Systems and methods for controlling photoactivatable agents

Abstract

A system for controlling a photoactivatable agent in a subject includes a light modulator and a controller. The light modulator is operable to emit light at a first wavelength and light at a second wavelength. The light at the first wavelength is configured to activate the photoactivatable agent and the light at the second wavelength is configured to deactivate the photoactivatable agent. The controller is operably coupled to the light modulator. The controller is operable to cause the light modulator to (1) emit light at the first wavelength, thereby activating the photoactivatable agent, and (2) emit light at the second wavelength, thereby deactivating the photoactivatable agent.

Description

Technical Field

[0001] The present disclosure relates to systems and methods for activating and inactivating agents within a subject's body. More specifically, the present disclosure relates to a light modulator system and method for controlling photoactivatable agents within a subject's body.

Background Art

[0002] The treatment of various local conditions, such as some forms of cancer and some skin conditions, typically involves generally (i.e., non-locally) providing one or more agents to a subject. Such treatments are typically used because it is not possible and / or effective to provide one or more agents locally. Such agents often have an adverse effect on healthy tissue even though they effectively treat the affected tissue. Therefore, there is a need for improved systems and methods for providing treatment via agents.

Summary of the Invention

[0003] The present disclosure provides a light modulator system and method for controlling one or more photoactivatable agents within a subject's body.

[0004] According to one embodiment of the present disclosure, a system for controlling a photoactivatable agent within a subject includes a light modulator and a controller. The light modulator is operable to emit light of a first wavelength and light of a second wavelength. The light of the first wavelength is configured to activate the photoactivatable agent, and the light of the second wavelength is configured to inactivate the photoactivatable agent. The controller is operably coupled to the light modulator, and the controller is operable to cause the light modulator to (1) emit light of the first wavelength, thereby activating the photoactivatable agent, and (2) emit light of the second wavelength, thereby inactivating the photoactivatable agent.

[0005] In some embodiments, activation is modulated by a physiological event (which may also be referred to as an "outer closed loop"). In some embodiments, activation is modulated by a measured level of an active compound in the body (which may also be referred to as an "inner closed loop").

[0006] In some embodiments, the light modulator includes a first emitter configured to emit light of a first wavelength and a second emitter configured to emit light of a second wavelength.

[0007] In some embodiments, the light modulator includes a plurality of first emitters configured to emit light of a first wavelength and a plurality of second emitters configured to emit light of a second wavelength.

[0008] In some embodiments, the plurality of second emitters are arranged to define at least a portion of the outer perimeter, and the plurality of first emitters are disposed within a portion of the outer perimeter.

[0009] In some embodiments, the system further includes a wearable device configured to be secured to the skin of the subject, and the wearable device includes the light modulator.

[0010] In some embodiments, the wearable device includes a controller.

[0011] In some embodiments, the system further includes an implantable device configured to be disposed within the body of the subject, and the implantable device includes the light modulator.

[0012] In some embodiments, the implantable device includes a controller.

[0013] In some embodiments, the system further includes an implantable device having an optical modulator and configured to be disposed within a subject's body. The implantable device includes an activation probe and an inactivation cuff. The activation probe is configured to be disposed within a target mass of the subject, and the activation probe includes a first emitter configured to emit light of a first wavelength. The inactivation cuff is configured to be secured to a blood vessel coupled to the target mass of the subject, and the inactivation cuff includes a second emitter configured to emit light of a second wavelength.

[0014] In some embodiments, the system further includes an optical element coupled to the optical modulator.

[0015] In some embodiments, the optical element is a microlens array.

[0016] In some embodiments, the microlens array includes an electrochromic coating.

[0017] In some embodiments, the optical element is a diffractive optical element.

[0018] In some embodiments, the controller is operable to cause the optical modulator to simultaneously emit light of the first wavelength and light of the second wavelength.

[0019] According to another embodiment of the present disclosure, a system for controlling a photoactivatable agent within a subject includes a light modulator, an activation sensor, and a controller. The light modulator is operable to emit light that is configured to activate the photoactivatable agent. The activation sensor (which may be part of an "inner closed loop", for example) is operable to determine the amount of activated photoactivatable agent within the subject. The controller is operably coupled to the light modulator and the activation sensor. The controller is operable to cause the light modulator to emit light, thereby activating the photoactivatable agent, and to modify the amount of light emitted by the light modulator in response to the amount of activated photoactivatable agent within the subject as determined by the activation sensor.

