Methods for evaluating a subject using data associated with a fluorescent analyte

Abstract

Methods, systems, devices and computer program product include: (i) administering a fluorescent analyte to a subject; (ii) repetitively emitting excitation light from a sensor over a desired monitoring period; (iii) detecting fluorescence intensity in response to the excitation light using the sensor that outputs the excitation light; and (iv) using data associated with the detected fluorescence intensity to perform at least one of: (a) calculate the concentration or dose of the analyte received proximate to the sensor site; (b) evaluate the pharmacodynamic or pharmacokinetic activity of the fluorescent analyte; (c) confirm Ab attachment to a tumor site; (d) monitor a non-target site to confirm it is not unduly affected by a therapy; (e) monitor for changes in cellular properties; (f) use the calculated dose or concentration data to adjust or customize a therapeutic amount of the analyte administered to the subject; (g) confirm micelle concentration at a target site and then stimulate toxin release based on the confirmation; and (h) monitor for the expression of a protein produced from a gene therapy modification. In particular embodiments, the intensity of the excitation signals emitted to the localized tissue can be varied in a predetermined manner to generate optical profiling data of the response of the tissue proximate the sensor.

1 . A method of evaluating a subject, comprising:
 administering a fluorescent analyte to a subject, the fluorescent analyte including at least one of a fluor-labeled analyte, a naturally fluorescent analyte and an analyte that exhibits fluorescence when internally administered to the subject;   repetitively emitting excitation light from an implanted sensor over a desired monitoring period;   electronically detecting fluorescence intensity over time to generate a time-dependent measurement profile of fluorescence in localized tissue in response to the excitation light using the implanted sensor that outputs the excitation light;   electronically using data associated with the detected fluorescence intensity to perform at least one of: (a) calculate the concentration or dose of the analyte received proximate to the implanted sensor; (b) evaluate the pharmacodynamic or pharmacokinetic activity of the fluorescent analyte; (c) confirm Ab attachment to a tumor site; (d) monitor a non-target site to confirm it is not unduly affected by a therapy; (e) monitor for changes in cellular properties; (f) use a calculated dose or concentration data to adjust or customize a therapeutic amount of an fluorescent analyte administered to the subject; (g) confirm micelle concentration at a target site and then stimulate toxin release based on the confirmation; and (h) monitor for the expression of a protein produced from a gene therapy modification.   
     
     
         2 . A method according to  claim 1 , further comprising varying the intensity of the excitation signals emitted to the localized tissue in a predetermined manner to generate optical profiling data of the response of the tissue proximate the sensor. 
     
     
         3 . A method according to  claim 1 , wherein the sensor is implanted in or proximate to a tumor. 
     
     
         4 . A method according to  claim 1 , wherein the sensor is adapted to be implanted at depths in the body up to about 5-25 cm below the skin of a patient. 
     
     
         5 . A method according to  claim 1 , wherein the sensor is adapted to be implanted at depths in the body between about 5-20 cm below the skin of a patient, the method further comprising pulsing a laser diode disposed in the implanted sensor to generate the excitation light. 
     
     
         6 . A method according to  claim 1 , wherein the sensor is adapted to be implanted at depths in the body from about 1 to about 25 cm below the skin of a patient, the method further comprising pulsing a laser diode disposed in the implanted sensor to generate the excitation light. 
     
     
         7 . A method according to  claim 5 , wherein the laser diode is operated with between about a 1-10% duty cycle to generate the excitation light. 
     
     
         8 . A method according to  claim 7 , wherein the repeated emissions of the excitation light and associated detecting steps are carried out at spaced apart intervals over at least 1 hour. 
     
     
         9 . A method according to  claim 8 , wherein the emitting and detecting steps are repeated at desired intervals over between about at least one 24-48 hour monitoring period. 
     
     
         10 . A method according to  claim 1 , wherein the emitting and detecting steps are repeated at desired intervals over from about a several seconds and about a several minute monitoring period. 
     
     
         11 . A method according to  claim 1 , wherein the detected data is used to carry out a plurality of operations (a)-(h). 
     
     
         12 . A method according to  claim 1 , wherein the detected data is used to carry out at least three of operations (a)-(h). 
     
     
         13 . A method according to  claim 1 , wherein the sensor projects the at least one excitation light signal outside the sensor at a distance sufficient to probe fluorescent activity at a location away from the sensor of several millimeters, wherein the excitation light signal has a wavelength that is between about 400 nm to about 900 nm. 
     
     
         14 . A method of evaluating a subject, comprising:
 administering a fluorescent analyte to a subject, the fluorescent analyte including at least one of a fluor-labeled analyte, a naturally fluorescent analyte and an analyte that exhibits fluorescence when internally administered to the subject;   repetitively emitting excitation light from at least one sensor over a desired monitoring period, wherein the step of administering the fluorescent analyte is carried out using a source other than the at least one sensor;   electronically detecting fluorescence intensity in response to the excitation light using the at least one sensor that outputs the excitation light over time to electronically generate a time-dependent measurement profile of fluorescence in the subject;   electronically using data associated with the detected fluorescence intensity to perform at least one of: (a) calculate the concentration or dose of the analyte received proximate to the sensor; (b) evaluate the pharmacodynamic or pharmacokinetic activity of the fluorescent analyte; (c) confirm Ab attachment to a tumor site; (d) monitor a non-target site to confirm it is not unduly affected by a therapy; (e) monitor for changes in cellular properties; (f) use a calculated dose or concentration data to adjust or customize a therapeutic amount of an fluorescent analyte administered to the subject; (g) confirm micelle concentration at a target site and then stimulate toxin release based on the confirmation; and (h) monitor for the expression of a protein produced from a gene therapy modification.   
     
     
         15 . A method according to  claim 14 , further comprising varying the intensity of the excitation signals emitted to the localized tissue in a predetermined manner to generate optical profiling data of the response of the tissue proximate the sensor. 
     
     
         16 . A method according to  claim 14 , wherein the at least one sensor is proximate to a tumor. 
     
     
         17 . A method according to  claim 14 , wherein the at least one sensor projects the excitation light signal outside the sensor at a distance sufficient to probe fluorescent activity at a location away from the sensor of several millimeters, and wherein the excitation light signal has a wavelength that is between about 400 nm to about 900 nm. 
     
     
         18 . A method according to  claim 14 , wherein the at least one sensor comprises an implanted sensor. 
     
     
         19 . A method according to  claim 14 , wherein the at least one sensor comprises one sensor placed proximate a tumor site and a second sensor placed away from the tumor site.