UV pathogen eradication

Abstract

1. A method and device for enhancing the effectiveness of UV light germicidal (UV wavelengths between 200 nm and 340 nm) transmitted onto or through a surface of a human or device, whether manual, automated, or high-volume, by at least one of the following steps: a) increasing the controllable output power of the UV-emitting device, including the use of a high-power UV laser or direct placement of a UV light source; b) improving the efficiency of the UV germicidal effect by placement of the UV-emitting device, including the use of a uniform output side-emitting fiber or remote placement directed at the surgical site, an otoscope-type handheld device directing UV light at an infected orifice, biofilm destruction, and fluorescent marking of pathogens; and c) providing protocols for various pathogen eradication enhancement applications, including tissue removal to increase depth of penetration, the use of aspiration needles to access pathogens, site sterilization to enhance cancer remission, and in situ sterilization of implants.

Description

[Technical Field]

[0001] This application claims priority from U.S. Provisional Patent Application No. 63 / 535,427, filed August 30, 2023, and is a continuation-in-part of U.S. Provisional Patent Application No. 18 / 097,367, filed January 16, 2023, which was filed April 29, 2021, and issued January 17, 2023, and is a continuation-in-part of U.S. Provisional Patent Application No. 63 / 017,407, filed April 29, 2020, and No. 63 / 044, filed June 26, 2020. This application is a continuation-in-part of U.S. patent application USSN 17 / 244,860, now U.S. Patent No. 11,554,187, which takes priority from U.S. Provisional Application No. 63 / 149611, filed February 15, 2021, and U.S. Provisional Application No. 63 / 139294, filed January 19, 2021, the disclosures of which are incorporated herein by reference.

[0002] The present invention relates primarily to methods and devices for remotely enhanced eradication of pathogens by UV light, and more particularly to eradication of pathogens by UV light in or on medical instruments and non-traumatic eradication of pathogens by UV light in or on human or animal bodies. Specifically, the present invention further relates to UV-transmitting pathogen eradication parameters, components, and applications involving operational feedback of preparation and effectiveness, and more particularly to transmission through collimating lenses, laser UV sources, pathogen sites, and preparation of transmissive devices coupled with eradication feedback in various sterilization or sanitization settings. [Background technology]

[0003] The parent patent application disclosed devices and methods for effectively eradicating pathogens, such as viruses, bacteria, and cancers (defined as pathogens), primarily through the remote application of UV light. Such UV light was specifically exemplified as coming from an LED UV light source (although other light sources were also described) through a transmission medium to infected areas, such as within the biopsy channel of an endoscope and within the human body, particularly with an embodiment using an optical fiber transmission medium. The specific route of eradication involved disrupting the DNA / RNA of pathogens (or cancer cells) at the molecular level, completely or nearly completely eliminating the pathogen, or significantly reducing its presence to alleviate the undesirable condition, without or with minimal physical trauma to cancer-bearing organs or healthy cells. However, such eradication effects were limited in their efficient use by considerations such as the application time and power of the applied UV light, the lack of effective feedback, the skill required for application, and limitations imposed by minimizing the depth of penetration of the UV light.

[0004] In further discussion below, the term "pathogen," as used herein, is defined to refer to harmful and / or toxic elements whose DNA / RNA are targeted for destruction, specifically viruses, bacteria, cancers (which are not technically pathogens but are toxic and have DNA / RNA), mold and mildew, and other microorganisms. For purposes of the inventions disclosed herein, the term "pathogen" also includes cells and tissues that are healthy in themselves but are in excess or in an inappropriate biological location, the excess of which results in a harmful condition. Additionally, healthy cells that are currently benign but may become toxic and develop due to their proximity to unhealthy cells, such as cancer cells or viruses and bacteria, are similarly defined herein as "pathogens" or "pathogenic" for purposes of destruction with UV light. Microorganisms and small insects that are susceptible to UV light due to reduced harmful activity are further included within the term "pathogen."

[0005] The term "eradication" as used herein refers to the inactivation of harmful and / or toxic elements by destruction of the DNA / RNA contained in these elements, accompanied by cleavage or alteration of the helical bonds of the DNA / RNA components. As used herein, the terms "disinfection," "sanitization," and "sterilization" are used interchangeably to refer to medically acceptable purification. The term "sterilization," when so indicated, is an FDA-recognized term for a total or log6 or greater reduction in pathogens.

[0006] As used herein and in the parent application, the terms "transmission" and "transmission medium(s)" of UV light refer to acting as a medium to transport a sufficient acceptable power output of UV inactivating energy to a pathogenic or potentially pathogenic site, including viruses, bacteria, cancer, and other known or otherwise defined pathogens. This term includes optical fibers, liquid light guides, light pipes, and optical lenses and lens systems specifically configured to collimate (essentially parallel light beams), focus, or otherwise act like fibers in transmitting destructive UV light from a UV source through other lenses, lens combinations, or lens and fiber combinations, transporting the light along its collimating or focal length and directing it toward the pathogen site. This is in contrast to simple transparent media, such as glass or clear plastic sheets used protectively in flashlights and the like, which simply allow light to pass through. The term "acceptance angle" is used generically with respect to all transmission media and refers to the angle or direction at which light, particularly UV light of a specified wavelength, is successfully introduced into the transmission medium for its transmission. The terms "energy" (power x time) and "power" (energy / time) are used interchangeably herein. The term "focusing" in this and the parent applications has the meaning of technical optical control, such as with a lens, or the general meaning of directing transmitted light within a small area, depending on the context. The term "collimating" means substantially maintaining the diameter of a light beam over a predetermined, relatively short distance while maintaining power until gradual dissipation. The term "reasonable period" used in conjunction with the duration of UV light pathogen eradication is a function of the specific application of pathogen eradication, reasonable economic or medical urgency, and the severity of the pathogen infection. Thus, sterilization of non-biological devices such as endoscopes may be longer (depending on the necessary processing requirements) than that required for sterilization of invasive medical procedures. A reasonable period for medical procedures such as cancer treatment may be longer than that for viral or bacterial treatment. Generally, without specific limitation, a reasonable period should typically not exceed 30 minutes for each pathogen eradication site, but is usually much shorter.Unless otherwise indicated, the term "site" as used herein refers to a single pathogenic or suspected pathogenic area exposed to UV light. As used herein, the term "complete" should be interpreted as "substantially complete" unless otherwise indicated.

[0007] While the prior applications have shown and demonstrated the reality of effectively delivering UV-C light at effective concentrations with sufficient power to eradicate pathogens in a reasonable time in a variety of settings in difficult or inaccessible areas, or at accessible sites, more effective uses and devices, more applications, and practical operational feedback have yet to be developed and implemented. Summary of the Invention

[0008] In view of the above, it is an object to provide methods and devices for increasing the effectiveness of UV light germicidal (UV wavelengths between 200 nm and 340 nm, most specifically the UV-C range between 250 nm and 285 nm, with peak effectiveness for DNA destruction at approximately 265 nm and 220 nm, which is considered safe for surface use only, but has essentially no penetration depth) and pathogen eradication by at least one of the following steps (among others): a) increasing the controllable output power of the UV emitting device; b) increasing the efficiency of the UV germicidal effect through the placement of the UV emitting device; and c) providing protocols for various pathogen eradication enhanced applications.

[0009] It is a further objective to use a laser UV light source with controlled characteristics to provide controlled, increased power within a DNA / RNA-destroying UV wavelength (most specifically centered around 266 nm, although other wavelengths in the UV-C range, such as 261 nm and 254 nm, are available and useful) and power range to eradicate pathogens before traumatic ablation or surgical cutting of tissue begins, optionally using at least some means of light diffusion to use a minimal level of ablation to remove dead pathogens or cancer cells. Lasers with UV-transparent media are known, but to the best of our knowledge, they have not been commonly used for sterilization and have been constructed and utilized for ablative purposes such as surgical ablation, general etching, or spectroscopic analysis.

[0010] It is a further object to provide a relatively high output power UV, particularly UV-C light emitting laser that can be coupled to or coupled to a transmission medium, such as a transmission fiber or other transmission medium, including lenses and lens systems, in an effective yet low-cost construction, making it useful in general sanitization or sterilization applications. The small beam diameter of the UV laser output also allows even lower output powers to be effectively used in very flexible fibers in the 100 micron or smaller diameter range. The small beam diameter also allows for the use of auxiliary illumination light-carrying fibers and the inclusion of camera elements for direct observation or recording of the sterilization site.

[0011] Another objective is to utilize the controlled, increased power of UV laser light and a very high-output UV LED or similar high-output power light source in combination with a side-emitting optical fiber with a gradient of light output and a substantially uniform power output along the side. Side-emitting fibers coupled with UV LED power, such as those disclosed in U.S. Patent Publication No. 2021 / 0122667, have demonstrated pathogen kill. However, this publication discloses a relatively low-power LED UV light source (which decreases with distance from the UV source) with microwatt output that requires well over 30 minutes to eradicate pathogens and only kills pathogens from the side about 8 inches. This is a highly inconsistent and unpredictable output, making it difficult to achieve effective pathogen sterilization in a reasonably predictable time. However, while significantly increasing UV output power, full-length fibers (typically 500-600 mm for a bronchoscope biopsy channel) or another suitable length can be fabricated to effectively fit fully into the biopsy channel of an endoscope with a uniform power output in the range of a few milliwatts. The UV light emission from its proximal to distal end is sufficient to rapidly kill pathogens within the exposed area, resulting in sterilization of the entire channel and a highly predictable pathogen eradication effect. With modifications, as described below, the entire side-emitting fiber can be made with an essentially uniform UV light side-emitting output with a relatively high pathogen kill power.

[0012] It is yet a further object to increase the efficiency of UV-emitting devices by using a lens transmission medium for relatively short-distance UV light transmission, particularly collimated transmission (or light transmission focusing, or a combination of collimation and focusing), while destroying pathogens in partially accessible areas of the human or animal body, such as in or near respiratory, digestive, or excretory openings. Alternatively, collimated (and / or focused) UV light pathogen destruction can be utilized in surgical procedures involving body incisions and to protect against common pathogens, such as MRSA (especially during surgical procedures), and SSIs that are difficult to eliminate with antibiotics or common sterilization methods. Due to its destruction of DNA / RNA, UV light is effective against any pathogen that contains DNA / RNA, including those that are resistant to other inactivation and sterilization methods.

[0013] The goal is to provide non-invasive soaking of the surgical site with directional and pathogen-removing UV light before, during, and after the surgical procedure to prevent MRSA staph infections and potential causes of sepsis that are not easily eliminated by normal antiseptic procedures and to maintain an acceptably sterile surgical site.

[0014] The objective is to provide a collimating lens with parameters that concentrate UV-C light as a transmission medium and extend its reach with more consistent and uniform pathogen eradication power in applications requiring only a power level that maintains a short distance. The collimating lens may be embodied as a lens in a penlight, otoscope, or other short-range pathogen eradication device, including, for example, treating bacterial infections of the oral or nasal cavity, hand hygiene, combing for head lice, sterilizing CPAP tubes, suppressing bacterial pathogen growth in refrigerators, and sanitizing cutting boards and food preparation areas. Because collimated light substantially maintains power density over the length of collimation, UV light from the light source can be placed at a distance (such as outside the surgical tract) while maintaining pathogen-killing effectiveness.

[0015] A relatively short-range, yet stable UV-C energy output that is uniform over a given distance before divergence through a collimating lens or lens array system finds application in sterilization devices, such as sterilization boxes for medical instruments, instruments, or tools, particularly during surgical procedures, to quickly sterilize these tools and instruments for reuse during surgery. These devices, instruments, and tools come in all shapes, sizes, and shapes, making uniformly and effectively sterilizing them challenging. The short-range, multidirectional light helps maximize the impact of effective UV sterilization light. While the gradual divergence occurs at an optically measurable distance from the light source, depending on the lens dimensions and parameters, sufficient concentrated UV-C energy can be effectively distributed across the diverging UV-C light for additional distances.

[0016] Collimation "transport" of light is understood to mean the delivery of substantially uniform pathogen-killing light over a pre-designed range of significant distances with minimal divergence. Generally, "transport" is the direction of light (not necessarily collimated), but should have the predetermined purpose or effect of directing or shaping the divergence of the beam. In contrast, "travel" of light is non-collimating, with substantially or virtually unlimited divergence, even through a transparent medium such as flat glass.

[0017] For another purpose, the surgical site may also optionally be bathed in light of other selected wavelengths with known parameters and procedures, causing bacteria to fluoresce and be more easily and effectively targeted in situ in real time, thereby providing real-time feedback with pathogen visualization and / or pathogen eradication efficacy to verify efficacy and enhance effective pathogen control and eradication.

[0018] It is yet another object to provide a pathogen treatment protocol to enhance pathogen eradication, such as by including eradication by sequential DNA / RNA disruption of surface pathogens followed by ablative removal of dead cells and tissue to increase effective UV light penetration and reach to underlying tissues.

[0019] Another objective is to avoid limitations on penetration depth through protocols involving surface treatments that help prevent the spread of surface pathogens. Internal reaming and enlargement of the access lumen is similarly possible with a UV-light-transmitting aspiration needle carrier. Once the access lumen is formed, convenient means such as aspiration and / or irrigation may be available to remove dead cells. Dead cell removal may also be achieved by phagocytic scavengers, but this convenient means, while useful, may be limited by the length of time required for effectiveness. Robotic or automated repetitive manipulations following pre-mapped manipulation paths are more effective at adequately covering the DNA / RNA destruction site.

[0020] Another goal to enhance pathogen eradication is achieved by making the pathogen site, such as cancerous tissue or the tumor site itself, more permeable to light penetration by increasing tissue transparency through known "tissue ablation" procedures, particularly by removing light-blocking pigments and light-scattering lipids with selected solvents, resulting in greater UV penetration depth, particularly useful for in vivo treatments.

[0021] Yet another object is to provide protocols and structures for UV light to effectively sterilize the surfaces of implants and implant leads in situ within the body without the need for surgical removal of the implant or its leads.

[0022] Another objective is to increase the degree of cancer remission by superficial UV treatment, particularly at cancer sites that are removed as part of a surgical procedure, and to provide a pathogen treatment protocol that is similarly useful for routine treatment after surgery. Prophylactic prevention of cancer can also be achieved by superficial treatment of potential cancer sites, such as the pancreas, stomach, and bladder.

[0023] As another goal for increasing power output for sterilization, under appropriate conditions, one or more UV LEDs or other miniature UV light sources can be placed directly into a sufficiently large volume insertion device, such as a catheter or the biopsy channel of an endoscope. The movably housed miniature UV light source, such as a UV LED, is appropriately oriented to impinge UV light directly on pathogens within the insertion device, thereby providing increased UV light power without the need for a transmission medium with coupling losses and attenuation.

