Apparatus, system, and method for cleaning, accelerating healing, and enhancing cellular activity for therapeutic effect

Abstract

An apparatus for generating a stream to treat a surface includes a base unit connected to a combined treatment unit (4, 14) including a body (4) defining a chamber to contain a liquid and discharge a stream of the liquid through the nozzle (14) toward the surface, and a manifold integrally formed together as a single piece with the body. The manifold is connected to a liquid supply conduit (42) to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber. The base unit includes an acoustic transducer positioned and configured to generate acoustic energy and to introduce the acoustic energy into the liquid contained in the chamber, and a casing (55) containing the acoustic transducer and having a mounting piece (52) engaged with the combined unit to releasably connect the combined unit to the base unit.

Description

Patent Application Attorney Docket No. 008634.01587VWOAPPARATUS, SYSTEM, AND METHOD FOR CLEANING, ACCELERATING HEALING, AND ENHANCING CELLULAR ACTIVITY FOR THERAPEUTIC EFFECTCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a nonprovisional of, and claims priority to, U.S. Provisional Application No. 63 / 683,534, filed August 15, 2024, the entire disclosure of which is incorporated by reference herein.FIELD OF THE INVENTION

[0002] This disclosure relates to an apparatus for various treatments, including cleaning and / or providing other biological therapeutic effects using ultrasonic techniques, and more specifically, to an apparatus using acoustic energy propagated through a stream of liquid and to methods for cleaning and providing therapeutic enhancement of biological mechanisms and / or pathways using such an apparatus.BACKGROUND

[0003] Cleaning, in general, is an essential part of everyday life used to prevent the transmission and acquisition of infectious or pathogenic contaminants causative of disease. There are many research, commercial, and public service areas, such as healthcare, laboratory work, joining, and manufacturing, including, but not limited to, processing and packaging produce and other beverage / food or biological products (e.g., enzyme-related substances, living cells, genetic material, forensic samples, tissues, organs, etc.), as well as in the defense, clean water, sewage, chemical, and nuclear sectors, where efficient cleaning, often with limitations in cleaning options, is paramount. Providing sufficient cleaning (dependent on risk) is often a complex process: the object to be cleaned may contain complex geometry and topography, with many crevices, peaks and troughs, or chambers that can be inaccessible to many cleaning techniques; and potential contaminants may be hazardous, providing a risk for secondary contamination or infection if not treated correctly (good examples being endoscopes, surgical instruments, and patients themselves). The objects to be cleaned may be delicate (good examples of this being salad and vegetable matter, electronic microchips, human or animal tissues, forensic material, etc.), limiting the practicality of harsh cleaning processes reliant on potentially damaging chemical or mechanicalPatent Application Attorney Docket No. 008634.01587VWO mechanisms of action. Furthermore, many delicate surfaces tolerate minimal levels (or indeed are not tolerant at all) of scratching and damage (such as contact lenses, photography optics, astronomical and scientific optics, astronomical and scientific optics, jewelry, prestige watch glasses and faces, prestige car finishes, surgical instruments, etc.). Surface damage can cause unwanted cosmetic defects, but more importantly scratches become reservoirs which can harbor further contaminants (e.g., dirt, biofilm, etc.) making subsequent cleaning more difficult, and increasing the risk of infection (e.g. in tissues and organs, salads, foliage, etc.). Often the time available for cleaning is limited, as there is an imperative to move the object along to the next stage of processing or usage after it is cleaned (either because the number of units available for use is limited - as with endoscopes and other surgical instruments - or because retardation of through-put cuts profile - as, for example, in the production and packaging of fresh produce like salad). Damage to the target may include, for example, degrading food or skin through the use of cleaning or disinfectant products, alcohol gel, etc., and / or excessive heating; scratching of surgical instruments, optical or electronic components through brushing or scrubbing, or other damage.

[0004] Cleaning often uses relatively large amounts of water, even for “natural” products: the production of 1 ton of wool currently requires use of around 500 tons of water. When one considers the biohazardous waste of a hospital or abattoir, or the cleaning associated with chemical and nuclear plants, water conservation becomes a very major concern. The requirement for thorough and efficient cleaning is often in conflict with the requirements not to damage the target to be cleaned or decontaminated, not to use excessive water or harsh cleaning chemistries, not to contaminate the environment with run-off containing chemicals (e.g. cleaning products) or removed contaminants (which might then enter groundwater supplies further complicating the treatment processes used to produce clean water), and not to use excessive energy or staff numbers or time. In certain scenarios, the required water and / or cleaning materials may be in limited supply, for example cleaning wounds or other human tissue (e.g. eyes) in a clinic or field setting (e.g. a healthcare worker travelling with all equipment in a car or motorcycle), in a battlefield, rescue, or refugee scenario. In other scenarios and settings (such as oral and other anatomical pockets and cavities), the user may require low volumes of liquid to avoid flooding the cavity or pocket which could hinder the user and cause discomfort for the patient.Patent Application Attorney Docket No. 008634.01587VWO

[0005] Ultrasonic cleaning has been known in the art for many years, by the use of “ultrasonic cleaning baths,” whereby inertial cavitation and the generation of high-speed liquid jets through bubble involution remove surface contaminants. The exploitation of cavitation in ultrasonic cleaning baths has for decades provided facilities that are suitable for applications which have robust objects to be cleaned (i.e. where cavitation erosion damage of the target is not an issue), where the size of the object to be cleaned is small enough to be immersed in the cleaning bath, ideally when the object contains minimal or no internal cavities or volumes requiring cleaning, and where the cleaning lacks the urgency which would necessitate a portable decontamination or cleaning unit to supply on-the-spot or in the field cleaning. In many instances of such cleaning, the ultrasonic cleaning bath is one process within a larger cleaning methodology where samples are either cleaned prior to further processing or dispersed within a suitable media as part of the larger methodological process. Cleaning or processing is facilitated by the employment of an ultrasonic bath, not always solely achieved by the ultrasonic bath alone. Ultrasonic bath cleaning involves the immersion of a suitable container within the bath, however, if the target to be cleaned is too large, or too remote from, an immovable cleaning system that requires immersion, the target may require disassembly into smaller components and transported for immersion cleaning. Such immersion systems can also result in re-contamination or secondary cross contamination of the target being cleaned. Consequently, there is particular utility in a cleaning apparatus that can be taken to the target to “clean in place,” reducing the need for disassembling and relocation of the parts, and that avoids immersion of the target reducing the chance of secondary contamination. If such an apparatus operates by a rinse, then the contamination can be flushed away, collected if the contamination is hazardous or environmentally unfriendly, or the collected run-off can be tested (e.g. by PCR (Polymerase Chain Reaction), genetic sequencing, or microbial culture), to aid medical diagnosis, and to identify both biological and non-biological contaminants that may require further cleaning or advanced therapeutic intervention.

[0006] The ultrasonic cleaning action is often attributed to the generation of violent cavitation within the vessel itself and the interaction of these phenomena with the walls of the obj ect being treated. These violent cavitation events occur where the inertia of the liquid has had a dominant effect on the bubble dynamics. As one example, such cavitation events may result when a high-speed liquid jet passes through the bubble as a result ofPatent Application Attorney Docket No. 008634.01587VWO involution of the bubble wall and generates a blast wave on impact with a liquid or solid (this is one source of the shock waves that are often associated with inertial cavitation). The subsequent dynamics of the gas torus associated with this jet may also generate cleaning and / or surface damage. As another example, such events may result when bubbles collapse with almost spherical symmetry in “transient” or “inertial” cavitation, causing both shock waves in the liquid, and generation of highly reactive chemical species such as free radicals. As a further example, such cavitation events may result when clouds of bubbles collapse in a concerted manner magnifying these effects to become greater than would be expected without the cloud effect. Hence the exact mechanism is often associated with “transient cavitation” or more precisely inertial cavitation where the violent collapse phase results in the local generation of extreme conditions such as shock waves, jets, high pressures, associated transient high temperatures, and the generation of free radicals.

[0007] However, such bath-based ultrasonic cleaning systems may suffer from one or more problems, including but not limited to, damage to the target, poor cleaning, a spatially inhomogeneous pattern of cleaning efficiency (where distances as small as a few millimetres or centimetres can take one from a region of good cleaning to one of poor cleaning, a variability that can change over time and as objects are inserted into the cleaning bath). There are particular problems associated with cleaning three- dimensional surfaces and targets containing internal pockets or spaces (e.g., with crevices and / or lumen and / or channels or interior compartments or volumes). There is also an inability to clean objects or surfaces that are larger than the bath itself. Furthermore, the insertion of the object to be cleaned into an ultrasonic cleaning bath may disturb the sound field in a manner which degrades the ability to clean the object, by shielding, attenuating, scattering or otherwise disturbing the sound field. Ultrasonic cleaning baths present additional difficulties such as limited size (which limits the maximum size of objects that can be placed within it), lack of portability, and difficulty in processing numerous objects simultaneously (e.g., because one object may shield another, or other parts of itself, from the sound field by acoustic scattering or attenuation) or in a short period of time.

[0008] One particular area of concern is wound cleaning and treatment, which can greatly benefit from improved cleaning techniques, therapeutics, and technologies. In 2017-Patent Application Attorney Docket No. 008634.01587VWO2018, the National Health Service (NHS) of the United Kingdom spent £8.3 -billion treating 3.8-million patients with wounds. Only 49% of chronic wounds healed in the study year, suggesting current ‘state of the art’ treatments are sub-optimal when used to treat chronic wounds. Furthermore, these results were described in the UK Parliament as “disappointing.” The NHS spends £1 billion amputating 6000 feet per year because of non-healing and currently unbeatable Diabetic Foot Ulcers (DFUs). Of special concern, 81% of patients with chronic Venous Leg Ulcers (VLUs) were prescribed antibiotics, contrary to UK National Institute for Health and Care Excellence (NICE) guidelines regarding antimicrobial stewardship, risking further development of antimicrobial resistance, although current healing rates for VLUs are low (<45%). Nonhealing wounds have a huge impact on quality-of-life (particularly in deprived communities), socio-economic impact, wasted resources on repeated treatments, can fuel antimicrobial resistance through inappropriate antibiotic use, and extend hospital stays.

[0009] Recently, professional guidelines have emphasized the contribution to hazard for all wounds made by microbial colonization. This colonization often occurs as a biofilm or as aggregates of cells. Such colonization increases the risk of systemic infection especially in chronic wound patients. These biofilms adhere strongly to many surfaces and environments, have increased resistance (compared to their planktonic counterparts) to the body’s own immune defenses and have increased tolerance to antimicrobials. Non-healing chronic wounds represent substantial morbidity for a patient and costs for healthcare system with some chronic wounds persisting for years, sometimes up to 17 years or more, even following ‘state of the art’ treatment regimes. They generate pain, ill health, mobility challenges, exudation, and odor, which can in turn lead to social isolation, worsening mental health, and increased social care costs. Healthcare costs attributable to non-healing wounds include staff and clinic time spent on repeated treatments over many months, as well as the cost of consumables used in treating the wound (dressings, drugs, antiseptics, chemicals, advanced treatments). As time progresses, repeated debridement (often invasive and painful) of necrotic tissue and bioburden is required. Moreover, there are long-term costs to society from the loss of contributions to society and the economy from people who would otherwise contribute. Accordingly, there is a great need for technologies that can improve the effectiveness, cost, and resource consumption of wound cleaning.Patent Application Attorney Docket No. 008634.01587VWO

[0010] Current ‘state of the art’ treatments used to clean and irrigate a wound (shown in FIG. 63) rely on simple irrigations with saline or water (with / without scrubbing) or with a soak in a chemical based antimicrobial wash. Before and after irrigation, debridement (primarily using sharp / surgical debridement, but sometimes involving chemical, autolytic, biological, and mechanical forms) is used to remove devitalized, necrotic, infected tissue, and other bioburden, to prepare an optimal wound bed. However, as mentioned previously, chronic wounds are persisting regardless of the current treatments available.

[0011] Ultrasonic technologies are utilized in wound cleaning and treatment; however, the majority of these technologies rely on direct contact of an ultrasonically driven curette / blade that uses the vibratory motion of the curette / blade and / or inertial / transient cavitation (as described previously) at the tip of the tool to debride necrotic tissue and other wound debris. Other ultrasonic wound technologies claim to treat wounds through ultrasonic stimulation delivered to the wound through a mist of saline. However the actual purpose of the ultrasound is to generate the mist, and the vast majority of the ultrasonic energy is attenuated prior to reaching the wound tissue and so does not penetrate the tissue to generate ultrasonic fields within the tissue that can stimulate healing. None of these ultrasonic wound technologies both clean the wound and enhance wound healing progression without having any potential damaging effects of the inertial cavitation described previously.

