Patent Description:
The current paradigm for reducing device related incidence of catheterrelated bloodstream infections (CRBSI), ventilator associated pneumonia (VAP), and urinary tract infections (UTI) utilizes drug or chemical eluding agents that are incorporated into or coated onto the devices used in these procedures. Due to their extensive utilization, many of the antimicrobial and antiseptic drugs used with these devices are showing an increasing incidence of hypersensitivity reactions as well as presensitization within the general population.

<CIT> purports to disclose an optical fiber device including a polymeric optical fiber having a proximal end for coupling to a source of light, and a diffusing region. The polymeric optical fiber includes a core and a cladding around the core. The diffusing region includes a length of the polymeric optical fiber in which the cladding is partially removed to expose the core and in which the exposed core and the remaining cladding have a roughened surface for outwardly diffusing light carried through the polymeric optical fiber. The diffusing region is preferably formed by abrasion, for example by directing a particle jet at the optical fiber while rotating and translating the optical fiber with respect to the particle jet. The particle jet may include microscopic glass beads which roughen the optical fiber core. The density of scattering sites may be varied along the length of the diffusing region to produce a desired light output pattern. The optical fiber device is useful in medical applications, including as a component of catheter or endoscopic systems. <CIT> purports to describe an optical fiber diffuser for emitting light cylindrically along a length of the fiber diffuser with preselected light intensity distributions along the length of the diffuser. The diffuser portion is defined by forming a distribution of scattering centers in a section of the optical fiber core having a modulated index of refraction which acts to couple light radially out of the fiber along the diffuser section. The intensity distribution of light coupled out of the diffuser section of the fiber is controlled by controlling the profile of the modulated index of refraction, namely the coupling coefficient, along the length of the grating. Writing a grating into a multimode fiber provides a method of monitoring transmission in the fiber since some of the light can be coupled out and detected and interrogated. The diffuser devices can be used as sensors, since they also couple light incident on the diffuser into the core where it is transmitted to a detector. <CIT> puports to relate to an assembly for disinfecting/sterilizing surfaces and lumens of a device with a light source which emits disinfecting/sterilizing light. The assembly comprises a device for transporting fluid having a lumen and a connector part at least one light source configured to emit light having disinfecting/sterilizing effect, and a separate unit ; where the light source comprises: a housing comprising a light emitting unit emitting light having disinfecting/sterilizing effect and a connector part. The separate unit comprises: an optical window being transparent for light emitted from the light emitting unit, a first coupling part and a second coupling part, where the first coupling part during use is attached to the connector part of the light source and the second coupling part during use is attached to the connector part of the device, such that the device are in complete extension of the light source with no overlap, and the first coupling part is located at one side of the optical window and the second coupling part is located on the other side of the optical window, when disinfection/sterilization of the device takes place.

<CIT> purports to present Systems, devices, methods, and compositions for providing an actively-controllable disinfecting implantable device configured to, for example, treat or prevent an infection in a biological subject. <CIT> purports to disclose an optical fiber having a cladding layer whose thickness is gradually reduced along the length of the fiber, with a view to controlling irradiation range and quantity.

A need exists for methods and systems that offer advantages to conventional infection control approaches while retaining or enhancing antimicrobial efficacy and extending device patency.

The foregoing needs are met by the present invention, described in the amended claims, wherein an ultraviolet irradiation system includes a medical device having a central lumen with an inner wall, an optical fiber disposed in the medical device and having a longitudinal length, a proximal end, a distal end, and a cladding layer, extending along the longitudinal length from the proximal end to the distal end, and an ultraviolet wave generator, wherein ultraviolet waves generated by the wave generator are dispersed along the longitudinal length of the optical fiber, uniformly from the proximal end to the distal end, to disinfect the central lumen of the medical device. The cladding layer having a varied thickness over the longitudinal length.

In accordance with other aspects of the present invention, the medical device includes a cylindrical wall surrounding the central lumen, and the optical fiber is embedded into the wall.