[0024] Another objective for increasing the efficient use of transmitted UV light relates to automation and computer-generated data, including the initial determination of actual available UV light power by means such as a power integrating measuring element (integrated with or separate from the UV light source).

[0025] In this regard, determining available UV power levels, combined with controlled minimum and maximum dose level determinations based on application distance, pathogen type, power level, and DNA / RNA destruction efficiency, results in an automated, reproducible level of effective UV light energy delivered. An April 16, 2020, IEEE Tech Talk Semiconductors Optoelectronics study and presentation on the effects of deep UV light on pathogens, presented by Seoul Viosys and written by Samuel K. Moore, titled "Ultraviolet-LED Maker Demonstrates 30 Second Coronavirus Kill," provides rough criteria for determining the UV light parameters (wavelength, application distance, applied power, and duration) required to have a destructive effect on pathogens. The study found results from the direct (not transmitted) output of a suboptimal 275 nm (compared to 265 nm) LED onto viral cells (coronaviruses) and concluded that the virus was effectively killed in 30 seconds with an output power of 20 mW (i.e., 600 mJ of energy) at a distance of 3 cm and an output beam angle of 120°. As a result of the inverse square law, the closer the distance, the more dramatically the applied effective power intensity increases. The parent application cited extensive prior art tables with detailed descriptions of hundreds of viral and bacterial pathogens and the amount of UV light treatment required for their eradication. These and other tables can be used in ad hoc determinations, whether manual or automated, of the parameters required for eradication of specific pathogens.

[0026] For non-biological disinfection applications, a still further objective to increase the efficiency and reliability of utilizing UV light for pathogen eradication is by including controlled and timed surface application of UV to pathogen-infected areas (or areas suspected of infection) and pre-treatment to enhance UV light impingement on pathogen-infected surfaces, particularly with biofilm disruption.

[0027] A further objective for increasing the efficiency of UV light utilization is to provide a feedback decision loop, whereby the application of appropriate UV light for pathogen eradication is controlled by real-time feedback of the degree of pathogen eradication depending on the degree of pathogen infection requiring sterilization.

[0028] Yet another objective for efficient UV light efficiency lies in automating the disinfection of pathogen-infected surfaces with controlled movement of the UV light source along the surface at an effectively determined speed, and application of controlled power levels and distances between the light source and the pathogens.

[0029] Another object is to utilize a small diameter aspiration needle to deliver UV optical fibers to almost any part of the human body in vivo to perform UV light disinfection treatment there, and to provide preparation materials for tissue removal and the like to such parts.

[0030] Yet another objective for efficient sterilization of items in high volume procedures is the objective of large scale automated sterilization of devices such as pipettes, hypodermic syringes, etc. that must be used under medically sterile conditions.

[0031] Another objective is to accommodate devices and protocols or additional sanitization or sterilization applications, including pathogen eradication, and dental and surgical site settings.

[0032] It is understood that the above objectives and goals are merely illustrative and in no way exhaustive or limiting.

[0033] As used herein, the terms "electrical power" and "energy" are used interchangeably in terms of pathogen-killing effectiveness. More specifically, however, energy output is the (cumulative) amount or dose of energy required to kill or inactivate a pathogen, and is described in units of joules, millijoules, or microjoules. Power is simply the rate of power output emitted from a light source, using units of watts, milliwatts, or microwatts. Time, when directed at a pathogen or biological entity, is the duration of the directed power output emitted from the light source to kill or inactivate the pathogen or biological entity, and is used in the cumulative effect of power to provide a measure of the total energy applied to the pathogen or pathogenic site.

[0034] Biological entities targeted for eradication include microorganisms in general, viruses, bacteria, fungi and / or ringworm, tumors, cancers, cysts, etc., but also cells or tissues that are not yet harmful but may become harmful later, e.g., cysts or growths that may become malignant, and small insects such as lice, whose harmful activity can be destroyed by UV light treatment.

[0035] Embodiments of the methods herein for enhancing the pathogen eradication effect of UV light at wavelengths between 200 nm and 340 nm in a pathogen-infected area include methods comprising at least one of the following steps:

[0036] The controllable output power of the UV light source emitting device is increased within and directed into hard-to-access pathogen-containing areas or areas requiring concentrated UV energy. Either direct placement of the UV light source within the area or directed transmission of UV light from the UV light source is provided. The direct or transmitted light maintains sufficient power to substantially eradicate pathogens in the pathogen-containing area through DNA / RNA destruction.

[0037] Before, during, and optionally after the surgical procedure, UV light is targeted to the surgical site by directional transmission to maintain a substantially pathogen-free environment during the surgical procedure. In another embodiment, UV light is directed through and transmitted onto infected openings to sterilize.

[0038] To increase the depth of penetration of UV light, the pathogen infection site is made susceptible to significant UV light penetration while eradicating the pathogen by: It makes the pathogen site more permeable to the penetration of UV light. Alternatively, pathogen-infected sites are separated from non-infected sites by: Utilizing UV light pathogen eradication to form a pathogen eradication barrier between pathogen-infected and non-pathogen-infected sites; or The repeated steps of pathogen eradication of infected areas and removal of the pathogen-eradicated areas make the pathogen-infected sites more susceptible to significant UV light penetration and expose additional pathogen-infected sites to UV light.

[0039] Increasing the applied UV output power Generally, in one embodiment, the present invention involves increasing input and output UV light power, particularly UV-C light, from the typically low single- and double-digit milliwatt output power practically available from readily available UV LED light sources to high-output UV light powers of triple-digit milliwatts or more by using lasers emitting light in the UV spectral range. Lasers currently exist in the 266 nm UV range, with output powers exceeding 1 watt. Such lasers are typically very expensive and are primarily used for high-power ablation purposes, and occasionally for tissue dissection applications, depending on the available power. These lasers are effectively indirectly coupled to optical fibers (direct coupling poses the problem of degradation of high-power fibers) for control in precisely positioning the output laser light for ablation or dissection cutting, particularly for corneal reshaping and ophthalmic surgery. Due to their inherent characteristics and short beam diameter, they have generally not been considered, constructed, or configured for sterilization purposes, where a large area is required for any useful or effective sterilization. Therefore, widely dispersed light sources such as direct LEDs and lamps have been utilized almost exclusively for such purposes. In this application, laser light characteristics require a minimum beam diameter to be properly coupled into a transmission medium, such as an optical fiber, through an acceptance angle to maintain power, but the output from the transmission medium is then specifically diffused, expanded, or dispersed to increase contact with pathogens and effectively destroy a wider area. UV lasers, particularly UV-C lasers such as the existing 261 nm or 266 nm or other UV pathogen or cancer-inactivating wavelengths, provide greater energy power output for greater flexibility in pathogen eradication applications with shorter durations and greater effectiveness. When properly optically coupled to a transmission medium, such as an optical fiber (as well as lenses and collimating lenses, or devices containing a UV light-transmitting medium), UV-C lasers enable the effective, controlled, and directed introduction of UV-C light into difficult-to-access areas of the body. These areas include various organ tissues and organs, such as the brain, breast, lungs, pancreas, and other body parts, such as bone and blood. Heat sinks or other adjustments may be required for the protection or use of optical fibers with pulsed lasers that generate high peak power.

[0040] A power output in the range of approximately 100 mW to 200 mW is considered a reasonable transition level between the traumatic destructive ablation and incision levels of 266 nm lasers and the lower, non-traumatic molecular level DNA / RNA destruction of UV-C, although the transition range may vary depending on UV source parameters and pathogen region characteristics.

[0041] Proper transmission coupling of laser light to an optical fiber involves various parameters of the laser light characteristics. These include the beam quality (typically, values ​​below 1.5 are more useful for coupling efficiency), M 2 These include the determination of the beam diameter relative to the fiber diameter, as well as the destructive heat considerations of pulsed lasers and the inherently high peak power of lasers. 2 Beam quality helps allow more usable light to enter the optical fiber without the need to further increase the peak power to maintain the desired output power through the optical fiber that would otherwise be required to enter the fiber core.

[0042] UV laser design configurations using coupled fibers (or other transmission media) should include excipients as needed to minimize the effects of high heat generation due to extended or short use of the coupled fiber. Continuous-wave UV lasers are desirable laser systems for their consistent, stable power output with minimal heat buildup; however, such lasers currently generally have higher cost, size, weight, and bulk, and generally lower output power. UV-C lasers can be configured with multiple pulsed or continuous-wave laser outputs to produce pathogen-eradicating UV wavelengths (such as 261 nm and 266 nm) and can further be configured with a single frequency and narrow linewidth. In some embodiments, such lasers involve the use of harmonic frequency conversion, using crystals such as BBO (beta-barium borate) and / or optically known crystals to convert from one wavelength to 261 nm or 266 nm, or other wavelengths in the UV DNA / RNA-destroying range, to achieve the desired UV output energy results.

[0043] Alternatively, laser diodes at UV DNA / RNA disruptive wavelengths (typically UV-C in the 200 nm to 285 nm range, with an optimal disruptive wavelength of approximately 265 nm) can be directly coupled to a transmission medium such as a mirror, optical lens, lens, or optical fiber, allowing for greater initial laser energy and ultimately more effective pathogen eradication energy.

[0044] Frequency doubling of 525 nm, 532 nm, or other wavelength lasers by direct conversion with BBO crystals can be used to achieve wavelength outputs of 261 nm or 266 nm, or other UV-destroying wavelengths, either pulsed or continuous-wave UV energy output. Narrow linewidths are preferred when frequency converting through nonlinear crystals such as BBO crystals for optimal UV conversion efficiency.

[0045] Optical fibers used in lasers can be specially treated to avoid burnout, especially when used with pulsed lasers with instantaneous high-power pulses. Side-emitting fibers typically cannot be used effectively to sterilize medical device channels, such as biopsy channels. Such fibers have been disclosed for use with relatively low-power LEDs (such as those cited above) with very low power outputs in the microwatt range, requiring very long exposure times (minimum 30 minutes, typically up to several hours). Furthermore, the power output along the side of such fibers has a variable power intensity that rapidly decreases with distance from the power source; fibers longer than about 8 inches (approximately 200 mm) have little or no output at the distal end. Meanwhile, endoscopic biopsy channels are typically much longer (e.g., 500 mm to 600 mm in bronchoscopes), and such fibers cannot efficiently reach and sanitize the entire length of the endoscope. Higher power allows even the distal end of a side-emitting UV-transmitting optical fiber to emit sufficient output power to eradicate pathogens for a more reasonable period of time, until it is long enough to effectively access the entire length of the biopsy channel.

[0046] An additional advantage of using lasers is their ability to emit very small diameter beams, which can be effectively directed into small-core optical fibers with diameters of 50 μm, 100 μm, or even smaller. These smaller-core fibers have greater flexibility, allowing for tighter bend radii, reducing the likelihood of breakage and improving maneuverability inside difficult or inaccessible areas, including endoscope channels and other curved geometries, including those inside the human or animal body. To minimize fiber damage that can result from the high-energy peak power pulses typical of pulsed laser designs, continuous-wave configurations are preferred when lasers are used in conjunction with smaller-core diameter fibers. Alternatively, shielding elements such as glass sleeves can be used to minimize such fiber damage.

[0047] In one embodiment, a smaller-core optical fiber compatible with UV lasers is inserted into a hollow, fine aspiration needle with a diameter of less than 1 mm. Fine aspiration needles, commonly used in EUS (endoscopic ultrasound), are delivered through an endoscope instrument channel and inserted into the bile duct of the pancreas to disrupt and destroy intraductal papillary mucosal neoplasia (IPMN), benign cysts, and cysts containing potential cancer precursors, and to prevent the formation of cancer in the pancreas. Non-limiting examples of other use embodiments include superficial, but difficult to target or reach cancer or cancer precursors, including, but not limited to, ovarian cysts, polyps, lymph nodes, and intestinal metaplasia in the gastric mucosa, commonly found in the antrum of the gastric mucosa.

[0048] In an alternative embodiment, the UV transmitting optical fiber itself provides a transparent needle end treatment for direct penetration and UV transmission into the tissue site.

[0049] High-power UV light sources, such as the UV lasers mentioned above, as well as UV LEDs with high power output and die size / fiber connection compatibility, can also be used to compensate for the non-uniform UV light output and exponential loss over distance of prior art side-emitting fibers. Microdots of black ink are formed during printing using a procedure similar to that known in the printing arts (known as "stochastic screening"). In this innovation, laser-formed microdots of light-penetrating holes are formed in the cladding, herein, to the depth of the fiber core. These microdot holes, along with cladding transparency, are generated with varying concentrations at points along the length of the cladding fiber to control the degree of UV light output and power. More microdot holes are formed at the distal end of the fiber compared to the proximal end, with a gradient of microdot concentration decreasing toward the proximal end. As a result, with this configuration and sufficient UV power, the final light transmitted at the end of the fiber is configured to provide a compensatory transparency gradient, so that the light side-emitted through the laser microdot holes has an inverse power output variation, i.e., the light output power at the end of the fiber closest to the light source has the lowest power emissivity, and the emissivity increases with distance from the light source. Thus, the strongest light emission fraction is at the distal end of the fiber farthest from the power source, and the weakest light emission fraction is at the proximal end of the fiber closest to the UV light source. With proper placement, the power output along each side can thereby be substantially uniform, or can be provided with a predictable available power output.

[0050] This readjustment of the optical output power can be used to compensate for otherwise increasing attenuation at the distal end. With this configuration, the entire length of the optical fiber can be fabricated with substantially uniform side emission along its entire length. While this results in a fiber with as much absolute side emission as possible, another advantage is that the fiber can be easily positioned within a pathogen-infected region, such as a biopsy channel, and remain stationary without requiring significant longitudinal movement. The higher-power UV laser light compensates for the blocked region from side emission, resulting in useful and uniform (or predictable) side-emission optical output power. This eliminates or minimizes fiber movement procedures, such as timed fiber removal or insertion, with its dwell time uncertainties and potential manual errors. To compensate for the loss of fiber core protection due to the array of protective polymer microdot additions, a UV-transparent outer layer can be used to surround the fiber with its microdot holes.

