WO2005049131A1 - Phototherapy device and system - Google Patents
Phototherapy device and system Download PDFInfo
- Publication number
- WO2005049131A1 WO2005049131A1 PCT/US2004/037559 US2004037559W WO2005049131A1 WO 2005049131 A1 WO2005049131 A1 WO 2005049131A1 US 2004037559 W US2004037559 W US 2004037559W WO 2005049131 A1 WO2005049131 A1 WO 2005049131A1
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- WO
- WIPO (PCT)
- Prior art keywords
- buss
- light
- radiation
- emitting devices
- coolant
- Prior art date
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
- A61N5/0603—Apparatus for use inside the body for treatment of body cavities
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1011—Multiple balloon catheters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
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- A61N5/06—Radiation therapy using light
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- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F21—LIGHTING
- F21S—NON-PORTABLE LIGHTING DEVICES; SYSTEMS THEREOF; VEHICLE LIGHTING DEVICES SPECIALLY ADAPTED FOR VEHICLE EXTERIORS
- F21S4/00—Lighting devices or systems using a string or strip of light sources
- F21S4/20—Lighting devices or systems using a string or strip of light sources with light sources held by or within elongate supports
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/03—Automatic limiting or abutting means, e.g. for safety
- A61B2090/033—Abutting means, stops, e.g. abutting on tissue or skin
- A61B2090/036—Abutting means, stops, e.g. abutting on tissue or skin abutting on tissue or skin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
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- A61N2005/002—Cooling systems
- A61N2005/005—Cooling systems for cooling the radiator
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61N5/0601—Apparatus for use inside the body
- A61N5/0603—Apparatus for use inside the body for treatment of body cavities
- A61N2005/0609—Stomach and/or esophagus
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
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- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0662—Visible light
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F21—LIGHTING
- F21Y—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES F21K, F21L, F21S and F21V, RELATING TO THE FORM OR THE KIND OF THE LIGHT SOURCES OR OF THE COLOUR OF THE LIGHT EMITTED
- F21Y2115/00—Light-generating elements of semiconductor light sources
- F21Y2115/10—Light-emitting diodes [LED]
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- H01L2224/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
- H01L2224/26—Layer connectors, e.g. plate connectors, solder or adhesive layers; Manufacturing methods related thereto
- H01L2224/31—Structure, shape, material or disposition of the layer connectors after the connecting process
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- H01L2224/00—Indexing scheme for arrangements for connecting or disconnecting semiconductor or solid-state bodies and methods related thereto as covered by H01L24/00
- H01L2224/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
- H01L2224/42—Wire connectors; Manufacturing methods related thereto
- H01L2224/47—Structure, shape, material or disposition of the wire connectors after the connecting process
- H01L2224/48—Structure, shape, material or disposition of the wire connectors after the connecting process of an individual wire connector
- H01L2224/4805—Shape
- H01L2224/4809—Loop shape
- H01L2224/48091—Arched
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
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- H01L2224/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
- H01L2224/42—Wire connectors; Manufacturing methods related thereto
- H01L2224/47—Structure, shape, material or disposition of the wire connectors after the connecting process
- H01L2224/48—Structure, shape, material or disposition of the wire connectors after the connecting process of an individual wire connector
- H01L2224/481—Disposition
- H01L2224/48151—Connecting between a semiconductor or solid-state body and an item not being a semiconductor or solid-state body, e.g. chip-to-substrate, chip-to-passive
- H01L2224/48221—Connecting between a semiconductor or solid-state body and an item not being a semiconductor or solid-state body, e.g. chip-to-substrate, chip-to-passive the body and the item being stacked
- H01L2224/48245—Connecting between a semiconductor or solid-state body and an item not being a semiconductor or solid-state body, e.g. chip-to-substrate, chip-to-passive the body and the item being stacked the item being metallic
- H01L2224/48247—Connecting between a semiconductor or solid-state body and an item not being a semiconductor or solid-state body, e.g. chip-to-substrate, chip-to-passive the body and the item being stacked the item being metallic connecting the wire to a bond pad of the item
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L2224/00—Indexing scheme for arrangements for connecting or disconnecting semiconductor or solid-state bodies and methods related thereto as covered by H01L24/00
- H01L2224/73—Means for bonding being of different types provided for in two or more of groups H01L2224/10, H01L2224/18, H01L2224/26, H01L2224/34, H01L2224/42, H01L2224/50, H01L2224/63, H01L2224/71
- H01L2224/732—Location after the connecting process
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- H01L2924/10—Details of semiconductor or other solid state devices to be connected
- H01L2924/11—Device type
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- H01L2924/1204—Optical Diode
- H01L2924/12044—OLED
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- H01—ELECTRIC ELEMENTS
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- H01L2924/3025—Electromagnetic shielding
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L33/00—Semiconductor devices having potential barriers specially adapted for light emission; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
- H01L33/48—Semiconductor devices having potential barriers specially adapted for light emission; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof characterised by the semiconductor body packages
- H01L33/62—Arrangements for conducting electric current to or from the semiconductor body, e.g. lead-frames, wire-bonds or solder balls
Definitions
- This invention relates to apparatus and methods for delivering radiation, including delivering radiation to a surface on or within a living body and, more particularly, to apparatus and methods for using light to debilitate or kill microorganisms on or within a body cavity of a patient.
- H. pylori Helicobacter pylori
- pylori can be asymptomatic, in a significant minority of infected people it is associated with serious conditions including gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and gastric lymphoma. H. pylori is believed to be responsible for approximately 90% of all reported duodenal ulcers, 50% of gastric ulcers, 85% of gastric cancer, and virtually 100% of gastric lymphoma.
- H. pylori infection The most common treatment currently available for H. pylori infection is a complex antibiotic regimen involving three or four expensive drugs given over a two-week period. Even with antibiotic treatment, 20% or more of those treated are not cured of their infection. Further, the powerful antibiotics used are not well tolerated by some patients, variously causing allergic reactions, nausea, an altered sense of taste and diarrhea. In addition, antibiotic resistance by this and many other pathogenic organisms is growing rapidly. Up to 50% of H. pylori isolates are now resistant to one or more of the best antibiotics known to cure the infection. No vaccine is yet available for H. pylori, despite years of intensive effort.