In accordance with yet other aspects of the present invention, the optical fiber is embedded into the wall in a helical pattern. The core may comprise a PMMA material extruded with a specific proportion of scattering particles compounded into the PMMA material.

In accordance with other aspects of the present invention, surface pitting and solvent voids may be formed in the cladding layer by a chemical abrasion process. In accordance with yet other aspects of the present invention, surface pores may be formed in the cladding layer by a micro abrasion process. Facets in the core may be formed by the micro abrasion process.

In accordance with other aspects of the present invention, the medical device may include an endotracheal tube, a central venous catheter stylet or a foley catheter stylet.

There has thus been outlined, rather broadly, certain aspects of the present disclosure in order that the detailed description herein may be better understood, and in order that the present contribution to the art may be better appreciated.

Ultraviolet light is a highly potent antiseptic and antimicrobial agent. Although most commonly used for sterilization of surfaces, air and water systems, light irradiation may be used as an infection control mechanism in a wide array of disposable in-dwelling and ex-vivo medical devices and disposable materials.

Ultraviolet irradiation offers several unique advantages for medical device infection control. Ultraviolet irradiation can be easily and completely controlled and it is not dependent on materials or manufacturing process variation. The mechanism of action of the irradiation energy is the direct disruption of molecular bonds within the organism's genetic material. Molecular bond energy is typically expressed in units of eV (Electron Volts) and the photonic energy of light is the product of its frequency multiplied by Plank's constant (~<NUM> x <NUM>^-<NUM>^<NUM> * Kg / Sec). Specific organisms can be targeted by adjusting the intensity and frequency of the ultraviolet irradiation. In addition, in vitro experiments have demonstrated a significant safety margin between microbe eradication dose levels and safe human endothelial cell exposures. Moreover, the effectiveness of ultraviolet irradiation as an antimicrobial agent does not diminish in long term indwelling applications.

A relatively narrow band source of light may be used in the irradiation devices described herein. For example, the frequency bandwidth of ~<NUM> with a spectral peak at <NUM> may be used due to a combination of Poly(methyl methacrylate) or PMMA transmissivity, cost, availability and antimicrobial efficacy. This peak frequency corresponds to an energy value range of <NUM> -<NUM>. 6eV which is also the disruption energy associated with the S-H and C-C (Sulfur-Hydrogen and Carbon-Carbon) molecular covalent bonds within the organisms genetic material. The theoretical eradication dose level for Staphylococcus Aureus (SA) bacteria is ~ <NUM>. 3J/cm<NUM>. This value corresponds to an optical energy fluence value of ~80uW/cm<NUM> for an <NUM> hour therapeutic exposure over the surface of the fiber. Experimentally, significantly lower optical fluence values have shown complete inhibition in <NUM> log inoculums of several species, including SA. This may be attributable to the integration of energies associated with the full spectral band of the irradiation source.

The primary components of an ultraviolet irradiation system in accordance with aspects of the present invention are a controllable programmable UV light source, a side emission delivery fiber, and coupling optics to efficiently launch source energy into the delivery fiber. The combination of these components as described herein provides ultraviolet delivery and irradiation into medical devices as an antimicrobial mechanism.

<FIG> illustrates an antimicrobial photonic (AMP) endotracheal tube (ETT) <NUM> having an embedded fiber helix <NUM>. The fiber helix <NUM> may be a spirally formed plastic optical fiber (PMMA) and configured as a molded structure on the surface of the ETT <NUM>, which may be made of a thermoplastic material, such as polyvinyl chloride (PVC). High efficiency ultraviolet side emission is gained by adjusting the helical curvature (pitch) to exceed the optical angle of total internal reflection. Additionally, to compensate for reduced optical power from distal to proximal tube ends, the helical pitch is varied to achieve uniform irradiation over the device length. The fiber helix <NUM> is a permanent and integral part of the ETT <NUM>.