[0020] According to another embodiment of the present disclosure, a system for controlling a photoactivatable agent within a subject includes a light modulator, an activation sensor, and a controller. The light modulator is operable to emit light that is configured to activate the photoactivatable agent. The activation sensor (which may be part of an "outer closed loop", for example) is operable to determine a physiological event that ensures activation of the agent within the subject. The controller is operably coupled to the light modulator and the activation sensor. The controller is operable to cause the light modulator to emit light, thereby activating the photoactivatable agent, and to modify the amount of light emitted by the light modulator in response to a change in the physiological state of the patient.

[0021] According to another embodiment, both the inner closed loop and the outer closed loop are implemented in the same system or device.

[0022] In some embodiments, the activation sensor includes an excitation emitter, a phosphor, and a fluorescence detector. The excitation emitter is operable to emit light of a first wavelength. The phosphor is configured to emit light of a second wavelength when the phosphor is in the presence of a photoactivatable agent that has been activated. The fluorescence detector is operable to detect the light of the second wavelength emitted by the phosphor.

[0023] In some embodiments, the activation sensor further includes a waveguide that optically couples the excitation emitter to the phosphor.

[0024] In some embodiments, the waveguide includes an optical fiber.

[0025] In some embodiments, the fluorescence detector includes a photodiode.

[0026] In some embodiments, the excitation emitter includes a light emitting diode.

[0027] In some embodiments, the system further includes an excitation filter that optically couples the excitation emitter to the phosphor.

[0028] In some embodiments, the system further includes an emission filter that optically couples the phosphor to the fluorescence detector.

[0029] In some embodiments, the activation sensor includes a chemical sensor.

[0030] In some embodiments, the activation sensor includes a plurality of chemical sensors.

[0031] In some embodiments, the activation sensor further includes an excitation emitter operable to emit light of a first wavelength, and each of the plurality of chemical sensors includes a phosphor configured to emit light of a second wavelength when receiving light of the first wavelength in the presence of a photoactivatable agent in which the phosphor is activated. The activation sensor further includes a fluorescence detector operable to detect the light of the second wavelength emitted by the phosphor.

[0032] In some embodiments, the activation sensor further includes a plurality of ring resonators operable to filter the light of the second wavelength emitted by the phosphor.

[0033] In some embodiments, the activation sensor further includes a waveguide optically coupling the excitation emitter to the plurality of chemical sensors.

[0034] In some embodiments, the activation sensor further includes a waveguide optically coupling the plurality of chemical sensors to the fluorescence detector.

[0035] In some embodiments, the waveguide includes an optical fiber.

[0036] In some embodiments, the activation sensor is a first activation sensor, and the system further includes a second activation sensor operable to determine a physiological event within a subject, and the controller is further operable to modify the amount of light emitted by the light modulator in response to the second activation sensor determining a physiological event within the subject.

Brief Description of the Drawings

[0037] The above and other advantages and objects of the present invention, and the manner in which they are achieved, will become more apparent by reference to the following description of embodiments of the present invention made in connection with the accompanying drawings, and the present invention itself will be better understood.

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[0038] Throughout the several views, corresponding reference numerals indicate corresponding parts. The drawings represent embodiments of the invention, but the drawings are not necessarily to scale, and certain features may be exaggerated or omitted in some of the views to better illustrate and explain the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0039] Systems and methods according to embodiments of the present disclosure facilitate controlling one or more photoactivatable agents, which may also be referred to as photoactivatable drugs or pharmaceuticals. Generally, a photoactivatable agent may be configured or activated into an active state by exposure to light of one or more wavelengths. In the active state, the photoactivatable agent is configured to cause one or more pharmacological effects on a subject's body. In other words, in the active state, the photoactivatable agent is configured to provide pharmacological treatment to the subject. A photoactivatable agent may also be configured or inactivated into an inactive state by exposure to light of one or more different wavelengths. In the inactive state, the photoactivatable agent does not cause a pharmacological effect on the subject's body. In other words, in the inactive state, the photoactivatable agent is inactive with respect to the subject's body.

[0040] Photoactivatable agents can include, for example, photocaged raseglurant, more specifically photocaged raseglurant as described by J. Font et al., “Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator”, eLife, vol. 6, p. e23545, Apr. 2017, doi:10.7554 / eLife.23545, or photocaged morphine, more specifically photocaged morphine as described by M. Lopez-Cano et al., “Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects”, British Journal of Pharmacology, p. bph.15645, Sep. 2021, doi:10.1111 / bph.15645. Both of the above publications are incorporated herein by reference.

[0041] A photoactivatable agent can first be administered to a subject, for example, in liquid form and / or via a syringe assembly or an intravenous (“IV”) catheter. The photoactivatable agent can then be distributed into the subject's body via the circulatory system.

[0042] The systems and methods according to embodiments of the present disclosure facilitate activating and inactivating photoactivatable agents at different body locations and / or at specific times. In other words, the systems and methods according to embodiments of the present disclosure facilitate the control of photoactivatable agents having spatial / temporal specificity.