[0012] The present disclosure is provided to address these problems and other problems in existing ultrasonic cleaning apparatuses and therapeutic methods. A full discussion of the features and advantages of the present disclosure is deferred to the following detailed description, which proceeds with reference to the accompanying drawings.BRIEF SUMMARY

[0013] Aspects of the disclosure relate to an apparatus including a combined unit and a base unit releasably connected to the combined unit. The combined unit includes a body defining a chamber configured to contain a liquid and having a nozzle located at a front end of the body and configured to discharge a stream of the liquid from the chamber toward a surface, and a manifold located at a rear of the body, where the body and the manifold are integrally formed together as a single piece. In one configuration, thePatent Application Attorney Docket No. 008634.01587VWO combined unit is molded as the single piece including the body and the manifold. The manifold is configured for connection to a liquid supply conduit to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber. The base unit includes an acoustic transducer positioned and configured to generate acoustic energy and to introduce the acoustic energy into the liquid contained in the chamber, and a casing containing the acoustic transducer and having a mounting piece engaged with the combined unit to releasably connect the combined unit to the base unit.

[0014] According to one aspect, the base unit further includes a rear wall connected to the casing and positioned at the rear of the body to at least partially define the chamber when the combined unit is connected to the base unit, where the acoustic transducer is positioned behind the rear wall and configured to transmit the acoustic energy through the rear wall into the chamber.

[0015] According to another aspect, the mounting piece includes a tab releasably engaging the combined unit to releasably connect the combined unit to the base unit. In one aspect, the combined unit has a slot, and the tab is received in the slot to releasably connect the combined unit to the base unit. In another aspect, the combined unit has a flange, and the tab has a front surface engaged with a rear surface of the flange to releasably connect the combined unit to the base unit.

[0016] According to a further aspect, the manifold has a manifold inlet configured for connection to the liquid supply conduit, and an internal conduit in fluid communication with the liquid supply conduit and the plurality of ports and configured to permit the inlet stream to flow from the manifold inlet to the plurality of ports. In one aspect, the internal conduit of the manifold is open on a rear side of the manifold, and the base unit engages the rear side of the manifold to define the internal conduit when the combined unit is engaged with the base unit. In another aspect, the manifold has an inner annular surface having an annular shape and positioned to be in communication with the chamber, with the ports extending through the inner annular surface, and the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface. In a further aspect, the manifold further includes a vent at a top of thePatent Application Attorney Docket No. 008634.01587VWO manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.

[0017] According to yet another aspect, the combined unit further includes a connecting structure configured to engage the mounting piece on the base unit to releasably connect the combined unit to the base unit, and the connecting structure is integrally formed as part of the single piece with the body and the manifold.

[0018] Additional aspects of the disclosure relate to a treatment unit configured for releasable connection to a base unit of an apparatus for treating a surface with a stream of a liquid, the treatment unit including a body, a manifold connected to the body, and a connecting structure configured to engage a complementary connecting structure on the base unit to releasably connect the treatment unit to the base unit, where the body, the manifold, and the connecting structure are integrally formed together as a single piece. In one configuration, the combined unit is molded as the single piece including the body, the manifold, and the connecting structure. The body has a base at a rear of the body, a cone extending forward from the base and defining a chamber configured to contain the liquid when connected to the base unit, and a nozzle located at a front end of the cone and configured to discharge the stream of the liquid from the chamber toward the surface. The manifold includes a manifold body connected to the base of the body, a manifold inlet configured for connection to a liquid supply conduit to receive an inlet stream of the liquid, a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber, and an internal conduit in fluid communication with the liquid supply conduit and the plurality of ports and extending through the manifold body to permit the inlet stream to flow from the manifold inlet to the plurality of ports.

[0019] According to one aspect, the connecting structure includes a slot configured to receive a tab on the base unit to releasably connect the treatment unit to the base unit.

[0020] According to another aspect, the connecting structure includes a flange having a rear surface configured to engage a tab on the base unit to releasably connect the treatment unit to the base unit.Patent Application Attorney Docket No. 008634.01587VWO

[0021] According to a further aspect, the internal conduit of the manifold is open on a rear side of the manifold, and the rear side of the manifold is configured to engage the base unit to define the internal conduit when the treatment unit is engaged with the base unit.

[0022] According to yet another aspect, the manifold body has an annular configuration with an inner annular surface positioned to be in communication with the chamber, with the ports extending through the inner annular surface. In one aspect, the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface.

[0023] According to a still further aspect, the manifold further includes a vent at a top of the manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.

[0024] Further aspects of the disclosure relate to an apparatus including a handset configured for user manipulation by hand, a body releasably connected to the handset at a rear of the body, and a manifold located at a rear of the body and releasably connected to the handset. The handset includes an acoustic transducer configured to generate acoustic energy, a user input device in electronic communication with the acoustic transducer and configured to receive user input to control the acoustic transducer, and a casing containing the acoustic transducer and supporting the user input device, where the casing has a handle configured for gripping by the user. The body defines a chamber configured to contain a liquid and has a nozzle located at a front end of the body and configured to discharge a stream of the liquid from the chamber toward a surface. The acoustic transducer is positioned to introduce the acoustic energy into the liquid contained in the chamber when the body is connected to the handset. The manifold has a manifold inlet configured for connection to a liquid supply conduit to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber and an internal conduit extending from the manifold inlet to the plurality of ports to place the ports in fluid communication with the manifold inlet.

[0025] According to one aspect, the handset further includes a rear wall connected to the casing and positioned at the rear of the body to at least partially define the chamber when the body is connected to the handset, where the acoustic transducer is positioned behindPatent Application Attorney Docket No. 008634.01587VWO the rear wall and configured to transmit the acoustic energy through the rear wall into the chamber.

[0026] According to another aspect, the casing has a tab releasably engaging the manifold to releasably connect the manifold to the handset. In one aspect, the manifold has a slot, and the tab is received in the slot to releasably connect the manifold to the handset. In another aspect, the manifold has a flange, and the tab has a front surface engaged with a rear surface of the flange to releasably connect the manifold to the handset.

[0027] According to a further aspect, the body and the manifold are connected together by being formed of a single, integral piece including the body and the manifold, such that the body is connected to the handset by connecting the manifold to the handset, thereby connecting the single, integral piece to the handset. In one configuration, the manifold further includes a connecting structure configured to engage the handset to releasably connect the manifold to the handset, and the connecting structure is integrally formed as part of the single, integral piece with the body and the manifold.

[0028] According to yet another aspect, the internal conduit of the manifold is open on a rear side of the manifold, and the handset engages the rear side of the manifold to define the internal conduit when the manifold is engaged with the handset.

[0029] According to a still further aspect, the manifold has an inner annular surface having an annular shape and positioned to be in communication with the chamber, with the ports extending through the inner annular surface, and the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface.

[0030] According to an additional aspect, the manifold further has a vent at a top of the manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.

[0031] According to an additional aspect, the user input device is further configured for controlling flow of the liquid into the manifold and out through the nozzle to discharge the stream.Patent Application Attorney Docket No. 008634.01587VWO

[0032] Still further aspects of the disclosure relate to a method for treatment of a surface using an apparatus including a base unit having an acoustic transducer configured to generate acoustic energy and a casing containing the acoustic transducer, and a first treatment unit releasably connected to the base unit and comprising a first body defining a first chamber configured to contain a liquid and having a first nozzle located at a front end of the first body and a first manifold integrally formed with the first body and connected to a liquid supply conduit in fluid communication with a liquid supply, with the first manifold having a plurality of first ports in communication with the first chamber. The method includes operating the apparatus to discharge a first stream of liquid through the first nozzle to the surface, such that the liquid flows from the liquid supply through the liquid supply conduit and to the first manifold, and then flows through the first ports into the first chamber and out through the first nozzle. Operating the apparatus in this manner also includes activating the acoustic transducer to direct the acoustic energy into the first chamber and down the first stream to the surface. The method also includes removing the first treatment unit from the base unit and connecting a second treatment unit to the base unit in place of the first treatment unit. The method further includes operating the apparatus to discharge a second stream of liquid through a second nozzle of the second treatment unit to the surface, which further includes activating the acoustic transducer to direct the acoustic energy into a second chamber of the second treatment unit and down the second stream to the surface. The second treatment unit may be identical to or different from the first treatment unit in some embodiments.

[0033] According to one aspect, the base unit includes a tab selectively and releasably engaging the first treatment unit or the second treatment unit to releasably connect the first treatment unit or the second treatment unit to the base unit, and removing the first treatment unit and connecting the second treatment unit includes rotating the first treatment unit and the second treatment unit with respect to the base unit.

[0034] According to another aspect, the second treatment unit is connected to a second liquid supply conduit, and the method further includes removing the liquid supply conduit along with the first treatment unit. In one aspect, the second liquid supply conduit is connected to a second liquid supply, and the method further includes removing the liquid supply along with the first treatment unit and the liquid supply conduit. In another aspect, operating the apparatus includes activating a pump connected to thePatent Application Attorney Docket No. 008634.01587VWO liquid supply conduit to force the liquid through the liquid supply conduit into the first manifold and out through the first nozzle to discharge the first stream, and the method further includes disconnecting the liquid supply conduit from the pump along with removing the first treatment unit and connecting the second liquid supply conduit to the pump along with connecting the second treatment unit to the base unit.

[0035] According to a further aspect, the method also includes removing the liquid supply conduit from the first treatment unit and connecting the liquid supply conduit to the second treatment unit.

[0036] According to yet another aspect, the method further includes adding an additive to the liquid supply before operating the apparatus to generate the first stream.

[0037] According to a still further aspect, operating the apparatus includes providing user input to a user input device in electronic communication with the acoustic transducer and a pump connected to the liquid supply conduit to control the acoustic transducer and to activate the pump to force the liquid through the liquid supply conduit into the first manifold and out through the first nozzle to discharge the first stream. In one aspect, the base unit is a handset having a handle for gripping by a user to direct the apparatus at the surface, and the user input device includes a button on the handle of the handset.

[0038] According to an additional aspect, the method further includes priming the apparatus prior to operating the apparatus to discharge the first stream to the surface, which includes operating the apparatus while the first nozzle is pointed upward to cause the liquid to discharge upward through the first nozzle.

[0039] Other aspects of the disclosure relate to a system that includes an apparatus and / or a treatment unit as disclosed herein, the liquid supply conduit connected to the manifold, a liquid supply connected to the liquid supply conduit, and a pump configured to pump the liquid from the liquid supply through the liquid supply conduit and to the manifold. The system may further include a control unit configured for controlling the pump, the acoustic transducer, and / or other components of the system.

[0040] Other features and advantages of the disclosure will be apparent from the following description taken in conjunction with the attached drawings.Patent Application Attorney Docket No. 008634.01587VWOBRIEF DESCRIPTION OF THE DRAWINGS

[0041] To allow for a more full understanding of the present disclosure, it will now be described by way of example, with reference to the accompanying drawings in which:

[0042] FIG. l is a schematic view of one embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure;

[0043] FIG. 2 is a schematic view of the system of FIG. 1, illustrating connection or interchanging of replaceable components of the system;

[0044] FIG. 3 is a perspective view of one embodiment of an apparatus for generating a stream with acoustic energy according to aspects of the present disclosure, in the form of a handheld device;

[0045] FIG. 4 is a rear perspective view of the apparatus of FIG. 3;

[0046] FIG. 5 is a front view of the apparatus of FIG. 3, with a removable combined unit including a body with a cone and a manifold shown connected to a handset of the apparatus;

[0047] FIG. 6 is a front view of the apparatus of FIG. 3, with the removable combined unit in the process of being connected to the handset;

[0048] FIG. 7 is a cross-section view taken along lines 7-7 of FIG. 5;

[0049] FIG. 8 is a cross-section view of the removable combined unit of the apparatus as shown in FIG. 7;

[0050] FIG. 9 is a rear perspective opened view of a portion of the handset of FIG. 3;

[0051] FIG. 10 is a perspective view of the handset of FIG. 3, without the removeable combined unit attached;

[0052] FIG. 11 is a front view of the removable combined unit of FIG. 3;

[0053] FIG. 12 is a cross-section view taken along lines 12-12 of FIG. 11;

[0054] FIG. 12A is a magnified view of a portion of FIG. 12 designated by “12A”;Patent Application Attorney Docket No. 008634.01587VWO

[0055] FIG. 13 is a cross-section view taken along lines 13-13 of FIG. 11;

[0056] FIG. 14 is a bottom perspective view of the removable combined unit of FIG. 3;

[0057] FIG. 15A is a bottom rear perspective view of the removable combined unit of FIG. 3;

[0058] FIG. 15B is a bottom rear perspective view of another embodiment of a removable combined unit usable with the apparatus of FIG. 3;

[0059] FIG. 16 is a side view of the removable combined unit of FIG. 3;