- Photodynamic therapy is a light therapy that includes pretreatment with a photosensitizing drug, followed by illumination of the treatment area to kill cells having a high concentration of the drug, which preferentially absorbs light at specific wavelengths.
- a typical application of this method is to debilitate or destroy malignant tumor cells that have preferentially retained the photosensitizing drug, while preserving adjacent normal tissue.
- Direct deactivation or killing of H. Pylori and other microorganisms has been demonstrated using light, without requiring pretreatment with a photosensitizer.
- An alternative approach for developing minimally invasive probes for intraluminal light therapy is to utilize electrically excited light-emitting devices such as light-emitting diodes within a probe.
- electrically excited light-emitting devices such as light-emitting diodes within a probe.
- One problem associated with this approach is that the light-emitting devices confined within an elongated probe produce waste heat when electrically excited, thereby significantly limiting the maximum average light output power achievable from the probe without thermally damaging the light-emitting devices, and without exceeding safe temperatures for exposure of the probe to body tissue at the treatment site.
- the present invention relates to delivering radiation or light to an interior of an object or an organism to effect or facilitate a chemical or biological reaction, including devices and methods for delivering light to the interior of a lumen, to effect a treatment at a wall of the lumen.
- the invention is particularly useful for performing therapeutic medical procedures on the interior of a lumen, for example, the gastrointestinal tract of a living human or animal.
- the invention can also be applied to deliver light to the interior surface of any structure into which the apparatus can be disposed.
- the invention also relates to systems for the diagnosis and treatment of infections within a lumen in a patient.
- One aspect of the present invention is an apparatus for delivering radiation.
- the apparatus includes a flexible shaft having a distal end and a proximal end. At least two internal channels extend along the shaft from the distal end to a location closer to the proximal end and are in fluid communication with each other at a location proximate to the distal end. At least one of the channels is adapted for coupling with a source of a coolant.
- the shaft may be made of a substantially biocompatible polymer.
- the shaft has a circular cross section.
- the apparatus also includes a plurality of radiation-emitting devices disposed within at least one of the channels. At least a portion of the shaft proximate to the radiation-emitting devices is transmissive of at least a portion of radiation capable of being emitted by the plurality of radiation-emitting devices.
- the plurality of radiation-emitting devices are at least partially in contact with the coolant flowing from the coolant source, and the coolant is substantially electrically nonconductive.
- the coolant also may be transmissive of at least a portion of radiation capable of being emitted by the plurality of radiation-emitting devices.
- the plurality of radiation-emitting devices are light- emitting diodes.
- at least one of the radiation-emitting devices may emit radiation substantially within a band of wavelengths that is adapted to treat diseased tissue.
- the band of wavelengths is substantially centered between approximately 400 nanometers and 410 nanometers.
- the band of wavelengths is adapted to modify the rate of a chemical reaction.
- the coolant has a boiling temperature below approximately 45 degrees Celsius.
- the coolant is a liquid selected from the group consisting of fluorinated organic compound, silicone oil, hydrocarbon oil and deionized water.
- at least one of the plurality of radiation-emitting devices includes a coating that provides refractive index matching between the at least one of the plurality of radiation-emitting diodes and the coolant.
- the flexible shaft is transmissive of at least a portion of radiation capable of being emitted by the plurality of radiation-emitting devices.
- the shaft may also include optically scattering material.
- a plurality of light-emitting diodes in the apparatus are arranged in at least one longitudinal array.
- the array includes a first flexible conductive buss and a second flexible conductive buss.
- the first the second buss are substantially parallel and not directly in contact with each other, and at least one of the first and the second buss includes a plurality of convolutions.
- a plurality of platforms is disposed substantially between the first buss and the second buss, and connected to the first buss by a first member and to the second buss by a second member.
- At least one light-emitting diode is disposed on each platform, and each of the at least one light-emitting diode is electrically coupled to the first buss and the second buss.
- the electrical coupling includes at least one electrical lead.
- each of the plurality of platforms has a top surface and a bottom surface and at least one of the plurality of light-emitting diodes is disposed on a top surface while another of the plurality of light-emitting diodes is disposed on a bottom surface.
- the apparatus includes at least two arrays. In still other embodiments, the at least two arrays are substantially parallel to each other or follow substantially parallel helical paths. At least one of the light-emitting diodes in an array may emit light substantially within a band of wavelengths adapted to treat diseased tissue or substantially within a band of wavelengths adapted to modify the rate of a chemical reaction.
- the apparatus includes a flexible shaft having a distal end and a proximal end, a bore extending from a location near the distal end to the proximal end, and an outer surface defining at least one groove extending from a location near the distal end to the proximal end.
- a flexible sheath is proximate to the shaft, for example, surrounding the shaft.
- the sheath and the at least one groove define at least one channel.
- the sheath and the distal end of the shaft define a distal volume, through which the at least one channel and the bore are in fluid communication.
- the apparatus has a substantially circular cross section.
- a plurality of radiation-emitting devices is disposed within the at least one channel.
- the radiation-emitting devices are adapted to be electrically connected to a power source and the sheath is transmissive, at a location proximate the plurality of radiation-emitting devices, of at least a portion of radiation capable of being emitted by the plurality of radiation-emitting devices.
- a source of a coolant is connected to the at least one channel, the coolant being at least partially transmissive of radiation and substantially electrically nonconductive, whereby the coolant source, the at least one channel, the distal volume and the bore comprise a coolant loop.
- the light-emitting devices are cooled through contact with the coolant.
- the plurality of radiation-emitting devices are light-emitting diodes.
- the at least one radiation-emitting device emits radiation substantially within a band of wavelengths adapted to treat diseased tissue.
- the at least one radiation-emitting device emits radiation substantially within a band of wavelengths adapted to modify the rate of a chemical reaction.
- the coolant may be a liquid selected from the group consisting of fluorinated organic compound, silicone oil, hydrocarbon oil and deionized water, and at least one of the plurality of radiation-emitting devices may include a coating substantially providing refractive index matching between the at least one of the plurality of radiation-emitting diodes and the coolant.