[0051] In another embodiment, in non-biological areas, such as the instrument or biopsy channel of an endoscope (e.g., a 4 mm diameter colonoscope) with a cross-sectional area greater than approximately 12 mm, output power can be increased by eliminating losses inherent in light collection and transmission; UV LEDs (generally with lower power output) with slightly smaller cross-sectional dimensions can be inserted directly into such areas, allowing full power LEDs (unattenuated by connection to a transmission medium) to be utilized for direct eradication of pathogens. While effectively small LEDs suitable for direct insertion generally have lower power output, the elimination of significant transmission losses with low-power UV LEDs more than compensates for the significant transmission power losses of high-power LEDs. UV LEDs on controller PC boards have been miniaturized to the extent that the diagonal dimension of the UV LEDs with PC boards is less than 3 mm. This allows them to be placed directly into the instrument channel of larger endoscopes, such as colonoscopes with long diameter instrument channels, typically 4 mm or larger. LEDs in such configurations are most effectively positioned along the length of the channel, with UV light directed toward the channel walls. A triangular configuration of three UV LEDs arranged to emit light at a 120 degree angle, alternately facing the channel wall, works to provide full 360° coverage of the channel wall for complete sterilization. These arrangements are exemplary only, and various numbers and arrangements of LEDs are possible depending on the area and volume available.

[0052] In a further area, in embodiments related to effectively high UV output power, optical lens transmission media can be utilized in UV light application devices, such as handheld otoscope-style configurations, that direct collimated UV light over short distances directly into orifices such as the nostrils or mouth and throat, or remotely into excretory areas even when positioned outside the orifices. Alternatively, an incision can provide access to an internal body site requiring sterilization. Light transmission through a collimating lens is more efficient due to lower transmission losses and more effective UV light power output. Using such directional high UV power devices, the surgical site, including the patient, and any surgical incision site itself can be safely and comprehensively sanitized before, during, and after surgery, eliminating even the most difficult-to-remove MRSA staphylococcus pathogens with rapid site sanitization. The collimated UV light is directed from outside the immediate surgical area without interfering with the surgery, and is directed only to the immediate surgical area where surgical personnel are wearing protective gloves and the directed UV light does not spill into unprotected areas. Germicidal UV-C light typically has little penetration depth, making it a safe and highly effective surface disinfection treatment against surface pathogens such as staphylococcal infections, MRSA, and other SSIs, thereby readily reducing the incidence of sepsis. Collimated light, in contrast to optically focused light, maintains a substantially constant intensity power output / unit area over the collimation distance, thereby effectively increasing the distance over which the light source can be placed without significant loss of delivered power.

[0053] Increased distance from the light source leads to increased light divergence, which proportionally offsets the effectiveness of UV disinfection or inactivation. Distance further attenuates UV light energy, resulting in less concentrated energy intensity, longer pathogen inactivation times, and potentially uneven and inconsistent pathogen destruction. Collimation of UV light using the methods and structures described herein functions to reduce divergence, even in the absence of visible perception of collimation of invisible UV-C light, with the associated elimination or minimization of distance variables. By using collimating optics to "transport" UV light along a determined length of minimal divergence, UV energy output can be maintained more predictably and stably, allowing for more consistent and uniform inactivation of a given pathogen within the collimation range, regardless of any perceptible light.

[0054] Collimation distance is generally a function of lens diameter; the larger the lens diameter, the longer the length of effectively uniform power and the longer the distance over which light remains substantially effectively collimated before dispersion and dissipation increase. It is understood that divergence always occurs, even from zero inches to 10 inches, but the collimating lens reduces or slows down the degree of divergence, thereby maintaining uniform, effective pathogen-killing power over a longer distance. The greater the dissipation, the less power is effectively exerted against pathogens and the longer it takes to eradicate them before they become essentially ineffective.

[0055] Indeed, a concern with longer inactivation times is that, while UV inactivation energy generally accumulates when directed toward a pathogen, excessive exposure distances can result in insufficient UV inactivation energy to destroy the pathogen in a timely manner, potentially allowing the pathogen to actually develop some resistance to UV eradication. Thus, the extended duration that may be required as a result of excessive distance between the UV light and the pathogen may allow resistance to UV eradication to develop in the absence of an adequate kill rate. As a result, rather than all pathogens being killed, some may mutate into harmful forms.

[0056] The use of the collimating structures disclosed herein mitigates this drawback by removing the distance variable from the inactivation equation, allowing for non- (or minimally) divergent light output over a defined, usually short, distance, while maintaining a constant or relatively consistent intensity of sufficient eradication energy throughout the entire collimating range. Because different distances are required to sanitize a contoured device, sanitization times vary, with some areas sanitizing before others. Other areas may still be in the process of being sterilized when UV-C light is prematurely blocked, resulting in incomplete sanitization. The collimating structures and configurations described herein result in more consistent pathogen inactivation regardless of distance location within the collimating range. Thus, the same or similar UV energy output is delivered to the entire pathogen site. For example, whether the pathogen site is 5 inches away or 8 inches away (a typical collimating distance with a collimating lens up to 2 inches in diameter, but not limited to the size of a 2-inch diameter lens), ensures more reliable and predictable sanitization of the entire device. The effective, but more divergent light may continue for additional useful distances depending on the retention of concentrated energy and pathogen susceptibility to UV-C light.

[0057] In biological applications, a small diameter LED can be placed directly inside the body in close proximity to the pathogen, and a collimating lens can be used to increase the effective power and reach of the UV output within a limited area. For example, the instrument channel of an endoscope can be provided with a collimating lens as an end cap, and a UV LED can be inserted directly into the instrument channel to a fixed position (or within a movable range) in optical alignment with the collimating lens, providing a power-conserving, collimated UV light output toward the pathogen. Similar body-inserted devices, such as catheters, can be used to achieve this effect.

[0058] In another embodiment, a comb-like transmission medium is provided that can be drawn through a person's hair to eliminate lice or nits. Alternatively, a UV light emitting penlight-type device is used with a comb-like attachment to separate the hair.

[0059] In a further embodiment, the fiber optic cable includes a 100 um core fiber for UV, a bundle fiber capable of carrying the camera sensor image, and an additional fiber capable of carrying white illumination for display. This allows for penetration into areas of the body such as IPMNs, lymph nodes, and bronchioles with actual visual capture capability and optionally including UV to inactivate problematic biological entities such as cancer. The bundled fiber optic assembly, if thin enough, can be inserted into an aspiration needle, such as an EUS, to penetrate inaccessible sites, including the pancreas.

[0060] Examples of short-range applications of the transmission media collimating lenses or lens systems described herein include: Emergency / medical sterilization environments for short-distance applications, · Throat, nose, cold, or ear infections, including ear tubes. · Infection of cuts, blisters, or wounds. · Ulcers caused by diabetes or other diseases. · Localized but hard-to-reach skin cancers or surgical or superficial cancers that may develop a scab, for example. The hand sanitization device is separate from or integrated into the hand drying or blower device. · Inactivation of drug-resistant pathogens, including MRSA, used to prevent surgical site infections (SSIs). Industrial sanitizing tools for cleaning surfaces, subsurfaces, or hard-to-reach areas. o military environment, · Sterilization and / or inactivation of biological agents on and off the battlefield. Treating infected wounds or other infections. o general environment; · Sanitizing hard-to-reach spaces such as bathrooms, kitchens, basements, attics, drains, ducts, or pipes.

[0061] In a further embodiment, a UV-C radiation mechanism, such as a penlight-like device, is used to target pathogen activity. In an in vivo environment, such as application to the human or animal body, UV-C light is targeted to the surface layer or tissue, with application to an internal orifice (i.e., oral, nasal, ear, or vagina) in close proximity to the accumulation of surface pathogens. Because the majority of pathogen occurrences are surface conditions, the unexpected nature of UV-C light makes it ideal for safe effects, with limited penetration while still having a lethal pathogen eradication effect. Thus, surface pathogens are effectively targeted with minimal impact on underlying healthy tissue. The LED or fiber optic end treatment, whether placed directly at or adjacent to the affected area, may include additional transmission media such as collimating lenses or other lens systems, mirrors, or light guides for beam direction and beam shaping, and may include the use of optical or transmission attachments that can transmit and "shape" or "bend" light in areas that are normally inaccessible, such as the pharynx, which extends along a vertical axis perpendicular to the mouth / oral cavity.

[0062] In UV-transmitting penlight embodiments, it consists of a camera sensor along with fluorescent stimulation LEDs (optionally with filters) to facilitate identification of pathogen activity, which may be activated by fluorescent stimulation LEDs. For some pathogens, even UV light induces fluorescence to simultaneously signal the pathogen targeting the pathogen-killing UV light and provide a measure of eradication effectiveness as a feedback mechanism. White, RGB, or natural cool / warm LEDs, such as those used for general lighting, may be included in other embodiments to emit light along with other emission wavelengths, or may be included separately from the light guide that carries the light toward the distal end of the penlight.

[0063] Further penlight embodiments are configured with attachment elements that snap into place or are attached to the top of the penlight-type device to control the shape, size, distance, etc. of the beam.

[0064] Additional embodiments of the penlight attachment element include an otoscope-type configured "head" or "imaging head" attachment. This "imaging head" optionally includes a camera sensor imaging system with an optional display to further clarify the diagnosis, activity of fluorescent pathogens, and the effectiveness of UV treatment delivery. Alternatively, the otoscope-type device is an integrated, self-contained device.

[0065] In another embodiment, the penlight configuration is adapted to fit into an otoscope-shaped shell, the penlight is converted to fit into the otoscope, and the larger diameter otoscope handle includes an auxiliary battery power source to increase the effective use time of the penlight / otoscope before it needs to be recharged or replaced. As used herein, the terms "penlight," "otoscope," or "otoscope-shaped device" are used to refer to any handheld or mounted device or fixture that includes a UV light source with a UV light transmitting medium.

[0066] As noted above, collimated UV light is particularly effective for hand or body sanitization or sterilization in the form of hand sanitizers. UV-C light transmission via collimation can be integrated with common hand blowers, such as those commonly found in corrections offices, airports, restaurants, parks, etc., to ensure sanitization in addition to less rigorous hand washing (and, if necessary, sterilization). In such an embodiment, a series of collimated UV-C LEDs are arranged to provide 360° radiation of UV light directed at a slot (preventing external leakage of UV-C light, but not necessarily limited to this structure) that is closed enough for a hand to be inserted. The collimated UV-C light is sufficient to fully sanitize (to the point of more rigorous sterilization) hands inserted therein within a few seconds (longer times are within the scope of the present invention, but shorter times may be more practical). Because of the limited penetration of UV-C light, such hand sanitization has minimal impact on the skin of the hands and is less severe than harsh soap and scrubbing. Alternative embodiments of hand sanitizers may also include an uncontained UV-C element. When combined with a hand dryer, the heat generated by the UV LEDs can be routed and directed for drying. Such devices may include an internal automatic shutoff timer to prevent excessively long exposure.

[0067] In an alternative embodiment, the number of collimated LEDs is minimized and the LEDs are positioned to provide either a mechanical or electronic scan of the inserted hand, achieving sanitization with simple hand insertion.

[0068] In a further embodiment, collimated UV light is used directly on the surgical site area during surgical procedures (at different times before, during, and after), particularly in open surgeries such as abdominal or cardiac surgery, which can be associated with a high incidence of drug-resistant MRSA and SSIs, leading to sepsis, organ failure, and death. While MRSA and SSIs are resistant to most drugs, they are nonetheless susceptible to UV light's DNA / RNA destruction for intraoperative eradication or minimization, simultaneously reducing instances of sepsis or other untoward conditions. Because UV light is essentially used only as a surface "disinfectant" with minimal penetration into skin or tissue, patient safety and the safety of surgical personnel are fortunately maintained, since pathogens such as MRSA and SSIs are almost always present as surface contaminants on the skin before incision during surgery. Surgical personnel are further protected by the use of surgical gloves, which remain sterile at all times due to the application of UV-C light.

[0069] Operating table lamps or other ceiling rigs or fixtures can be easily configured to include extended-range collimated UV-C light sufficient to minimize divergence and conserve energy at the surgical site. In further improved embodiments, collimated UV-C light is included within or adjacent to surgical light headgear to ensure sufficient UV-C disinfection or sterilization conditions at the surgical site. Because UV light is essentially invisible, it does not visually interfere with the viewing conditions at the surgical site. Alternatively, collimated UV-C light can be individually directed to the surgical site, either automatically (with timed emission) or manually, such as with a handheld device that a physician or other surgical site personnel can use and place over the patient. The distant collimated light source is maintained in a position that does not interfere with, or at most minimally interferes with, any surgical procedures. Additionally, operating lamps can further include a camera sensor module with image and video capture and fluorescence feedback detection, as further described herein, to help highlight the location of pathogen activity before its destruction by UV light. The term "invisible" is used as a general characteristic of UV-C light (i.e., not in the visible wavelength range), not as a requirement.

[0070] Transmission media for transporting UV-C light while maintaining effective energy for sanitization include optical fibers and light guides, as well as any solid or liquid medium, such as collimating or non-collimating lenses or lens systems, total internal reflection (TIR) ​​lenses, and mirrors, such as parabolic and off-axis parabolic mirrors. These or other related optical media can be used alone or in combination with different media to transmit sufficient UV energy output to destroy pathogen activity in harmful or potentially harmful biological entities.

[0071] In embodiments, at least one collimating transmission medium is fixedly coupled to the output of the UV-C light source to provide a more consistent, more uniform, and more stable energy output "safe transport" or "safe pass" over the operating distance, resulting in consistent and timely inactivation results in the inactivation of pathogens or other harmful or potentially harmful agents defined as biological entities (having DNA / RNA that are subject to UV-C destruction), i.e., cancers, cysts, etc.

[0072] Another type of biological entity is the sore or inflamed mucous membrane or tissue layer in the throat. While there is usually no infection, the tonsils and other tissues in the throat may swell, causing discomfort or the sensation of a lump in the throat. Ablation of the biofilm and / or affected tissue with UV-C light can alleviate some of the discomfort while allowing for the regeneration of new surface tissue.

[0073] Collimating transmission media in optical lenses or lens systems reduce divergence and allow for effective channeling and control of UV-C light, thereby improving quality and efficacy and maintaining a more consistent energy output. Typically, but not exclusively, such lenses may be double convex structures where light directly incident on the convex surface is refracted or bent, resulting in a substantially parallel output due to the length of its focal length, before diverging and dissipating until the light becomes relatively ineffective.

[0074] Increasing the effectiveness of UV light applications A further embodiment for increasing the penetration depth involves making the pathogen site, such as cancerous tissue or tumor, more transparent, by removing lipids and pigments in the pathogen-containing tissue in vivo, in situ, using known methods, such as using appropriate solvents and detergents in controlled amounts to prevent or minimize side effects. An example of the process of "optical clearing" of tissue in vivo is described in Physical and Chemical Mechanisms of Tissue Optical Clearing, Volume 24, Issue 3, 19 March 2021, 102178 in iScience. Optical tissue removal, especially for in vivo purposes, is an ongoing field of research, and many improved methods and materials are constantly being developed that are more efficient, faster, and have fewer side effects for biological observation purposes.

