Degradable carbon nanotube-containing biosensors and methods for target clinical marker detection

Abstract

The invention relates to carbon nanotube-containing composites as biosensors to detect the presence of target clinical markers, methods of their preparation and uses in the medical field. The invention is particularly suitable for the detection in patient biological specimens of bone markers and tissue markers. The biosensors of the invention include carbon nanotubes deposited on a substrate, gold nanoparticles deposited on the carbon nanotubes and, binder material and biomolecule deposited on the gold-coated carbon nanotubes. The biomolecule is selected to interact with the target clinical markers. The biosensor can be used as an in-situ or an ex-situ device to detect and measure the presence of the target clinical markers.

1 . An ex-situ, biosensor to detect a target clinical marker in a biological fluid sample of a patient, comprising:
 a substrate;   a plurality of carbon nanotubes deposited on the substrate;   a plurality of gold nanoparticles electrodeposited on the plurality of carbon nanotubes;   a binding material adsorbed on the plurality of gold nanoparticles;   a biotinylated biomolecule selected from the group consisting of antibody and aptamer, deposited on the binding material;   a target clinical marker selected from the group consisting of a bone marker and a tissue marker,   wherein the biotinylated biomolecule binds with the binding material, and interacts with the target clinical marker in the biological fluid sample of the patient; and   a mechanism to provide an indication of the presence or absence of the target clinical marker in the biological fluid sample of the patient.   
     
     
         2 . The biosensor of  claim 1 , wherein the target clinical marker is selected from the group consisting of c-terminal telopeptide, n-terminal telopeptide, alkaline phosphatase, Troponin I and myoglobin. 
     
     
         3 . The biosensor of  claim 1 , wherein the biotinylated biomolecule is selected from the group consisting of c-terminal telopeptide antibody, n-terminal telopeptide antibody, alkaline phosphatase antibody, Troponin I antibody and myoglobin antibody. 
     
     
         4 . The biosensor of  claim 1 , wherein the biotinylated biomolecule is aptamer selected specifically for c-terminal telopeptide, n-terminal telopeptide, alkaline phosphatase, Troponin I and myoglobin. 
     
     
         5 . The biosensor composite of  claim 1 , wherein the binding material is selected from the group consisting of avidin, neutravidin and mixtures thereof. 
     
     
         6 . A method of preparing an in-situ, impedimetric, biodegradable biosensor to detect a target clinical marker in a body of a patient, comprising:
 providing a biodegradable scaffold structured to be implanted in the body of the patient;   depositing a plurality of carbon nanotubes on the scaffold;   electrodepositing a plurality of gold nanoparticles on the plurality of carbon nanotubes;   adsorbing a binding material on the plurality of gold nanoparticles;   binding a biotinylated biomolecule selected from the group consisting of antibody and aptamer, to the binding material; and   interacting the biotinylated biomolecule with the target clinical marker selected from the group consisting of a bone marker and a tissue marker.   
     
     
         7 . The method of  claim 6 , wherein the plurality of carbon nanotubes are deposited using chemical vapor deposition. 
     
     
         8 . The method of  claim 6 , further comprising depositing bovine serum albumin on the biotinylated biomolecule. 
     
     
         9 . A method for detecting a target clinical marker in a body of a patient, comprising:
 forming a biosensor, comprising:
 providing a substrate; 
 depositing a plurality of carbon nanotubes on the substrate; 
 electrodepositing a plurality of gold nanoparticles on the plurality of carbon nanotubes; 
 adsorbing a binding material on the plurality of gold nanoparticles; 
 binding a biotinylated biomolecule selected from the group consisting of antibody and amptamer, to the binding material; and 
 interacting the biotinylated biomolecule with the target clinical marker selected from the group consisting of a bone marker and a tissue marker; 
   providing a biological fluid of the patient;   contacting at least a portion of the biological fluid with the biosensor; and   employing a mechanism to provide indication of the presence or absence of the target clinical marker in the biological fluid.   
     
     
         10 . The method of  claim 9 , wherein the biosensor is employed in-situ, comprising:
 implanting the biosensor in the body of the patient;   contacting the biosensor with the biological fluid in the body of the patient;   implanting a transmitting device in the body of the patient that is effective to generate impedimetric signals corresponding to the target clinical marker detected on the biosensor;   providing a measuring device ex-situ to receive the impedimetric signals generated by the transmitting device and correlate the signals to determine the presence or absence of the target clinical marker; and   providing an indication of the presence or absence of the target clinical marker.   
     
     
         11 . The method of  claim 9 , wherein the biosensor is employed ex-situ, comprising:
 providing the biosensor in the form of a handheld device;   removing the biological fluid as a sample from the body of the patient;   contacting at least a portion of the sample with the handheld device;   observing a visual change to the handheld device; and   correlating the visual change with a chart or key to determine the presence or absence of the clinical marker in the biological sample.   
     
     
         12 . The ex-situ, biosensor of  claim 1 , wherein the biosensor is in the form of a handheld device. 
     
     
         13 . The ex-situ, biosensor of  claim 12 , wherein the indication of the presence or absence of the target clinical marker in the biological fluid sample of the patient is a visual change to the handheld device. 
     
     
         14 . The ex-situ, biosensor of  claim 13 , further comprising a chart or key to correlate the visual change to the presence or absence of the clinical marker in the biological sample. 
     
     
         15 . The ex-situ, biosensor of  claim 1 , wherein the target clinical marker is Tartrate resistant acid phosphatase. 
     
     
         16 . The method of  claim 6 , wherein the binding material is selected from the group consisting of avidin, neutravidin and mixtures thereof. 
     
     
         17 . The method of  claim 6 , wherein the the target clinical marker selected from the group consisting of c-terminal telopeptide, n-terminal telopeptide, alkaline phosphatase, Troponin I and myoglobin.