[0060] FIG. 17 is a cross-section view taken along lines 17-17 of FIG. 16;

[0061] FIG. 18 is a cross-section view illustrating a portion of another embodiment of an apparatus according to aspects of this disclosure;

[0062] FIG. 18A is a magnified view of an area of FIG. 18 designated by “18A”;

[0063] FIG. 19A is a schematic view illustrating one embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0064] FIG. 19B is a schematic view illustrating another embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0065] FIG. 20A is a graph illustrating the microbial bioburden (expressed as the number of colony forming units (CFU) / ml) remaining post treatment following single-species infection of ex vivo porcine skin explant wound models, for treatments as described herein, which can be summarized as a saline rinse, a commercial silver dressing, and treatments (labelled LAWS (Liquid Acoustic Wound Stream)) lasting 10s, 30s and 60s using an apparatus as shown in FIG. 1 using a cone as shown in FIG. 18;

[0066] FIG. 20B is a graph illustrating the percentage removal (over and above the saline rinse baseline for each microbe species) of single-species microbial bioburden from infected ex vivo porcine skin explant wound models, for treatments as described herein, which can be summarized as a commercial silver dressing and treatments (labelled LAWS) lasting 10s, 30s and 60s using the embodiment of an apparatus as shown in FIG. 1 using a cone as shown in FIG. 18;Patent Application Attorney Docket No. 008634.01587VWO

[0067] FIG. 20C is a graph illustrating the microbial bioburden (expressed as the number of colony forming units (CFU) / ml) remaining post treatment following dual-species infection (Methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii of ex vivo porcine skin explant wound models, for treatments as described herein, which can be summarized as a saline rinse, a commercial silver dressing, and treatments (labelled LAWS) lasting 10s, 30s and 60s using an apparatus as shown in FIG. 1 using a cone as shown in FIG. 18;

[0068] FIG. 20D is a graph illustrating the percentage removal (over and above the saline rinse baseline for each microbe species) of dual-species (Methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii) microbial bioburden from infected ex vivo porcine skin explant wound models, for treatments as described herein, which can be summarized as a commercial silver dressing and treatments (labelled LAWS) lasting 10s, 30s and 60s using an apparatus as shown in FIG. 1 using a cone as shown in FIG. 18;

[0069] FIG. 21 is a graph illustrating the cleaning performance (evaluated by comparing the microbial load of treated samples against control samples and expressed as log reduction of colony forming units (CFU) / g) achieved using a benchtop ultrasonic bath (labelled UB) at 50% power and 100% power, a handheld embodiment of the apparatus disclosed herein (labelled SS-UAS), and an apparatus as disclosed herein using a gooseneck faucet-like nozzle (labelled ARI-UAS);

[0070] FIGS. 22A-E are Episcopic Differential Interference Contrast (EDIC) micrographs acquired at 400X total magnification showing the adaxial (left) and abaxial (right) surface of uncleaned spinach leaf samples and spinach leaf samples cleaned using techniques as in FIG. 21;

[0071] FIG. 23 is a graph illustrating the microbial bioburden (expressed as the number of colony forming units (CFU) / ml) remaining post treatment (using a saline rinse, the cone embodiment SI as in FIG. 25 A and FIGS. 38A-C, and cone embodiment R4 as in FIG. 26D and FIGS. 46A-B) following single-species infection (Methicillin-resistant Staphylococcus aureus) of ex vivo porcine skin explant wound models;Patent Application Attorney Docket No. 008634.01587VWO

[0072] FIG. 24A is a plot of one embodiment of a conical inner wall shape for use in connection with an apparatus according to aspects of the disclosure (e.g., for the cone type shown in FIG. 3);

[0073] FIG. 24B is a plot of one embodiment of a conical outer wall shape for use in connection with an apparatus according to aspects of the disclosure (e.g., for the cone type shown in FIG. 3);

[0074] FIGS. 25A-D are photographs showing four illustrative example embodiments of nozzles with rectangular outflow orifices (labelled SI, S2, S3, and S4) according to aspects of the disclosure;

[0075] FIGS. 26A-E show five cones tested with circular outflow orifices smaller than 10 mm diameter (labelled R1 to R5) according to aspects of the disclosure;

[0076] FIG. 27 is a schematic view illustrating another embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0077] FIG. 28 is a schematic view illustrating another embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0078] FIG. 29 is a schematic view illustrating another embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0079] FIG. 30 is a schematic view illustrating another embodiment of a method of use of an apparatus according to aspects of the present disclosure;

[0080] FIGS. 31A-C are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure (for scale, the black circle perimeter in each target has a diameter of 10 mm);

[0081] FIGS. 32A-F are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at a distance of 30 mm from the nozzle orifice; showing the results of cleaning using the cone R2 (for scale, the black circle perimeter in each target has a diameter of 10 mm);Patent Application Attorney Docket No. 008634.01587VWO

[0082] FIGS. 33A-F are photographs illustrating cleaning performance of the same apparatus as FIGS. 32A-F at a distance of 90 mm from the nozzle orifice using cone R2 (for scale, the black circle perimeter in each target has a diameter of 10 mm);

[0083] FIGS. 34A-B are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at distances of 8 mm and 20 mm from the cleaning targetusing cone R1 (for scale, the black circle perimeter in each target has a diameter of 10 mm);

[0084] FIG. 35 is a plot of one embodiment of a conical inner wall shape for use in connection with an apparatus according to aspects of the disclosure;

[0085] FIG. 36 is a plot of one embodiment of a conical inner wall shape for use in connection with an apparatus according to aspects of the disclosure;

[0086] FIG. 37 is a plot of one embodiment of a conical inner wall shape for use in connection with an apparatus according to aspects of the disclosure;

[0087] FIG. 38A is a front view of a cone having the dimensions of the cone SI of FIG. 25 A;

[0088] FIG. 38B is a cross-section view taken along lines Y-Y of FIG. 38A;

[0089] FIG. 38C is a cross-section view taken along lines Z-Z of FIG. 38 A;

[0090] FIG. 39A is a front view of a cone having the dimensions of the cone S2 of FIG. 25B;

[0091] FIG. 39B is a cross-section view taken along lines Y-Y of FIG. 39A;

[0092] FIG. 39C is a cross-section view taken along lines Z-Z of FIG. 39A;

[0093] FIG. 40A is a front view of a cone having the dimensions of the cone S3 of FIG. 25C;

[0094] FIG. 40B is a cross-section view taken along lines Y-Y of FIG. 40A;

[0095] FIG. 40C is a cross-section view taken along lines Z-Z of FIG. 40A;

[0096] FIG. 41 A is a front view of a cone having the dimensions of the cone S4 of FIG. 25D;

[0097] FIG. 41B is a cross-section view taken along lines Y-Y of FIG. 41 A;Patent Application Attorney Docket No. 008634.01587VWO

[0098] FIG. 41C is a cross-section view taken along lines Z-Z of FIG. 41 A;

[0099] FIG. 42A is a cross-section view showing one example embodiment of a manifold useable with a cone with a rectangular opening, such as shown in FIGS. 25A-C and 38A-40C;

[0100] FIG. 42B is a cross-section view showing one example embodiment of a manifold useable with a cone with a square opening, such as shown in FIGS. 41 A-C;

[0101] FIG. 43A is a front view of a cone having the dimensions of the cone R1 of FIG. 26A;

[0102] FIG. 43B is a perspective view of the cone of FIG. 43A;

[0103] FIG. 43C is a cross-section view taken along lines Z-Z of FIG. 43 A;

[0104] FIG. 44A is a front view of a cone having the dimensions of the cone R2 of FIG. 26B;

[0105] FIG. 44B is a perspective view of the cone of FIG. 44A;

[0106] FIG. 44C is a cross-section view taken along lines Z-Z of FIG. 44A;

[0107] FIG. 45A is a front view of a cone having the dimensions of the cone R3 of FIG. 26C;

[0108] FIG. 45B is a perspective view of the cone of FIG. 45A;

[0109] FIG. 45C is a cross-section view taken along lines Z-Z of FIG. 45A;

[0110] FIG. 46A is a front view of a cone having the dimensions of the cone R4 of FIG. 26D;

[0111] FIG. 46B is a cross-section view taken along lines Z-Z of FIG. 46A;

[0112] FIG. 47A is a front view of a cone having the dimensions of the cone R5 of FIG. 26E;

[0113] FIG. 47B is a cross-section view taken along lines Z-Z of FIG. 47A;

[0114] FIG. 48A is a cross-section view showing one example embodiment of a manifold useable with a cone with a circular opening, such as shown in FIGS. 26A-E and 43 A- 47B;Patent Application Attorney Docket No. 008634.01587VWO

[0115] FIG. 48B is a cross-section view showing another example embodiment of a manifold useable with a cone with a circular opening, such as a scaled version of the cones shown in FIGS. 26A-E and 43A-47B;

[0116] FIG. 48C is a cross-section view showing another example embodiment of a manifold useable with a cone with a circular opening, such as a scaled version of the cones shown in FIGS. 26A-E and 43A-47B;

[0117] FIG. 49 is a schematic view of one embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply;

[0118] FIG. 50 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, connected to a mains water supply or other pressurized liquid supply;

[0119] FIG. 51 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, connected to a mains water supply or other pressurized liquid supply;

[0120] FIGS. 52A-G are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at various ranges (in mm) from the nozzle to the target using cone SI shown in FIGS. 25A and 38A-C;

[0121] FIG. 52H is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone SI shown in FIGS. 25 A and 38A-C, using the parameters described with respect to FIGS. 52A-G, with the horizontal dashed line showing the area of the outflow orifice;

[0122] FIGS. 53A-G are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at various ranges (in mm) from the nozzle to the target using cone S2 shown in FIGS. 25B and 39A-C;

[0123] FIG. 53H is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone S2 shown in FIGS. 25B and 39A-C, using the parameters described with respect to FIGS. 53A-G, with the horizontal dashed line showing the area of the outflow orifice;Patent Application Attorney Docket No. 008634.01587VWO

[0124] FIGS. 54A-F are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at various ranges (in mm) from the nozzle to the target using cone S3 shown in FIGS. 25C and 40A-C;

[0125] FIG. 54G is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone S3 shown in FIGS. 25C and 40A-C, using the parameters described with respect to FIGS. 53A-F, with the horizontal dashed line showing the area of the outflow orifice;

[0126] FIGS. 55A-F are photographs illustrating cleaning performance of an apparatus according to aspects of the present disclosure at various ranges (in mm) from the nozzle to the target using cone S4 shown in FIGS. 25D and 41 A-C;

[0127] FIGS. 56A-D are schematic views illustrating various embodiments of methods and configurations for use of an apparatus according to aspects of the present disclosure;

[0128] FIG. 57 is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone R1 shown in FIGS. 26A and 43 A-C with the horizontal dashed line showing the area of the outflow orifice

[0129] FIG. 58 is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone R2 shown in FIGS. 26B and 44A-C with the horizontal dashed line showing the area of the outflow orifice;

[0130] FIG. 59 is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone R3 shown in FIGS. 26C and 45 A-C with the horizontal dashed line showing the area of the outflow orifice;

[0131] FIG. 60 is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone R4 shown in FIGS. 26D and 46A-B with the horizontal dashed line showing the area of the outflow orifice;

[0132] FIG. 61 is a graph showing complete and partial cleaning performance (in mm2) as a function of range (in mm) from the nozzle to the target for cone R5 shown in FIGS. 26E and 47A-B with the horizontal dashed line showing the area of the outflow orifice;Patent Application Attorney Docket No. 008634.01587VWO

[0133] FIG. 62 is a graph showing complete and partial cleaning performance (in mm2) for cones SI -S3 shown in FIGS. 25A-C and 38A-40C and cones R1-R5 shown in FIGS. 26A-E and 43A-47B, and at a distance of 10 mm from the nozzle to the target, with flow rate and flow velocity shown in the caption beneath the graph;

[0134] FIG. 63 shows a sequence of events in a clinic appointment that provides Standard of Care using a current treatment approach;

[0135] FIG. 64 shows an example embodiment of a sequence of events in a clinic appointment that incorporates use of an apparatus and method as described herein in place of the wound cleaning step;

[0136] FIGS. 65A-C are schematic diagrams illustrating embodiments of a kit and method of use for an apparatus according to aspects of the present disclosure incorporating a single-use treatment pack or reusable, single-patient components;

[0137] FIG. 66 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply and a treatment pack with a port and a regulator to allow the addition of additives to the liquid supply after it leaves the reservoir;

[0138] FIG. 67 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply with a port to allow the addition of additives to the liquid supply;

[0139] FIG. 68 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply with pulse dampeners shown connected at various locations along the fluid line;

[0140] FIG. 69 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply with a peristaltic pump having multiple rollers;