- the sheath is made of a substantially biocompatible polymer.
- the sheath, the shaft, or both are transmissive of at least a portion of radiation capable of being emitted by the plurality of radiation-emitting devices, and may contain optically scattering material.
- the plurality of radiation-emitting devices are arranged in at least one longitudinal array.
- the at least one array includes a first flexible conductive buss and a second flexible conductive buss, the busses being substantially parallel to each other and not directly in contact with each other.
- At least one of the first buss and the second buss includes a plurality of convolutions.
- a plurality of platforms are disposed between the first buss and the second buss, the platforms being connected to the first buss by a first member and to the second buss by a second member.
- a radiation-emitting device is disposed on each platform, and each radiation-emitting device is electrically coupled to the first buss and the second buss.
- the electrical coupling may include at least one electrical lead.
- each platform has a top surface and a bottom surface and a radiation-emitting device is disposed on each surface.
- the plurality of radiation-emitting devices are arranged in at least two arrays. The at least two arrays may be parallel and may follow parallel helical paths.
- Yet another aspect of the present invention is an apparatus that includes a first flexible conductive buss and a second flexible conductive buss, the first buss and the second buss being substantially parallel and not directly in contact with each other, at least one of the first buss and the second buss forming a plurality of convolutions.
- a plurality of platforms is disposed between the first buss and the second buss, the platforms being connected to the first buss by a first member and to the second buss by a second member.
- a plurality of electronic devices is disposed on the plurality of platforms, and electrically coupled to the first buss and the second buss.
- the electronic devices may be light-emitting devices.
- the apparatus also includes a flexible shaft that has a distal end and a proximal end, and an outer surface defining at least one groove extending from a location near the distal end to the proximal end.
- a flexible sheath is proximate the shaft, the sheath and the at least one groove defining at least one channel.
- the at least one array is disposed in the at least one channel.
- Still another aspect of the present invention is a system for delivering light.
- the system includes a light-emitting probe.
- the probe includes a flexible shaft having a distal end and a proximal end, at least two internal channels extending from the distal end to a location closer to the proximal end and in fluid communication with each other within the shaft at a location proximate to the distal end, a plurality of light-emitting devices disposed within at least one of the channels, and a plurality of electrical leads adapted for electrically coupling the plurality of light-emitting devices to a source of electrical power.
- the system also includes a coolant system coupled to at least one channel.
- the coolant system provides a coolant for flowing through the at least two channels, the coolant and at least a portion of the shaft proximate to the light-emitting devices being transmissive of at least a portion of light capable of being emitted by the plurality of light-emitting devices.
- the system further includes an electrical power supply coupled to the plurality of electrical leads. The electrical power supply provides a source of electrical power for energizing the plurality of light-emitting devices.
- FIG. 1 is a schematic cross sectional overview of a light-emitting probe system according to the present invention.
- FIG. 2 is a distal end view cross section of light probe shown in FIG. 1.
- FIG. 3 is a perspective view of a light probe of the present invention having four passages for light-emitting devices.
- FIG. 4 is a distal end view cross section of the light probe shown in FIG. 3.
- FIG. 5 is a perspective view of a light probe of the present invention having helical passages for light-emitting devices.
- FIG. 6 is a cross sectional view of another light probe of the present invention.
- FIG. 7 is a perspective view of a flexible light-emitting diode array of the present invention.
- FIG. 8 is an electrical schematic of a series-parallel circuit showing parallel groups of four light-emitting diodes in series.
- FIG. 9A and FIG.9B illustrate a side view of the light-emitting diode array of FIG. 8, and an out-of-plane flexion of the array, respectively.
- FIG. 10A and FIG 10B illustrate a plan view of the light-emitting diode array of FIG. 8, and an in-plane flexion of the array, respectively.
- FIG. 11 is a perspective view of a light-emitting probe of the present invention incorporating the light-emitting array of FIG. 7
- FIG. 12 is a side view of a two-sided light-emitting diode array of the present invention.
- FIG. 13 is a perspective view of another flexible light-emitting diode array of the present invention having transverse positioning members.
- FIG. 14 shows a segmented light-emitting array of the present invention.
- FIG. 15 shows an exemplary segment of the segmented array of FIG. 14.
- FIG 16 is an end view of the segmented array of FIG. 14, centered in a cylindrical passage.
- FIG. 17 shows an example of a three-dimensional lead structure of a segmented array of the present invention.
- FIG 18 is an end view of the segmented array of FIG. 17, centered in a cylindrical passage.
- FIG. 19 shows a phototherapy system of the present invention, deployed in a human gastrointestinal tract.
- FIG. 20 shows a light-emitting probe 650 of the present invention including a positioning means.
- lumen is used herein to mean the interior of a hollow organ in a human or animal body, and more generally to refer to any tubular or hollow item.
- the invention also relates to systems for the diagnosis and treatment of infections within a lumen in a patient.
- the light-generating system 100 includes an elongate light-emitting probe 102, a coolant supply 104 for cooling the probe, and a power supply 106 for energizing the probe.
- the probe 102 includes a flexible shaft 108 having a distal shaft end 110, a proximal shaft end 112 and a bore 114 extending longitudinally through the shaft 108 between the distal shaft end 110 and the proximal shaft end 112.
- the shaft 108 may comprise a flexible material that is electrically nonconductive.
- electrically nonconductive and electrically insulating are used interchangeably herein.
- Examples of materials appropriate for constructing the shaft 108 include natural and synthetic polymers such as polyolefins, fluoropolymers, polyurethanes, polyesters, and rubber products.
- the material of the shaft 108 is also chosen to be optically transparent, translucent or reflective at an optical emission wavelength of the light-emitting probe.
- the material of the shaft 108 is chosen to be compatible with selected liquid coolants discussed hereinbelow.
- the material of the shaft 108 is chosen to be biocompatible, that is, safe for direct contact with living tissue.
- the shaft 108 is made of Fluorinated Ethylene Propylene polymer (FEP).
- the shaft 108 is made of polytetrafluoroethylene (Teflon). FEP and Teflon are trademarks of DuPont.