[0043] The system according to an embodiment of the present disclosure is generally operated by a user (e.g., a medical professional, a caregiver, or another person) in the manner described herein to control one or more photoactivatable agents within a subject (e.g., another person or the user).

[0044] FIG. 1 schematically illustrates a system 100 for controlling one or more photoactivatable agents within a subject according to an embodiment of the present disclosure. Generally, the system 100 includes a control module 102 operably coupled to one or more light modulators 104 (exemplarily, when used in this application, the term “operably coupled” via wireless communication includes wired data communication and wireless data communication, whether direct or indirect via one or more intervening devices or components, and such data communication can be continuous or intermittent). The control module 102 is operable to cause the light modulator 104 to emit light of one or more wavelengths that activate a photoactivatable agent and light of one or more different wavelengths that inactivate the photoactivatable agent. These aspects are described in more detail below.

[0045] Continuing to refer to FIG. 1, the control module 102 can be any device or component capable of executing stored software and / or firmware code that, when executed by the controller 106, causes the system 100 to perform the functions described herein. The controller 106 can be, for example, an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), a digital signal processor (DSP), hardwired logic, combinations thereof, and the like.

[0046] The controller 106 is operatively coupled (exemplarily, via wired communication) to a memory 108 for storing, for example, software or firmware code or sensed parameters, as will be described in more detail below. The memory 108 can be any suitable computer-readable medium accessible by the processor 106. The memory 108 can be a single storage device or multiple storage devices, can be located internal or external to the controller 106, and can include both volatile and non-volatile media. The memory 108 can be, for example, a random-access memory (RAM), a read-only memory (ROM), an electrically erasable programmable ROM (EEPROM), a flash memory, a magnetic storage device, an optical disk storage device, or any other suitable medium capable of storing data and accessible by the controller 106.

[0047] The controller 106 is also operably coupled (exemplarily, via wired communication) to a power source 110 for providing power to various components of the system 100. The power source 110 can be, for example, one or more rechargeable batteries, one or more inductive / wireless power receivers, and the like.

[0048] The controller 106 is further operably coupled (exemplarily, via wired communication) to a transmitter 112 for wirelessly transmitting information such as sensed parameters (which can be sensed as part of an "outer closed loop") to one or more remote devices (not shown) such as a mobile device including a smartphone, smartwatch, or tablet device, a personal computer, a remote computer, or a database. The transmitter 112 can be, for example, a Bluetooth transmitter, an IEEE 802.11 transmitter, a cellular communication transmitter, a short-range communication transmitter, and the like. The transmitter 112 can be continuously or intermittently coupled to the remote device. A transceiver (not shown) can be used instead of the transmitter 112 to facilitate the provision of information from the remote device to the system 100. Such information can include, for example, software updates.

[0049] Continuing to refer to FIG. 1, the optical modulator 104 includes one or more first emitters 114 and one or more second emitters 116. The first emitter 114 emits light of a first wavelength that activates a photoactivatable agent. More specifically, the first emitter 114 can be configured to emit light having a wavelength of, for example, about 450 nm, or blue light. Illustratively, the first emitter 114 can emit only light of the first wavelength. Alternatively, the first emitter 114 may be capable of emitting light of multiple wavelengths, and the controller 106 can cause the first emitter 114 to emit light of the first wavelength. The first emitter 114 can be a light-emitting diode (“LED”), etc. Similarly, the second emitter 116 emits light of a second wavelength that deactivates a photoactivatable agent. More specifically, the second emitter 116 can be configured to emit light having a wavelength of, for example, about 550 nm, or green light. Illustratively, the second emitter 116 can emit only light of the second wavelength. Alternatively, the second emitter 116 may be capable of emitting light of multiple wavelengths, and the controller 106 can cause the second emitter 116 to emit light of the second wavelength. The second emitter 116 can be an LED, etc.

[0050] Alternatively, instead of including the first emitter 114 and the second emitter 116 as described above, the optical modulator 104 can include one or more emitters configured to emit light of a first wavelength (e.g., based on a particular time and / or sensed parameter) and light of a second wavelength (e.g., based on another time and / or another sensed parameter).

[0051] Referring further to FIG. 1, the optical modulator 104 also includes one or more sensors 118. The sensors 118 can sense physiological parameters and / or parameters related to photoactivatable agents. Physiological parameters can include, for example, physiological parameters indicating pain experienced by the subject, physiological parameters indicating inflammation (such as cytokine levels), the temperature of the subject and / or a body part of the subject, physiological parameters indicating diabetic events (such as changes in glucose levels), changes in heart rate, and characteristics of a target mass (such as diseased tissue). Parameters related to photoactivatable agents can include, for example, the presence or amount of an inactivated photoactivatable agent and / or the presence or amount of an activated photoactivatable agent. As will be described in more detail below, the controller 106 can modify the operation of the system 100, and more specifically, the amount of light emitted by the optical modulator 104, based on the parameters sensed by the sensors 118.

