table 1 infra.

Referring toFIG. 10, when the tube8in apparatus31is a stent, the apparatus50may function to monitor for restenosis in a post-angioplasty medical procedure and to deliver a thrombolytic and thrombolytic dose that includes the thrombolytics listed in Table 1 supra.

The devices ofFIGS. 1–3and10may include a polymer coat for embedded circuitry, RF transmission device and pharamaceutical micro or nanotubes. The pharmaceuticals may be embedded in a nanodevice such as nanotubes, nanoparticles or buckyballs. The nanodevices may be in a reservoir, in the stent or stent sheath. The luminal face of the stent will release the pharmaceutical by an induced signal via changes in a vascular occlusive event. One technique would be a current induced by changes in biopolymer permeability or gold.

Referring toFIG. 11, an elastic/stretchable sheath100,110is disclosed containing flexible circuitry embedded within the sheath. The sheath is made from a biocompatible material such as Gortex® (a waterproof breathable material), polytetrafluoroethylene, stainless steel, carbon structure (e.g., carbon nanotube/nanostructure), or other material as disclosed herein for sheath materials. The sheath is depicted prior to expansion100and after expansion110. Prior to expansion100, a balloon catheter is used to insert the sheath into the body. The sheath diameter is maintained by a rigid structure such as a stent (e.g. stainless steel mesh stent), catheter, or endoscope. The balloon catheter and rigid structure are used to expand the sheath into position.

FIG. 12depicts a flexible/expandable stent sheath200,210containing multiple predetermined expansion sites212,214,216. The circumference of the sheathing contains a plurality of predetermined sites. The sheath is made from a biocompatible material such as Gortex® (a waterproof breathable material), polytetrafluoroethylene, stainless steel, carbon structure (e.g., carbon nanotube/nanostructure), or other material as disclosed herein for sheath materials. Prior to expansion200, a balloon catheter is used to insert the sheath into the body. The balloon catheter expands the sheath210.

FIG. 13depicts two alternative embodiments of a semi-rigid stent sheath with predetermined expansion folds. The two embodiments shown each depict a different configuration for the expansion folds. One type of expansion fold embodiment is a flexible hinge fold300. The fold expansion sites302located between semi-rigid sheath sites304maintain proper orientation of biodetectors (e.g., microdiodes). In the flexible hinge alternative302the flexible region322folds flat towards the semi-rigid biodetectors a, b, c, d. The second type of expansion fold embodiment is an accordion fold310. The fold expansion sites312located between semi-rigid sheath sites314maintain proper orientation of biodetectors (e.g., microdiodes). The location of the biodetectors a, b, c, d in relation to the accordion folds is shown330. Flexible circuitry is embedded within the expansion folds of both alternatives.FIG. 13also depicts the sheath prior to, and after, balloon angioplasty expansion. Prior to expansion340, a balloon catheter is used to insert the sheath into the body. The balloon catheter then expands the sheath350.

FIG. 14shows a cross-section of a pharmaceutical delivery device. The pharmaceutical delivery device400. The pharmaceutical delivery device includes biosensors402,404for detecting an occlusive effect or change in diameter Dv. A signal is transmitted through circuit410,412to an integral microchip420. The circuit may include a nanowire or nanotube or standard circuitry with a biocompatible polymer such as polytetrafluoroethylene or other material as disclosed herein. The microchip420calculates the occlusive event and allows pharmaceutical release through microtube430.

FIG. 15shows a biodetection catheter500having a biodetector502embedded in the luminal and external surfaces of the catheter tip. The biodetector502includes circuitry as described in the embodiments ofFIGS. 1–3,10and14. Alternatively, the microchip and sensor may be external and include an external indicator510. The biosensor will detect whether a substrate or occlusion is absent520, present530or whether an infection is present540.

FIGS. 16 and 17disclose biodetection of nanodevices. A stent600is shown which includes biosensors602,604,606,608,610, and612. An RF antenna615is disclosed. The biosensors transmit data through circuits616to a microchip630. The circuitry is covered by a sheath or biocompatible material640as hereinbefore disclosed. Blood flows through the stent in the direction650. The blood includes nanodevices which are either extracellular660or intracellular666. The intracellular nanodevice is enclosed in a red blood cell665through a process such as reverse osmotic lysis or injection.

FIG. 18shows instrumented stent oximetry circuitry700for biosensing bodily conditions about a stent705. The circuitry includes a power supply710, a clock720, a digital controller730which are operatively attached to photodiodes732,734with tranconductance OpAmp740. The OpAmp740and circuit are attached to a serial A/D converter760which is attached to a transmitter780for conveying an RF signal to an external source.

FIG. 19shows a circuit800embedded in a stent805. The circuit800includes an integral capacitor810operatively attached to an differential amplifier815and an A/D converter. The converter is attached to a transmitter880and an RF antenna888. External to the device is a receiver900. The receiver900may be in the form of a watch, necklace, palm pilot, computer, bracelet or the like. The receiver900receives a signal from the circuit800through a receiver910which processes the information in a processor920and provides an output such as an alarm930. The receiver may also include a battery950, an inductive charger960and a data port970.