[0075] In the described process, methyl benzoate (MBe), approved for use as a food-grade flavoring ingredient by the U.S. FDA (21 CFR 172.515, FDA 2015) and the European Union (EU Regulations 1334 / 2008 and 178 / 2002, EU 2015), and methyl salicylate (another food flavoring) are described as being among the chemicals that help make tissues substantially clear. These compounds are non-toxic or only mildly toxic, especially in small doses, and are currently used in foods, beverages, and topical applications.

[0076] Tissue clearing, including tumors, has generally been performed on dead animal specimens, primarily for the purpose of examining the specimens using instruments such as microscopes. Recently, tissue clearing (tissue removal) has been performed with minimal toxic effects in in vivo studies, such as those cited above, to transparentize animal (especially mouse) skin and allow direct visualization of ongoing biological processes. The use of an aspiration needle with controlled solvents and / or other tissue-removing chemicals (determined by volumetric mapping of the tumor or cancer site) to minimally target only the tumor site (and some peripheral cells or tissues) using dye- or lipid-removing solvents or detergents minimizes concerns due to the limited amount of solvent introduced. Furthermore, the generally minimally or nontoxic nature of the solvents and the fact that the tumor site is excised in any case further minimize any safety concerns. Furthermore, it should be noted that the clearing effect may only be temporary, as the replenished lipids and pigments are formed in the excluded site.

[0077] As the pathogen site becomes more transparent (tissue essentially does not absorb light waves), the optical penetration depth of DNA / RNA-destroying UV light significantly increases. Pathogen-destroying removal becomes more complete and efficient when combined with phagocytic and / or ablative procedures. This increased transparency, coupled with increased applied UV power, allows for effective removal of entire pathogen sites, such as cancer tumors, with minimal side effects and significantly less trauma, without surgery or common current highly traumatic and destructive radiation, such as X-rays and gamma rays. UV fiber-containing needles can be inserted into the tissue to be removed, emitting UV light depending on the fiber's final treatment. Thus, a fiber with a complete diffuser tip has a circular emission and deep penetration on each side of the fiber over a 360° range. The needle moves the diffuser tip deep into the tumor, allowing at least a significant portion of the tumor to be exposed to the pathogen-killing UV light. Transparent tissue removal allows for a more complete depth of penetration, allowing the fiber-tipped needle to be effectively used at the surface of the tumor and moved to various areas on the surface to ensure more complete UV coverage of the entire tumor or cancerous tissue site. The substantially complete side-emitting fiber can further enhance the degree of coverage of pathogen-eradicating UV light.

[0078] It should be understood that current procedures for tissue transparency take time, which can be hours or days, and that this procedure may be considered pre-operative, requiring a return for the actual UV light treatment during the time frame of maximum transparency. An article in Advanced Drug Delivery Reviews, volume 180, January 2022, 114037, examines in vivo tissue removal for the introduction of treatment and confirmation of results, describing the removal of tumor tissue in order to introduce infrared radiation and heat for the treatment.

[0079] To enhance overall pathogen eradication despite the lack of typical UV light penetration depth (generally on the order of about 40 microns), effective treatment embodiments include various protocols without any penetrating pretreatment.

[0080] A first protocol embodiment involves surface treatment of tumor removal sites, such as the inner surface of the bladder, with UV light. Particularly when performed periodically as determined by the specific type and / or aggressiveness of the cancer, the effect of such surface treatment is to prevent or delay the recurrence of aggressive cancer at the original tumor or surrounding sites. This effectively serves to extend remission time without any surgical intervention or in combination with known remission control treatments or surgical interventions. A specific example of such surface treatment is the treatment of the bladder lining, which is currently treated with BCG (attenuated or killed tuberculosis bacteria) to provide a similar preventative treatment.

[0081] A second protocol embodiment involves the formation of a perimeter firewall-like effect, including the reduction or elimination of blood channels with nutrient supply at the interface between existing cancer cells and healthy cells, substantially retarding the metastasis of cancer cells to healthy cells. UV light is directed at the surface and below the interface to a predetermined effective level by a penetrating hollow needle, such as an aspiration needle commonly used to obtain biopsy samples, exemplified by EBUS and EUS needles containing a UV-transmitting fiber or medium.

[0082] The third protocol involves multiple insertions of light-emitting aspiration needles with UV fiber transmitters in close proximity, widening the area of ​​the cored lumen suitable for UV light treatment of the inner surface, followed by sequential removal of dead cells by phagocytosis or physical ablation by aspiration or lavage.

[0083] Implant sterilization In another embodiment, direct in situ sterilization of surgically implanted medical devices, including pacemakers, drug delivery implants or other electrical devices, prosthetic devices such as hip and knee replacements, and rods or other structural devices, is performed with minimal surgical intervention. In situ application of UV light to the surface of a superficially implanted medical device at the interface between tissue and tissue can avoid surgical removal for sterilization and reimplantation (with reduced surgical side effects and costs). Some medical devices, such as pacemakers and drug delivery devices, are implanted in a pocket between the patient's outer skin and underlying muscle, such as in the patient's left shoulder area just beneath the skin. The sterilization procedure involves making an access incision adjacent to the implant to insert a UV delivery fiber laparoscopically (as a non-limiting example of a guided insertion device). The UV fiber is inserted between the implant and the holding pocket, and sterilization is achieved by the applied UV light. In various embodiments, multiple insertions may be required. The fiber end configuration may be modified to provide radial UV light output limited only in the direction of the implant. For fibers inserted directly through a skin incision, the fiber end may also be provided with a rigid, transparent, elongated or extended surface-probing blade that serves the purpose of moving the skin away from the implant, facilitating insertion of the fiber end between the pocket wall and the implant and allowing the fiber end to move against the implant surface to fully sterilize its coverage. The blade itself diffuses the UV light through it, increasing the surface area of ​​contact. A surgical instrument such as a retractor may be used to separate the implant surface from the pocket wall to insert the fiber, but not remove the implant.

[0084] For deeply implanted devices such as rods and hip and knee replacements, endoscopic fiber carriers, as described in the parent patents, can be used to access pathogen (or potential pathogen) detection or suspected areas of such implants for sterilization. The minimal penetration depth of UV light typically allows it to be safely used on accessible surfaces of implants for sterilization while minimizing impact on surrounding tissue or cells.

[0085] Instrument sterilization Sterilization of instruments with hard-to-reach or hard-to-sterilize areas, such as the biopsy or instrument channel of an endoscope, has been described in the parent application with the introduction of UV-transmitting fibers passing through the channel at a rate sufficient to achieve substantially complete sanitization. In embodiments herein, such sterilization procedures can be enhanced (e.g., shortening sanitization time or using lower power) by physically pretreating the interior walls of the channel using, for example, thin, absorbent strands similar to dental sponge-like "super" floss, a type of floss used to remove and / or dislodge any debris under or around dental "bridge" teeth by brushing in a circular motion or pulling in one direction, and to absorb and / or destroy any biofilms that may protect pathogens from UV light penetration. Alternatively, existing sterilization procedures, such as brushes that remove physical residue within the biopsy channel but are ineffective against pathogens, can be utilized to enhance the UV light pathogen-destroying effect by destroying the light-blocking biopsy film. Biopsy film grows and thickens over time, but it is understood that this is not usually a major issue for endoscopes, which are sterilized immediately after each use before biofilm can form to any harmful extent. However, in some cases, ineffective reprocessing procedures leave pathogens in place, allowing them to grow and build biofilm. Alternatively, a small rubber collar around the insertion string or rod can similarly provide a "squeegee" biopsy film removal effect, similar to window cleaners. As a proper precaution, the endoscope channel should be internally exposed to sanitizing UV light before any endoscopic procedure.

[0086] All endoscope sterilization Because endoscopes are primarily constructed of polymeric materials that are susceptible to degradation when exposed to UV light, the exterior of endoscopes is not typically sterilized with UV light. Indeed, studies have demonstrated the harmful effects of UV light on endoscopes. While endoscope channels are lined with UV-resistant PTFE, the exterior of the endoscope is completely exposed to reduce friction on inserts such as biopsy instruments. Therefore, the parent application describes the use of a transparent medium, such as an optical fiber, inserted into such channels to direct UV light directly against the PTFE-lined walls for sterilization purposes without harmful effects.

[0087] However, studies demonstrating the harmful effects of UV light on endoscopes have specifically involved long-term storage and exposure of polymer endoscope materials over several days. According to another embodiment of the present invention, the outer surface of an endoscope is exposed to UV light, particularly UV-C light, for a relatively short period of time—even just a few seconds, up to a few minutes, per exposure site, depending on the exposure distance and power output. This is much shorter than the time required for UV photolysis of polymers by breaking polymer bonds, as opposed to the extremely short period of time required for DNA / RNA destruction due to cleavage of phosphorus bonds, as used to sterilize pathogens. In an embodiment, a ring structure with a diameter sufficient to accommodate the cross-sectional width of the endoscope, UV light directed 360° inward, is used to sterilize the lowered endoscope (or the ring moved along the length of the endoscope) at a controlled rate. Due to differences in the dimensions of the endoscope insertion tube, body, and handle, several light-emitting rings can be utilized for separate, different-sized components of the endoscope to maximize the UV sanitizing effect due to their proximity. Alternatively, a flexible expanding and contracting ring that maintains full 360° UV light exposure can be utilized to expose the entire endoscope body to UV for sterilization.

[0088] Another embodiment includes a sterilization box sized to accommodate typical devices and instruments, with the interior walls lined with UV-C LED light combined with a collimating lens with overlapping areas of light impingement, resulting in multidirectional output for rapid, efficient, and reliable sanitization or sterilization. The UV-C light output from the collimating lens leads to a more consistent energy density output, impinging on different curvatures and contours of devices, instruments, or tools with the same or similar UV energy output requirements to inactivate pathogens in a relatively similar time. Effective external sterilization time can be reduced to a few seconds, allowing even devices with polymeric materials to be sterilized before any harmful effects of UV-C can be felt on the polymer. A supportive UV-C light-transmitting backing is used to support the instrument or tool and box, enabling thorough sterilization.

[0089] Characteristics of UV-C light applied using a collimating medium for sanitization or sterilization purposes include controlled, more consistent, and more uniform energy application at different distances along the collimated path with a relatively low divergence angle, resulting in more controlled application and a relatively short duration of UV-C light that takes into account the curvature and other surface irregularities and general dimensions of the area and device to be sterilized.

[0090] For rapid, non-destructive applications, a 360° sanitizing or sterile wash is achieved by exposing the surrounding surgical instruments or tools (supported on a UV-C light-conductive, transparent medium support for full exposure) to a minimum of UV-C light exposure within a predetermined period of time to a level sufficient to effectively sanitize or sterilize with a safety margin. The terms "sanitization," "disinfection," and "sterilization" are used interchangeably herein, with "sterilization" often being used as the most complete of the three, especially in medical applications.

[0091] Increasing the efficiency of UV light applications In further enhancing sterilization procedures for endoscopes and the like, the use of a timed retraction mechanism at the proximal end of the insertion fiber allows the fiber to move through the endoscope channel at a speed that is controlled enough to ensure more uniform and widespread UV light exposure to the inner walls of the endoscope channel, greatly reducing the opportunity for human error and allowing for more effective pathogen removal.

[0092] As a double-safe method to ensure sterilization, since sterilization does not provide a visible indication (though procedures such as final ATP testing can help certify proper sterilization, such testing is expensive), UV light output is first measured with a power-integrating device such as an integrating sphere, integrating aspheric geometry, or calibrated UV intensity sensor. The power output, along with relative channel and fiber diameter parameters, is then calculated to determine the distance of UV light application. If the pathogen is known, its susceptibility to degradation by UV light can be further considered when determining the fiber's dwell time and retraction speed. In either case, a large safety margin must be taken into account to ensure eradication of all pathogens likely to be contacted.

[0093] A further embodiment of sanitization involves large-scale simultaneous direct sterilization of devices requiring cleaning, such as cylindrical pipettes, catheters, syringes, or similar laboratory or medical equipment, by insertion of multiple UV fibers and UV sterilization on an assembly line. Arrays of devices are processed sequentially on a conveyor belt facing a single direction parallel to the openings of the devices, whereby a corresponding array of UV light-conducting fibers is simultaneously lowered into the array of devices for a period of time sufficient to sterilize each of the devices, and then lifted to allow the conveyor belt line to move a new array of devices into position for sterilization.

[0094] Preventive treatment using UV light to remove cysts and cancer precursor growths, similar to the removal of polyps during a routine colonoscopy, helps eliminate the risk of potential precancerous lesions. Removal of pancreatic IPMN cysts and gastric antral intestinal metaplasia helps minimize irregular cellular activity in those areas and eliminate the risk of cancer and metastatic cancer. Furthermore, the use of UV light to affect cysts and intestinal metaplasia involves minimally traumatic resection of adjacent healthy tissue, reducing the incidence of pancreatitis or similar side effects of prior art treatments. In such treatments, fluid is first aspirated from the cyst using an aspiration needle, and then the interior of the cyst is treated with DNA / RNA-disrupting UV light using a UV-transmitting fiber, essentially destroying it. Once removed or destroyed, cysts rarely regenerate.

[0095] Another preventative use of UV-C light occurs after surgical removal of cancer cells or tumors. The uncertainty associated with such surgical removal is the uncertainty of ensuring that all cancerous cells have been removed. The current procedure to ensure such complete removal is cauterization of the surgical site. However, this is traumatic, comes with its own side effects, and is prone to missing some cells or incomplete destruction of cancer cells or possible precursor cells. UV-C light aimed at the surgical site results in more effective destruction of any remaining cancerous cells and a safe destruction of the surface layer of possible precursor cells, truly increasing the time of remission, if not preventing cancer recurrence.

[0096] Deep Tissue Penetration Protocol Optionally, protocols for achieving deeper tissue penetration with UV-C light for superficial cancers, such as those described above, are performed by first ablating the top or proximal layer of mucosal tissue with UV-C light to a depth of approximately 20–40 μm. Additional ablative procedures, whether immediately followed or in additional treatment sessions, ablate the next or subsequent layers of affected, problematic, or cancerous cells or tissue, approximately 40 μm or even 100 μm. Cancer treatment does not necessarily involve simply killing cancerous cells. Rather, it is sometimes sufficient to injure cells, including cancerous ones, which then triggers a small inflammatory response, triggering macrophages or phagocytes to ingest and eliminate the cancer cells. This form of therapy relies on the fact that cancer cells lack repair mechanisms, whereas healthy cells are able to repair themselves. Cell damage should not be of a nature that could lead to cellular mutations.

[0097] The advantage of using UV light is that alternative, current non-UV methods use ionizing radiation therapy, such as X-rays or gamma rays, which can cause a significant inflammatory response that is highly traumatic to adjacent healthy tissue or organs. This is in addition to the trauma caused by the ablative or cauterizing methods used, which involve heat. In contrast, UV light induces little or no inflammatory response, and the trauma is minimal.