[0052] The system according to the present disclosure can be incorporated into a device configured to be worn by a subject or a wearable device. Referring now to FIGS. 2 and 3, a wearable device 200 according to an embodiment of the present disclosure is illustrated. The wearable device 200 is a more specific embodiment of the system 100 described above. Thus, the wearable device 200 includes some of the same components and operates in a manner similar to the system 100 described above. Generally, the wearable device 200 is configured in the form of a patch. More specifically, the wearable device 200 includes a flexible base or housing 202 configured to be removably secured to the skin of the subject (e.g., via one or more adhesives (not shown)). The side 204 of the base 202 facing the subject is configured to be secured to the skin of the subject. The opposing surface 206 of the base 202 carries an optical element 208 (FIG. 3), an optical modulator 210 (FIG. 3), a control module 212 (FIG. 3), and a flexible cover 214 for securing these components to the base 202. The base 202 can further include a transparent portion 216 (FIG. 3) adjacent to the optical element 208 and the optical modulator 210 to facilitate the emission of light from the wearable device 200.

[0053] Referring particularly to FIG. 3, the control module 212 may be the same as or similar to the control module 102 described above. Similarly, the optical modulator 210 may be the same as or similar to the optical modulator 104 described above. More specifically, the optical modulator 210 includes one or more first emitters 218 configured to emit light of a first wavelength and one or more second emitters 220 configured to emit light of a second wavelength. The optical modulator 210 also includes a plurality of sensors 222. The optical element 208 is configured to receive light from the first emitter 218 and the second emitter 220 and direct the light more uniformly towards the target. The optical element 208 may take various forms, and exemplary details will be described below.

[0054] Continuing to refer to FIG. 3, the first emitter 218 and the second emitter 220 are arranged in a grid, more specifically in a 3x3 grid. Exemplarily, the first emitter 218 is disposed at the center of the grid, and the second emitter 220 forms the outer perimeter of the grid. Thus, the wearable device 200 may be positioned such that the first emitter 218 is adjacent to the target mass (e.g., diseased tissue). The first emitter 218 may emit light of the first wavelength to activate a photoactivatable agent within the target mass, and the second emitter 220 may simultaneously emit light of the second wavelength to inactivate the photoactivatable agent as it circulates away from the target mass. In other embodiments, the first emitter 218 and the second emitter 220 may have different arrangements.

[0055] Referring now to FIGS. 4 and 5, a wearable device 300 according to an embodiment of the present disclosure is illustrated. The wearable device 300 is similar to the wearable device 200 described above. More specifically, the wearable device 300 includes a base (not shown) carrying an optical element 302, a light modulator 304, a control module (not shown), and a cover 306 for fixing based on these components. Referring particularly to FIG. 5, the first emitter 308 and the second emitter 310 of the light modulator 304 are substantially arranged in the shape of a plus sign (i.e., “+”). Exemplarily, the first emitter 308 is disposed on the side of the symbol, and the second emitter 310 forms the outer periphery of the symbol. Thus, the wearable device 300 can be positioned such that the first emitter 308 is adjacent to the target mass. The first emitter 308 may emit light of a first wavelength to activate a photoactivatable agent in the target mass, and the second emitter 310 may simultaneously emit light of a second wavelength to inactivate the photoactivatable agent as the photoactivatable agent circulates away from the target mass.

[0056] As briefly described above, the device according to the present disclosure may include an optical element for directing light towards a target. Such an optical element may take various forms. For example, the optical element may include a lens or a diffractive optical element, an element including a pattern of opaque and transparent portions. FIGS. 6 and 7 illustrate an exemplary diffractive optical element 400. The diffractive optical element 400 includes a grid of circular zone plates 402 (three of which are identified in FIG. 6), and each circular zone plate 402 includes alternating and concentric opaque rings 404 and transparent rings 406 (two of each are identified in FIG. 7). Exemplarily, the rings 404, 406 decrease in thickness as they move away from the center of each circular zone plate 402. The thicknesses of the rings 404, 406 may also be adjusted to create a desired optical wavefront at the target mass through diffraction. Factors such as the position of the light source, the position of the target mass, and the wavelength of the light to be diffracted affect the final thickness selected for the zone plate rings. The circular zone plates 402 may be provided in different sizes, and FIG. 6 illustrates two such sizes.

