Measurement of a fluorescent analyte using tissue excitation

Abstract

An apparatus and method for noninvasive measurement of a fluorescent analyte concentration in the blood of a patient by exciting the blood and the analyte at two wavelength ranges and measuring the emission spectrum of the fluorescent analyte when (i) the difference of emission intensities at the excitation wavelength ranges of the fluorescent analyte is greater than that of background fluorophores, and (ii) when blood absorbance at the two excitation wavelength ranges is similar. An apparatus and method for measurement of a fluorescent analyte concentration in the blood of a patient is provided.

1 - 109 . (canceled) 
     
     
         110 . An apparatus for noninvasive simultaneous measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) and erythrocyte protoporphyrin IX (ePP) as the eZnPP/heme ratio and the ePP/heme ratio in the blood of a patient comprising:
 a light source operatively associated with a tunable optical filter, such that the light source is adapted to excite the tissue of the patient at alternating first wavelength and second wavelength ranges, wherein the first wavelength range is selected to encompass an eZnPP excitation peak and the second excitation wavelength range is selected so that the absorbance of blood is similar to that of the first excitation wavelength range;   one or more spectrometers for detecting a portion of the emission spectrum of the eZnPP and the ePP excited at the first excitation wavelength and the second excitation wavelength;   and a processor adapted to determine a derived signal representative of the concentration of the eZnPP and the ePP based on the difference between portions of the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range and determine whether the detected concentration of the eZnPP or the ePP is below a preselected concentration; and provide an indication that the eZnPP or the ePP concentration is below the preselected concentration.   
     
     
         111 . The apparatus of  claim 110  wherein the light source is adapted to provide the first wavelength range centered at about 425 nm and the second wavelength range centered at about 407 nm. 
     
     
         112 . The apparatus of  claim 110  wherein the processor quantifies the eZnPP/heme ratio based on the emission wavelength band centered at about 593 nm. 
     
     
         113 . The apparatus of  claim 110  wherein the processor quantifies the ePP/heme ratio based on the emission wavelength band centered at about 627 nm. 
     
     
         114 . The apparatus of  claim 110  wherein the processor quantifies the eZnPP/heme ratio based on the difference of intensity between the emission spectrum excited at about 425 nm and the background emission spectrum excited at about 407 nm, wherein the difference is quantified at a wavelength band centered at about 593 nm. 
     
     
         115 . The apparatus of  claim 110  wherein the processor quantifies the ePP/heme ratio based on a linear combination of eZnPP and PP fluorescence centered at about 627 nm as the difference between the emission spectrum intensity of the eZnPP and the detected fluorescence, compared to the background emission spectrum. 
     
     
         116 . The apparatus of  claim 110 , wherein the tunable filter unit comprises a first optical filter and a second optical filter, the first and second optical filters capable of independent variation of the angle of incidence of light provided by the light source. 
     
     
         117 . The apparatus of  claim 110 , wherein the emission spectra of the eZnPP and ePP define a wavelength range, and wherein the detector includes one or more light sensitive elements receiving light through the one or more optical filters transmitting light in the wavelength range of the emission spectra of the eZnPP and ePP. 
     
     
         118 . The apparatus of  claim 110 , further comprising a probe comprising an optical fiber associated with the light source and an optical fiber associated with the one or more spectrometers. 
     
     
         119 . The apparatus of  claim 118 , wherein interfiber spacing of the optical fiber associated with the light source and the optical fiber associated with the one or more spectrometers is selected such that the derived signal is insensitive to the blood volume fraction. 
     
     
         120 . The apparatus of  claim 118 , wherein interfiber spacing of the optical fiber associated with the light source and the optical fiber associated with the one or more spectrometers is selected to achieve a maximum detection sensitivity at a selected depth of the tissue. 
     
     
         121 . The apparatus of  claim 120 , wherein the selected depth of the tissue is selected as the depth having the highest expected concentration of eZnPP. 
     
     
         122 . The apparatus of  claim 110 , further comprising at least one additional unit selected from a memory unit, an output component, a communications component, and a monitor unit. 
     
     
         123 . A method for noninvasive simultaneous measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) and erythrocyte protoporphyrin IX (ePP) as the eZnPP/heme ratio and the ePP/heme ratio in the blood of a patient comprising:
 exciting the tissue at alternating first wavelength and second wavelength ranges, the first and second excitation wavelength ranges selected such that the first wavelength range is selected to encompass an eZnPP excitation peak and the second excitation wavelength range is selected so that the absorbance of blood is similar to that of the first excitation wavelength range and the emission spectra excited at the first and second excitation wavelength ranges exhibit a difference in emission intensities is greater than that of background fluorophores and light absorbance by blood is similar;   detecting a portion of the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range;   and using a processor, determining the concentration of the eZnPP and the ePP based on the difference between the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range, determining whether the detected concentration of the eZnPP or the ePP is below a preselected concentration, and providing an indication that the eZnPP or the ePP concentration is below the preselected concentration.   
     
     
         124 . The method of  claim 123  wherein first wavelength range is centered at about 425 nm and the second wavelength range is centered at about 407 nm and wherein the processor quantifies the eZnPP/heme ratio based on the emission wavelength band centered at about 593 nm the processor quantifies the ePP/heme ratio based on the emission wavelength band centered at about 627 nm. 
     
     
         125 . The method of  claim 123  wherein the processor further determines whether the eZnPP or the ePP concentrations are increasing or decreasing when successive analyte readings are obtained for a particular patient and provides an indication that the eZnPP or the ePP concentration is increasing or decreasing. 
     
     
         126 . A system for noninvasive simultaneous measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) and erythrocyte protoporphyrin IX (ePP) as the eZnPP/heme ratio and the ePP/heme ratio in the blood of a patient comprising:
 the apparatus of claim  1 ; and   at least one additional component selected from a memory unit, an output component, a communications component, and a monitor unit.   
     
     
         127 . The system of  claim 126 , wherein the memory unit stores multiple eZnPP or ePP readings, wherein the apparatus is configured to determine whether the eZnPP or the ePP concentrations are increasing or decreasing when successive readings are obtained for a particular patient and provide an indication that the eZnPP or the ePP concentration is increasing or decreasing. 
     
     
         128 . The system of  claim 126 , wherein the memory unit stores health goals for a patient wherein the apparatus is configured to compare the detected eZnPP or ePP concentration to a target concentration and provide an indication whether the target concentration is reached. 
     
     
         129 . The system of  claim 126  wherein the apparatus is configured to provide a treatment suggestion to a patient after determining the concentration of eZnPP or ePP.