The manufacturing process involves pre-forming of the optical fiber (heating and dwelling at glassification temperatures) over a mandrel (pitch guide). This technique relieves stress within the fiber and facilitates the solvent based PVC overmolding process. A proximal end of the fiber may be mirrored by metallic sputter deposition to increase overall emission efficiency and a distal end may be strain relieved and terminated with a low cost optical connector. A programmable light source <NUM> may be used to generate the ultraviolet radiation using either a single or multiple element non-coherent light emitting diodes (LED) array. LED power may be supplied from a constant current source that can be programmed for specific power levels, "on" durations, or repetitive dose regiments.

<NUM><FIG> illustrates an AMP central venous catheter (CVC) stylet <NUM>. The stylet <NUM> incorporates a length of plastic optical fiber (PMMA) as a stylet to be inserted into a CVC lumen <NUM>. High efficiency ultraviolet side emission may be gained by a combination of chemical solvent and/or mechanical etching of the fiber clad material of the stylet to disrupt the evanescent field. In addition, optical scattering nano-particles may be added to the clad, and the addition of nano-particles to the PMMA core material may also be used to enhance the efficiency of side emissions by altering the distribution of light within the fiber. Additionally, to compensate for reduced optical power along the fiber length, the emission enhancing process can be varied to achieve uniform irradiation along the entire stylet <NUM>. For example, compensation for optical power variation may be achieved by a "Bump" extrusion process where the diameter of the fiber is varied over a specific length. This approach enhances side emission efficiency of the stylet <NUM> by a corresponding increase in the numerical aperture (NA) of the fiber as the diameter diminishes.

The fiber stylet <NUM> may be an independent disposable element that may either be included in a CVC kit or provided separately as needed. The manufacturing process involves a rate controlled exposure of the fiber to an etching medium containing a dispersion of scattering particles. Alternatively, the base PMMA fiber core may be extruded with a specific proportion of scattering particles compounded into the base material. The proximal end of the fiber stylet <NUM> may be mirrored by metallic sputter deposition to increase overall emission efficiency and the distal end of the fiber stylet <NUM> may be strain relieved and terminated with a low cost optical connector. The stylet <NUM> may be introduced into a saline charged CVC lumen <NUM>, for example, by way of Tuohy Borst adapter attached to the luer fitting of an extension line. This connectivity facilitates access to the CVC lumen while preventing luminal fluid discharge.

A programmable light source <NUM> may be used to generate the ultraviolet radiation in the stylet <NUM> using either a single or multiple element non-coherent light emitting diodes (LED) array. <FIG> shows a functional block diagram for a programmable light source <NUM> in accordance with aspects of the present invention. The light source <NUM> may have a user interface <NUM> that includes a liquid crystal display (LCD) and a switch assembly for control of the programmable light source <NUM>. A microcontroller <NUM> may respond to input from the user interface to control the LED constant current controller <NUM>. For example, the user interface <NUM> may be used to program the programmable light source for specific power levels, "on" durations, or repetitive dose regiments. A power source, such as a lithium battery <NUM>, a battery charger circuit <NUM> and a power regulation circuit <NUM> may be included to generate and regulate power for the constant current controller <NUM> in order to provide a constant current to the ultraviolet light engine <NUM>. The ultraviolet radiation generated by the ultraviolet LEDs in the light engine <NUM> are delivered through an optic coupling assembly <NUM>, which may include focusing lenses for collimation of the ultraviolet light delivered to the fiber optic connector assembly <NUM>. A device identification and connection detection mechanism <NUM> may be provided to provide a signal to the user interface <NUM> when the light source <NUM> is properly connected via the fiber optic connector assembly <NUM> to a side emission light fiber.

In accordance with yet other aspects of the present invention, an AMP foley catheter stylet may be similarly formed by incorporating a length of plastic optical fiber (PMMA) as a stylet to be inserted into a catheter lumen. High efficiency ultraviolet side emission may be gained by a combination of chemical solvent and/or mechanical etching of the fiber clad material to disrupt the evanescent field. The addition of optical scattering nano-particles to the clad, and the addition of nano-particles to the PMMA core material may be used to enhance the efficiency of side emissions by altering the distribution of light within the fiber. Compensation for optical power variation may also be achieved by a "Bump" extrusion process where the diameter of the fiber is varied over a specific length. This approach enhances side emission efficiency by a corresponding increase in the numerical aperture (NA) of the fiber as the diameter diminishes.