[0098] In further embodiments of the transmission medium, for deeper tissue penetration protocols, optical fibers with UV-transparent needle-like distal end treatments or other end treatments are used to penetrate tissues and organs and transmit UV DNA / RNA inactivating light directly into tissue layers, thereby more directly destroying pathogen activity, including cancer cells or tissues, while minimizing trauma to healthy tissue.

[0099] Feedback Detection Recognizing pathogen kill time and effectively knowing the time when pathogen kill is achieved is extremely useful. To ensure effective pathogen eradication and the reliability of UV-C for pathogen killing, it is necessary to maintain sufficient energy intensity from the energy output, especially when UV light penetrates at variable distances. It was first understood that UV-C light is essentially invisible and tends to dissipate or attenuate. Similarly, pathogens (especially in their early stages) are not directly visible (although the effects of the pathogens can be seen), and eradicated pathogens are usually not identifiable.

[0100] A very useful embodiment for use in conjunction with UV light eradication of pathogens is feedback of eradication detection to a user or professional before, during, and after application of UV light, identifying pathogen activity, particularly the type, location, and extent of bacteria. Such pre-UV light feedback activity allows for more efficient and effective application of UV light to bacteria, ensuring more effective eradication. Such post-UV light treatment feedback activity serves as a useful indicator of the eradication effectiveness of the applied UV light. It is understood that such feedback may be used in other applications unrelated to UV eradication, such as assessing the extent of pathogen infection and the degree of improvement in infection status.

[0101] In practice, collecting eradication feedback during the exposure session generates a bacterial "heartbeat"-type profile, a real-time connecting line plot, and a graph of growth over time, allowing the doctor, specialist, or patient to see the initial activity level of the bacteria before the UV was turned on. As the pathogens are subsequently killed by the UV, a declining level of activity is observed, culminating in a slow, plateau-like portion of the graph, until virtually all bacteria are eliminated. If desired, even an enhanced version of the time-lapse photography can be used to display motion video of the precise location and speed of pathogen sterilization. The enhancement is that time compression of the pathogen sterilization "movie" averages the frames between sampled frames via a computer, rather than skipping every frame between sampled time-lapse frames, thereby increasing signal strength and signal-to-noise ratio, resulting in better, higher dynamic range video, while still maintaining the desirable element of increased viewing speed.

[0102] Because DNA / RNA, a universal characteristic of pathogens, is targeted, the actual identity of the pathogen is less relevant. Rather, the location and extent of the bacteria are of primary interest. While colorimetry, originally designed to facilitate color matching across a wide variety of additive and subtractive color reproduction devices such as displays and printers, is useful for providing the necessary information, other methods are feasible in accordance with the present invention. In one embodiment, colorimetry is used to determine the extent and location of fluorescence by comparing the perceived color and brightness of each pixel using colorimetry, which numerically quantifies the color perceived by the human eye and can accurately compare that color to a similar view without a stimulus light. In one embodiment, as an example, 405 nm visible light is used, and the color and brightness of the same pixel location after the stimulus light is turned on are compared. Pixels of any of the known fluorescent colors are used within the perception threshold to compare the two Lab values ​​using a colorimetric difference metric called "Delta-E." The stimulus light is flashed when modulated on and off to provide a direct indication of bacterial fluorescence with a high degree of reliability. The degree of bacterial growth is indicated by the intensity of the fluorescence, and the combination of the exact color of the fluorescence and the correlation of the nature of the blinking to the blinking modulation signal, when both are detected or observed in epithelial tissue, allows for a highly reliable determination of the blinking in the presence of bacteria or other pathogens.

[0103] It is a characteristic of bacteria to fluoresce when exposed to light of a specific wavelength, and most bacteria fluoresce under light of wavelengths below 405 nm, typically produced by specific wavelength LEDs. The wavelength used to cause bacteria to fluoresce is defined herein and referred to as the "stimulation wavelength." Many different types of bacteria can be made to fluoresce using the same or shorter wavelengths (higher energy photons). The wavelengths of fluorescence produced by different bacteria can vary considerably, even when using the same stimulation wavelength.

[0104] A straightforward, yet complex and expensive, method for determining and classifying which types of bacteria are fluorescent is to measure the wavelength of the emitted fluorescence, defined herein as the "fluorescence wavelength." Identifying the type of bacteria through that wavelength measurement utilizes specialized optical hardware, such as optical low-pass, high-pass, or band-pass filters, and combinations thereof. Other hardware used to detect wavelengths can be spectrometers or Bragg (tunable) filters, including "demultiplexer configurations," which use successive sections of specialized optical fiber with variable refractive index to filter and sequentially split multiple wavelengths.

[0105] While the science of colorimetry was originally designed and useful to facilitate color matching across a wide variety of additive and subtractive color reproduction devices, such as displays and printers, other color matching and identification methods according to the present invention are equally viable. Colorimetry involves: 1) creating a "standard observer" and quantifying his or her perception; 2) creating a specific color space, specifically "Lab," which facilitates the quantification of color differences by providing color difference numbers that are highly linearly proportional to differences in human perception, even across wide differences in color; and 3) completely classifying color perception using only a triplet of L, a, and b numbers, rather than by working with a broad spectral array of data covering the entire visible wavelength range. Using only three numbers to specify color perception speeds computations compared to operations across the broad visible spectrum. Dealing with entire raster frames of color pixels involves fewer calculations per pixel, desirably allowing more video processing to be accomplished in software, both flexibly and at low cost. (Note that implementations using precalculated lookup tables are particularly fast in such color space conversions and difference calculations.)

[0106] The colorimetric assay with multiplexed fluorescence detection incorporates several techniques to ensure accuracy and speed. 1) Pre-calculated Lab values ​​for every fluorescence wavelength you want to detect. 2) Time-synchronized CW (continuous wave, on / off) modulation. The fluorescence stimulus light source is flashed at a specific rate. For a pixel to be counted as due to fluorescence, it must also flash in time with the stimulus light. 3) An optical notch filter can be used in the light path of the detection camera to filter out flickering of the direct stimulus light resulting from white or shiny surfaces. 4) The "a" and "b" components of the pixel's light Lab value should have a small delta-E difference from one of a list of pre-calculated Lab values ​​for fluorescence.

[0107] The fluorescence provides contrast with the patient's baseline pixel characteristics, causing the tissue area to fluoresce and rapidly flashing a 405 nm or other fluorescent wavelength LED to generate a color video clip (e.g., a 1 second or 100 frame grab) for analysis to "call out" pathogens. Instead of or in combination with colorimetric measurements, filters are used to separate color and intensity.

[0108] Feedback detection is useful for the effective treatment of bacterial infections, such as throat or fungal infections, as well as life-threatening infections, such as in diabetic patients who may have foot ulcers that could lead to amputation if the pathogens are not quickly cleared from the wound.

[0109] More specifically, when a certain wavelength of light is shone on many living bacteria, the bacteria also emit a very different but specific wavelength, as if they were a flashing light of a different wavelength. This is called induction fluorescence. Like a flashing light, the light they emit stops for a split second when the flashing light is turned off. Therefore, by flickering the light shining on them, the light they emit will flicker accordingly.

[0110] The amount of live bacteria in a field of view can be determined by detecting a particular color of fluorescence and measuring the brightness of that emission across the field of view. Generally, different types of bacteria emit several wavelengths, many in response to the same stimulus light, while a few bacteria may require different wavelengths for stimulation.

[0111] If there is also general illumination of the surface containing the bacteria, detection of the bacteria is improved by using an optical notch filter on the camera or detection device as described above to ensure that the emitted light of the bacteria is seen and not just the reflection of the general illumination.

[0112] There are two criteria for verifying proper detection:

[0113] a) The first method is to make sure that the detected light you are looking at is flashing in time with the flashing of the stimulus light.

[0114] b) The second verification method is to verify that the wavelength being emitted is the same as, or very close to, a known wavelength that the bacteria emits upon stimulation.

[0115] The method in paragraph a) is relatively simple to employ as the stimulus light is typically flashed using highly controllable solid state LEDs or lasers.

[0116] In the method of paragraph b), the wavelength detector is typically a common and expensive spectrometer, or, if only a few wavelengths need to be detected, a series of bandpass filters. Spectrometers and optical filters can be used, but are limited by the fact that the former do not have a wide field of view, and the latter cannot be stacked together, since when one filter blocks all but one specific wavelength, it also blocks all other wavelengths, including those of other bacteria. Depending on the particular application, the choice of one, the other, or a combination may be effective.

[0117] Fortunately, while each specific wavelength appears to the human eye as its own color when it comes from a monochromatic light source such as a laser, the converse is far from true. A specific perception of color need not be caused by a specific wavelength, or even by a specific combination of wavelengths. Color film, as well as all digital still and video cameras, effectively simulate the perception of all visible colors using a combination of light from three relatively non-overlapping spectral sections of the entire visible spectrum, roughly centered on red, green, and blue. A hypothetical entity known as the standard observer has been defined. Observer color perception is classified by a different set of three numerical values, one derivable from RGB space. A useful method for matching color perception from very different light sources, such as light (additive space) and the reflection of light from illuminated print, is the aforementioned "Lab" space.

[0118] As a prerequisite for some procedures, preparation and removal of debris or other obstructing factors, such as biofilm, plaque, or mucus, further facilitates the sterilization or inactivation process. Limited UV light penetration is generally mitigated to some extent by preparatory cleaning processes to remove debris that may block or interfere with external application, such as endoscope reprocessing to sterilize small channels such as instrument channels, or in vivo medical ablation procedures, such as draining cyst mucus prior to inactivation of cystic tissue, or physically cleaning a wound prior to the introduction of UV therapy for more effective treatment.

[0119] dentistry In another embodiment, UV light in the germicidal wavelength range (as opposed to UV at the upper, longer wavelength end commonly used to harden dental resins and implants) is used in dentistry, whether in the mouth of a human or animal, to help remove infection and decay on or inside impacted teeth, such as cavities, and to alleviate root canal conditions. Optical fibers are inserted into the cracks and fissures of decayed teeth to kill bacteria and prevent further caries, where the caries and bacteria are present on accessible surfaces. Collimated UV light is used to the same effect.

[0120] In non-sterilizing embodiments, the fibers used for UV light disinfection provide imaging assistance, and a camera sensor image-carrying fiber bundle, used separately or bundled together with the UV-carrying optical fiber, can gain access to inaccessible areas of organs, such as ducts or lymph nodes, facilitating direct "line of sight" diagnostic viewing and / or administration of UV treatment without the assistance of more mundane viewing methods such as ultrasound or x-ray.

[0121] This image-carrying fiber optic assembly, optionally with UV radiation output for the destruction or inactivation of harmful or potentially harmful biological entities, may also be used for insertion through thin aspiration needles, such as EUS or EBUS, to enter organs or tissues that are otherwise inaccessible by "direct" observation. In effect, when inserted through the biopsy channel of an endoscope, it becomes an endoscope within an endoscope.

[0122] As used herein, "safety" includes safety of the materials or equipment of the device in addition to safety of the human body, ensuring that excessive energy output is not directed to any part of the device during sterilization so that damage or degradation of the device does not occur, as excessive UV light (energy and / or duration) is known to degrade materials.

[0123] The above objects, features, and advantages will become more apparent from the following description and drawings. [Brief explanation of the drawings]