- a continuous groove 116 extends longitudinally along the shaft 108 from the distal shaft end 110 substantially to the proximal shaft end 112.
- a sheath 118 that may be flexible and transparent closely surrounds the shaft 108, defining a continuous longitudinal channel or passage 120 within the groove 116.
- the sheath 118 has a distal sheath end 122 and a proximal sheath end 124.
- the distal sheath end 122 extends distally beyond the distal shaft end 110 and is closed, defining a plenum volume 126 between the distal sheath end 122 and the distal shaft end 110.
- the passage 120 is in fluid communication with the bore 114 substantially at the distal shaft end 110.
- Fluid communication between the passage 120 and the bore 114 may be provided by the plenum volume 126.
- An interior channel 127 may also be provided to provide fluid communication between the passage 120 and the bore 114.
- the sheath 1 18 preferably comprises a flexible polymeric material that is electrically nonconductive.
- the sheath 118 and the shaft 108 may be fabricated or formed as a unitary part.
- strips of any appropriate shape of material adapted to the shape, width and length of the groove 116 may be secured over the groove 1 16 to form a passage 120.
- a cap or similar item may be secured at the distal shaft end 110 to define a plenum volume.
- Examples of materials appropriate for constructing the sheath 118 include natural and synthetic polymers such as polyolefins, fluoropolymers, polyurethanes, polyesters, and rubber products.
- the material of the sheath 118 is also chosen to be optically transparent, translucent or reflective at an optical emission wavelength of the light-emitting probe.
- the optical properties of the sheath 118 may also be patterned to selectively transmit, scatter, reflect, or absorb light at an optical emission wavelength of the probe 102 as a function of position along the probe 102 or circumferentially about the probe 102.
- the material of the shaft 108 is also chosen to be compatible with selected liquid coolants discussed hereinbelow.
- the material of the sheath 118 is preferably chosen to be biocompatible.
- the sheath 118 is preferably made of Fluorinated Ethylene Propylene polymer (FEP).
- FEP Fluorinated Ethylene Propylene polymer
- the sheath 118 is preferably made of polyethylene.
- one or both of the sheath 118 and the shaft 108 is impregnated with an optically scattering material, is provided with a reflective coating or includes a wavelength-converting material.
- the sheath may also be patterned to provide different optical properties depending on a position along the probe 102.
- the passage 120 and the bore 114 together define a coolant loop within the probe 102.
- each of the bore 114 and the passage 120 is coupled to the coolant supply 104 for flowing an electrically nonconductive liquid coolant through the loop.
- the coolant has optical properties suitable for passing light out of the probe and, for use in medical applications, is preferably chosen to be a room-temperature liquid that is safe for contact with living tissue (a biosafe liquid).
- Examples of coolants suitable for use in a probe of the present invention include fluorinated organic compounds, silicone oils, hydrocarbon oils and deionized water.
- a coolant may also be selected to have a boiling temperature that is lower than a scalding temperature of living tissue. Such a fluid vaporizes before becoming hot enough to scald tissue.
- the coolant is selected to have a boiling temperature lower than about 45 degrees Celsius. Coolants having a boiling point suitable for preventing scalding of tissue are available commercially. For example, 3M Corporation manufactures such a coolant under the trade name Fluorinert.
- coupling between the loop and the coolant supply 104 can be any fluid coupling means appropriate for incorporation into medical apparatus.
- coupling between the loop and the coolant source comprises quick-connect plumbing fittings.
- the coolant supply 124 is a recirculating coolant system that maintains coolant flowing through the loop at substantially a constant temperature.
- coolant flows distally through the bore 114 and proximally through the passage 120.
- coolant flows distally through the passage 120 and proximally through the bore 114.
- a plurality of light-emitting devices 128 is disposed within the passage 120, spaced apart as a longitudinal array.
- the plurality of light-emitting devices 128 is immersed in the coolant within the passage 120 and oriented to direct emitted light out of the probe 102 through the coolant and the sheath 118.
- the plurality of light-emitting devices 128 may also include passive or active electronic sensors, active devices such as acoustic or ultrasonic transducers, radiation-emitting devices, electrically-energized radiation sources such as x-ray sources (which are very short wavelength light sources) or combinations thereof.
- the light-emitting devices may be substituted in whole or in part by the foregoing electronic devices in a probe of the present invention.
- the sheath 118 may be opaque in particular in probes lacking optical sensors or light-emitting devices. In an embodiment, preferably all or substantially all of the sheath 118 near the plurality of light-emitting devices 128 is optically transparent, translucent or reflective at an optical emission wavelength of the light-emitting probe 102.
- Each of the plurality of light-emitting devices 128 is electrically connected in a circuit that is energized through a plurality of electrical leads 130 routed through the passage 120 to the proximal shaft end 112, and coupled to the power supply 106 for energizing the plurality of light-emitting devices 128.
- coupling between the plurality of electrical leads 130 and the power supply 106 can be any electrical coupling means appropriate for incorporation into a medical apparatus.
- the electrical leads 130 are coupled to the power supply 106 by an electrically shielded in-line connector.
- the proximal shaft end 112 and the proximal sheath end 124 are connected to an integrated assembly having both coolant and electrical connectors mounted thereon.
- the electrical power supply 106 is a regulated power supply that regulates light output from the plurality of light-emitting devices 128.
- a signal provided by a sensor mounted within the probe 102 is used to control the power supply 106.
- the effects of light incident on a biological tissue or on a non-living material can depend on the wavelength of the incident light. For example, light in the wavelength range of 360 nanometers (nm) to 650 nm, and preferably in a wavelength range of 400 nm to 410 nm, centered near 405 nm, has been demonstrated to disable or kill H. Pylori bacteria without substantial damage to adjacent healthy tissue.
- the plurality of light-emitting devices 128 can be constructed to emit light within one or more predetermined range of wavelengths (emission band) targeting absorption bands of a selected photosensitizer.
- the plurality of light-emitting elements 128 can comprise light-emitting diodes manufactured to have an emission band centered at a selected infrared, visible or near-ultraviolet wavelength that induces a photochemical reaction in a target material.
- the plurality of light-emitting devices 128 emits light substantially within an emission band operative to disable or kill a bacterium without substantially damaging adjacent healthy tissue.
