MEASUREMENT OF A FLUORESCENT ANALYTE USING TISSUE EXCITATION

• US 20140235973A1
• Filed: 03/14/2014
• Published: 08/21/2014
• Est. Priority Date: 09/15/2011
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Stepp, Herbert, Brittenham, Gary M, Hennig, Georg
• Granted Patent: US 9,999,382 B2
• Time in Patent Office: Days
• US Class Current: 600/317
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0088 for oral or dental tissue
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/74 Details of notification to user or communication with user or patient indicating measured values G01D7/00; user input means input or output arrangements for computers G06F3/00
• CPC Class Codes: A61K 49/0036 Porphyrins used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546
• CPC Class Codes: G02B 26/001 based on interference in an adjustable optical cavity interference filters G02B5/28; devices or arrangements using multiple reflections in spectrometry or monochromators G01J3/26

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.

Claims

1. An apparatus for noninvasive measurement of a concentration of a fluorescent analyte in the blood of a patient comprising:

a light source for providing excitation of the analyte and the blood at a first wavelength range and a second wavelength range, the first and second excitation wavelength ranges selected such that the analyte exhibits a difference in emission intensities at the first and second excitation wavelength ranges and such that light absorbance of blood at the first and second wavelength ranges is similar;

one or more detectors for detecting a portion of the emission spectra of the fluorescent analyte at the first excitation wavelength range and the second excitation wavelength range; and

a processor adapted to determine a derived signal representative of the concentration of the analyte based on the difference between the portion of the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range.

2. An apparatus of claim 1, wherein the apparatus is for measurement of a concentration of a fluorescent analyte in whole blood.

3. An apparatus of claim 1, further comprising a tunable filter unit providing excitation of the blood and the analyte at the first wavelength range and the second wavelength range.

4. An apparatus of claim 3, 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.

5. An apparatus of claim 3, wherein the tunable filter unit comprises two tunable bandpass filters.

6. An apparatus of claim 3, wherein the tunable filter unit comprises a first optical filter and a second optical filter and a third filter to correct for offset of the light passing through the first and second optical filters.

7. An apparatus of claim 1, further comprising one or more optical filters,

wherein the emission spectra of the fluorescent analyte defines 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 fluorescent analyte.

8. An apparatus of claim 7, wherein the emission spectra of the fluorescent analyte define an emission maximum,

wherein a first portion of the detector receives light through the optical filters transmitting light in the wavelength range of the emission spectra of the fluorescent analyte, and

wherein a second portion of the detector receives light through optical filters transmitting light in a wavelength range outside the emission maximum of the fluorescent analyte.

14. An apparatus of claim 1, further comprising a probe comprising an optical fiber associated with the light source and an optical fiber associated with the detector.

15. An apparatus of claim 14, wherein the probe comprises a plurality of optical fibers associated with the light source surrounding an optical fiber associated with the detector.

16. An apparatus of claim 14, wherein the probe comprises a plurality of optical fibers associated with the detector surrounding the optical fiber associated with the light source.

17. An apparatus of claim 14, wherein interfiber spacing of the optical fiber associated with the light source and the optical fiber associated with the detector is selected such that the derived signal is insensitive to the blood volume fraction.

18. An apparatus of claim 14, wherein interfiber spacing of the optical fiber associated with the light source and the optical fiber associated with the detector is selected to achieve a maximum detection sensitivity at a selected depth of the tissue.

19. An apparatus of claim 18, wherein the selected depth of the tissue is selected as the depth having the highest expected concentration of the fluorescent analyte.

9-13. -13. (canceled)

20-50. -50. (canceled)

51. An apparatus for noninvasive measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) as the eZnPP/heme ratio in the blood of a patient comprising:

a light source for providing excitation of the tissue at a first wavelength range and a second wavelength range, the first excitation wavelength range selected at the excitation peak of eZnPP and the second excitation wavelength range selected so that the absorbance of blood is similar to that of the first excitation wavelength range;

one or more detectors for detecting a portion of the emission spectra at the first excitation wavelength range and the second excitation wavelength range; and

a processor for determining the concentration of eZnPP based on the difference between the portion of the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range.

52. An apparatus of claim 51, wherein the apparatus is for measurement of a concentration of eZnPP in whole blood.

57. An apparatus of claim 51, further comprising one or more optical filters,

wherein the emission spectra of the eZnPP defines 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.

58. An apparatus of claim 57, wherein the emission spectra of the eZnPP define an emission maximum,

wherein a first portion of the detectors receive light through the optical filters transmitting light in the wavelength range of the emission spectra of the eZnPP, and

wherein a second portion of the detectors receive light through optical filters transmitting light in a wavelength range outside the emission maximum of the eZnPP.

53-56. -56. (canceled)

59-102. -102. (canceled)

103. An apparatus for simultaneous measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) and erythrocyte protoporphyrin IX (ePP) as the eZnPP/heme ratio and ePP/heme ratio in the blood of a patient comprising:

a light source for providing excitation of the tissue at a first wavelength range and a second wavelength range, the first excitation wavelength range selected at the excitation peak of eZnPP and the second excitation wavelength range selected so that the absorbance of blood is similar to that of the first excitation wavelength range;

one or more detectors for detecting a portion of the emission spectra at the first excitation wavelength range and the second excitation wavelength range; and

a processor for determining the concentration of eZnPP and ePP based on the difference between the portion of the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range.

104. An apparatus for noninvasive measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) as the eZnPP/heme ratio in the blood of a patient comprising:

a light source for providing excitation of the tissue at about 425 nm and about 407 nm;

a detector for detecting a portion of the emission spectra excited at about 425 nm and about 407 nm; and

a processor for determining the concentration of eZnPP based on the difference between the portion of the emission spectra excited at about 425 nm and about 407 nm.

105. An apparatus for measurement of a concentration of erythrocyte zinc protoporphyrin (eZnPP) as the eZnPP/heme ratio in the blood of a patient comprising:

a light source for providing excitation of the tissue at about 425 nm and about 407 nm;

a detector for detecting a portion of the emission spectra excited at about 425 nm and about 407 nm; and

a processor for determining the concentration of eZnPP based on the difference between the portion of the emission spectra excited at about 425 nm and about 407 nm.

106. A method for noninvasive measurement of a concentration of a fluorescent analyte in the blood of a patient comprising:

exciting the tissue at a first wavelength range and a second wavelength range, the first and second excitation wavelength ranges selected such that the fluorescent analyte exhibits a difference in emission intensities at the first and second excitation wavelength ranges that is greater than that of background fluorophores and light absorbance by blood at the first and second excitation wavelength ranges is similar;

detecting a portion of the emission spectra at the first excitation wavelength range and the second excitation wavelength range; and

determining the concentration of the fluorescent analyte based on the difference between the emission spectra excited at the first excitation wavelength range and the second excitation wavelength range.

107. An apparatus for filtering a beam of light or images, comprising:

a first optical filter defining an adjustable angle of incidence with respect to the beam of light;

a second optical filter defining an adjustable angle of incidence with respect to the beam of light;

wherein the angle of incidence of the first optical filter and the angle of incidence of the second optical filter are independently adjustable;

wherein a central wavelength of light passing through first and second optical filters is tunable by adjustment of the angle of incidence of the first filter with respect to the beam of light; and

wherein the spectral bandwidth of light passing through the first and second optical filters is tunable by adjustment of the angle of incidence of the first filter and the second filter with respect to the beam of light.

108. The apparatus of claim 107, wherein each of the first and second optical filters comprises a tunable bandpass filter.

109. The apparatus of claim 107, further comprising a third optical element to correct for offset of the light passing through the first and second optical filters.