[0124] [Figure 1-1] 1 schematically depicts a side view of a pulsed 266 nm laser immobile and fixed in a fixed optical connection to a fiber optic cable with a pathogen-destroying output. [Figure 1-2] A shows a schematic of the 266 nm laser of FIG. 1-1 with the components of an 808 nm laser diode converted to a 266 nm laser output with output power measurements. [Figure 1-3] C-D show the components and structure of a UV light emitting laser. [Figure 2A] 1 shows a side-emitting optical fiber modified to provide uniform power output along its entire length. [Figure 2B] 2B shows a fiber etched lighted stencil for producing the apertured side-emitting fiber of FIG. 2A. [Figure 3] Schematic depictions of staggered plane (side view in FIG. 3A ) and single plane (end view in FIG. 3B ) cross sections of an endoscopic biopsy channel with a three UV LED structure with 360° radial UV light output, and FIG. 3C (side view outside the channel) depicts a single LED with forward-extending UV light output. [Figure 4] 4A and 4B schematically depict a side cross-sectional view of an optical fiber directing UV light to a surgical site where a tumor has been removed, and FIG. 4A depicts the application of a bladder to direct UV light to a site where a cancer tumor has been removed for the purpose of extending the period of remission. [Figure 5A] Schematic representation of an optical fiber directing UV light into healthy cells at the periphery of a tumor, isolating the tumor from the healthy cells. [Figure 5B] 10A-B are schematic depictions of multiple depths of UV light application around the tumor. [Figure 5C] Figures 5A and 5B show cross-sectional side views of the colon showing various stages of cancer development and an illustration of tumor isolation in which a UV-emitting fiber-carrying aspiration needle is used to create a dead cell and nutrient supply barrier around a stage 2 tumor to existing cancer cells and healthy cells after repeated insertion. [Figure 6] Depicts the insertion of multiple aspiration needles for cancer tissue core surgery, forming a lumen that expands with repeated application of UV light to kill surrounding cancer cells. [Figure 7] FIG. 7A is a cross-sectional side view showing a schematic diagram of a process using UV light in a raster fashion to destroy the RNA / DNA of cancer cells and remove the cancer layer (FIG. 7A), followed by a process using higher power UV light to remove the dead cancer cells (FIG. 7B), followed by a process using lower power UV light to again destroy the RNA / DNA of exposed cancer cells (FIG. 7C). [Figure 8] 1 shows a process for the removal of precancerous near-surface cysts by the use of UV light, with the cyst drainage followed by UV light deployment of the internal cyst. [Figure 9-1] AB show the use of UV light deployment with an EUS needle carrier for evacuation of a pancreatic cyst with UV light and internal treatment of any remaining cysts. [Figure 9-2] C shows the use of UV light deployment with an EUS needle carrier for evacuation of pancreatic cysts using UV light and internal treatment of residual cysts. [Figure 10] 1 shows UV light treatment of the inner surface of the stomach (antrum) to treat intestinal metaplasia. [Figure 11] 1 shows the cancerous pancreas with an entrance in the duodenum for aspiration needle for delipidation and removal of pigment and subsequent insertion application of UV light. [Figure 12] FIG. 12A depicts the insertion of an aspiration needle into the lung through an endoscope for treatment of cancer in the lymph nodes with UV light, and FIG. 12B shows a close-up of section A of FIG. 12C shows a close-up of the UV fiber carried by the aspiration needle of FIG. 12A and FIG. 12B. [Figure 13] This shows the collimating effect of a specially constructed lens in extending the output of UV light over distance at a relatively uniform, maintained power level. [Figure 14-1] 1A-B show various views of a penlight-shaped device configured to emit collimated UV-C light, along with an exploded view and internal components. [Figure 14-2]C, D, and E respectively show a lateral cross-sectional view of a human head and diagrams illustrating various speculums for insertion into the mouth and targeting UV light therein against infection. [Figure 15] 15A shows an embodiment of an otoscope-shaped device emitting UV light and its use in sterilizing a surgical site (FIG. 15B), which is a perspective view of a surgical site in which the otoscope-type instrument is equipped with a 405 nm LED light source that periodically illuminates the surgical site with unobtrusive germicidal UV light from outside the operating area of ​​the surgical instruments, causing bacteria to fluoresce. [Figure 16] 16A and 16B are diagrams of the display screen of the otoscope device of FIGS. 15A and 15B, in which the device emits light at a wavelength that fluoresces bacteria, initially depicting a non-fluorescent area (FIG. 16A), and then depicting a viewing area for targeting the fluorescing bacteria (FIG. 16B). [Figure 17] 15B is a flow chart of the operation of the feedback fluorescence and otoscope-shaped device of FIG. 15A with fluorescence operation of the surgical site 15B. [Figure 18] Figure 15A is a ray tracing simulation of the collimated UV, white, and 405 nm fluorescent light output emitted from the otoscope. [Figure 19] The arrangement of the collimating lens of the otoscope and the UV, white, and fluorescent light sources is shown. [Figure 20] 1 depicts a nasal endoscope currently used for treatment of the nose, pharynx, and larynx, reaching down to the inner ear, retrofitted with UV light emission for sterilization and treatment of bacterial infections in those areas, and used for nasal disinfection. [Figure 21] 1 depicts a laparoscopically directed UV light delivery fiber placed adjacent to an infected medical implant pacemaker for in situ UV light disinfection. [Figure 21A] FIG. 1 is a side cross-sectional view of a medical implant pacemaker in a pocket between the skin and muscle, with UV-transmitting optical fibers inserted between the pacemaker and the skin and between the pacemaker and the muscle within the retention pocket. [Figure 22]1 depicts an elongated element with an expanding element for disrupting biofilm in an endoscope biopsy channel prior to UV light treatment. [Figure 22A] 1 shows the elongated elements in place and in an expanded configuration to effect biofilm disruption. [Figure 23-1] 1 is a flowchart showing steps for removing lipids and dyes from cancerous tissue to make it more transparent with less light scattering from the lipids it contains, less light absorption by the dyes, and more penetration of UV light. [Figure 23-2] A and B show the progression of prior art tissue removal to transparency over time for mouse brain (A) and tumor (B), respectively. [Figure 24-1] A-D show the complete exterior of an endoscope being sterilized with timely insertion of the endoscope through a ring of UV light that minimizes the distance of UV surface application, Figure 24A shows an endoscope housed in protective glass and then rotating in a cylinder of corresponding size, with an internal LED (Figure 24B), a vertically suspended endoscope with a small ring of LED light that runs along the outer surface of the insertion tube (Figure 24C), and a larger ring for the handle (Figure 10D). [Figure 24-2] A-D show the complete exterior of an endoscope being sterilized with timely insertion of the endoscope through a ring of UV light that minimizes the distance of UV surface application, Figure 24A shows an endoscope housed in protective glass and then rotating in a cylinder of corresponding size, with an internal LED (Figure 24B), a vertically suspended endoscope with a small ring of LED light that runs along the outer surface of the insertion tube (Figure 24C), and a larger ring for the handle (Figure 10D). [Figure 25] A shows a batch tray with an array of pipettes requiring sterilization, and B depicts an array of pipettes being simultaneously sterilized with fiber insertion and UV treatment in a batch tray on an assembly line, where the pipettes are positioned with a movable matching array of UV-transmitting optical fibers for simultaneous sterilization. [Figure 26]As an alternative to the integrated power measurement of FIG. 1A, a biopsy channel sterilization procedure using the device of the present invention starting with the determination of power output (FIG. 26A) is shown, where A shows the free end of the fiber coupled to a UV light source inserted into an integrating sphere with power reading, and B shows the fiber fully inserted into the biopsy channel of the endoscope being pulled out in a linear trajectory by a retractor with a timing mechanism, moving at a calculated predetermined speed. [Figure 27] 1 shows an embodiment of a sterilization box having an array of collimated lenses for disinfecting and maintaining uniform power levels on sterilizing instruments (scalpels shown) such as those used in surgery. [Figure 28] 1A-1C depict diagrams of a hand sanitization device that emits UV-C light onto the surface of a hand placed in close proximity for sanitization. [Figure 29-1] AC show the dental application of UV light in a dental laboratory environment (FIGS. 28A, B and C), with UV treatment of caries and periodontal disease. [Figure 29-2] AC show the dental application of UV light in a dental laboratory environment (FIGS. 28A, B and C), with UV treatment of caries and periodontal disease. [Figure 30] AB show the incorporation of a UV light transmitting light element, modified from a penlight configuration to a surgical light with a camera element. DETAILED DESCRIPTION OF THE INVENTION

[0125] Referring to the drawings, Figure 1 depicts a UV light-emitting laser 10 with a wavelength of 266 nm (at or near the optimal DNA / RNA disruption level of 265 nm). The emitted UV light 12 is collimated into a narrow beam of 100-200 microns and optically aligned in brace 13 with an optical fiber 18 of the same or larger diameter through an appropriate acceptance angle (defined as the input angle at which the light is accepted for output at the distal end of the fiber). With such small dimensions, the laser beam cannot be subject to slight movements that would cause the beam to be improperly angled and absorbed by a protective optical fiber shield. Therefore, fiber 18 is locked into an essentially immovable position, such as with an SMA connector 14 shown, on a rigidly fixed brace 15 without play, by adhesive or connector application. Laser 10 is similarly locked into position on support 16, and brace element 17 locks output 11 in place. Laser light 12 is collimated and undiverged, but is slightly diverged at output 18b by approximately 0.5° in each direction as it passes through fiber 18. The additional diffusion necessary for effective sterilization can be obtained by treating the distal or emitting end of fiber 12a to provide the desired spread of light. Alternatively, light can be emitted along substantially the entire length of the fiber.

[0126] Figure 1A shows the components of laser 10, starting with an 808 nm (and can range up to 885 nm) laser diode 1, whose optical output is sent through coupling fiber 1a to coupling lens 2, where the output light is focused at 2a into crystals 3 and 4, converted to 1064 nm, and sent through filter 5 to crystal 6 for a second conversion to 532 nm. The light then passes through crystal 6, filter 7, BBO crystal 8, and filter 9, resulting in a 266 nm laser output. Beam splitter 9a extracts some of the light for power measurement, and the remaining light exits as laser light 12 with a 266 nm UV laser light output.

[0127] FIG. 1B shows a schematic of a UV-emitting laser configuration 300 with a laser diode (200-280 nm) lens system directing the emitted UV light into a flexible 50 um core optical fiber suitable for mobile use inside the body, such as an endoscopic instrument channel (not shown).

[0128] Figures C and D show typical components of a laser 301 with light generation 302 and transmission, including wavelength tuning crystals 303a, 303b, power supply 304, and driver 305. Figure 1D illustrates a 442 nm pump laser in which generated light 306 travels through an F50 lens 307 to a PnYLF crystal 303b, an F50 lens 307a, a 520 nm bandpass filter 308, a BBO longpass filter 303a, an HR mirror 309, with the 266 nm (UV) light output directed by the lens system into a 50 um core fiber 310.

[0129] 2A shows a side-emitting fiber 18' having a cladding 28 perforated with microdot holes 29 exposing the fiber within the cladding to side-emit UV substantially entirely with a substantially uniform power output through the microdot holes, as shown (and otherwise predictably controlled) output intensity. The microdot holes create small openings that allow some of the light and output intensity to be emitted, yet the fiber maintains sufficient structural integrity to protect the fragile fiber core. With such a fiber configuration, high-power light sources such as lasers or high-power LEDs can be used to provide effective pathogen eradication.

[0130] FIG. 2B shows a cylindrical stencil 180 configured with the calculated hole arrangement and having an appearance corresponding to the fiber 18′ shown in FIG. 1A (with stencil holes 129 corresponding to the microdot holes 29 formed in the fiber 18′) used to form an array of microdot holes 29 in the desired configuration in the fiber 18′. The cylinder 180 has a diameter D+ slightly longer than the diameter D of the fiber 18′, sufficient to encapsulate the fiber 18′ within it while forming the etching microdot holes. The stencil cylinder 180 is of a laser-etching-impermeable material, such as metal (a laser light etcher 130 is configured to etch or perforate the glass of the fiber buffer and cladding). A glass-etching laser beam 131 is aimed at the stencil-encapsulated fiber to efficiently form the microdot holes 29 through the stencil holes 129 in the desired configuration as shown in FIG. 2A. Multiple laser etchers 130 surround the stencil to efficiently form the required microdot holes in the fiber 18′.

[0131] Simple side emission of light (as in the prior art with LEDs in the 65 mW output range) or a uniform microdot density (not shown) would result in a side-emitting structure with significantly reduced output intensity, often fading to little or no pathogen-eradicating light emission at the distal end of an 8-inch fiber at greater distances from the light source. The graduated microdot hole density in distal end section 18a' of fiber 18' at section 28c allows distal end 18a' to emit at least milliwatts of UV light originally emitted by laser 10, thereby effectively sterilizing distal end 20' of biopsy channel 20 within minutes. The remaining sections 28a and 28b of fiber cladding 28 are configured to be more opaque with fewer microdot holes along an appropriate calculated side emission power curve to compensate for the greater power emission of UV light from fiber section 18b' closer to UV laser source 10 and the substantially uniform side output power along the length of the fiber.

[0132] Using an endoscopic biopsy channel 20 or a catheter with a relatively long diameter, e.g., 4 mm or greater, a series of offset, connected, vertical UV LEDs 21a, 21b, and 21c contained within a transparent, UV-light-transmitting sleeve 24 is inserted into the end of the biopsy channel 20, as shown in FIG. 3A. Each LED faces the biopsy channel's inner wall 20a and is offset from one another by 120° to ensure total UV light coverage of the inner wall 20a, which is 360°. During sterilization, the LEDs first rotate fully to ensure full UV light coverage with the stationary base of the stacked series of LEDs before extracting the sterilizing agent.

[0133] In FIG. 3B, an end view of biopsy channel 20 shows an alternative single-plane version with three inserted LEDs 22a, 22b, and 22c arranged in a single plane in a triangular configuration, such that the LEDs each emit UV light at an angle of 120° relative to the inner wall of biopsy channel 20a.

[0134] FIG. 3C depicts a single LED 23 on top of a cylindrical copper heat sink structure 24a sized to be placed longitudinally in the biopsy channel, with the LED providing a conical circular UV light output at an angle that strikes the wall 20a of the biopsy channel into which it is inserted.

[0135] Due to size constraints, the LEDs are low powered to a size suitable to fit inside the channel, but full power without attenuation losses is directed to the channel walls. The LED arrangement is provided with a power input and is provided with a sufficiently rigid positioning rod, wire, or cord (not shown) used for positioning and controlled movement.

[0136] 4 schematically illustrates a cancer tumor site 30 where the tumor has been surgically removed, with the removal area 32 depicted in phantom by a dashed line. UV light 19 directed from a fiber 18 delivered to the tumor removal site 30 by an endoscope (not shown) is spread prophylactically over at least the tumor removal area 32 and an adjacent area 31, as depicted by the circular area 19a, which delays the return of invasive cancer and increases the duration of remission. This is similar to BCG treatment of a bladder cancer site with a superficial treatment to prevent recurrence. The superficial treatment may be used in conjunction with or instead of an existing superficial treatment.

[0137] Figure 4A shows the general procedure of Figure 4, in which a bladder 40 has had a tumor removed at site 42 on the interior wall 41 of the bladder. UV light 19 from a fiber 18 inserted through the urethra 43 is aimed at at least site 42 and the surrounding tissue of wall 41 to maintain remission and prevent tumor regrowth.

[0138] A cancer treatment protocol is depicted diagrammatically in FIG. 5A, in which the periphery of a cancer site 100 or its interface 33 with healthy cells is detected and defined by a biopsy procedure. UV light 19 from fiber 18 is directed at adjacent healthy cells 19b at the periphery, creating a separation line or "firebreak" of dead cells 33a and disrupting cellular nutrient pathways therein. As shown in FIG. 5B, a deeper "firebreak" or cancer growth barrier is achieved by surface treatment of approximately 40 microns, including UV light-directing fiber 18 (delivered to the site through a biopsy channel by an endoscope, not shown, as described in the parent application) extending from aspiration needle 18a, penetrating region 31 at a lower depth of the interface to increase the depth of the "firebreak," resulting in increased depths 19c and 19d, as shown. This inhibits cancer cell growth and limits metastasis. Phagocytic cells, which remove dead cells, create a separation between cancer cells and healthy cells, and blood vessels responsible for supplying nutrients are also destroyed to prevent cancer growth and progression.

[0139] Figure 5C is a depiction of a cross-section of a colon 105, showing various stages of cancer tumor growth, ranging from a non-surface colonic tumor 99, through stage 1 (101) with mild superficial invasion, stage 2 (102) with superficial invasion, stage 3 (103) with complete superficial invasion, and stage 4 (104) with complete invasion and extracolonic spread and spread to other organs (metastasis). A stage 2 cancer is shown as an example of treatment using the treatment protocol in Figures 5A and 5B (because the colon has a lumen and the cancer is a superficial type, it is best removed surgically). Multiple needles are penetrated while deploying UV light from fibers 18 (19a) in the tissue surrounding the tumor 102, creating a "firebreak" of dead cells around the tumor and slowing further spread of the cancer into the surrounding colonic surface tissue.

[0140] 6 illustrates another UV treatment protocol for a cancer site 100 in which the tumor 100 itself is completely penetrated by an aspiration needle 18a, followed by extending the fiber 18 to treat the surrounding tissue laterally. As shown by the dashed lines, the needle 18a of the fiber 18 is withdrawn and inserted multiple times around the initial needle placement to expand a core region of dead cancerous tissue 19c for coring treatment. Ablative removal of the core tissue is achieved by deploying a secondary needle in the core region while applying suction or fluid lavage (or allowing phagocytes to remove the dead cells in time) to enlarge the small lumens within the tumor, further expanding the UV treatment and allowing for the continued destruction and formation of a dead cell layer for sustained removal.