[0057] FIGS. 8 and 9 illustrate another exemplary diffractive optical element 500. The diffractive optical element 500 includes a grid of hexagons 502 (three of which are identified in FIG. 8), and each hexagon 502 includes alternating and concentric opaque rings 504 and translucent rings 506 (two of each are identified in FIG. 9). Exemplarily, the rings 504, 506 are cut near the edges of each hexagon 502, and the rings 504, 506 decrease in thickness as they move away from the center of each hexagon 502.

[0058] FIG. 10 illustrates another exemplary diffractive optical element 600. The diffractive optical element 600 includes a grid of circles 602 (two of which are identified in FIG. 10), each circle 602 including alternating and concentric opaque rings 604 and translucent rings 606 (two of each are identified in FIG. 10). Exemplarily, the rings 604, 606 decrease in thickness as they move away from the center of each circle 602. The diffractive optical element 600 also includes substantially triangular shapes 608 between adjacent circles 602 (two of which are identified in FIG. 10). Each triangle 608 includes alternating and concentric opaque triangles 610 and translucent triangles 612 (two of each are identified in FIG. 10). Exemplarily, the triangles 610, 612 decrease in thickness as they move away from the center of each triangle 608.

[0059] FIG. 11 illustrates yet another exemplary diffractive optical element 700. The diffractive optical element 700 includes a grid of hexagons 702 (two of which are identified in FIG. 11), each hexagon 702 including alternating and concentric opaque hexagons 704 and translucent hexagons 706 (two of each are identified in FIG. 11). Exemplarily, the hexagons 704, 706 decrease in thickness as they move away from the center of each hexagon 702.

[0060] As another example, the optical element may be a microlens array or an array including a plurality of relatively small lenses. Such an array may direct light more uniformly towards the subject and can be relatively compact compared to a standard lens. FIG. 12 provides a profile view (i.e., a view from the side) of an exemplary microlens array 800. The array 800 includes a plurality of relatively small lenses 802, which may be arranged in a grid pattern. More specifically, the lenses 802 may be arranged horizontally as illustrated and may extend within the page. The microlens array 800 may be constructed from one or more flexible biocompatible materials. The lenses 802 may have an electrochromic coating (not shown), and each lens 802 may be controlled in a manner similar to a pixel. As a result, the microlens array 800 may facilitate emitting light of a first wavelength and / or a second wavelength to a relatively small area of the subject's body.

[0061] The wearable device according to the present disclosure can be modified in various other ways. For example, one or more components of the system 100 may be disposed remotely from the wearable device according to the present disclosure. As a more specific example, FIGS. 13 and 14 illustrate a wearable device 900 according to another embodiment of the present disclosure. The wearable device 900 is similar to the wearable device described above. More specifically, the wearable device 900 includes a housing 902 that carries a flexible substrate 904, and the flexible substrate 904 carries an optical modulator 906. The optical modulator 906 includes one or more first emitters 908 and one or more second emitters 910. The flexible substrate 904 also carries a sensor 912. The optical modulator 906 and the sensor 912 are operatively coupled to a control module (not shown) via wired communication. Alternatively, the optical modulator 906 and the sensor 912 are operatively coupled to the control module via wireless communication. The control module may be part of another wearable device (not shown) or a non-wearable device (not shown).

[0062] The system according to the present disclosure can be configured to be embedded in a target or incorporated into an implantable device. Referring now to FIG. 15, an implantable device 1000 according to an embodiment of the present disclosure is illustrated. The implantable device 1000 is a more specific embodiment of the system 100 described above. Thus, the implantable device 1000 includes some of the same components and operates in the same manner as the system 100 described above. Generally, the implantable device 1000 includes a housing 1002 configured to be embedded in a target. The housing 1002 carries a control module 1004, and the control module 1004 is operably coupled to an optical modulator 1006 via a wired communication. The control module 1004 can be the same as or similar to the control module 102 described above. The optical modulator 1006 includes an activation probe 1008 configured to be disposed within the target mass TM. The probe 1008 has one or more first emitters 1010 configured to emit light of a first wavelength to the target tissue TM. The optical modulator 1006 also includes a plurality of inactivation cuffs 1012 configured to extend around or otherwise be secured to a blood vessel BV coupled to the target mass TM. Each cuff 1012 includes one or more second emitters 1014 configured to emit light of a second wavelength. Thus, the first emitter 1010 may emit light of the first wavelength to activate a photoactivatable agent within the target mass TM, and the second emitter 1014 may emit the second wavelength to inactivate the photoactivatable agent when the photoactivatable agent moves away from the target mass TM through the blood vessel BV.