- the coolant and the sheath 118 transmit at least a portion of the light emitted by the plurality of light-emitting devices 128.
- the coolant may be either substantially transparent to the light or may scatter the light, in the latter case making the coolant appear translucent.
- the sheath 1 18 may be either substantially transparent or translucent in its entirety or substantially solely in locations proximate to the light-emitting devices 128.
- each of the coolant and the sheath 118 is substantially transparent to light emitted by the plurality of light-emitting devices.
- Optically transparent materials for probes of the present invention are preferably selected so as to transmit least approximately 50% and preferably greater than 80% of the light emitted by light-emitting devices in the probe and directed through the transparent materials to exit the probe.
- Light-emitting surfaces of the light-emitting devices may be coated with a transparent film that grades the refractive index at the interface between the light-emitting device and the coolant, thereby reducing reflective losses at that interface.
- the refractive index-grading material may comprise a curable silicone adhesive.
- the refractive index grading material is a silicone encapsulant having a refractive index in the range of about 1.45 to 1.55.
- FIG. 2 is a distal end view of the probe 102 of FIG. 1.
- the bore 114 is shown substantially centered in the shaft 108.
- the plurality of light-emitting devices 128 is maintained substantially centered in the passage 120 by retention on a mounting member 132, thereby providing immersion of the plurality of light-emitting devices 128 in the coolant flowing through the passage 120.
- the probe 102 is shown to be substantially cylindrical in cross section, but probes of the present invention may have any convenient cross section. For example, a probe of the present invention may have an oval or a polygonal cross section.
- FIG. 3 shows a distal end section of another exemplary embodiment of a probe 150 of the present invention.
- the probe 150 is similar in structure to the embodiment of the probe 102 illustrated in FIGS. 1 and 2, but the probe 150 includes four passages 152 distributed circumferentially between a shaft 154 and a sheath 156.
- the shaft 154 has a distal shaft end 158 and the sheath 156 has a distal sheath end 160 that is closed.
- a plurality of light-emitting devices 162 is disposed in each of the four passages 152.
- the shaft 154 includes a longitudinal bore 164 that is in fluid communication with each of the four passages 152.
- the probe 150 may be configured for coolant to flow distally through the bore 164 and proximally through each of the four passages 152.
- the probe 150 may alternatively be configured for coolant to flow distally through each of the four passages 152 and proximally through the bore 164.
- the four passages 152 and the bore 164 are preferably dimensioned so as to provide a substantially equal distribution of coolant flow among the four passages.
- FIG. 4 is a distal end view of the probe shown in FIG. 3.
- the plurality of light- emitting devices 162 in each of the four passages 152 is preferably maintained substantially centered in the each of the four passages 152 by retention on a mounting member 166, thereby providing immersion of the plurality of light-emitting devices 162 in the coolant.
- a probe of the present invention may include any number of passages and corresponding pluralities of light- emitting devices disposed therein.
- a probe of the present invention includes a plurality of light-emitting devices disposed in each of six passages circumferentially distributed around a shaft.
- FIG. 5 illustrates an embodiment of a distal end section of another probe 200 of the present invention.
- the probe 200 includes a shaft 202 having a distal shaft end 204 and a longitudinal bore 206.
- the probe also includes a sheath 208 and at least one helical passage 210 defined between the sheath 208 and the shaft 202 for receiving a plurality of light-emitting devices 212.
- the probe 200 is illustrated with two helical passages, but a probe of the present invention may include any number of helical passages, each with a corresponding plurality of light-emitting devices. Other than including helical rather than longitudinal passages, the probe 200 may be of similar construction to the other embodiments of probes described previously.
- FIG. 6 illustrates a distal section of another embodiment of a light-emitting probe 250 of the present invention.
- the probe 250 includes a flexible tube 252 preferably polymeric having a distal end 254 and a proximal end 256.
- the tube 252 has a first longitudinal internal channel or passage 258 in fluid communication with the proximal end 226.
- the tube 252 also has a second longitudinal internal passage 260 substantially parallel to the first passage 258.
- the second passage is in fluid communication with the proximal end 256.
- the first passage 258 is in fluid communication with the second passage 260 at a junction 262 within the tube 252.
- the first passage 258 and the second passage 260 are adapted at the proximal end 256 for coupling to an external coolant source for flowing a coolant through the first 258 and second passage 260.
- One or more light-emitting device 264 is disposed in one or both of the first internal passage 258 and the second internal passage 260.
- a plurality of electrical leads 266 electrically connects the one or more light-emitting device 264 through the proximal end 256 to an external electric power source for energizing the one or more light-emitting device.
- the one or more light-emitting device 264 may be one or more light-emitting diode.
- the one or more light-emitting device 264 is a plurality of light-emitting diodes in a spaced-apart longitudinal array along at least one of the first internal passage 258 and the second internal passage 260.
- the tube is at least partially transmissive of light emitted by the one or more light- emitting device 264 either in whole or at locations proximate to the one or more light-emitting device 264.
- the tube is biocompatible.
- Liquid-cooled probes of the present invention can be constructed to produce high light output power in small diameter packages.
- one light-emitting probe of the present invention 5 mm in diameter and having four passages for arrays of light-emitting diodes longitudinally spaced one millimeter apart and operating in a wavelength band near 405 nm has an approximate output power substantially equal to or greater than one watt per centimeter of probe length.
- a light-emitting probe of the present invention having a radius of substantially 5 millimeters produces light having an optical power of approximately five watts per centimeter of probe length.
- a plurality of light-emitting devices for inclusion in a flexible, light-emitting probe of the present invention can be configured as a unitary longitudinal array of light-emitting devices for assembly into the probe, or can be configured in segments.
- FIGS. 7 through 13 and the discussions thereof illustrate examples of unitary light-emitting arrays for use in conjunction with the probes illustrated in FIGS. 1 through 6 and the discussions thereof, as well as with other probes.
- FIG. 7 shows an embodiment of a portion of an elongate light-emitting diode array 300 of the present invention.
- the array 300 includes a first flexible, electrically conductive buss 302 and a second flexible, electrically conductive buss 304 disposed opposite the first buss 302.