[0141] Figures 7A-7C illustrate such extended cancer cell removal using a fiber 18 shown directing UV light onto (or within) cancer tissue 100 located at healthy cells 31 (cells are depicted schematically as light and dark brick components representing healthy cells 31 and cancer cells 101a, respectively). Raster deployment of UV light 19 at destructive power levels kills cancer cells in the layer exposed to the UV light (Figure 7A). The dead cells are then treated in a raster deployment by ablative power levels of UV light 190, which results in removal of the dead cells by fluid washing and / or fluid aspiration, as shown in Figure 7B. The destructive power levels of UV light (typically in the double-digit milliwatt range) are sufficient to kill cancer cells, which are unable to self-heal compared to healthy cells. Dead cells have reduced cell-to-cell adhesion and are easier to remove by ablative means. The destruction / ablation raster procedure is repeated (preferably automatically or robotically) to successively kill and ablate cancer tissue cells 100a, as shown in FIG. 7C, to reduce the size of or eliminate the tumor.

[0142] In the non-traumatic ablation of cancer cells depicted in the sequential figures in Figures 7A-C, the surface layer of cancer cells is treated with UV light to the point of DNA / RNA destruction and eradication (Figure 7A). The UV power level is then increased to a minimum ablative power, aimed at the dead surface cancer cells to effectively wipe them out (Figure 7B). The exposed new surface cancer cells are then treated again with UV light, which destroys and ablates them in a raster pattern. Depending on the duration of each cycle, and assuming 10-second cycles and 40 microns of ablation per cycle, a total treatment time of approximately 2500 seconds per cancer site, or approximately 42 minutes, is required to remove a 1-cm-thick layer of cancer. The destruction is at the molecular level and not physically discernible, and the ablation cycle requires the minimum effective power, if any, to remove dead cells with minimal trauma (less than that required to ablate live cells), certainly orders of magnitude less than standard radiation therapy. Fiber-optic endoscopes used for destruction / ablation procedures have water, air, and suction channels that are used during and after the ablation procedure to expose additional cell surfaces to facilitate cleanup and removal of dead cells. Biofeedback, such as the emission of cancer cells, provides a visible indication of the effectiveness of cancer cell removal.

[0143] FIG. 8 shows schematically the removal of the cyst 320 by surgical excision 321 (FIG. 8, steps A-E) and subsequent UV light treatment (step F) via optical fibers that deliver UV light to the exposed surface of the cyst to prevent further growth of cancer cells 323, etc.

[0144] Figures 9A and 9B illustrate the specific preventative inactivation of pancreatic cysts 330 (a precursor to the development of many pancreatic cancers). As shown in Figure 9A, pancreatic cyst fluid 331 (containing DNA) is inactivated by UV light 332, and the fluid 331 is drained. Alternatively, the fluid 331 can be removed first, and the remaining cavity surface 334 treated with UV light 332b (Figure 9B) to prevent the development of pancreatic cancer therefrom.

[0145] 9C shows the application of UV light 342 inactivation treatment to epithelial cells 341 in the antrum 340, which are prone to intestinal metaplasia by becoming enterocytes. Because such cells are indistinguishable, surgical removal of them is nearly impossible. Instead, UV light 342 is delivered using an endoscope 345 to reach the stomach lining in areas prone to intestinal metaplasia, "photon-ablation" of enterocytes in a thin layer across the entire surface, allowing fresh epithelial cells to grow to replace them.

[0146] As shown in FIG. 10 , UV light treatment of pancreatic cancer, shown as tumors 111 and 112 in pancreas 110, facilitates initial tissue removal by inserting an ablative chemical into the tumor via an aspiration needle 118, which reaches the tumor via the duodenum 113 adjacent to the pancreas. The tumor is made more transparent to light, thereby effectively increasing the penetration of UV light subsequently applied to the tumor using the aspiration needle from approximately 40 microns to at least one to several millimeters, thereby providing an effective, non-traumatic tumor-killing means not previously available. This treatment is effective against all cancers, since they all contain DNA / RNA that is destroyed by UV light. While needles or similar devices are used to deliver the chemicals to ablate the tissue, fibers themselves, as well as needles, can be used to penetrate cancerous tissue and directly deliver the cancer-destroying UV light.

[0147] 11A and 11B illustrate the use of an endoscope 120 to deliver an aspiration needle 153 to a cancerous tumor 151 above a lymph node 152, and the needle 153 (used in the prior art to deliver ultrasound instruments for EBUS and TEBUS, tumor mapping and therapeutic procedures) also delivers a UV-emitting fiber to the tumor and a solvent to clear the tumor. As shown, the endoscope 120 is inserted into the patient's esophagus 154, and the endoscope's insertion tube 121a delivers the needle 153 to a position adjacent to the cancerous tumor 151. As shown in the enlarged view of FIG. 11B, a biopsy channel elevator 123 within the insertion tube 121a controls the placement of the needle 153 relative to the tumor 151. Control of needle 153 is independent of control of fiber 18 contained therein (as shown in FIG. 12 ), whereby needle 153 with fiber 18 inside is inserted into tumor 151 and needle 153 is retracted, leaving the UV-emitting distal end of fiber 18 embedded within tumor 151. UV light transmitted through fiber 18 as light 19 effectively kills pathogenic (as defined) cancer cells from within the tumor without significantly affecting healthy cells.

[0148] Figure 13 shows a schematic of a collimated output beam 350 from a single LED light source 351. Multiple arrays of LEDs provide increased output power and / or increased surface area for sterilization. The single collimating lens 350 and array of collimating lenses in Figure 13 maintain an output beam with a controlled, substantially uniform diameter over a given collimation distance. This output is suitable for maintaining substantially full, effective DNA / RNA-destroying UV power for relatively short-distance applications.

[0149] Figure 14A depicts one embodiment of a penlight-style device 360 ​​configured to emit collimated UV light. The minor diameter of the penlight-style device 360 ​​is approximately 15-20 mm, as described, to facilitate ready use in a child's mouth. Figure 14B is a partial cross-sectional aperture view of the optical section of the penlight, which includes an LED emitting element (UV 361 and illumination 363) light with a collimating lens 362 inside a position-locking housing with a protective, flat, transparent closure.

[0150] As shown in Figure 14B, a camera 365 is included to detect the response from a fluorescent stimulation LED 366, which causes bacteria to fluoresce at a specific wavelength. This allows for detection of the effectiveness of UV light in inactivating bacteria and / or viruses, allowing for proper targeting of the penlight-style device toward pathogens. A ribbed control element 367 is used to control light emission, and an optional light guide prevents stray UV light from escaping from the designated path. A metal container body 368 is used to avoid UV degradation of plastic or polymeric elements. A rechargeable battery pack 369 is enclosed in the distal region of the penlight structure. The battery provides at least 30 minutes of typical UV light use; the battery pack may be interchangeable and may be separately rechargeable. Various sizes of speculum 370 for removable use with the penlight-style device are shown in Figure 14C.

[0151] Use of the penlight-style device 360 ​​is shown in Figure 14C as a lateral cross-sectional view of bacterial and viral infection sites in the nasal cavity, mouth, and throat. Figures 14D and 14E show schematically the area 371 where UV light can be directed for maximum pathogen inactivation with a suitable speculum.

[0152] FIG. 15A shows a cross-sectional view of an otoscope-type device 50 commonly used to apply light to exposed orifices, such as those for breathing, feeding, and excretion, to visualize these areas. The device is modified to effectively transmit UV light and bacterial fluorescent light to areas infected with bacteria or other pathogens. The device 50 includes a built-in power supply 51 in the handle housing 52 (power lines for additional power can also be attached to the handle), which provides power to pathogen-destroying UV radiation from a UV LED 57. The UV light is transmitted and directed through the transmission medium of a collimating lens 56 and a beam splitter 55 to a speculum 58 aimed at the area infected with bacteria or other pathogens.

[0153] The configuration of the otoscope 50 includes the ability to snap on a removable speculum-type adapter 58, which may contain additional optics such as lenses, fibers, or light pipes, to provide further access to inaccessible or difficult-to-reach areas such as the Eustachian tube, trachea, sinuses, surgical openings, and wounds, e.g., access openings for sterilization of implanted devices.

[0154] The reduced cone portion 59 has an external distal white LED 59a for illuminating the target site. A CCD camera chip 53a receives an image of the target area and transmits it for viewing on the screen 53. UV light 190 emitted from the cone portion 59 illuminates the viewing site with UV-destructive light to kill pathogens in the viewing area. As shown in FIGS. 16A and 16B, light of a wavelength such as 405 nm fluoresces bacteria 64 at the surgical site 62, and the otoscope device includes an LED 57a that emits such light on demand, allowing the user to view the fluoresced bacteria 64 on the display screen 61 and move the aim of the otoscope device 50 to direct the fluorescent light and UV light to facilitate eradication of pathogens at the bacterial infection site 64. Alternatively, a fluorescent light source, which may include several light sources (of different wavelengths that fluoresce different bacteria), may be incorporated into the ring 59a along with the white light illumination LED.

[0155] Target sites include sore throats in the mouth or surgical sites 62, as shown in FIG. 16D. When used pre-, intra-, and post-operatively, targeted collimated UV light from a device such as otoscope-like device 50 significantly reduces even the most disinfectant-resistant bacteria from the site by eliminating MRSA and reducing, if not eliminating, SSIs. While shown as handheld in FIG. 15B, the device could be supported on a motion-controlled stand (away from the surgical procedure) and even be automatically guided by feedback provided by bacterial fluorescence to apply UV light 190 thereto. While the UV light is shown as being offset 90° from the generating LED, it could be applied more directly by repositioning the light source within the device to output the UV light directly through output section 59 directly from the transmission lens.

[0156] The UV light-emitting otoscope shown in Figure 15A is similar in concept to the penlight-style configuration of Figures 14A-14D, but with a larger battery in the handle and an otoscope configuration. A UV-emitting LED in the handle directs UV light to a beam splitter, which directs it to a collimating lens, transmitting a substantially uniform, collimated beam from the end of the speculum that maintains UV germicidal power for a distance of approximately 6-8 inches, sufficient for entering and disinfecting human orifices such as the mouth, nose, and anus. The otoscope is equipped with a display screen and CCD camera for direct inspection of bacterial fluorescent areas stimulated to become visible by a 405 nm stimulating LED. The camera display is viewable on a separate, magnified screen via HDMI®, which wirelessly transmits images and video to a receiver linked to the screen. The otoscope can be used to disinfect a surgical site and monitor bacterial kill, as shown in Figure 15B. Figure 15B shows a displayed image of real-time bacterial kill status during a surgical procedure.

[0157] FIG. 17 is a flow chart illustrating a process for bacterial fluorescence detection for use in an otoscope, such as during a surgical procedure shown in FIG. 15B. The process begins with raster imaging of the site being examined after calculated fluorescent illumination of the site. By calculating the fluorescent images captured at rasters of different colors and intensities (for different types of bacteria and their respective fluorescent responses), bacterial pathogenic activity can be determined. Both the initial detection of pathogenic sites (intensity indicating the degree of bacterial infection) and a decrease in intensity indicate real-time UV light germicidal effectiveness.

[0158] Figure 18 is a ray tracing simulation 390 of the collimated UV 391, white 392, and 405 nm fluorescent 393 light output emitted from the otoscope of Figure 15A. Figure 19 shows the placement of the collimating lenses and respective UV 391', white 392', and fluorescent 393' light sources within the otoscope, and includes a close-up view of the otoscope's optical system, including the white light illumination light guide 395, UV, white, and blue LEDs (indicators that UV light generation is active), UV and blue light collimating lenses, camera lens, and camera sensor.

[0159] FIG. 20 depicts a currently used nasal endoscope configuration 50′ fitted with a UV delivery fiber 18c (and built-in UV light source and power source—not shown) for disinfecting bacteria in areas requiring a fiber extension to reach, such as the inner ear 150 suffering from an ear infection via the Eustachian tube 151.

[0160] FIG. 21 shows a cross-sectional view of an implanted pacemaker 71 in a human body, in which a UV optical fiber 180 is used to sterilize the pacemaker in situ. FIG. 21A illustrates the sterilization procedure in a cross-sectional view of a pacemaker implanted in a pocket 74 between the outer skin 72 and a muscle layer 73. The UV delivery fiber 180 is inserted into a skin incision adjacent to the pacemaker and then travels across the surface 71a of the pacemaker, providing in situ sterilization without the need for surgical removal and its attendant complications. To facilitate sterilization, and because the fiber is inserted laparoscopically rather than through an endoscope, the fiber can be provided with a wide UV light-dispersing end that can also serve as a wedge to separate the surrounding skin from the pacemaker surface. Other implantable devices can be similarly sterilized in situ.

[0161] 22 and 22A illustrate additional embodiments for use in endoscope biopsy channels, particularly in endoscopes that are not readily sterilized and in which biofilms have begun to form on pathogens contained within the biopsy channel. This biofilm can slow the action of UV light on the pathogens by limiting penetration. The combination wire with integrated absorbent material 80 functions to destroy the biofilm and any UV light-blocking properties. As shown in FIG. 22A, a relatively stiff wire element 81 with a spongy absorbent section 82 (similar to a dental floss-type configuration) of the combination 80 is inserted into the biopsy channel 20 prior to insertion of the UV light-emitting fiber. The absorbent section 82 expands radially in the direction of the arrow, fully engaging the channel wall 20a and the biofilm 83. The absorbent section material 82 destroys any biofilm by absorption and physical engagement, particularly as the absorbent section 82 is moved by retraction of the wire support 81 and removal of the combination from the biopsy channel.

[0162] The chart in the flow chart of Figure 23 shows that light (including UV light) is normally prevented from passing through tissue 91 as a result of the presence of light-scattering lipids and light-absorbing pigments in the tissue. Collagen dissociation, delipidation, decalcification, dehydration, and refractive index matching with superhydration serve to reduce light-scattering effects within tissues and cells. Pigment removal, followed by bleaching, serves to reduce light absorption within tissues and cells to the extent that tissue removal renders the tissue essentially transparent. This has been done in vivo to directly observe biological processes in animals and some functions relevant to humans.

[0163] Figure 23A shows prior art work, Sung, K. et al. Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping. Sci. Rep. 6, 30736; doi: 10.1038 / srep30736 (2016), in which a mouse brain 92 was cleared from opaque to translucent 92a (12 days) to completely transparent 92b (19 days), with marks 94 on the base support 93 visible through it. Figure 9C shows similar prior art tissue clearing of a human basal tumor 96 from opaque to translucent / transparent 96a (21 days). Thus, these studies demonstrate tissue clearing in human tumors, whereby UV light extends from a penetration depth of at least one millimeter to penetration throughout the tumor and UV light treatment of all cancer cells in the tumor without trauma such as X-rays or gamma rays. Furthermore, tumor size can be controlled without trauma, sometimes even reaching the size of stage 4 cancer treatment.

[0164] It will be appreciated that the procedures described in Figures 4-12 may be used in combination with tissue removal procedures to facilitate operations with increased penetration depth of UV light.

