Measurement of a fluorescent analyte using tissue excitation

• US 9,999,382 B2
• Filed: 03/14/2014
• Issued: 06/19/2018
• 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: Brittenham, Gary M, Stepp, Herbert, Hennig, Georg
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US14/212,557
• Publication Number:
  US 20140235973A1
• Time in Patent Office: 1,558 Days
• 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 operatively associated with a tunable optical filter, such that the light source is adapted to excite an analyte and blood at alternating first and second wavelengths,

one or more spectrometers for detecting a portion of the emission spectra of the fluorescent analyte 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 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; and

determine whether the detected concentration of the fluorescent analyte is below a preselected concentration; and

provide an indication that the fluorescent analyte concentration is below the preselected concentration,

wherein the analyte is selected from the group consisting of;

erythrocyte zinc protoporphyrin and erythrocyte protoporphyrin IX, or a combination thereof, and the first and second alternating wavelengths are selected such that the analyte exhibits first and second emission intensities at the first and second wavelengths, the first and second emission intensities being different, and the blood exhibits first and second absorbances at the first and second wavelengths, the first and second absorbances being similar.

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, 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.

4. An apparatus of claim 3, wherein the first optical filter and the second optical filter comprises two tunable bandpass filters.

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

6. An apparatus of claim 1, 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.

7. An apparatus of claim 6, wherein the emission spectra of the fluorescent analyte define an emission maximum, wherein a first portion of the one or more spectrometers 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 one or more spectrometers receives light through optical filters transmitting light in a wavelength range outside the emission maximum of the fluorescent analyte.

8. 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 one or more spectrometers.

9. An apparatus of claim 8, wherein the probe comprises a plurality of optical fibers associated with the light source surrounding an optical fiber associated with the one or more spectrometers.

10. An apparatus of claim 8, wherein the probe comprises a plurality of optical fibers associated with the one or more spectrometers surrounding the optical fiber associated with the light source.

11. An apparatus of claim 8, 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.

12. An apparatus of claim 8, 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.

13. An apparatus of claim 12, wherein the selected depth of the tissue is selected as the depth having the highest expected concentration of the fluorescent analyte.

14. The apparatus of claim 1 wherein the apparatus further comprises a memory that stores multiple analyte readings, wherein the apparatus is configured to determine whether the analyte concentrations are increasing or decreasing when successive analyte readings are obtained for a particular patient and provide an indication that the fluorescent analyte concentration is increasing or decreasing.

15. The apparatus of claim 1 wherein the apparatus further comprises a memory to store health goals for a patient wherein the apparatus is configured to compare the detected analyte concentration to a target concentration and provide an indication whether the target concentration is reached.

16. The apparatus of claim 1 wherein the apparatus is configured to provide a treatment suggestion to a patient after determining the analyst concentration.

17. 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 operatively associated with a tunable optical filter for providing alternating excitation of the tissue at a first wavelength of about 425 nm and a second wavelength of 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.

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

exciting the tissue at an alternating first wavelength and second wavelength, the first and second excitation wavelengths selected such that the fluorescent analyte exhibits a difference in emission intensities at the first and second excitation wavelengths 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

using a processor, 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;

determining whether the detected concentration of the fluorescent analyte is below a preselected concentration;

providing an indication that the fluorescent analyte concentration is below the preselected concentration, and determining whether the analyte concentrations are increasing or decreasing when successive analyte readings are obtained for a particular patient and providing an indication that the fluorescent analyte concentration is increasing or decreasing.

19. The method of claim 18 further comprising comparing the detected analyte concentration to a target concentration and providing an indication whether the target concentration is reached.

20. The method of claim 18 further comprising providing a treatment suggestion to a patient after determining the analyst concentration.