Nmr systems for in vivo detection of analytes

Abstract

This invention relates generally to NMR systems for in vivo detection of analytes. More particularly, in certain embodiments, the invention relates to systems in which superparamagnetic nanoparticles are exposed to a magnetic field and radio frequency (RF) excitation at or near the Larmor frequency, such that the aggregation and/or disaggregation of the nanoparticles caused by the presence and/or concentration of a given analyte in a biological fluid is detected in vivo from a monitored RF echo response.

What is claimed is: 
     
         1 . A nuclear magnetic resonance system for assessing the presence or concentration of an analyte contained in a body fluid of a mammal in-vivo, the system comprising:
 (a) a sensor suitable for partial or complete implantation within the mammal's body, the sensor comprising structure defining a sample volume and a port, the sample volume containing magnetic particles, and the port allowing the analyte to enter the sample volume and preventing, partly or completely, the magnetic particles from leaving the sample volume, the extent of aggregation of the magnetic particles being indicative of the presence or concentration of the analyte in the sample volume;   (b) a reader for disposition outside the mammal's body, the reader providing results based on sensor indication of presence or concentration of the analyte in the sample volume;   (c) a magnet or magnetic field generator;   (d) a radiofrequency coil for applying a radiofrequency pulse sequence to the sample volume in the presence of a magnetic field provided by the magnet or magnetic field generator; and   (e) means for determining the position of the sensor within the mammal's body.   
     
     
         2 . The system of  claim 1 , wherein the radiofrequency coil acts as a sensing radiofrequency coil and an excitation radiofrequency coil. 
     
     
         3 . The system of  claim 1 , wherein the sensor comprises the radiofrequency coil of (d) or a further radiofrequency coil. 
     
     
         4 . The system of  claim 1 , wherein the reader comprises the radiofrequency coil of (d) or a further radiofrequency coil. 
     
     
         5 . The system of  claim 1 , wherein the magnet or magnetic field generator of (c) is included in the sensor. 
     
     
         6 . The system of  claim 1 , further comprising:
 (f) logic circuitry for calculation of the Larmor frequency of water within the sample volume or a portion thereof based on the position of the sensor provided by the means of (e).   
     
     
         7 . The system of  claim 6 , wherein the reader comprises the radiofrequency coil of (d), the means of (e) and the logic circuitry of (f), further comprising logic circuitry for determining a nuclear magnetic resonance parameter influenced by the analyte within the sample volume. 
     
     
         8 . The system of  claim 7 , wherein the nuclear magnetic resonance parameter is T 2 . 
     
     
         9 . The system of  claim 1 , wherein the means of (e) is based on x-ray telemetric location determination, near IR telemetric location determination, ultrasonic telemetric location determination, or magnetic resonance telemetric location determination. 
     
     
         10 . The system of  claim 1 , wherein the sensor further comprises a radiofrequency identification (RFID) emitter for emitting radiofrequency signals, and the means of (e) comprising (i) a radiofrequency receiver for receiving the emitted radiofrequency signals, and (ii) logic circuitry for determining the position of the sample volume from the received radiofrequency signals. 
     
     
         11 . The system of  claim 1 , wherein the magnetic particles are paramagnetic. 
     
     
         12 . The system of  claim 1 , wherein the magnetic particles are superparamagnetic. 
     
     
         13 . The system of  claim 1 , wherein the magnetic particles are functionalized with one or more binding moieties that bind to one or more target analytes. 
     
     
         14 . The system of  claim 1 , wherein at least one of the magnetic particles comprises a polymer matrix coating. 
     
     
         15 . The reagent composition of  claim 1 , wherein the magnetic particles have an average particle size of between about 1 nm and 5 μm. 
     
     
         16 . The system of  claim 13 , wherein at least one of the one or more binding moieties comprises at least one of an amino group, a carboxyl group, a sulfhydryl group, an amine group, an imine group, an epoxy group, a hydroxyl group, a thiol group, an acrylate group, or an isocyano group. 
     
     
         17 . The system of  claim 13 , wherein at least one of the one or more binding moieties comprises at least one of an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, a peptide, a polypeptide, a protein, a carbohydrate, a polysaccharide, a virus, or a bacteria. 
     
     
         18 . The system of  claim 1 , wherein the sensor further comprises a transmitting antenna for transmission of data received from the logic circuitry to the reader. 
     
     
         19 . The system of  claim 1 , wherein the sensor further comprises
 a magnetic field detector for detecting the strengths of a magnetic field within or adjacent to the sample volume; and   a transmitter for transmitting a signal indicative of the strength of the magnetic field;   and the reader further comprises a receiver for receiving the signal indicative of the strength of the magnetic field.