[0141] FIG. 70 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply having greater fluid volume;Patent Application Attorney Docket No. 008634.01587VWO

[0142] FIG. 71 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, using a portable liquid supply with an apparatus for changing a height of the liquid supply relative to the apparatus;

[0143] FIG. 72 is a schematic view of another embodiment of a system for generating a liquid stream with acoustic energy according to aspects of the present disclosure, with a flow meter connected to the fluid line;

[0144] FIG. 73A is a cross-sectional view of one embodiment of a spike assembly usable with a portable liquid supply such as shown in FIG. 67;

[0145] FIG. 73B is an exploded cross-sectional view of the spike assembly of FIG. 73 A;

[0146] FIG. 74 is a schematic, broken cross-sectional view of one embodiment of a fluid line having the spike assembly of FIG. 73 A at one end and a cone for discharge of fluid at an opposite end;

[0147] FIGS. 75A-F are example micrographs of X / Y scans (lOOx total magnification) of a wounded area of ex vivo human skin tissue sections following H&E staining, with scale bars on all images representing 200 pm;

[0148] FIGS. 76A-K are example micrographs of X / Y scans (lOOx total magnification) of a wounded area of ex vivo human skin tissue sections following H&E staining, with scale bars on all images representing 200 pm;

[0149] FIG. 77A is a graph showing image analysis measurements comparing wound width and wound depth, with error bars representing the Standard Error of the Mean (SEM, n = 3-5 measurements);

[0150] FIG. 77B is a graph showing image analysis measurements comparing wound width and wound depth, with error bars representing the Standard Error of the Mean (SEM, n = 3-5 measurements);

[0151] FIGS. 78A-F are example micrographs of X / Y scans (lOOx total magnification) of a wounded area of ex vivo human skin tissue sections following H&E staining, with scale bars on all images representing 100 pm;Patent Application Attorney Docket No. 008634.01587VWO

[0152] FIGS. 79A-F are example micrographs of X / Y scans (lOOx total magnification) of a wounded area of ex vivo human skin tissue sections following Masson-Trichrome staining, with scale bars on all images representing 200 pm;

[0153] FIG. 80 is a graph showing image analysis quantification of the density (integrated density) of Masson-Trichrome stained dermal collagen in sections of human skin, with error bars representing the Standard Error of the Mean (SEM, n = 3-5 measurements);

[0154] FIG. 81 is an example micrograph of an X / Y scan (600x total magnification) of the whole wound bed of an MRSA infected ex vivo human skin section following a 5 second saline treatment, with inlays (A - D) shown at lOOOx total magnification, and with a scale bar representing 200 pm; and

[0155] FIG. 82 is an example micrograph of an X / Y scan (600x total magnification) of the whole wound bed of an MRSA infected ex vivo human skin section following a 5 second treatment with an apparatus according to aspects of the present disclosure, with inlays (A - D) shown at lOOOx total magnification, and with a scale bar representing 200 pm.DETAILED DESCRIPTION

[0156] While this invention is capable of embodiments in many different forms, there are shown in the drawings and will herein be described in detail, example embodiments of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated. In the following description of various example structures according to the invention, reference is made to the accompanying drawings, which form a part hereof, and in which are shown by way of illustration, various example devices, systems, and environments in which aspects of the invention may be practiced. It is to be understood that other specific arrangements of parts, example devices, systems, and environments may be utilized, and structural and functional modifications may be made without departing from the scope of the present invention.

[0157] In this specification, the term “wound” is defined as including (but is not restricted to) sites formed by the removal or transformation or inflammation of the normal human orPatent Application Attorney Docket No. 008634.01587VWO animal or plant-based tissue (epidermis, gum, salad leaves etc.) to produce abnormal exposure of underlying tissue or transform healthy tissue into unhealthy tissue. Trauma, burning, sun exposure, cutting, the formation of ulcers and abscesses, infection, disease (including gum disease, acne, fungal infections, dermatological conditions) are all included. Specific circumstances would be abrasion or cutting or burning or solar exposure of the epidermis to expose the dermis, subcutaneous fat, and / or bone; or abrasion / cutting to the gum; or damage to the surface of an organ and / or internal tissue. Additionally, in this specification, the term “anatomical pocket” is defined as including (but is not restricted to) periodontal pockets, cavities associated with the eye, the urinary-genital system, ears, and oral, nasal and digestive systems, other anatomical cavities or spaces, or wound crevices. Further, in this specification, the term “carrier frequency” is borrowed from the convention used in signal processing, and here indicates the frequency of the ultrasonic wave that is intended to activate the bubbles and tissue, and which may be modulated in amplitude (and potentially, frequency) and, in the time history may be divided into pulses.

[0158] In some embodiments, the stream of liquid for therapeutic use can be chemical free, and may comprise or consist of water, optionally in the form of a conventional saline solution which in this context means that the solution is approximately isotonic with human tissue fluid, or solution of sodium chloride 0.9% w / v, and may be free of biocides and / or drugs or other pharmaceutical compositions. The use of bagged saline (e.g., an IV (intra-venous) bag or an irrigation bag) is particularly convenient because it is available in clinical settings, and it is sterile and sealed until use, making it suitable for transport, (e.g. in a vehicle for treatment in the field or battlefield or community setting, or to bedside locations that are not close to suitable sources of liquid such as bedside locations in wards). As other examples, the liquid may be sterile water or potable water, which may be bagged, pumped, from a water main, or from a pressurized supply. The use of water or a saline solution for cleaning reduces the risk of adverse reactions in tissue, such as tissue that has been severely traumatized (e.g. bums) or as a result of allergic reaction or damage through repeated chemical use (e.g., hand sanitizer). The use of water or a saline solution for cleaning also reduces the provision in waste of dilute forms of pharmaceuticals (such as antibiotics) which are known to contribute to the development of antimicrobial resistance (such as antibiotic resistance in bacteria, the resistance of viruses to antivirals, the resistance of fungi to antifungals,Patent Application Attorney Docket No. 008634.01587VWO and the resistance of parasites to antiparasitic drugs). In another embodiment, bottled liquids (e.g., bottled water) may be used, as the near uniformity of screw cap fittings for bottled water means that a widely deployable attachment to such liquid sources can be made, e.g., for field use.

[0159] Generally, this disclosure relates to an apparatus and method for delivering one or more streams of water or other liquid (which may, in some embodiments, carry active agents such as biocides, cleaning agents, drugs, industrial chemicals (e.g. Isopropanol or Ethanol), etc.) and acoustically activated bubbles to a target to provide beneficial effects (e.g., rinsing and cleaning) to the target. The stream(s) individually or collectively include acoustic waves (e.g., ultrasound) and bubbles of a suitable size and concentration to be effective in cleaning the target and / or producing other beneficial effects. The general principle supporting the efficacy of this apparatus and method is the delivery of bubbles of a suitable size at a suitable time to produce beneficial effects at the target and acoustic waves that engage the bubbles at or near the target to produce these beneficial effects. If a gas bubble in a liquid is subjected to the oscillating pressure field of an acoustic wave, it pulsates with close to spherical symmetry. However, if the conditions are tuned properly, the acoustic wave can cause tiny asymmetries on the bubble wall to grow very rapidly during this pulsation, so that instead of dissipating, these bubble wall instabilities grow to form surface waves that ripple across the bubble wall, having amplitudes that can be 1-4 orders of magnitude (usually 2-3 orders of magnitude) higher than the amplitude of the original spherical pulsation, and usually have frequencies of around half that of the spherical pulsation.

[0160] As used herein, the term “resonant bubbles” refers to bubbles that are of a size that is sufficiently close to the bubble size that would be in pulsation resonance with the sound field to have these surface waves excited upon their individual bubble walls, provided that the amplitude of the acoustic field at the location (typically at the target) of the bubble of relevance exceeds the threshold required to excite these surface waves, for bubbles of this size and an acoustic wave of this frequency. Bubbles that are either too large or too small to have such surface waves stimulated on them, in the sound field (given its frequency and amplitude) that is present at the target, are referred to herein as “unwanted bubbles” or “sub-optimal bubbles.” According to one embodiment, the apparatus and method described herein is configured such that resonant bubbles andPatent Application Attorney Docket No. 008634.01587VWO acoustic waves arrive at the target at the same optimal time. According to an additional embodiment, the apparatus and method described herein are configured such that the number of unwanted bubbles is minimized and such that the number of bubbles in the travel path of the acoustic waves to the target is minimized.

[0161] These surface waves on the bubble wall generate a number of actions that produce beneficial effects associated with the target. For example, these surface waves produce liquid shear and flow (often circulating flow) in the liquid close to the bubble, i.e. from next to the bubble wall to a distance of up to 50 bubble radii, and this shear and flow produce beneficial effects associated with the target. One such effect is the removal of contaminants adhered to the target, and it has been found that such acoustically-excited bubbles clean surfaces more gently (i.e., without causing damage to the target) than can the cavitation generated in ultrasonic baths. Other such beneficial effects include accelerating wound healing and other forms of regeneration and / or treatment, and eliciting change to biological cellular pathways and gene expression to produce beneficial stimulation to the target underlying tissue. As one example, the shear and primary and secondary acoustic waves generated in an anatomical pocket can achieve the removal of microbes without compromising the host immune system (e.g. of the plant or patient, be it human or animal). As another example, the convection of material in and out of the anatomical pocket, resulting from such shear and flow, would flush fresh water / saline solution and any chemical agent (e.g., biocide) or drug from the solution into the pocket which would not normally penetrate so rapidly, or in such high concentrations, by diffusion alone. Effects such as ultrasonically induced microstreaming, convection, and bubble wake effects promote penetration of any such additives into pockets or crevices where they would normally not penetrate. Additionally, after microbes have been dislodged, e.g., by bubble-generated shear, the convection would flush them out of the wound crevice. As a further example, many cells in a wound (or any biological cellular environment, not limited to wounds), including keratinocytes and fibroblasts, are mechano-transducers. Such cells will respond to the mechanical forces generated by the shear and flow by up-regulating production of the chemical signals such as growth factors that accelerate the healing process. Furthermore, chemokines and cytokines can be up and / or down regulated to elicit controlled response of the biological substrate to the acoustical stimuli. Similarly, the forces exerted by the presence of the bubbles stretch activated cell wall receptors,Patent Application Attorney Docket No. 008634.01587VWO stimulating the release of intracellular signals that in turn up-regulate the expression of genes and improve healing. The sound waves can also stimulate beneficial effects on the vascular system surrounding the target to be treated, such mechanisms of action include increase in vasodilation and angiogenesis. Additionally, the imposition of an oscillatory pressure and particle velocity field on bulk tissue and its constituent components, vasculature, intercellular porous fluids and the items they host etc., can impose rectified motion towards, or away from, the sound source, such transport generating beneficial healing. Furthermore, the ultrasonic waves can also stimulate the release of extracellular enzymes (e.g. matrix-metalloproteinases) that are involved in the collagen scaffold formation and degradation in wound remodeling processes.

[0162] Other examples of beneficial actions generated by the surface waves on the bubble wall include hydrodynamic pressure fluctuations close to the bubbles and acoustic signals generated and scattered by the bubble. These are generated even if the entire system is simply two-phase (bubble gas and liquid). Another such beneficial action includes mixing, for example, to avoid deleterious effects that can occur in the absence of mixing. An example of such a deleterious effect is if the target substrate is interacting through the generation or transfer of chemical species into and out of the liquid, this action may form a depletion layer adjacent to the target substrate in the liquid (e.g., a layer that is depleted of dissolved or chemical species that have been saturated by the target, such as dissolved oxygen, chemical species, reactive agents), or a liquid layer that contains an elevated concentration of species generated by or emitted from the target (e.g. CO2 from the respiring living tissue layer). These strong concentration gradients caused by chemical species that are depleted or elevated in the liquid layer next to the target can be reduced, often in a beneficial way, to remove the unwanted excess or depletion of chemical species, by mixing the liquid close to the surface (where the strong concentration gradient occurs) with the liquid further from the target. Such mixing can increase the efficiency of reaction at, or transfer across the interface with, the target substrate, by the circulation currents set up by the surface waves on the bubble wall and by the motion of bubbles towards the target under the influence of radiation forces. In this way, the liquid close to the surface is refreshed by mixing in liquid from further away from the surface.Patent Application Attorney Docket No. 008634.01587VWO

[0163] Still further beneficial actions can be created by the addition of chemicals to the liquid as discussed elsewhere herein. Such chemicals may be doped or built on or within the bubble wall, including in the form of chemically distinctive layers forming that wall, both to stabilize the wall and to impact a chemical or biological effect upon the target. Such chemicals could additionally or alternately be placed within the bubble gas. These chemicals may impart change upon the target and / or affect (e.g., stabilize) the fragmentation or dissolution of the bubble.