- first buss 302 and the second buss 304 are positioned substantially parallel, but are not in electrical contact with one another.
- the first buss 302 and the second buss 304 define a plane 306 and an axis 308 in the plane.
- the first buss 302 has a first buss top surface 310 defined here as being above the plane 306 and a first buss bottom surface 312 below the plane 306.
- the second buss has a second buss top surface 314 above the plane 306 and a second buss bottom surface 316 below the plane 306.
- Each of the first buss 302 and the second buss 304 includes a plurality of longitudinally spaced-apart convolutions 318.
- first buss 302 and the second buss 304 are described as being positioned substantially parallel to each other, in an alternative embodiment the first buss 302 and the second buss 304 may be substantially coplanar, while not being substantially parallel or in electrical contact to each other. In another embodiment, first buss 302 and the second buss 304 may be in relative close proximity to each other, while not being substantially parallel, coplanar or in electrical contact to each other.
- a plurality of electrically conductive platforms or islands 320 are spaced apart along the axis 308 between the first buss 302 and the second buss 304.
- Each of the plurality of islands has an island top surface 322 above the plane 306 and an island bottom surface 324 below the plane 306.
- the first buss 302, the second buss 304 and the plurality of islands are fabricated from a single planar strip of a metal.
- the metal is copper.
- Each of the plurality of islands 320 is preferably connected to the first buss 302 and the second buss 304 through at least one flexible hinge member 326.
- the at least one hinge member 326 may be discontinuous and may comprise a flexible curable adhesive.
- One of a plurality of light-emitting diodes 328 is electrically and mechanically mounted to the island top surface of each of the plurality of islands 320.
- the plurality of light- emitting diodes 328 may be mounted using soldering, an electrically conductive epoxy, or any mounting means compatible with the materials and structure of the array 300.
- the plurality of light-emitting diodes 328 is mounted at an orientation to direct emitted light in a direction generally away from the plane 306.
- a plurality of flexible electrical leads 330 electrically interconnect the plurality of light-emitting diodes 328 in an electrical circuit between the first buss 302 and the second buss 304.
- the first buss 302 is electrically connected as a cathode and the second buss 304 is electrically connected as an anode.
- the electrical circuit is a series-parallel circuit wherein groups of electrically series-connected light-emitting diodes of the plurality of light-emitting diodes 328, are electrically connected in parallel between the first buss 302 and the second buss 304.
- FIG. 8 shows schematically a series-parallel electrical circuit 350 between a cathode buss 352 and an anode buss 354.
- the circuit 352 includes groups of four light-emitting diodes 356 electrically connected in series, each of the groups 356 electrically connected in parallel between the cathode 352 and the anode 354.
- each group of light-emitting diodes 356 in each group of light-emitting diodes 356 may be varied, and each group can include one or more light-emitting diodes 356.
- Each of the light-emitting diodes 356 in each group of light-emitting diodes 356 is considered to be electrically connected to the first buss 302 or the second buss 304 either directly or indirectly.
- FIG. 7 The array 300 of FIG. 7 is flexible about the axis 308.
- FIGS. 9A and 9B illustrate flexibility of the array 300 out of the plane 306.
- FIG. 9A illustrates a side view of the array 300 without flexion.
- the plurality of flexible electrical leads 330 which flex easily with flexion of the array 300, are not shown in FIGS. 9A or 9B.
- FIG. 9B illustrates a side view of the array 300 in flexion out of the plane 306. Flexion of the array 300 out of the plane 306 comprises flexion of the first buss 302, the second buss 304, and the at least one flexible hinge member 326 (not visible in FIGS. 9A and 9B).
- FIGS. 10A and 10B illustrate flexibility of the array 300 in the plane 306.
- FIG. 10A illustrates the array 300 in plan view, without flexion.
- the plurality of flexible electrical leads 330 which flex easily with flexion of the array 300, are not shown in FIGS. 10A or 10B.
- FIG. 10B illustrates a plan view of the array 300 in flexion in the plane 306.
- Flexion of the array 300 in the plane 306 comprises extension or compression of the at least one the plurality convolutions 318 along at least one of the first buss 302 and the second buss 304, along with flexion, expansion or compression of the at least one flexible hinge member 326.
- FIG. 11 illustrates an embodiment of a flexible probe 360 of the present invention incorporating the light-emitting array 300.
- a flexible shaft 362 having a shaft axis 364 has four longitudinal grooves 366, each configured for mounting the light-emitting array 300.
- a sheath 368 closely surrounds the shaft 362. The in-plane and out-of-plane flexibility of each array 300 enables the flexible shaft 362 to be bent in any direction about the shaft axis 364 without damaging any of the arrays 300. Flexibility is improved through the structure of the light- emitting array 300, which can be referred to as an "open frame" structure.
- FIG. 12 shows a side view of an embodiment of a two-sided light-emitting array 400 of the present invention.
- the two-sided array 400 resembles the array 300 of FIG. 7 with the exception that the two-sided array 400 of FIG. 11 additionally may accommodate light-emitting diodes 402 mounted to the island bottom surface 324 of each of the plurality of islands 320.
- a corresponding plurality of flexible electrical leads 404 electrically interconnect the complementary plurality of light-emitting diodes 402 in an electrical circuit between the first buss 302 and the second buss 304.
- FIG. 13 shows an embodiment of a portion of an elongate light-emitting diode array 450 of the present invention that has an electrical buss structure similar to the embodiment illustrated in FIG. 7, but wherein electrically conductive islands for mounting light-emitting diodes are positioned out of the plane defined by the busses, and include transverse positioning members.
- the array 450 includes a first flexible, electrically conductive buss 452 and a second flexible, electrically conductive buss 454 disposed opposite the first buss 452.
- the first buss 452 and the second buss 454 are substantially parallel to one another, defining a plane 456 and an axis 458 in the plane.
- the first buss 452 has a first buss top surface 460 defined here as being above the plane 456 and a first buss bottom surface 462 below the plane 456.
- the second buss 454 has a second buss top surface 464 above the plane 456 and a second buss bottom surface 466 below the plane 456.