The fiber stylet may be an independent disposable element that may either be included in a Foley package or provided separately as needed. The manufacturing process of the Foley catheter stylet involves a rate controlled exposure of the fiber to an etching medium containing a dispersion of scattering particles. Alternatively, the base PMMA fiber core may be extruded with a specific proportion of scattering particles compounded into the base material. The proximal end of the fiber may be mirrored by metallic sputter deposition to increase overall emission efficiency and the distal end may be strain relieved and terminated with a low cost optical connector.

The stylet may be introduced into the Foley catheter by a modified Tuohy Borst adapter attached to the port of a secondary lumen or by way of a secondary access port to the Foley central lumen. This connectivity facilitates irradiation of the central Foley catheter lumen while permitting normal urine drainage and collection bag attachment.

A programmable light source <NUM> may be used to generate the ultraviolet radiation in the Foley catheter stylet by using either a single or multiple element non-coherent light emitting diodes (LED) array. LED power may be supplied from a constant current source that can be programmed for specific power levels, "on" durations, or repetitive dose regiments.

In accordance with other aspects of the present disclosure, an AMP Foley catheter or a Urethane Chronic Hemodialysis catheter, for example, may include an embedded side emission fiber. The catheters may incorporate a length of plastic optical fiber (PMMA) permanently into either the webbing structure or a dedicated lumen of the catheters. High efficiency ultraviolet side emission may be gained by a combination of chemical solvent and/or mechanical etching of the fiber clad material to disrupt the evanescent field. The addition of optical scattering nano-particles to the clad, and the addition of nano-particles to the PMMA core material may also be used to enhance the efficiency of side emissions by altering the distribution of light within the fiber. Additionally, to compensate for reduced optical power along the fiber length, the emission enhancing process can be varied to achieve uniform irradiation along the entire fiber.

Compensation for optical power variation may also be achieved by a "Bump" extrusion process where the diameter of the fiber is varied over a specific length. This approach enhances side emission efficiency by a corresponding increase in the numerical aperture (NA) of the fiber as the diameter diminishes. The manufacturing process involves a rate controlled exposure of the fiber to an etching medium containing a dispersion of scattering particles. Alternatively, the base PMMA fiber core may be extruded with a specific proportion of scattering particles compounded into the base material. The proximal end of the fiber may be mirrored by metallic sputter deposition to increase overall emission efficiency and the distal end may be strain relieved and terminated with a low cost optical connector.

A programmable light source <NUM> may be used to generate the ultraviolet radiation in the embedded fiber Foley catheter using either a single or multiple element non-coherent light emitting diodes (LED) array. LED power may be supplied from a constant current source that can be programmed for specific power levels, "on" durations, or repetitive dose regiments.

<FIG> illustrates a chemical abrasion process flow for forming a side emission optical fiber configured for use in the systems and devices described above. A piece of polymer optical fiber (POF) is first cut to a predetermined length at step <NUM> and then loaded into a vertical dipper at step <NUM>. The POF may be configured to have a core layer made of a suitable material, such as PMMA or polystyrene, with higher refractive indices of <NUM> and <NUM> respectively. A cladding layer may be provided made of a silicone resin, or a fluorinated polymer or perfluorinated polymer, for example, having a lower refractive index of approximately <NUM>.

At step <NUM>, the chemical to be used is determined and the dip tube filled. As shown, the component content of the chemical may be derived through a series of checks at step <NUM> in which it is determined whether the chemical comprises, for example, <NUM>% acetone, a <NUM>% acetone and <NUM>% methanol mix, a <NUM>% acetone and <NUM>% methanol mix, or a <NUM>% acetone, <NUM>% aluminum carbonate (Al<NUM>O<NUM>, and. <NUM>% polyvinylidene fluoride (PVDF) mix.