[0164] The embodiments of the apparatus 2 described herein can also be used to clean inert non-biological surfaces, without damaging, including, but not limited to: microchips, industrial plant equipment, pharmaceutical and food processing apparatus and plant equipment, and surgical and medical instruments, etc. The apparatus 2 can also be used for depowdering, e.g., in additive manufacturing, including manufacturing of medical, aeronautical, and space components. The apparatus 2 can also be used to clean items and products, their containers, and the associated tools and surfaces. Such applications may require that the cleaning liquid must be pure to a high specification in terms of chemical content (e.g., for silicon wafers, contact lenses, photographic, scientific and astronomical optics, etc.). However, in certain aspects, the apparatus 2 may be particularly useful in the cleaning and treatment of biological substrates, and the apparatus and methods disclosed herein may produce tissue regeneration and cellular enhancements in such applications.

[0165] FIGS. 1-17 illustrate one general embodiment of a system 100 that includes an apparatus 2 for delivering a stream of liquid including bubbles and acoustic waves to a target. FIGS. 1-2 illustrate the system 100 schematically, in a configuration intended for use in wound cleaning applications. FIGS. 3-17 illustrate an example embodiment of an apparatus 2 usable with the system 100 in FIGS. 1-2. The apparatus 2 in this embodiment includes a hollow body 4 having a substantially conical wall or cone 10 defining a chamber 6, with a rear wall 8 forming a rear boundary of the chamber 6. During operation, the chamber 6 will be filled with liquid that issues from the nozzle 14 as a stream (as shown schematically in FIGS. 19A-B). The body 4 has a base 11 positioned adjacent to the rear wall 8, with the cone 10 extending forwardly from the base 11. The cone 10 terminates in an outlet nozzle 14 forming an outlet of the hollow body 4, and the nozzle 14 includes an orifice 12 through which the liquid exits thePatent Application Attorney Docket No. 008634.01587VWO chamber 6. Both the cone 10 and the outlet nozzle 14 in FIGS. 1-17 are rotationally symmetric, i.e. circular, although other geometric shapes may be used. For example, FIGS. 24-30 depict some additional embodiments of configurations for the outlet nozzle 14 described elsewhere herein, which may have linear or planar symmetry but not rotational symmetry. As used in this specification, the term “conical” should be interpreted broadly to encompass structures that have a narrowing width / diameter and cross-sectional area along the length thereof. The term “conical” therefore encompasses structures which are not only geometrically conical, and for example have a linear, convex or concave wall, but also structures which for example are bell-like and have a concave contour as seen from inside the chamber 6, or have a constant half-angle as shown, or are horn-like and have a convex contour as seen from the inside the chamber 6, or have a combination of surface contours, such as having a combination of concave and convex contours when seen from inside the chamber 6. The cone 10 in FIGS. 1-17 has a convex portion that is outwardly curved near the rear wall 8 and a concave portion that is inwardly curved near the nozzle 14. The base 11 in the embodiment of FIGS. 1-17 includes reinforcing structures for the cone 10 and the connections to the casing 55 (described herein), including an outer reinforcing ring 27 and reinforcing ribs 28 extending between the cone 10 and the reinforcing ring 27. These structures (of which are one design demonstrated in this embodiment of the invention, but different designs that serve the same purpose can be used in further embodiments of this invention) serve to stiffen the structure of the cone 10 to improve the efficiency of the passage of ultrasonic energy from the transducer 22 to the liquid stream. The cone 10 in FIGS. 3-17 is dimensioned to have a nozzle 14 with an orifice 12 having an inner diameter of 10 mm in one embodiment. However, the size of the cone 10 can be scaled as described herein, which may include exact scaling of the inner and / or outer profiles of the cone 10. In various embodiments, the cone 10 may be scaled to have an orifice 12 with an inner diameter of, but not limited to, 4 mm, 2 mm, or 1.4 mm. For example, a cone 10 with a 2 mm nozzle 14, one effective transducer frequency usable with such a cone 10 is about 1 MHz.

[0166] The system 100 includes the apparatus 2, as well as a control unit 60, a liquid supply 61, a liquid supply conduit 20 and an electrical cord 62 connecting the apparatus 2 to the control unit 60, alongside other conduits and components. The control unit 60 includes electronic components (e.g., a computer device containing one or morePatent Application Attorney Docket No. 008634.01587VWO processors and / or memories), internal power supply components (not shown), and an electrical port 63 connected to the electrical cord 62, which provides electrical power to the apparatus 2 and permits electronic communication between the apparatus 2 and the control unit 60. An external power supply 66 may be used in one embodiment, and may be connected to the control unit 60 via a power cord 67. The external power supply 66 may be a power main, but a different type of power supply may be used in other embodiments, such as a battery or a vehicle power connection. The control unit 60 also includes pumping components, such as a pump 64, which may be a peristaltic pump in one embodiment. The pump 64 is connected to the liquid supply conduit 20, which is connected to the liquid supply 61, to pump liquid from the liquid supply 61 to the apparatus 2. The control unit 60 may include further components, such as a display 68, user input controls 69, etc., and generally includes a casing 70 to contain and / or support such components. A stand or receptacle 71 for the apparatus 2 when not in use, or which in some embodiments of this disclosure may be used to hold apparatus 2 while the system 100 completes a priming sequence, may also be connected to or adjacent to the control unit 60. Additionally, the control unit 60 may be provided with a support 72, such as a stand or table, which may be integral with, or separate from, the control unit 60. The liquid supply 61 is shown hanging from an IV stand in FIGS. 1-2, but alternately, the support 72 and / or the casing 70 of the control unit 60 may have a holder for retaining the liquid supply 61.

[0167] The pump 64 is a peristaltic pump in one embodiment, as noted herein. In such a pump 64, the flow rate may be passive and dependent on preset revolutions per minute (RPM) of the pump or may be a closed loop and react to measurement from an ultrasonic or optical flow meter 91 clamped or otherwise connected to part of the tubing of the liquid supply conduit 20, as shown in FIG. 72. The flow meter 91 may be ultrasonic, optical, or another device capable of measuring the speed of the liquid flow through the supply tube in various embodiments, and the flow meter 91 may be placed over the external surface of the liquid supply conduit 20, preserving the sterility / cleanliness of the liquid supply. In one embodiment, the flow meter 91 may be positioned along the liquid supply conduit 20 either before or after the peristaltic pump 64, as illustrated in FIG. 72. In another embodiment, the flow meter 91 may be incorporated within the pump 64 or within the apparatus 2. In general, the flow meter 91 should be placed along the liquid line downstream of the point where all liquid sources within the liquid supply 61Patent Application Attorney Docket No. 008634.01587VWO have merged. In one embodiment, the flow meter 91 may be included in a consumable kit 86 as described elsewhere herein, connected or connectable to the liquid supply conduit 20 that is passed through the peristaltic pump 64, thereby not compromising the sterile liquid path. In one embodiment, the peristaltic pump 64 may be provided with jaws (see FIGS. 66-67 and 70-72) of a “clamp down” type, such that the user opens the jaws and places the tube within them, before then closing the jaws. In this configuration, the flow meter 91 could be used for closed loop control of flow rate for best treatment, accurate tracking of amount of liquid used, and preserving the sterility / cleanliness of the liquid. The flow meter 91 may be augmented with sensors for the detection, sizing, counting and / or other form of quantification of bubbles in the liquid, or quantification of the void fraction in the liquid (the percentage of gas therein), or to identify bubbles in the liquid flow, or such sensors may be provided via a separate, additional device. For example, sensors may be placed on the outside of the liquid supply conduit 20 and may make such measurements by changes (e.g. scattering, Doppler effect, and / or effects on the sound speed, coherence or received acoustic energy) in a given radiation (e.g., ultrasonic or optical) or other property (e.g., the capacitance of a volume that includes the liquid).

[0168] Different flow rates may be required at different points in the treatment. The pump is preferably easily opened via a quick-release opening 23 to facilitate the clinician in changing the liquid supply conduit 20 between uses. Separation of the liquid supply 61 offers the potential to use the hydrostatic head of the liquid supply 61, if it is raised sufficiently high, to provide flow, but in the preferred option, this is less convenient than adding a pump 64. Furthermore, separation of the liquid 61 flowing through the liquid conduit 20 from the internals of the pump 64 reduces the risk of crosscontamination from the pump 64 to the liquid 61. Pressurized systems may be used to produce the required water flow, although if gas pressurization (pressurizing the gas space above the liquid) is used, it can adversely affect the performance of the apparatus 2 by forcing gas into solution in the liquid. This can produce excess bubbles in the liquid via exsolution when the liquid is used in the device (unwanted bubbles which adversely attenuate the sound field in the liquid through scattering or absorption). A pressurization technique that does not use gas exposed to the liquid may be advantageous for this reason (e.g. pressurized by a piston, or a weight or pressure applied externally to the bag, such pressure being applied by solid, liquid or gas optionsPatent Application Attorney Docket No. 008634.01587VWO external to the bag and the bag material being not conducive to allowing gas to pass through it within the relevant timescales).

[0169] Whilst the peristatic pump 64 provides separation between the pump mechanism and the liquid, helping to sustain the sterility / cleanliness of the liquid, the pump 64 can also introduce regular regions of higher pressure / flow rate as the rollers pass over the conduit 20. These can generate strong oscillatory variations in the thickness of the liquid stream (pearling) as it exits the nozzle 14, and these pearls travel downstream. These pearling oscillations may cause breakup of the stream if the amplitude of the pearling oscillations is sufficiently great (as a result of there being enough energy in the regions of high pressure flowing with the stream from the pump 64 and / or the ultrasound field) such that the minima in stream cross-sectional area between the pearls cause the stream to break up into large droplets. If the stream breaks up, no ultrasound can be transmitted beyond the breakup point, because of the strong impedance mismatch between liquid and air. Further, f the stream narrows to a diameter that makes the ultrasonic frequency lower than the cut-off frequency for that mode in the waveguide, no sound will propagate further down the stream beyond that point. Instead, acoustic energy will be reflected back up the stream. Since such narrowing can be oscillatory, these restrictions in allowing the sound to propagate down the stream may be temporary but repeated at a rate associated with the rate at which the stream narrows to this extent. This reflection of energy back up the stream at the narrowings between the pearls is associated with a reduction in the acoustic energy travelling down the stream, and hence a degradation in the performance of the apparatus. The system 100 may be provided with pulse dampeners 95, which can mitigate this degradation in the performance, as shown in FIG. 68. Such pulse dampeners 95 are devices that remove the energy in the regular regions of higher pressure / flow rate (e.g., generated in the liquid supply conduit 20 as the rollers of the pump 64 pass over the flow) before they reach the nozzle 14. In this way, pulse dampeners 64 reduce the amplitude of the pearling wave, and so ensure that the cross-sectional area between pearls does not decrease as much. In one embodiment, pulse dampeners 65 constituting flow path diffusers and a flexible membrane are used to smooth out over time the flow energy in the liquid from the pump 64. This may done by two mechanisms, separately or together. One such mechanism is by extension of the member, movement of the piston, or compression of a gas space, converting mechanical energy to small amounts of heat byPatent Application Attorney Docket No. 008634.01587VWO the alternating pushes and pulls of the liquid flow from the pump 64 moving the piston in an oscillatory fashion and thereby generating friction, distending the membrane (e.g. a rubber membrane) in an oscillatory fashion and thereby generating viscothermal losses, or creating oscillatory temperature oscillations and irreversible thermal losses in the gas as it is compressed and then put under reduced pressure in an oscillatory fashion. If this gas space technique is used, the gas must have low solubility in the liquid, or it will tend to cause gas exsolution in the cone via rectified diffusion and the seeding of bubbles. Another such mechanism by which the pulse dampeners 95 work is by introducing a phase delay in the imposition of pressure fluctuations, as pressure fluctuations in the regular regions of higher pressure / flow rate (generated as the rollers of the pump 64 pass over the flow) exert work on the piston, membrane or gas head space, which then exert similar work back on the liquid, spreading out the disparities in energy that occurred along the flow as a result of the pump, and making the pressure in the flow more even along the length of the flow. A check valve (not shown), e.g., a one way valve, can also be added to reduce pressure inhomogeneities introduced along the length of the flow in the liquid tube by the pump 64.

[0170] The pulse dampener 95 could be a stand-alone device or a separate component that is part of the liquid pathway, or the pulse dampener could be integrated into the liquid pathway. For example, the pulse dampener may be integrated into the liquid supply conduit 20 upstream or downstream of the pump 64 and / or into the hollow body 4 and / or the manifold 40, all of which configurations are shown in FIG. 68. The features of a pulse dampener 95 may be designed into a combined unit 5 as disclosed herein. For example, in one embodiment, a flexible membrane providing a pulse dampening feature could be overmolded by injection molding at the same time as a seal / gasket 78 for engagement with the rear wall 8.