[0165] Proper mapping of the tumor with controlled administration of tissue-ablation chemicals effectively limits the chemical effects of tissue ablation to the tumor and some surrounding tissue (ensuring complete eradication of the cancerous tumor). Tissue ablation, especially when so limited, is not itself a significant toxic procedure, and lipid and pigment recovery to the ablated tissue is also believed to occur over time. Limiting tissue ablation to the tumor (and surrounding tissue) also provides an automatic barrier to prevent the spread of tissue necrosis by UV light applied to areas surrounding the tumor that were not ablated due to the lack of significant penetration depth in those areas.

[0166] Figures 24A-24C illustrate various embodiments in which UV light may be utilized to rapidly sterilize the exterior of an endoscope or other similar medical instrument. As previously mentioned, fears of UV light destroying endoscope polymers have discouraged complete endoscope sterilization with UV light, but the device embodiment of Figure 24A allows for very rapid sterilization before the UV used for sterilization has time to affect the polymer (UV destruction of DNA / RNA in pathogens is much more rapid than degradation of polymer bonds). Figure 24A illustrates an endoscope 120 in which a first diameter operating handle portion 120b and a shorter diameter insertion tube 120a are enclosed and locked into position within a transparent protective housing 121 having a longer diameter 121 and a shorter diameter 122.

[0167] Endoscope 120 is enclosed in protective housing 121 and fits into larger corresponding structures 221 and 222, shown in FIG. 24B, with structure 221 having an array of UV-emitting LEDs on its inner surface. Protective housing 121 engages with rotating element 225 powered by motor 223. This allows endoscope 120 to be fully exposed to UV light (passing through protective housing 121) from a short distance, and once the calculated complete sanitization has occurred, the LEDs are turned off, the protective housing is removed from structure 221, and the endoscope is removed from protective housing 121. The endoscope's UV light exposure time can be as little as a few seconds to a few minutes, depending on the output of the LEDs, and is well short of any time that the UV light will affect the endoscope's polymeric components. The automatically controlled timing of LED activation with rotation ensures that the endoscope is not exposed to UV light for any additional time beyond the time required for sanitization.

[0168] Figures 24C and 24D depict another automated method for sterilizing endoscopes using UV light. In Figure 24C, an endoscope 120 with a small diameter insertion tube 120a and a larger diameter handle 120b is suspended by a hook 120'. A track element 126 has a track groove 127 with a length A equal to or greater than the insertion tube 120a. A movable track element 129 controllably moves up and down the length of the track groove 127 and includes a handle portion 128 and a small ring 128a (sized to closely accommodate, but not touch, the insertion tube 120a), with UV LEDs distributed around its inner periphery. During use, the track groove 127 is aligned with the insertion tube 120a, and the insertion tube is inserted into the ring 128a. The LED within ring 128a is activated, and ring 128a is moved manually using handle 128 or mechanically with movement of track element 129 along the length of track groove 127, so that every portion of insertion tube 120a is immersed in UV light for a sufficient time for sanitization thereof.

[0169] 24D shows a similar track element 126a with a track groove 127a of length B (the same as or greater than the handle portion 120b of the endoscope), with a track element 129a, a handle portion 128', and a larger ring 128'a sized to accommodate the longer diameter of the handle 120B. The handle 120b of the endoscope 120 is sanitized in a manner similar to that used with the insertion tube. UV exposure time should be limited to the time necessary for sanitization and no longer to avoid any impact on the integrity of the polymer.

[0170] 25A and 25B illustrate an example of a manufacturing procedure requiring the sanitization of large quantities of items, such as laboratory pipettes, syringes, or catheters (almost all of a cylindrical configuration). FIG. 25A depicts an array of manufactured pipettes 131 in a processing case 130, each with its open end facing upward. The conveyor sanitization station 135 in FIG. 25B shows a linear arrangement of multiple cases 130 with an array of pipettes, as shown in FIG. 25A, where the pipette cases are arranged on an assembly line in a uniform bulk configuration. In the illustrated station position, a bulk sanitization element 136 is movably positioned on a track 137. The sanitization element 136 includes short, downwardly extending UV-transmitting fibers 138 whose relative positions and numbers correspond to the pipettes in the cases 130 within the array. The sanitization element 136 is moved sequentially into alignment with the pipettes 131 in the cases 130 and then stopped. An array of aligned short UV-transmitting fibers is lowered together and inserted into the aligned pipettes 131, and UV light is transmitted through the fibers into each of the aligned pipettes for a time sufficient to effect sanitization. The fibers are withdrawn for sanitizing in the next batch, and the sanitizing elements are moved to the next case for the same sanitization, making the process continuous, fast, economical, and reliable sanitizing procedure, requiring no chemicals or cleaning.

[0171] An automated and data-controlled biopsy channel sterilization apparatus is shown in Figures 26A-26B along with a sterilization protocol. As a first step, in Figure 26A, the distal end 18" of the UV-emitting fiber 18 is inserted into a power measurement device to verify the amount of UV power emitted by an integrating sphere 145 that collects the power impinging on the wall 148 and measures the collected power onto a detector 147. The alternative UV-emitting laser apparatus 10 shown in Figure 1A has a built-in power output measurement meter positioned to measure the UV power output 9a.

[0172] The output power from either the detector 147 in FIG. 26A or the power meter in FIG. 1A is fed to a computer (not shown), which also factors in the fiber diameter and inner diameter of the biopsy channel to determine the distance between the fiber to be sterilized and the biopsy wall. A table of pathogens with their individual requirements for DNA / RNA destruction is included in a computer database that calculates the appropriate in-position dwell time for effective sterilization (with an additional safety margin). The computer output is sent via input 143 to the timer 141 and retraction device 140 in FIG. 12B for control of the fiber retraction time by the retraction device 140. The UV-emitting fiber 18 is fully inserted into the biopsy channel 120 in FIG. 12B and connected to the puller element 142, and the retraction device 140 is activated to retract the fiber 18 while UV light continuously passes through the fiber 18 and exits its distal end along with the UV light 19, sanitizing the walls of the biopsy channel with continuous in-position UV radiation and a dwell time consistent with the calculation for complete sterilization. The retraction device may be either linear (having a length longer than the length of the biopsy channel on the fiber guide bed 246) with a relatively inflexible fiber, or spool-shaped with a flexible fiber. This process may be a single step or may be repeated as needed to further ensure sterilization. In either case, sterilization time generally ranges from approximately 1 to 5 minutes, depending on the UV power and application distance. Automation and computer control minimize human error and inconsistency, ensuring more reliable sterilization, especially since direct visual control is not possible. It is understood that the sterilization time via UV light application is extended to include a safety buffer period to ensure complete sterilization regardless of the nature of the pathogen being eradicated.

[0173] Fiber 18 may also be provided with an RFID device or the like to verify that the fiber is an authentic fiber with adequate UV solarization resistance and UV transmission capabilities. The RFID device may also be configured to shut down operation at a predetermined point of unacceptable fiber degradation and to track the number of times the fiber has been used to transmit UV light.

[0174] FIG. 27 illustrates an embodiment that utilizes a collimated lens 410 to rapidly sterilize medical instruments, particularly during surgical procedures. A housing or box 411 is configured to hold a medical instrument, such as the illustrated scalpel, and an array of collimated UV light 410 completely surrounds the scalpel 412. The scalpel is mounted on a UV-light-transmitting support 413, allowing the UV light to completely sterilize it from all directions. Because various surgical instruments vary in size and configuration, a distance from the support to the UV LED light sufficient for the size of the instrument to be sterilized may be required, or the distance may be variably adjustable. However, the collimated lens 410 substantially maintains the radiant power of the sterilizing UV light over the short distance between the light source and the sterilization site of the instrument, rather than the UV light typically dissipating with a significant loss of sterilizing power.

[0175] The UV LED array can statically surround the scalpel, or it can rotate around the scalpel. Alternatively, the UV LED array can move in a linear direction. The movement of the UV LED array helps ensure that the UV light completely sterilizes the instrument, including crevices and irregular surfaces. Current UV sanitizing boxes without collimation, such as those used to sanitize cell phones, suffer from UV light dissipation and typically require at least 10 minutes to provide acceptable sanitization. However, this is unacceptable in surgical situations where instruments need to be sterilized or replaced quickly. As shown, these boxes effectively provide complete sterilization in less than one minute.

[0176] Figure 28A is a side view of a UV light hand sanitizer 500 showing the flow of sanitizing UV light 510. A hand 511 is inserted into the slot, and the entire surface of the hand is bombarded and sanitized. The UV-C light has minimal surface effect (approximately 40 microns), thereby leaving the skin unaffected but inactivating biological hand contaminants and pathogens on the surface. It is understood that use of this device is combined with a hand cleaner and dryer to remove soiling that may interfere with the UV light. The sanitizer is integrated with a hand blower or used as a separate final hand hygiene step. Figure 28B depicts external hand sanitization, in which the hand 511 is exposed to the emitted (downward) UV light 510 while the hand is moved and rotated, similar to the operation of a hand dryer. The UV light is directed downward to avoid potentially irritating eye contact. FIG. 28C shows an embodiment of a sanitizing device 500' with a circular opening 500a for hand insertion, with 360° placement of UV emitting diodes.

[0177] Figures 29A-C show the dental application of UV light in a dental office environment 600, with UV treatment 610 for tooth decay and periodontal disease. In Figure 29A, a young patient is shown wearing a UV-emitting instrument 640 used to treat tooth decay (bacterial infection) as shown in Figure 29B. The instrument has a speculum 641 that is curved to easily reach the surface area of ​​the tooth 650 or gums 651. Figure 29C schematically depicts, in cross section, an extension of a short diameter (50-100 um) embedded optical fiber that can be inserted into the fissures of a tooth to reach and disinfect the site of a bacterial infection, including the root cavity, through which UV light is transmitted.

[0178] Dental instruments, including saliva evacuation systems, are not disposable, are not removable, and often have parts that cannot be autoclaved or otherwise easily sterilized. Instruments such as the aforementioned penlight or UV-emitting otoscope devices are readily available to provide focused sterilization of patient-accumulated pathogens, thereby reducing the incidence of cross-contamination by patients.

[0179] 30A-30B show the incorporation of a UV light transmitting light element 700 modified from a penlight configuration into a surgical light 710 with a camera element 720. A headlamp used by a surgeon during a surgical procedure that is closest to the surgical site can similarly be utilized to sterilize the surgical site.

[0180] It will be understood that the above description and examples of the invention are merely illustrative and that changes in components and procedures may be made without departing from the scope of the following claims.

Claims

1. 1. A method for enhancing the pathogen eradication effect of UV light at wavelengths between 200 nm and 340 nm in a pathogen-infected area, comprising: a. increasing the effective controllable output power of a UV light source emitting device and directing the increased output power of UV light into the pathogen-containing difficult-to-access region by either direct placement of the UV light source within the difficult-to-access region or directional transmission of UV light from the UV light source into the difficult-to-access region, wherein the direct or transmitted light maintains sufficient power to substantially eradicate pathogens in the pathogen-containing region accompanied by DNA / RNA destruction; b. positioning said UV light with directional transmission of said UV light at a surgical site before, during, and optionally after a surgical procedure to maintain a substantially pathogen-free environment during said surgical procedure, or directing transmission of UV light at an infected opening to disinfect; c. Making a pathogen-infected site susceptible to significant UV light penetration for eradication of the pathogen, or i. making the pathogen site more permeable to penetration of UV light; ii. Using UV light pathogen eradication to form a pathogen eradication barrier between the pathogen-infected site and a non-pathogen-infected site; or iii. Making the pathogen-infected site more susceptible to the significant UV light penetration by repeated steps of pathogen eradication of infected areas and removal of the pathogen-eradicated areas, and isolating additional pathogen-infected sites by exposing them to the UV light.

2. 10. The method of claim 1, wherein the UV light source is a UV light emitting laser having a relatively high UV light output power sufficient to provide pathogen eradication power along substantially the entire length of a side-emitting optical fiber attached in optical alignment with the output of the laser.

3. The method of claim 1 , wherein a handheld device is configured to deliver pathogen-eradicating UV light from a location remote from the surgical site or infected orifice.

4. 10. The method of claim 1, wherein the pathogen infection site is in or on a human or animal body, and the pathogen infection site is tissue that has been removed to make it more permeable to UV light penetration.

5. 10. The method of claim 1, wherein the UV light is collimated at a distance where pathogens are located and the output power is maintained at such distance for eradication of said pathogens.

6. 6. The method of claim 5, wherein the UV light is collimated within a handheld device comprising a penlight or otoscope configuration, whereby collimated light is emitted therefrom for pathogen eradication within a collimated distance that maintains said power.

7. 7. The method of claim 6, wherein the handheld device is configured to emit light at a wavelength that causes bacteria to fluoresce to enable identification of bacterial infection sites and provide feedback on the effectiveness of the UV light in eradicating the pathogens.

8. 10. A handheld device configured to perform the method of claim 6, comprising a UV light source, a source, that emits light of a wavelength that causes bacteria to fluoresce to a degree and extent that enables the use of fluorescence in UV light direction for pathogen eradication and that determines the effectiveness of such pathogen eradication.

9. 6. A device for performing the method of claim 5, comprising the collimated UV light from a light source, the direction of the collimated UV light being directed toward a hand positioned within a distance at which the power is maintained for hand hygiene.

10. 10. A medical instrument sterilization enclosure for performing the method of claim 5, comprising a stationary or moving array of collimated UV light aimed at an instrument for rapid sterilization of the instrument.

11. A method for providing prophylactic prevention of any one of bladder cancer, stomach cancer, and pancreatic cancer, the method comprising the respective steps of emitting UV light to eradicate potentially cancer-forming cells in situ in the bladder wall, stomach lining, and pancreatic cysts, respectively, with UV light of sufficient power to eradicate said potentially cancer-forming cells.

12. 10. A device for performing the method of claim 5, comprising a catheter or endoscope having an instrument channel, the catheter or endoscope containing at least one UV-emitting LED in the catheter or instrument channel, the distal open end of the catheter comprising a collimating lens whereby UV light is emitted from the catheter or endoscope for a collimated optical distance with sufficient power to eradicate pathogens in the collimated optical path.

13. 10. A device for performing the method of claim 5, comprising a UV light source configured to emit UV light to eradicate pathogens at a surgical site within a distance of the collimated light.

14. 6. A device for performing the method of claim 5, comprising a UV light source configured to emit UV light to eradicate dental site pathogens on teeth or gums within the distance of the collimated light.

15. 10. The method of claim 1, wherein the medical implant is sterilized in situ by introducing UV light into the body and aimed at the surface of the medical implant at a power and for a duration sufficient to sterilize the medical implant of the pathogen.

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