At step <NUM> a number of parameters are determined and set for operation of the vertical dipping machine, including, for example, those shown at <NUM>, which include determining dip distance, deceleration rate, soak time, withdraw ramp or constant, and withdraw acceleration. With the dip tube filled with an appropriate chemical determined at <NUM> and the parameters set at step <NUM>, the vertical dipping machine is activated at step <NUM>. At step <NUM>, the POF is lowered into the dip tube filled with the chemical at the determined deceleration rate and distance. At step <NUM>, the POF is soaked for the predetermined soak time duration. At step <NUM>, the POF is raised from the dip tube. Depending on whether the traverse is determined to be constant or ramped, the rate at which the POF is withdrawn from the chemical bath may be increased or decreased. The acetone removes the POF cladding while also creating micro porosity within the cladding that remains. The rate of cladding removal and porosity size in the cladding are dependent on the dipping machine parameters determined in step <NUM>. For example, the soak time and/or the POF withdraw rate from the chemical directly impact the final cladding thickness and porosity. Accordingly, the rate of acceleration from the chemical bath may be used to taper the cladding thickness from a proximal to distal end of the POF in addition to creating porosity variation. For example, <FIG> is a cross-sectional view of a POF <NUM> illustrating the core <NUM> and cladding <NUM> from a proximal end <NUM> to a distal end <NUM>. The same POF <NUM> is shown three times to illustrate the impact of an increased soak time and/or decreased rate of withdraw on a thickness of the cladding <NUM>. As illustrated by the arrow on the right, with increased soak time and/or a decrease in the rate of withdraw, the cladding thickness decreases and depth of porosity increases from the proximal end <NUM> to distal end <NUM> of the POF <NUM>.

Referring back to <FIG>, with the POF withdrawn from the dipping tube, the POF may be held stationary at step <NUM> for a predetermined amount of time, such as <NUM> minute, to allow the chemical to evaporate from the POF. At step <NUM>, a determination is made whether to perform a repeat dip of the POF. The dipping process described above may be performed again. If a repeat dip is not necessary, the POF may be removed from the dipping machine at step <NUM>. At step <NUM>, the POF is washed in an aqueous bath and dried. As shown in step <NUM>, the washed and dried POF may be trimmed to a desired length. Optical fiber connectors, which may be FC, SC, ST, LC, MTRJ, or SMA type connectors, may be configured onto the POF. The side emission fiber may then undergo an optical inspection prior to being used as described above in one of the various devices.

<FIG> illustrate aspects of a POF <NUM> chemically abraded with an acetone solvent in accordance with the process described above. <FIG> is a cross-sectional view of the POF <NUM> illustrating the core <NUM> and cladding <NUM>. A zoomed portion of the cladding <NUM> is shown to illustrate the surface pitting <NUM> and voids <NUM> that are formed as a result of the chemical abrasion process. <FIG> illustrates a surface view of a portion of the cladding <NUM> with surface pitting <NUM>. The amount of surface pitting <NUM> and voids <NUM> may be closely controlled by the parameters set forth in the dipping machine during the abrasion process. The pitting <NUM> and voids <NUM> in the POF enhance the dispersion of the ultraviolet radiation through side emission.

In accordance with other aspects of the present invention, the acetone solvent may be mixed with a particulate compound, such as aluminum carbonate. As shown in <FIG>, the aluminum carbonate particles <NUM> become embedded in the cladding <NUM> during the abrasion process. In combination with the surface pitting <NUM> and voids <NUM> generated by the acetone, the embedded particles <NUM> may further enhance side emission of the ultraviolet radiation.

<NUM> illustrates a micro abrasion process flow for forming a side emission optical fiber configured for use in the systems and devices described above. A piece of polymer optical fiber (POF) is first cut to a predetermined length at step <NUM> and then loaded into a lathe at step <NUM>. The POF may be configured to have a core layer made of a suitable material, such as PMMA or polystyrene, with higher refractive indices of <NUM> and <NUM> respectively. A cladding layer may be provided made of a silicone resin, or a fluorinated polymer or perfluorinated polymer, for example, having a lower refractive index of approximately <NUM>.