[0171] Other types of pump 64 (not just peristaltic) can also generate pearling, to a greater or lesser extent. Pulse dampeners 95 can be effective at mitigating the adverse effects of these on the performance of the apparatus 2. Indeed, even if the liquid flow is supplied without a pump (e.g., via a hydrostatic head, pressurized container, or mains tap water) the ultrasound alone can generate pearling. Pulse dampeners are generally less effective at reducing these amplitude of the ultrasonically-induced pearling. However, pearlingPatent Application Attorney Docket No. 008634.01587VWO from the ultrasound and the pump will superimpose and can interact, and thus, minimizing pearling occurring from the pump 64 is desirable.

[0172] In a further embodiment, a peristaltic pump 64 may be provided with multiple peristaltic pump pathways 96, such as by the use of a pump 64 with multiple rotors 97 as shown in FIG. 69, or alternatively, by the use of multiple peristaltic pumps 64, to optimize the flow pulse. The liquid flow path would run in parallel through the multiple pathways 96, which would be rotationally offset to cancel out the oscillations on pressure that occur in the liquid supply flow. In a further embodiment, the outflows of two or more pumps 64 could be connected by a manifold that combines the flow in such a way as to homogenize the pressure in the liquid along the flow path of the liquid supply conduit 20. Setting and maintaining the desired phase offset between the rollers on different rotors of the pump 64 is facilitated if the rotors are run from the same shaft but out of phase, so that the positive pressure generated by one roller coincides with the reduced pressure that is generated by the other rotor, due to the offset in the positions of the rollers at that time.

[0173] The liquid supply 61 in one embodiment may be a container having a limited liquid supply. The use of a container as a liquid supply enables precise liquid formulations to be provided to improve healing, such as water with various formulations in solution, e.g., biocides, cleaning agents, drugs, or other pharmaceutical compositions. In one example, the liquid provided by the liquid supply may be a conventional saline solution, which in this context means that the solution is approximately isotonic with human tissue fluid, or solution of sodium chloride 0.9% w / v, and may be free of biocides and / or drugs or other pharmaceutical compositions. FIGS. 1 and 2 illustrate an embodiment where an IV bag or an irrigation bag is used as the liquid supply. The use of a container as a liquid supply also permits different types or formulations of liquid to be used as desired, and also permits usage of the apparatus 2 and system 100 in locations where a supply line (e.g., a water main) having sufficient liquid quality is not available. In other embodiments, a different type of liquid supply 61 may be used, including water mains or other bulk liquid supply. The liquid supply conduit 20 is typically in the form of a flexible hose, although rigid piping may be used for the supply conduit 20 in some embodiments.Patent Application Attorney Docket No. 008634.01587VWO

[0174] The cone 10 and / or the nozzle 14 may be formed of a material or construction such that the acoustic energy transmitted into the stream (see FIGS. 19A, 19B, 27, 28, 29 and 30) is maximized, and the amount of acoustic energy that is reflected back into the cone at the nozzle-stream interface is minimized. In one embodiment the outer perimeter (the outer wall of these structures) from which acoustical signals in the liquid are reflected has a pressure amplitude reflection coefficient (R) close to -1, such as -0.95 to -1.0, or -0.99 to -1.0. In this configuration, almost all the incident energy is reflected back into the liquid, with a 180-degree phase change occurring in the pressure waveform on reflection. This can be achieved by material selection for the cone 10 and / or the thickness of the wall of the cone 10 may be configured to provide a specific ‘pressure release boundary’ (also known as a ‘free’ boundary in acoustic terminology). A reflection coefficient close to -1 in the wall of the cone and nozzle (as experienced by ultrasonic waves propagating towards them from the liquid) minimizes the amount of acoustic energy that is reflected back into the cone at the nozzle / stream interface, because it matches the acoustic boundary conditions found at the perimeter of the nozzle 14 and the curved outer perimeter of the stream. In another embodiment, the material and dimensions of the cone 10 and / or nozzle 14 are chosen such that acoustic field couples with the cone and / or nozzle in a manner that aids in the transmission of acoustic energy from the nozzle into the stream. In a further embodiment, the materials and dimensions of the cone 10 and / or nozzle 14 are chosen such that surface waves are generated in the cone and / or nozzle shell. These surface waves act to couple the acoustic field in the nozzle 14 and the stream.

[0175] The apparatus 2 can be used in any orientation, and some orientations may benefit from a venting or exhaust system and / or a choking mechanism, as described in U.S. Patent Application Publication No. 2021 / 0387237 Al, which is incorporated by reference herein in its entirety. In particular, a venting and / or choking mechanism may be useful in an operation with an unlimited (or less limited) liquid supply, such as when connecting the apparatus to a water main, while such a venting mechanism may cause unacceptable water usage when the apparatus is connected to a limited liquid supply. It is understood that US 2021 / 0387237 Al describes a wide variety of applications for use of an apparatus for generating a stream using acoustic energy, and that aspects of the apparatus 2 disclosed herein may be used in some or all of the applications disclosed in US 2021 / 0387237 Al, with appropriate adaptations if necessary.Patent Application Attorney Docket No. 008634.01587VWO

[0176] The apparatus 2 further includes an acoustic transducer 22 positioned at or adjacent to the rear wall 8 and configured to introduce acoustic energy into the liquid within the chamber 6. The acoustic transducer 22 is mounted in engagement with the rear surface of the rear wall 8 in the embodiment of FIGS. 1-17. A controller 19 controls the operation of the transducer 22, and may be provided as a computer device including one or more processors and / or memories. The controller 19 is shown schematically in FIG. 4 as being located in the apparatus 2, but it is understood that the controller 19 may be located in the control unit 60 in another embodiment, or that the controller 19 may be made of multiple computer components that are located in multiple locations (e.g., in the apparatus 2 and the control unit 60). The controller 19 may perform signal generation that controls the operation of the transducer 22 and the acoustic energy emitted therefrom, including its form, temporal profile and frequency content, the timing of any pulsing of the signal and its relationship to the timing of a bubble generation signal, and the amplitude of the signal as supplied to a power amplifier, which may also be included in the controller 19. Typically, the transducer 22 is mounted on the rear surface of the rear wall 8 and extends over a substantial proportion of the surface area of the rear wall 8. Alternatively, the transducer 22 may have a portion exposed to the chamber 6, such as by being mounted on the front surface of the rear wall 8 (facing the chamber 6), extending through the rear wall 8, or replacing the rear wall 8. If the transducer 22 is embedded through the rear wall 8, seals may be provided between the transducer 22 and the rear wall 8. The transducer 22 may be mounted elsewhere at a location associated with conical body 4 provided that the transducer 22 is configured to introduce acoustic energy into the liquid within the chamber 6 whereby the acoustic energy is present in an output stream from the nozzle 14.

[0177] In one embodiment, the controller 19 may include preset settings for operating the transducer 22 and / or the pump 64 based on the characteristics of various bodies 4 that may be used. Different bodies 4 with different cones 10 could be attached to handset which are optimised to run at different flow rates or frequencies, allowing different treatment options. Each body 4 and cone 10 are designed effectively to transmit the waves into the stream, which includes both the design of the acoustic boundary condition at the nozzle / liquid interface, as well as the coupling of acoustic waves in the liquid and the material of the cone 10. A pre-defined setting may be provided for eachPatent Application Attorney Docket No. 008634.01587VWO body 4, including settings for flow rate, acoustic properties and pulsing, etc. Such settings may be automatically selected in one embodiment, by use of an automatic identification technique for each body 4, such as an RFID (Radio Frequency Identification) tag which is uniquely identified to the body 4. The apparatus 2 may have a sensor (not shown) for this purpose, which is in communication with the controller 19. Such a unique identifier could also be used to identify and track whether a specific body 4 has been used before on that handset 50.

[0178] In some embodiments, an outgasser may be used for the liquid supplied to the conical body 4 to reduce the build-up of gas within the conical body 4, such as an outgasser that uses a microporous filter. An outgasser may be contained in the control unit 60 in one embodiment, such that liquid delivered to the liquid supply line 20 passes through the outgasser between the liquid supply 61 and the apparatus 2. Other example embodiments of outgassers that may be used in connection with the apparatus 2 as described herein are shown and described in International Publication No. WO 2018 / 228848, which is incorporated by reference herein. Nevertheless, certain circumstances (for example, prolonged use, air leaks in the pump, insufficiently smooth pumping, variation in the gas content of the liquid coming from the source, etc.) can cause gas to build up in the chamber 6 that needs to be vented. Thus, the apparatus 2 may include both an outgasser and one or more vents in one embodiment.

[0179] The conical body 4 also includes one or more liquid inlets located at or adjacent to the rear wall 8. In the embodiment of FIGS. 1-17, the apparatus 2 includes a manifold 40 located at the base 11 of the body 4 that includes a manifold body 45 having one port 41 (see FIG. 15B) or multiple ports 41 (FIG. 15 A) that operate as the inlet(s) of the body 4. In general, the manifold 40 includes a manifold inlet 42 that is connected to the liquid supply conduit 20 and one or more internal conduits 44 that extend from the manifold inlet 42 through the manifold body 45 to the port or the plurality of ports 41 to distribute the liquid flow from the manifold inlet 42 to the port or ports 41, where the liquid enters the body 4. FIGS. 7-8 and 17 illustrate the manifold 40 of the embodiment of FIGS. 1-17 in greater detail. In the embodiment of FIGS. 1-17, the manifold 40 is integrally formed as part of the body 4, and the manifold body 45 is integral with the base 11. The manifold 40 is also connected directly to the rear wall 8 by connection of the manifold body 45 and the base 11 to the rear wall 8, such that a portion of thePatent Application Attorney Docket No. 008634.01587VWO manifold body 45 is directly engaged with the rear wall 8. The port or ports 41 in the embodiment of FIGS. 1-17 are formed by notches at the rear of the body 4, such that the rear wall 8 partially defines the periphery of the port or ports 41 by engagement of the body 4 with the rear wall 8. In another embodiment, the port or ports 41 may be formed by holes defined completely within the body 4. The manifold inlet 42 is in the form of a tube that extends outwardly from the bottom side of the manifold body 45. If the apparatus 2 is provided with a vent as described herein, such a vent may be located at the top of the manifold body 45, generally opposite the manifold inlet 42.

[0180] In one embodiment, the apparatus 2 is configured so that the inlet(s) introduce(s) the liquid into the chamber 6 in a flow direction that is radially inward with respect to the periphery of the cone 10 and parallel to the rear wall 8 and / or parallel to the face 25 of the transducer 22. In the embodiment of FIGS. 1-17, the manifold body 45 is formed in an annular shape with an inner annular surface 46, and the port or ports 41 of the manifold 40 are open on the inner annular surface 46 and directed to introduce the liquid radially inwardly from the inner annular surface 46. In this configuration, the manifold body 45 partially defines the chamber 6 and covers a portion of the rear wall 8. The direction of the liquid flow in this embodiment assists in removing bubbles that may adhere to the rear wall 8. The internal conduit 44 in the embodiment of FIGS. 1-17 branches in diverging directions away from the manifold inlet 42 and forms an annular or semi-annular shape that extends around at least the majority of the inner annular surface 46. In the embodiment of FIGS. 1-15A and FIGS. 16 and 17, the ports 41 are distributed at irregular intervals around the inner annular surface, but alternately may be distributed at regular intervals around the inner annular surface 46 in one configuration. In the embodiment of FIGS. 1-15 A and FIGS. 16 and 17, the manifold 40 has twelve total ports 41 that are distributed in four groups of three ports 41 around the inner annular surface 46. The use of the inlets configured as shown in FIGS. 1-17 may reduce the amount of hydrodynamic turbulence within the chamber 6 and ensure a symmetric flow pattern to match the symmetric acoustic field generated by the transducer 22. In particular, the turbulence is reduced compared to a configuration having fewer, larger inlets, because smaller length-scales of turbulence have less energy and are more rapidly dissipated by the liquid viscosity.Patent Application Attorney Docket No. 008634.01587VWO

[0181] It should be noted that the embodiment of the manifold 40 shown in FIGS. 1-17 is only one potential embodiment. Incorporated document US 2021 / 0387237 Al discloses multiple different manifold configurations, and these manifolds (or components and features thereof) may be incorporated into the apparatus 2 of FIGS. 1-17. In a further embodiment, no manifold may be used, and the apparatus 2 may instead by configured for direct feed of the liquid into the cone, such as the configurations disclosed in U.S. Patent No. 11,577,284, issued on February 14, 2023, which is incorporated by reference herein in its entirety.

