In vivo fluorescence sensors, systems, and related methods operating in conjunction with fluorescent analytes
First Claim
1. A method for determining the in vivo clinical efficacy of a treatment in a subject, comprising:
- positioning at least one sensor in tissue in a region of interest in the body;
administering a fluorescent analyte to a subject, the fluorescent analyte including at least one of a fluorescently pre-labeled analyte, a naturally fluorescent analyte and an analyte that exhibits fluorescence when internally administered to the subject;
emitting at least one excitation light signal from the at least one sensor to tissue proximate the at least one sensor;
detecting in vivo from the at least one sensor a signal corresponding to the fluorescence in the region of interest in the subject responsive to the administering step;
relaying the signal to a location external of the subject'"'"'s body; and
monitoring the signal over time to determine the localized fluorescence response of the subject to the administered fluorescently pre-labeled analyte, naturally fluorescent analyte and/or analyte that exhibits fluorescence when in the subject.
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Accused Products
Abstract
Methods, systems, devices and computer program product include: (i) administering a fluorescent analyte to a subject; (ii) repetitively emitting excitation light from an implanted sensor over a desired monitoring period; (iii) detecting fluorescence intensity in response to the excitation light using the implanted 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 implanted 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.
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Citations
104 Claims
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1. A method for determining the in vivo clinical efficacy of a treatment in a subject, comprising:
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positioning at least one sensor in tissue in a region of interest in the body;
administering a fluorescent analyte to a subject, the fluorescent analyte including at least one of a fluorescently pre-labeled analyte, a naturally fluorescent analyte and an analyte that exhibits fluorescence when internally administered to the subject;
emitting at least one excitation light signal from the at least one sensor to tissue proximate the at least one sensor;
detecting in vivo from the at least one sensor a signal corresponding to the fluorescence in the region of interest in the subject responsive to the administering step;
relaying the signal to a location external of the subject'"'"'s body; and
monitoring the signal over time to determine the localized fluorescence response of the subject to the administered fluorescently pre-labeled analyte, naturally fluorescent analyte and/or analyte that exhibits fluorescence when in the subject. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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31. A method of evaluating a subject, comprising:
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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;
detecting fluorescence intensity in response to the excitation light using the implanted sensor that outputs the excitation light;
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 the 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 confimiation; and
(h) monitor for the expression of a protein produced from a gene therapy modification. - View Dependent Claims (32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)
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43. A detection system for detecting fluorescence in a subject associated with an internally administered fluorescent analyte, 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, the detection system comprising:
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at least one fluorescence sensor configured for in vivo operation, the at least one sensor being configured to emit an excitation light signal and to detect fluoresence from a fluorescent analyte in localized tissue in the body in response to the emitted excitation light signal, at least intermittently, over a period of time extending for at least about 24 hours after administration of a fluorescent analyte; and
a processor operably associated with the at least one sensor configured to direct the output of the excitation signal and to receive fluorescence intensity signal data associated with the detected fluoresence from the at least one sensor, wherein said processor includes computer program code for monitoring intensity over time associated with one or more of the uptake and retention of the fluorescent analyte in the targeted localized tissue at a plurality of points in time over at least one monitoring period. - View Dependent Claims (44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69)
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70. An implantable fluorescence sensor, comprising:
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an elongated substantially cylindrical sensor body;
a cylindrical optical filter formed over the outer surface of the elongated sensor body;
at least one excitation light source held in the sensor body configured to generate excitation light from the sensor at a predetermined wavelength of interest having an power less than about 20 mW; and
at least one detector held in the sensor body configured to detect fluorescence at predetermined wavelengths of interest, wherein the sensor is configured to be intermittently operated at plurality of sampling intervals over a monitoring period of interest. - View Dependent Claims (71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88)
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89. A computer program product for evaluating a subject'"'"'s in vivo response to a fluorescent analyte, the fluorescent analyte including at least one of a fluorescently pre-labeled analyte, a naturally fluorescent analyte and an analyte that exhibits fluorescence when internally administered to the subject, the computer program product comprising a computer readable storage medium having computer readable program code embodied in said medium, said computer-readable program code comprising:
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computer readable program code for directing the emission of at least one excitation light signal using a sensor into a subject about a local targeted site in the body of a subject at depths up to about 25 cm in vivo a plurality of times during a monitoring period having a duration of at least 1 hour;
computer readable program code for serially receiving a plurality of fluorescence intensity count data detected in vivo in tissue proximate the target site from the sensor over time, the detected intensity data corresponding to fluorescence generated from tissue having a fluorescent analyte that is administered to a subject, responsive to exposure to the excitation light; and
computer readable program code for generating a time-dependent measurement profile for evaluating selected parameters associated with at least one of the signal intensity, concentration, uptake and retention of the fluorescent analyte in the localized tissue of the subject. - View Dependent Claims (90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104)
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Specification