[0063] Referring now to FIGS. 16 and 17, an implantable device 1100 according to an embodiment of the present disclosure is illustrated. The implantable device 1100 is a more specific embodiment of the system 100 described above. Thus, the implantable device 1100 includes some of the same components and operates in the same manner as the system 100 described above. Generally, the implantable device 1100 is constructed in the form of a capsule and can be implanted percutaneously via an introducer I. More specifically, the implantable device 1100 includes a housing 1102 configured to be implanted into a subject. The housing 1102 carries an optical modulator 1104 and a control module 1106 (FIG. 17). The control module 1106 may be the same as or similar to the control module 102. Similarly, the optical modulator 1104 may be the same as or similar to the optical modulator 104 described above. More specifically, the optical modulator 1104 includes one or more first emitters 1108 configured to emit light of a first wavelength and one or more second emitters 1110 configured to emit light of a second wavelength. The first emitter 1108 and the second emitter 1110 may emit light simultaneously or at different times, or the implantable device 1100 may emit light of a first wavelength and a similar implantable device (not shown) may emit light of a second wavelength. Alternatively, in some embodiments, the first emitter 1108 and the second emitter 1110 may be of the same type of emitter and may be collectively configured to emit light of a first wavelength at a first time and light of a second wavelength at a second different time. In some embodiments, the implantable device 1100 includes one or more sensors (such as sensor 118 shown elsewhere) for sensing physiological parameters and / or parameters related to a photoactivatable agent. The sensors may be disposed adjacent to the first emitter 1108 and the second emitter 1110 or at other locations on or within the implantable device 1100.

[0064] As briefly described above, the operation of system 100 can be modified based on the parameters sensed by sensor 118. More specifically, system 100 can modify the amount of light emitted by optical modulator 104 based on the parameters sensed by sensor 118. Modifying the amount of light emitted by optical modulator 104 can include, for example, modifying the intensity of the emitted light, modifying the duration of light emission, modifying the pattern of light emission (e.g., varying the timing at which light is emitted and not omitted), and modifying the size of the region where light is emitted (even if the intensity per unit area remains constant).

[0065] Sensor 118 can take various forms. For example, one or more sensors 118 can sense parameters related to a photoactivatable agent. FIG. 18 schematically illustrates an exemplary operating sensor 1200 for sensing such parameters. More specifically, activation sensor 1200 is configured to sense the presence and amount of an activated photoactivatable agent within a subject. Sensor 1200 is configured to be disposed internally with respect to the subject. Generally, sensor 1200 includes a waveguide 1202, such as an optical fiber, for transmitting light EL of a first wavelength (which may be referred to as "excitation light" and has, for example, a wavelength of about 475 nm) to phosphor 1204. When receiving light EL of the first wavelength, phosphor 1204 emits light FL of a second wavelength (which may be referred to as "fluorescence" and has, for example, a wavelength of about 515 nm) in the presence of an activated photoactivatable agent AA (determined based on the activated agent itself or a biomarker indicating an activated substance such as calcium ions). Phosphor 1204 emits an amount of light FL of the second wavelength corresponding to the current amount of the activated photoactivatable agent AA. Waveguide 1202 transmits the light FL of the second wavelength emitted by phosphor 1204 back to a sensor that detects and / or measures the amount of light FL of the second wavelength, and system 100 can modify the amount of light emitted by optical modulator 104 (FIG. 1) based on the amount of light FL of the second wavelength transmitted by waveguide 1202.

[0066] FIG. 19 schematically illustrates an exemplary electronic device assembly 1300 for use with an actuation sensor 1200 (FIG. 18). The electronic device assembly 1300 includes a power source or power supply 1302 for providing power to various components of the electronic device assembly 1300. The power supply 1302 may be, for example, the same power supply 110 as described above, or a different device. The power supply 1302 is operably coupled (exemplarily, via wired communication) to a power regulator 1304 that includes one or more low dropout regulators (not shown). The power regulator 1304 is operably coupled (exemplarily, via wired communication) to one or more amplifiers and filters 1306, a controller or microcontroller 1310, and a constant current driver 1311. The amplifier and filter 1306 is operably coupled (exemplarily, via wired communication) to a fluorescence detector or optical sensor 1308. The controller 1310 may be, for example, the same as the controller 106 described above, or a different device. The controller 1310 is operably coupled (exemplarily, via wired communication) to the amplifier and filter 1306 via an analog-to-digital converter 1312. The controller 1310 is also operably coupled to a transmitter or antenna 1314 via a radio 1315. The controller 1310 is also operably coupled (exemplarily, via wired communication) to the constant current driver 1311 via a digital-to-analog converter 1316. The constant current source converter 1311 is operably coupled (exemplarily, via wired communication) to an excitation emitter or light source 1318. The excitation emitter 1318 emits excitation light into the waveguide 1202 of the sensor 1200 (FIG. 18), and the waveguide 1202 transmits fluorescence to the fluorescence detector 1308. The controller 1310 detects the fluorescence received by the fluorescence detector 1308 to determine the presence and amount of an activated photoactivatable agent within the subject, whereby the system 100 can modify the amount of light emitted by the light modulator 104 (FIG. 1).