[0182] The rear wall 8 is positioned adjacent to the base 11 of the body 4 and defines at least a portion of the rear of the chamber 6. The rear wall 8 comprises a plate, for example of glass, ceramic, plastics / polymers, such as polycarbonate, acrylic, or rubber, a metal such as aluminum, brass, stainless steel, or copper, or composites such as carbon fiber and resin. The material may be provided with anti-microbial properties as well (e.g., copper), which may be useful in clinical or other settings. It is understood that the rear wall 8 may be made from multiple materials. In one embodiment, the acoustic transducer 22 is mounted in engagement with the rear surface of the rear wall 8, and may be mounted on the rear wall 8 or otherwise connected to the rear wall 8. For example, the transducer 22 may be connected to the rear side 9 of the rear wall 8 by a bonding material or technique such as an adhesive that will not delaminate or fracture under the expected usage, welding, brazing, soldering, etc., and / or by a mechanical connection. For example, in one embodiment, a mechanical connection may be made by the transducer 22 having a threaded hole that receives a bolt or threaded stud that is attached or welded to the rear wall 8. As another example, in one embodiment, clamps with some vacuum grease or coupling gel may be used. In other embodiments, as described elsewhere herein, the transducer 22 may extend through a hole in the rear wall 8 (or multiple holes if multiple transducers 22 are used), or the transducer 22 may be mounted directly in contact with the base 11 of the conical body 4 without a rear wall 8 being present. In another embodiment, the faceplate of the transducer 22 can form the entire surface of the rear wall 8 that is in contact with the liquid, which may include an appropriate flange to aid connection to the cone 10 and / or the manifold 40. In this configuration, the “headmass” of the transducer 22 may function in place of the rear wall, with the flange (not shown) constituting the headmass where it contacts the liquid, having a diameter required for suitable performance. The rear wall 8 in FIGS.Patent Application Attorney Docket No. 008634.01587VWO1-17 is connected to the front side of a permanent portion (e.g., the casing) of the apparatus 2 and is engaged with the rear side of the manifold body 45 as described herein to define the rear end of the chamber 6. In this configuration, the liquid inlet ports 41 are directed parallel and adjacent to the portions of the rear wall 8 exposed within the chamber 6. An inner housing 29 is also mounted at the rear side 9 of the rear wall 8 to enclose the transducer 22. In another embodiment, multiple transducers 22 may be connected to the rear wall 8 or otherwise configured to pass acoustic energy through the rear wall 8, as described below.

[0183] The configuration of the manifold 40 is designed to reduce the introduction of unwanted bubbles into the chamber 6, reduce the unwanted generation of bubbles during the transportation of the liquid through the liquid delivery system, and reduce the entrapment of gas within the manifold 40. All of these occurrences may reduce the efficiency by which the cone 10 transmits acoustic energy from the transducer 22 into the stream, by absorbing or scattering the acoustic energy, or by adversely affecting the acoustic boundary conditions at a region of the sound field. The depth or cross-section of the internal conduit 44 can vary to optimize the flow through them and through the ports 41, to reduce the likelihood of gas being trapped in the internal conduit 44, while making the volume flow rate of the radial inward flow across the rear wall 8 even with respect to angular direction as measured from the axis of symmetry of the rear wall 8. This can be supported by varying the size and spacing of the ports 41 in various embodiments (FIG. 15A). The internal conduit 44 in the embodiment of FIGS. 1-17 has a narrowed portion 44A at the top end thereof, to assist in ejecting bubbles from the internal conduit 44 via a conduit vent 33, rather than allowing bubbles to build up in the internal conduit 44. In the embodiment of FIG. 15 A, the port 41 that is adjacent to the narrowed portion 44 A of the conduit 44 functions as a conduit vent 33, to permit bubbles to be ejected from the conduit 44 into the cone 10. In this embodiment, the narrowed portion 44 A and the conduit vent 33 are usually positioned at the top (with respect to the direction of gravitational acceleration) of the conduit 44, so that buoyancy works with flow to expel the bubbles from the conduit 44 at the conduit vent 33. The flow out of the conduit vent could take the bubbles into the cone 10, to be expelled, e.g., when the nozzle 14 is tipped nearly vertically upwards. In the embodiment of FIG. 15 A, there are multiple ports 41 in the manifold 40, but the embodiment in FIG. 15B could be used when the liquid supply to the cone contains excess bubbles, such that thePatent Application Attorney Docket No. 008634.01587VWO passage of all the inlet liquid through the single port 41 aids expulsion of bubbles from the manifold conduit 44. In another embodiment, the flow out of the conduit vent 33 may be removed by suction from a siphon, pump, or other mechanism capable of applying suction (such as a venturi), so that bubbles from the conduit are expelled to a drain or back into the water feed prior to some outgasser, in a similar manner to the way that suction can be applied to the cone vent 43 in embodiments described herein and incorporated in WO 2021 / 250645. The conduit vent 33 may be configured or located differently in another embodiment. In further embodiment, the conduit vent 33 may be located at the position shown in FIG. 15B, with another port 41 (e.g., a smaller port in one embodiment) being positioned close to the liquid inlet 42 to introduce liquid into the cone 10. In yet another embodiment, a single port 41 (which may be wider than the port 41 shown in FIG. 15B) positioned close to the liquid inlet 42 could act as both conduit vent 33 and the port 41 that supplies liquid to the cone 10, in which case only a very short conduit 44 would be required. Note that no cone vent 43 (see FIGS. 42 A- B and 43A-C) is required in the embodiments of FIGS. 1-18, because the gas in the cone can be expelled by periodically angling the nozzle upwards at times that may be indicated by the apparatus 2, e.g., through alarms (audible, visual or tactile) that are triggered by the passage of countdowns, and / or triggered by monitoring the performance of the apparatus (e.g., as cleaning efficiency, or the signal across the transducer, are monitored).

[0184] If the liquid entering the manifold is particularly prone to the causing gas build up in the internal conduit 44 (for example because of recent warming that causes gas to come out of solution, or because of a pump generating unwanted free gas in the liquid) then the manifold 40 can be adapted in several ways to enhance its ability to eject gas from the internal conduit 44 via the conduit vent during priming or at other times when gas has built up in the manifold conduit. One example embodiment that illustrates this is shown in FIG. 15B, where the manifold 40 includes only one port 41 , generally opposite the manifold inlet 42 and at the top of the manifold 40 next to the conduit vent 33, to enhance the ability of the manifold 40 to eject gas out through the vent. In the embodiment of FIG. 15B, the body 4 (including the cone 10 and the base 11) are provided with the manifold 40 as a combined unit 5, and the structure of the combined unit 5 is generally the same as the combined unit 5 in FIG. 15 A, except as described herein. These shared or common features between the embodiments of FIG. 15A andPatent Application Attorney Docket No. 008634.01587VWOFIG. 15B are not described again in detail with respect to the embodiment of FIG. 15B for the sake of brevity, and the same reference numbers are used in the drawings to reference similar components. The combined unit 5 having the structure shown in FIG. 15B and described herein is suitable for use with the apparatus 2 as shown in FIGS. 3- 10, as an alternative to the combined unit 5 shown in FIGS. 11-15A and 16-17.

[0185] The shape and design of the cone 10 is designed to maximize the transmission of acoustic energy from the transducer 22 to the point of treatment, by minimizing turbulence and vorticity in the cone (which can trap bubbles there, generating unwanted and excessive acoustic attenuation); optimizing the modal and transient forms of the sound field in the water in the cone and stream, and optimizing the coupled waves at the interface between the liquid and the solid material of the cone; and by reducing the instabilities in the liquid stream that issues out of the nozzle 14. If the stream breaks up due to instabilities (or thins to a diameter too small to allow acoustic waves to propagate because of wave-guide cut-off), then the acoustic energy will not reach further than that point down the stream. Such thinning can be oscillatory, generating alternating thicker and thinner parts of the stream, so that reducing the amplitude of these oscillations can be beneficial to the sound propagation to distance within the stream. The thickness of the cone wall can be uniform or tapered to better facilitate transmission of acoustic energy from the transducer to the liquid stream. Other advantages of tapering include saving material and weight in the consumable cone and facilitating the releasing of an injection molded part from the mold (the taper is more commonly known as the draft angle in injection molding). In the embodiment of FIGS. 1-17, the thickness of the wall of the cone 10 tapers from thick near the transducer 22 to thin at the orifice 12. This may be done by changing the thickness in a linear relationship with the length of the cone 10 or to the internal diameter of the cone 10. For example, the thickness of the cone 10 in the embodiments of FIGS. 1-17 is t = 0. Ir + 0.5, where t is the thickness in mm and r is the inner radius in mm, though other embodiments may have different linear relationships. The wall thickness may be configured to be suitable for injection molding in one embodiment, e.g., to use a 3 mm maximum wall thickness and a 1 mm minimum wall thickness. For other manufacturing techniques such as blow molding, vacuum forming, or 3D printing, other wall thicknesses may be used and / or may be optimal. FIGS. 24A and 24B illustrate advantageous shape profiles for the cone 10 according to one embodiment.Patent Application Attorney Docket No. 008634.01587VWO

[0186] The rear wall 8 in one embodiment is configured to efficiently transmit the acoustic energy (and therefore should not unduly absorb the energy) and has a thickness (compared to the acoustic wavelength in the material of the rear wall 8) that ideally causes an acoustic particle displacement antinode where the rear wall 8 meets the liquid. Departures from this ideal condition can still achieve satisfactory operation, although usually with reduced efficiency in terms of the therapeutic effect as a function of the electrical power. Electrical power usage is important, however, because the transducer 22 is sealed, and overheating is a concern. The time-averaged electrical drive power should be low enough to avoid overheating, which can be done by reducing the amplitude of the electrical signal and by reducing the duty cycle of the ultrasonic pulses, if necessary. The acoustic condition where the rear wall 8 meets the liquid is not simple. If the rear wall 8 were radiating into an infinite half space, the incident and reflected pressure waves in the rear wall 8 (going from a higher acoustic impedance to a lower, i.e., the liquid) would be of opposite phase and would produce a particle displacement antinode. When factoring in the reflections back from the nozzle 14 and walls of the cone 10, they will shift the phase relationship at the boundary. The antinode will shift into either the rear wall 8 or the liquid depending on the phase relationship. If it is assumed that the reflections are sufficiently small, then the interface would be a particle displacement antinode or near to a particle displacement antinode. In general, the interface between the liquid and the rear wall 8 can deviate from a particle displacement antinode when standing waves are formed in the cone 10, but over the majority of frequencies, the interface will be close to becoming a particle displacement antinode. Note that, for an 145 kHz ultrasound field in a borosilicate glass rear wall 8 that is 7.5 mm thick, although the rear wall 8 is only 0.19 wavelengths thick, in terms of the acoustics model, the rear wall 8 acts as part of the headmass of the transducer 22, and so one acoustical perspective would be to consider that they can be modeled as entity consisting of the transducer headmass combined with the rear wall 8, and considering that together they form an idealized boundary.

[0187] Additionally, the rear wall 8 and the adhesive (if present) should be free of acoustic scatterers that hinder the passage of acoustic energy therethrough. Both the rear wall 8 and the adhesive used to connect it to the transducer 22 should be tough enough to withstand the fatigue of ultrasonic vibrations, the cycling to high temperatures and back that can occur during normal use as the transducer 22 heats up, and other effects of thePatent Application Attorney Docket No. 008634.01587VWO prolonged use of ultrasound (rectified diffusion if, for example, the constituency of the adhesive makes it a possibility). Microparticles should not be shed into the liquid (e.g., through cavitation erosion where the rear wall 8 meets the liquid). The adhesive material and the material of the rear wall 8 should be capable of bonding the rear wall 8 to the transducer 22 without degrading during thermal cycling with ultrasonic exposure, and to survive drop testing. A glass rear wall 8 may be preferable to one made from metal, because a metal wall may form an electrical pathway from the transducer 22 to the target (e.g., a patient). Thus, a metal rear wall 8 could provide a point of failure hazard from the electrical pathway to the patient (depending on the resistance of the liquid path), and if so, it would need to be mitigated using other protections (e.g. overcurrent protection). Use of a borosilicate glass backplate (the thickness of which is 0.1942 + / - 30%, or + / - 10% wavelengths of the compressive longitudinal wave in the rear wall 8) eliminates this possibility, which is especially important for wound treatment on live patients. As examples, this requires that the borosilicate glass rear wall 8, when driven at ultrasonic frequencies of 400 kHz, 700 kHz, and 1 MHz, should have thicknesses of 2.7 mm, 1.6 mm, and 1.1 mm, respectively. Other types of glass or ceramics would work, but borosilicate glass provides good performance and is transparent to permit light to be transmitted through the rear wall 8, the use for which is described herein. Polymer and plastic backplates may also work for the rear wall 8, but are less efficient and can be less resistant to damage, and less biocompatible, requiring higher transducer powers and so greater transducer heating. For the purpose of driving a device ultrasonically at 145 kHz, the longitudinal compressional wave speed in borosilicate glass is 5600 m / s, and for this usage, the thickness of a borosilicate glass backplate is 7.5 mm in one embodiment. The usage of the device on patients means that choice of materials should ensure biocompatibility and biosafety (e.g., so that no toxins leach from the materials of the device into the liquid supply, and no hazardous particulates are washed onto the wound).