- Each of the first buss 452 and the second buss 454 preferably includes a plurality of longitudinally spaced-apart convolutions 468.
- the plurality of convolutions 468 imparts flexibility of the array 450 in the plane 456. Flexibility of the first buss 452 and the second buss 454 impart flexibility of the array 450 out of the plane 456.
- a plurality of electrically conductive islands 470 are preferably spaced apart along the axis 458 bridging the first buss 452 and the second buss 454.
- Each of the plurality of islands has an island top surface 472 and a island bottom surface 474.
- the first buss 452, the second buss 454 and the plurality of islands 470 are all made of copper.
- the island bottom surface 474 of each of the plurality of islands 470 is connected to the first buss top surface 460 through a first hinge member 475 which is preferably flexible.
- the island bottom surface 474 of each of the plurality of islands 470 is connected to the second buss top surface 464 through a second hinge member 476 which is preferably flexible.
- Each of the first 475 and the second hinge member 476 may comprise a flexible curable adhesive.
- One of a plurality of light-emitting diodes 478 is electrically and mechanically mounted to the island top surface of each of the plurality of islands 470.
- the plurality of light- emitting diodes 478 may be mounted using soldering, an electrically conductive epoxy, or any mounting means compatible with the materials and structure of the array 450.
- the plurality of light-emitting diodes 478 is mounted at an orientation to direct emitted light in a direction generally away from the plane 456.
- a plurality of flexible electrical leads 480 electrically interconnect the plurality of light-emitting diodes 478 in an electrical circuit between the first buss 452 and the second buss 454.
- first buss 452 is electrically connected as a cathode and the second buss 454 is electrically connected as an anode.
- the plurality of islands 470 also position the array 450 when it is disposed in a passage of a light-emitting probe.
- FIG. 14 shows an embodiment of a section of a segmented light-emitting array 500 of the present invention.
- the segmented array 500 includes a plurality of light-emitting segments 502 structurally and electrically interconnected by a plurality of flexible electrical leads 504.
- the plurality of flexible electrical leads 504 interconnects the plurality of light-emitting segments 502 in electrical parallel.
- the plurality of flexible electrical leads 504 comprises longitudinal convolutions along the segmented array.
- An exemplary segment 506 of the plurality of light-emitting segments 502 is shown schematically in FIG. 15.
- the exemplary segment 506 includes two electrical busses 508 that provide electrically parallel connections to the plurality of electrical leads 504.
- the segmented light-emitting array 500 may include any number of light-emitting diodes within each segment of a plurality of segments 502. In another embodiment, each segment of the plurality segments 502 includes one light-emitting diode.
- the plurality of electrical leads 504 also serves as a plurality of positioning members to physically center the segmented array 500 within an internal passage of a light-emitting probe of the present invention.
- FIG. 16 is an end view of the segmented array 500 of FIG. 14.
- Each of the plurality of light-emitting segments 502 is substantially centered in a passage 512 by the plurality of flexible electrical leads 504.
- the passage 512 has a circular cross section.
- the passage 512 has a polygonal cross section having an even number of vertices for orienting the segmented array 500.
- the passage 512 includes longitudinal features for registering the plurality of electrical leads 504, thereby orienting the segmented array 500 within the passage 512.
- FIG. 17 shows an exemplary embodiment of a segmented light-emitting array 550 of the present invention including a plurality of light-emitting segments 552 interconnected by a plurality of flexible electrical leads 554 configured as a three-dimensional structure.
- FIG. 18 is an end view of the segmented array 550 of FIG. 17.
- Each of the plurality of light-emitting segments 552 is substantially centered in a passage 556 by the plurality of flexible electrical leads 554.
- the passage 556 has a circular cross section.
- the passage 556 has a polygonal cross section having an integral multiple of four vertices for orienting the segmented array 550.
- the passage 512 includes longitudinal features for registering the plurality of electrical leads 504, thereby orienting the segmented array 500 within the passage 512.
- Embodiments of segmented light-emitting arrays of the present invention may be physically flexible through flexion of the plurality of flexible electrical leads that interconnect light-emitting segments.
- the flexible electrical leads also may provide flexibility for a segmented light-emitting array by compression or extension of individual leads between adjacent light-emitting segments, in a manner similar to in-plane flexion of the plurality of convolutions 318 of the electrical busses 302, 304 shown in FIG. 10B.
- FIG. 19 shows an embodiment of a phototherapy system 600 of the present invention.
- the phototherapy system 600 includes a light-emitting probe 602 for delivering light to the interior of a body lumen 604 (shown as a human stomach in FIG. 19).
- the phototherapy system 600 also includes a control unit 606 that provides electrical power and coolant for the probe 602.
- the control unit 606 also includes a user interface 608 for controlling the probe 602.
- the phototherapy system 600 may also include a balloon catheter 610 for guiding the probe 602 into the body lumen. The balloon catheter maintains a minimum distance between the probe 602 and a wall of the lumen 604 to limit the maximum intensity of light from the probe 602 reaching a treatment site.
- the balloon catheter 610 may be a multi-balloon catheter. Both the catheter 610 and the probe 602 may be controlled (inflated, deflated) through the user interface 606, or the catheter 608 may be controlled through a separate interface (not shown in FIG. 19).
- An embodiment of a light-emitting probe of the present invention may include means to maintain a minimum distance from a wall of a lumen or for centering in a lumen.
- FIG. 20 illustrates an embodiment of a light-emitting probe 650 of the present invention including a positioning means.
- the probe 650 includes a probe body 652 having a distal end 654, a proximal end 656, a length therebetween and an outer surface 658 along the length.
- the outer surface 658 includes a reversibly inflatable member 660 surrounding the probe body 652 along at least a portion of the length.
- the inflatable member 660 is preferably circumferential and can be inflated or deflated through a longitudinal tube 662 adapted for connection at the proximal end 656 to an external inflation device providing a gaseous or a liquid working fluid.
- the longitudinal inflation tube 662 may be located external to the outer surface 658 or may be a longitudinal passage within the probe body 652.
- the inflatable member inflates to a substantially predetermined working diameter.
- the inflatable member is an elastic balloon.