[0067] Referring now to FIG. 20, a sensor 1400 according to one embodiment of the present disclosure is illustrated. Sensor 1400 is a more specific embodiment of the sensor 1200 described above. Thus, sensor 1400 includes some of the same components and operates in the same manner as the sensor 1200 described above. Sensor 1400 may also be used with the electronic device assembly 1300 (FIG. 19). Sensor 1400 includes a housing 1402 that carries various components, including the excitation emitter 1318 of the electronic device assembly 1300. The excitation emitter 1318 transmits excitation light to the waveguide 1202 (FIG. 18) via a first lens 1404, an excitation filter 1406, a beam splitter 1408, and a second lens 1410. The waveguide 1202 is carried by a mechanical coupler 1411. The waveguide 1202 transmits the excitation light to an opto-load 1412 that includes a phosphor 1204 (FIG. 18). As described above, upon receiving the excitation light, in the presence of an activated photoactivatable agent, the phosphor 1204 emits fluorescence into the waveguide 1202. The waveguide 1202 transmits the fluorescent light to a fluorescence detector 1308 via the second lens 1410, the beam splitter 1408, and an emission filter 1414. The controller 1310 (FIG. 19) detects the fluorescence received by the fluorescence detector 1308 and determines the presence and amount of the activated photoactivatable agent within the subject, whereby the system 100 may modify the amount of light emitted by the optical modulator 104 (FIG. 1).

[0068] FIG. 21 schematically illustrates another exemplary activation sensor 1500 for sensing parameters related to a photoactivatable agent. The activation sensor 1500 can be used instead of, or in addition to, the sensor 1200 (FIG. 18). The activation sensor 1500 is configured to sense the presence, amount, and location of an activated photoactivatable agent within a subject. The sensor 1500 is configured to be disposed internally with respect to the subject. Generally, the sensor 1500 includes a first waveguide 1502, such as an optical fiber, for transmitting excitation light EL to one or more chemical sensors 1504 (two of which are identified). Each chemical sensor 1504 includes a phosphor 1506 that emits fluorescence in the presence of an activated photoactivatable agent AA (determined based on the activated agent itself or a biomarker indicating an activated substance such as calcium ions) when receiving the excitation light EL. Each phosphor 1506 emits an amount of fluorescence corresponding to the adjacent amount of the activated photoactivatable agent AA. That is, the phosphors 1506 are configured to independently emit various amounts of fluorescence. The fluorescence emitted by the phosphors 1506 is filtered by a plurality of ring resonators 1508 (two of which are identified). The ring resonator 1508 drawn with a dashed line indicates a "treatment area" ring resonator configured to be disposed adjacent to the target treatment area of the subject, while the ring resonator 1508 drawn with a solid line depicts a "boundary" ring resonator configured to be disposed along the boundary or outer periphery of the target treatment area. Each ring resonator filters the light emitted by the phosphor 1506 to pass light having a specific frequency and remove light having other frequencies. The filtered fluorescence is received by a second waveguide 1510, such as an optical fiber. The second waveguide 1510 transmits the filtered fluorescence FL, and the system 100 can modify the amount of light emitted by the light modulator 104 (FIG. 1) based on the amount of the fluorescence FL and / or the location information encoded within the fluorescence FL.

[0069] FIG. 22 illustrates the spectrum of the chemical sensor 1504 (FIG. 21). As can be seen from the figure, each chemical sensor emits light at a plurality of frequencies. FIG. 23 illustrates the transmission spectra (i.e., the amount of light that is transmitted and not filtered out) of the “treatment region” ring resonator 1508 (FIG. 21, i.e., the ring resonator 1508 drawn with a virtual line) and the “boundary” ring resonator 1508 (i.e., the ring resonator 1508 drawn with a solid line). FIG. 24 illustrates the spectrum of the fluorescence from the chemical sensor 1504 after being filtered through the ring resonator 1508 and transmitted to the second waveguide 1510 (FIG. 21). As can be seen in FIG. 24, the filtered light is expected to occupy two frequency regions, i.e., a first frequency region that includes the light filtered through the “treatment region” ring resonator 1508 and a second frequency region that includes the light filtered through the “boundary” ring resonator 1508. In this embodiment, the first frequency region is at a lower frequency than the second frequency region, but the activation sensor 1500 can alternatively be configured such that the first frequency region is at a higher frequency than the second frequency region. By measuring the intensity of the filtered light transmitted to the second waveguide 1510 in each of these different frequency regions, the measurement system can separately determine (i) the amount of light emitted by the chemical sensors adjacent to the treatment region, and (ii) the amount of light emitted by the chemical sensors disposed along the boundary or outer perimeter of the target treatment region. In this way, the measurement system can separately determine the amount of the photoactivatable agent AA activated in the treatment region and the boundary region.