At step <NUM>, the lathe parameters are determined, including, for example, the parameters shown in box <NUM> of RPM, carriage travel distance, carriage traverse profile, and a nozzle distance from the POF. At step <NUM> a number of parameters are determined and set for operation of the micro abrasion machine, including, for example, those shown at <NUM>, which include determining nozzle size, media size, the media, air pressure, and media mixture ratio. In accordance with certain aspects of the present disclosure, a sodium bicarbonate media may be used. The media is used to remove the POF cladding and/or create micro porosity in the cladding and/or the core by being blasted at the surface of the POF.

With the micro abrasion machine parameters and the lather parameters set, the abrasion machine is activated at step <NUM>. Concurrently, at steps <NUM>, <NUM>, and <NUM>, respectively, the micro abrasion element activates, the lathe carriage starts a longitudinal traverse of the POF, and the lathe spins the POF at a specified RPM. As shown in step <NUM>, the media is blasted onto the surface of the POF as the carriage traverses the POF at step <NUM> while the rotational speed of the lathe is maintained at step <NUM>. The speed that the carriage traverses the POF may be controlled, e.g., maintained at a constant traverse speed, or an acceleration or deceleration of the carriage traverse speed may be introduced, depending on the desired properties of the finished POF.

When the carriage reaches the end of the traverse at step <NUM>, all operation of the micro abrasion machine is halted. <FIG> is a cross-sectional view of a POF <NUM> illustrating the core <NUM> and cladding <NUM> from a proximal end <NUM> to a distal end <NUM>. The same POF <NUM> is shown three times to illustrate the impact of an increased number of abrasion passes and/or the blasting aggressiveness of a single pass on the thickness of the cladding <NUM>. As the medium (e.g., sodium bicarbonate) is blasted onto the POF, the cladding <NUM> is slowly abraded. The blasted sodium bicarbonate removes some of the POF cladding <NUM> while also creating micro porosity within the cladding that remains. The rate of abrasion is dependent on the various parameters determined in steps <NUM> and <NUM>, including but not limited to nozzle geometry, air pressure, media mixture, media size, RPM of the POF, carriage traverse rate and nozzle distance from the fiber. As illustrated by the arrow on the right, with increased number of abrasion passes and/or aggressiveness of a single pass, the cladding thickness decreases and the depth and frequency of porosity may increase from the proximal end <NUM> to distal end <NUM> of the POF <NUM>. In addition, as the abrasion process begins, a small number of sodium bicarbonate particles may break entirely through the cladding <NUM> and facet the core <NUM>. The core faceting <NUM> is illustrated in <FIG>. The faceting on the core <NUM> may be increased by both quantity and depth pending the aggressiveness of the operation parameters and/or the number of abrasion passes. As the cladding <NUM> becomes thinner, the faceting effect on the core <NUM> increases.

Claim 1:
An ultraviolet irradiation system comprising:
a medical device having a central lumen with an inner wall;
an optical fiber (<NUM>) disposed in the medical device, the optical fiber having a longitudinal length, a proximal end (<NUM>, <NUM>), a distal end (<NUM>, <NUM>), and a cladding layer (<NUM>, <NUM>) extending along the longitudinal length from the proximal end (<NUM>, <NUM>) to the distal end (<NUM>, <NUM>);
and an ultraviolet wave generator, wherein ultraviolet waves generated by the wave generator are dispersed along the longitudinal length of the optical fiber (<NUM>) from the proximal end (<NUM>, <NUM>) to the distal end (<NUM>, <NUM>), and wherein the ultraviolet waves are uniformly emitted along the longitudinal length of the optical fiber (<NUM>) from the proximal end (<NUM>, <NUM>) to the distal end (<NUM>, <NUM>), characterised in that the cladding layer (<NUM>) has a thickness decreasing from the proximal end (<NUM>, <NUM>) to the distal end (<NUM>, <NUM>).