- the light-emitting probes and systems disclosed herein have many advantages, including but not limited to advantages related to liquid cooling.
- Liquid cooling of light-emitting diodes may enable these devices to output approximately four to ten times their nominal factory- specified light power without overheating.
- an individual light-emitting diode having a manufacturer's specification of a maximum light power output of 12 milliwatts in air may be operated continuously at a light output power of approximately 120 milliwatts using liquid cooling.
- This increase in light output may enable a probe of the present invention to be used to treat a dramatically larger surface in a lumen, or to similarly decrease a treatment time, relative to known probes that are either uncooled, passively cooled, or air-cooled.
- Liquid cooling of light-emitting probes that incorporate these energy-consuming, active devices also may dramatically enhance patient safety over what can be achieved using other cooling means.
- An exemplary embodiment of a medical procedure performed according to the present invention is the treatment of H. Pylori infection of the human stomach.
- Steps in an H. Pylori treatment procedure may include setting up a light-emitting probe for use. Setting up the probe may include attachment to a power source and a coolant source, calibration of the probe's light emission, and evaluation of the probe's condition and history to ensure patient safety and efficacy of the procedure.
- the physician inserts an endoscope into the patient's stomach and performs a diagnostic endoscopy.
- a guidewire may be placed in a biopsy channel of the endoscope and into the stomach, and the endoscope may be removed, leaving the guidewire in place.
- the light-emitting probe placed in a catheter that may be a balloon catheter, is introduced into the stomach over the guidewire, which may then be removed, leaving the probe and the catheter in place in the stomach.
- One or more balloon of the catheter may be inflated, positioning the probe in the stomach, and the probe may be turned on to deliver a therapeutic dose of light to the stomach wall.
- the dose may be a predetermined, timed dose, or the dose may be measured and controlled during the light exposure using feedback from one or more sensor that may be incorporated into the probe.
- the one or more balloon is deflated and the probe is withdrawn from the stomach.
- the probe may then cleaned and disinfected, for example, using glutaraldehyde, in preparation for use in another procedure.
- the probe includes a mechanism or electronics to determine its remaining useful functional life.
- Examples of non-medical applications of light probes disclosed herein in lumens include internal disinfection of pipes and ventilation ducts, rapid curing of internal coatings such as epoxy repairs of pipes, chemical cross-linking of polymeric surfaces to reduce susceptibility to chemical damage or wear, and photochemical deposition of optical or electronic materials within confined spaces.
- a probe to be used in a specific application may be designed to include light-emitting elements that emit light in a predetermined wavelength band for accelerating specific target chemical reactions for the application. For example, near ultraviolet light is used in the automotive industry and in and other industries to cure paint rapidly without thermal damage to the paint or an underlying part.
- the enhanced physical flexibility of embodiments of light-emitting diode arrays disclosed herein may also be advantageous.
- the structure of the arrays enables the arrays to be flexed in any direction about a longitudinal array axis.
- Known flexible arrays of light-emitting diodes are built on substrates that restrict flexibility in the substrate plane. Flexibility can be especially important, for example, in high-output probes that include circumferentially-distributed arrays of light-emitting diodes, where the arrays are oriented at a range of angles about their respective axes within the probe.
- the structure of arrays also facilitates contact between the light-emitting diodes and a coolant in a liquid-cooled probe, for optimal heat transfer.
- Embodiments of arrays disclosed herein can be applied advantageously not only to liquid-cooled probes, but to any type of radiation-emitting probe, or probes utilizing other electrical devices.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pulmonology (AREA)
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- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Radiation-Therapy Devices (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
Abstract
Description
Claims
Priority Applications (4)
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JP2006539824A JP2007511280A (en) | 2003-11-14 | 2004-11-10 | Apparatus and system for phototherapy |
EP04810702A EP1696996A1 (en) | 2003-11-14 | 2004-11-10 | Phototherapy device and system |
AU2004291071A AU2004291071A1 (en) | 2003-11-14 | 2004-11-10 | Phototherapy device and system |
CA002545922A CA2545922A1 (en) | 2003-11-14 | 2004-11-10 | Phototherapy device and system |
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US10/878,649 US7261730B2 (en) | 2003-11-14 | 2004-06-28 | Phototherapy device and system |
US10/878,648 | 2004-06-28 | ||
US10/878,649 | 2004-06-28 |
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PCT/US2004/037559 WO2005049131A1 (en) | 2003-11-14 | 2004-11-10 | Phototherapy device and system |
PCT/US2004/037846 WO2005049127A1 (en) | 2003-11-14 | 2004-11-12 | Intra-cavity catheters and emthods of use |
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PCT/US2004/037846 WO2005049127A1 (en) | 2003-11-14 | 2004-11-12 | Intra-cavity catheters and emthods of use |
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EP (3) | EP1689492A1 (en) |
JP (3) | JP2007511280A (en) |
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- 2004-11-10 EP EP04810690A patent/EP1689492A1/en not_active Withdrawn
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Also Published As
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US20050106710A1 (en) | 2005-05-19 |
JP2007511279A (en) | 2007-05-10 |
JP2007511280A (en) | 2007-05-10 |
US20050104059A1 (en) | 2005-05-19 |
US20070123957A1 (en) | 2007-05-31 |
US7449026B2 (en) | 2008-11-11 |
CA2545922A1 (en) | 2005-06-02 |
EP1696992A1 (en) | 2006-09-06 |
EP1696996A1 (en) | 2006-09-06 |
CA2545932A1 (en) | 2005-06-02 |
US7135034B2 (en) | 2006-11-14 |
AU2004291071A1 (en) | 2005-06-02 |
AU2004291070A1 (en) | 2005-06-02 |
WO2005049138A1 (en) | 2005-06-02 |
CA2545920A1 (en) | 2005-06-02 |
AU2004291100A1 (en) | 2005-06-02 |
US20050131500A1 (en) | 2005-06-16 |
WO2005049127A1 (en) | 2005-06-02 |
US7261730B2 (en) | 2007-08-28 |
EP1689492A1 (en) | 2006-08-16 |
US20080015661A1 (en) | 2008-01-17 |
JP2007511286A (en) | 2007-05-10 |
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