[0070] The invention has been shown and described in terms of a preferred design, but the invention may be modified within the spirit and scope of the present disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice within the art to which this invention pertains.

Claims

1. A system for controlling a photoactivatable agent within a subject, comprising: A light modulator operable to emit light of a first wavelength and light of a second wavelength, wherein the light of the first wavelength is configured to activate the photoactivatable agent, and the light of the second wavelength is configured to inactivate the photoactivatable agent; and A controller operably coupled to the light modulator; The controller is operable to cause the light modulator to (1) emit light of the first wavelength, thereby activating the photoactivatable agent, and (2) emit light of the second wavelength, thereby inactivating the photoactivatable agent; A diffractive optical element coupled to the light modulator and configured to receive light from the light modulator and direct the light towards the subject, the diffractive optical element including a plurality of shaped grids, each shape of the plurality of shaped grids including alternating and concentric opaque and transparent shapes; Further comprising an activation sensor operable to determine an amount of the photoactivatable agent activated within the subject; The controller is operably coupled to the light modulator and the activation sensor, and is operable to modify at least one of an amount of the light of the first wavelength and an amount of the light of the second wavelength emitted by the light modulator in response to the amount of the photoactivatable agent activated within the subject determined by the activation sensor.

2. The system of claim 1, wherein the light modulator comprises a first emitter configured to emit light of the first wavelength and a second emitter configured to emit light of the second wavelength.

3. The system of claim 1, wherein the light modulator comprises a plurality of first emitters configured to emit light of the first wavelength and a plurality of second emitters configured to emit light of the second wavelength.

4. The system of claim 3, wherein the plurality of second emitters are arranged to define at least a portion of an outer perimeter, and the plurality of first emitters are disposed within the portion of the outer perimeter.

5. The system according to any one of claims 1 to 4, further comprising a wearable device configured to be fixed to the skin of the subject, wherein the wearable device includes the light modulator.

6. The system according to any one of claims 1 to 4, further comprising a microlens array coupled to the light modulator.

7. The system according to claim 6, wherein the microlens array includes an electrochromic coating.

8. The system according to any one of claims 1 to 4, wherein the controller is operable to cause the light modulator to emit the light of the first wavelength and the light of the second wavelength simultaneously.

9. The activation sensor an excitation emitter operable to emit light of a third wavelength, a phosphor configured to emit light of a fourth wavelength when receiving the light of the third wavelength in the presence of a photoactivatable agent in which the phosphor is activated, and a fluorescence detector operable to detect the light of the fourth wavelength emitted by the phosphor, the system according to claim 1.

10. The system according to claim 9, wherein the activation sensor further comprises an optical waveguide optically coupling the excitation emitter to the phosphor.

11. The system according to claim 9, wherein the fluorescence detector comprises a photodiode.

12. The system according to claim 9, wherein the excitation emitter comprises a light emitting diode.

13. The system according to claim 1, wherein the activation sensor includes a chemical sensor.

14. The activation sensor includes a plurality of chemical sensors and an excitation emitter operable to emit light of a third wavelength, each of the plurality of chemical sensors being a phosphor configured to emit light of a fourth wavelength when receiving the light of the third wavelength in the presence of a photoactivatable agent in which the phosphor is activated, the activation sensor further comprising a fluorescence detector operable to detect the light of the fourth wavelength emitted by the phosphor, the system according to claim 1.

15. The system according to claim 14, wherein the activation sensor further comprises a plurality of ring resonators operable to filter the light of the fourth wavelength emitted by the phosphor.

16. The system according to claim 14, wherein the activation sensor further comprises a waveguide that optically couples the excitation emitter to the plurality of chemical sensors.

17. The system according to claim 14, wherein the activation sensor further comprises a waveguide that optically couples the plurality of chemical sensors to the fluorescence detector.

18. The activation sensor is a first activation sensor, and further comprises a second activation sensor operable to determine a physiological parameter within the subject, and the controller is configured to: in response to the second activation sensor determining the physiological parameter within the subject, further operable to modify at least one of the amount of light of the first wavelength emitted by the optical modulator and the amount of light of the second wavelength. The system according to claim 1.

19. The system according to claim 1, wherein each shape of the plurality of shaped grids includes alternating and concentric opaque and transparent rings whose thickness decreases as the distance from the center of each shape of the plurality of shaped grids increases.

20. The system according to claim 19, wherein the plurality of shaped grids are circular grids or hexagonal grids.

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