[0188] The apparatus 2 of FIGS. 1-17 is configured as a self-contained handheld delivery device and includes a casing 55 configured to facilitate handheld use. The casing 55 in this embodiment is shown in FIGS. 3-7 and 9-10 and includes a handle 56 and a main housing 57. The casing 55 may be formed in various manners, including by use of two front and rear half-pieces 58A,B that may be separate or configured as a clamshell piece, which are joined together by fasteners, clips or sealed with adhesive or ultrasonicPatent Application Attorney Docket No. 008634.01587VWO welding, as well as a mounting piece 52 (or pieces), which in the embodiment of FIGS. 1-17 is in the form of an attachment ring that connects to the front piece 58 A. FIG. 9 illustrates the casing 55 with the rear piece 58B removed, and the two pieces 58A,B combine to form the handle 56 and the main housing 57 in this configuration. The handle 56 is connected to the main housing 57 and is configured for gripping by the operator to move and direct the apparatus 2. The apparatus 2 in FIGS. 1-17 includes a display 54 (e.g., a screen) mounted on the rear of the main housing 57, which displays information to the user and may optionally include user input devices such as buttons and / or a touch screen. The apparatus 2 in this embodiment also includes an additional user input device in the form of a button 59 located on the handle 56, which can be used to initiate the liquid flow and the transducer 22. The handle 56 and the main housing 57 also encloses electrical components, i.e., to receive input from the button 59 and operate the transducer 22, the display 54, as well as to interact with other components of the apparatus. For example, one or more printed circuit boards (PCB) may be located within the handle 56 and / or the main housing 57. It is noted that various components of the apparatus that are contained within the casing 55 may be held in place by fasteners, clips, bonding, and / or sandwiching the components between the two pieces of the casing 55, among other structures.

[0189] The main housing 57 in FIGS. 1-17 encloses various electronic components of the apparatus 2, and the rear wall 8 is mounted at the front of the main housing 57 and is exposed within a front opening 53 of the casing 55. The rear wall 8 and the main housing 57 together enclose the transducer 22 in this configuration. The apparatus 2 also has an inner housing 29 that combines with the rear wall 8 to enclose the transducer 22 within the main housing 57. In the embodiment of FIGS. 1-17, the inner housing 29 is defined by a recessed portion of the front piece 58A of the main housing 57, and an inner opening 51 is defined by the front piece 58A around the inner housing 29. The rear wall 8 is engaged with the front piece 58A to cover the inner opening 51, and the mounting piece 52 is connected to the front piece 58A (e.g., by fasteners) to secure the rear wall 8 to the main housing 57. As shown in FIGS. 7 and 10, the front piece 58A of the main housing 57 has an annular recess 47 around the inner opening 51, and the periphery of the rear wall 8 is seated within the annular recess 47. A seal 48 (e.g., an O-ring or gasket) is also positioned within the annular recess 47 to seal the inner housing 29 against ingress of liquid from the chamber 6. The mounting piece 52Patent Application Attorney Docket No. 008634.01587VWO engages the front side of the rear wall 8 around the periphery to secure the rear wall 8 between the mounting piece 52 and the front piece 58A of the main housing 57. As shown in FIG. 7, the mounting piece 52 has a flange 49 that extends annularly around the inner opening 51 and defines the front opening 53 of the casing 55. The rear wall 8 is engaged on front and rear sides by the mounting piece 52 and the front surface of the annular recess 47, respectively, to secure the rear wall 8 to the main housing 57. In this configuration, the rear wall 8 is exposed within the front opening 53.

[0190] In one embodiment, the body 4 and / or the manifold 40 may be removable and interchangeable components, and the remainder of the apparatus 2 may constitute a permanent or reusable base unit, which in the embodiments disclosed herein, is or includes a handset 50 configured for hand manipulation by a user. In other embodiments, the base unit may have a different configuration, including a fixed or automated positionable unit. For example, the body 4 and / or the manifold 40 may be single-use articles that are removed and replaced after each use, and may be disposed of or separately cleaned and reused (FIGS. 65A-C). The combined body 4 (optionally including the manifold 40 as a combined unit 5), liquid supply conduit 20, and consumable liquid supply 61 may be provided as a consumable kit or single-use treatment pack 86 (FIG. 65 A) that is used on a per-treatment or per-patient basis, in one embodiment. FIG. 65B shows the apparatus and the consumable kit 86 connected to a control unit 60 as disclosed herein, and FIG. 65C shows the apparatus 2 in use cleaning a wound on a patient’s leg. This also permits interchanging of different bodies 4, e.g., having different conical walls 10 and / or nozzles 14, for different uses. The body 4 and the manifold 40 may be provided as a combined unit 5 that is removable from and / or reconnectable to the handset 50, such as by releasable connection to the casing 55. The apparatus 2 of FIGS. 1-17 has the body 4 and the manifold 40 formed together as the combined unit 5 in the form of a single, integral body that is releasably and interchangeably connected to the casing 55. In this configuration, the manifold 40 and the body 4 may be formed as a single molded piece. The manifold 40 has the internal conduit 44 open on the rear side of the manifold body 45, such that the internal conduit 44 is bounded on the rear side by the rear wall 8 or another portion of the handset 50 and the engagement between the manifold body 45 and the rear wall 8 (or other portion of the handset 50) seals the internal conduit 44. This configuration of the manifold 40, with the internal conduits 44 open on the rear side of the manifold body 45, facilitatesPatent Application Attorney Docket No. 008634.01587VWO manufacturing of the body 4 and the manifold 40 as the combined unit 5 by molding. A great range of materials can be used for injection molding, but stiffer materials may perform better in some aspects. Example materials that may be used include Polycarbonate (PC), Polypropylene (PP), POM (Polyoxymethylene), PEEK (Polyether ether ketone), ABS (Acrylonitrile butadiene styrene), and PET (Polyethylene terephthalate). Other materials, which may not be suitable for injection molding, but which may produce a satisfactory cone 10, include glass and metal. In one embodiment, the combined unit 5, or at least the cone 10, may be made from a transparent or semitransparent material, so that the user can better see the priming operation has been successful and check for the presence of unwanted bubbles in the chamber 6. The transparent cone also has advantages in terms of ensuring cleanliness. Other manufacturing techniques for plastics such as 3D printing, blow molding, vacuum forming could also be used, and other known techniques may be used for non-plastic materials.

[0191] The combined unit 5 and the handset 50 may have complementary connecting structures for removable engagement to connect the combined unit 5 to the handset 50. In the embodiment of FIGS. 1-17, the mounting piece 52 of the casing 55 of the handset 50 has tabs 73 on the top and the bottom at the front of the casing 55, and the base 11 of the body 4 has slots 74 at the top and bottom thereof that receive the tabs 73 to connect the combined unit 5 to the casing 55 of the handset 50. The slots 74 are defined by inwardly extending flanges 75 in the embodiment of FIGS. 1-17, such that the front surfaces of the flanges 75 engage the rear surfaces of the tabs 73.

[0192] The combined unit 5 is connected to the casing 55 by rotation in the embodiment of FIGS. 1-17, as shown in FIGS. 5-6, where the combined unit 5 is pushed against the casing 55 (FIG. 6) and then rotated clockwise to a locked position (FIG. 5) where the tabs 73 are received in the slots 74. Each of the slots 74 is open on at least one end (the clockwise end when viewed from the front of the casing 55 in the embodiment of FIGS. 1-17) to allow the respective tab 73 to pass into the slot 74 by rotation. Each of the tabs 73 in the embodiment of FIGS. 1-17 has a ramped surface 76 on the rear surface, such that the tab 73 has a smaller thickness on the counterclockwise end and a larger thickness on the clockwise end (when viewed from the front of the casing 55). Additionally, each of the flanges 75 has a ramped surface 77 on the front surface, suchPatent Application Attorney Docket No. 008634.01587VWO that the flange 75 has a smaller thickness on the clockwise end and a larger thickness on the counterclockwise end (when viewed from the front of the casing 55). In this configuration, the engagement of the ramped surfaces 76, 77 pulls the combined unit 5 of the body 4 and the manifold 40 into closer engagement with the casing 55 of the handset 50, to achieve tighter connection and improved sealing. The ramped surfaces 76 of the tabs 73 may have a “double” ramped configuration, with the first ramped portion of each ramped surface 76 facilitating the initial engagement with the flange 75 and the second ramped portion serving to tighten the connection near the end of rotation. The connection structure between the combined unit 5 and the handset 50 is configured such that the combined unit 5 may only be connectible to the handset 50 in one orientation.

[0193] The combined unit 5 may further have one or more seals 78 (e.g., an O-ring or gasket) at the base 11 of the body 4 for improved sealing against the rear wall 8, e.g., within a groove 32 on the rear side of the base 11 (see FIG. 12A). The seal 78 may alternately be provided by a rubber or silicone material attached to the rear surface of the base 11, such as by using a two-step molding or co-molding process with the combined unit 5. In another embodiment, a different type of releasable connection structure may be used, such as brackets, clamps, clips, latches, hooks, or similar structures, which may use at least two connection points; bolts, screws, or other threaded member; elastic bands or straps; other bands or straps (e.g., using a ratchet for tightening); sliding retainers (e.g., tab / slot); complementary threads between the handset 50 and the combined unit 5, a twist on bayonet-like structure; or other mechanical locking structures or combinations of the listed structures; magnets in the handset 50 and / or the combined unit 5 or in a separate retaining ring.

[0194] The mounting piece 52 may be made from a material which is harder than the material of the body 4 and / or the combined unit 5 in one embodiment, to ensure that wear occurs only on the replaceable component (the body 4 / the combined unit 5), which may only be used once, rather than the mounting piece 52 that may last the life of the product. Potential materials for the mounting piece 52 include stainless steel or PEEK, although many other materials may be usable.

[0195] The apparatus 2 may include features to ensure that the body 4 and / or the combined unit 5 is fitted correctly to the handset 50 before use. For example, one or morePatent Application Attorney Docket No. 008634.01587VWO microswitches 30 in communication with the controller 19 can be used in conjunction with the rotatable connection mechanism to ensure the apparatus 2 is not run without the cone 10 fitted correctly. The microswitch 30 can be mounted in the handle 56 of the handset 50 and positioned adjacent to the lowermost tab 74 of the mounting piece 52 (see FIG. 7), so as to be difficult to access to override either by accident or on purpose. Other connection detection techniques may include an optical sensor, a light sensor, a Hall effect sensor, a photoelectric sensor, a camera or QR scanner, a capacitive sensor, a reed switch or RFID sensor matched with a detail, sticker, feature or RFID tab on the body 4 which can trigger an identifying signal from the relevant sensor.

[0196] FIGS. 19A and 19B illustrate schematically some methods of use of the apparatus 2 and the cone 10 in FIGS. 1-17. FIG. 19A illustrates the apparatus 2 being used in treating a wound on a patient’s knee. FIG. 19B illustrates an apparatus using the cone 10 in treating or cleaning a patient’s hands.

[0197] The apparatus 2 is configured such that the ultrasonic system has low damping and energy loss at its resonance frequency, which allows it to more efficiently transmit a cleaning action to the target (note that this refers to the resonance of the ultrasonic generation system, which is different from the pulsation resonance of the bubble as described elsewhere herein, although the system operates efficiently in cleaning / healing when the frequencies of the two are equal). The resonance of the ultrasonic system occurs at the frequency at which we see maximum efficiency (for converting electrical to acoustical power) in the generation of the chosen mode of vibration of the transducer when it is attached to the rest of the apparatus (the backplate, and the liquid-filled cone), that mode being chosen to be at the frequency that generates the desired cleaning and / or tissue regeneration. However, the ultrasonic system is a complex entity containing many components, as the transducer 22 is loaded by the structure and the flowing liquid. To obtain efficient operation of the apparatus 2 the apparatus 2 may be operated close to a resonance frequency in one embodiment. The frequency can be tuned to the resonance during manufacturing for maximum performance, in order to compensate for manufacturing variability of the components of the apparatus 2. Additionally, the apparatus 2 can be recalibrated in the field while in use using a frequency follower to monitor the efficiency and adjust the frequency accordingly to keep the drive signal at peak efficiency. Any changes in impedance due to temperature, variations in flow rate,Patent Application Attorney Docket No. 008634.01587VWO difference in cones 10, etc., can be tracked during treatment and the drive signal can be optimized within pre-determined boundaries using a frequency-tracker circuitry and software, which may be incorporated into the controller 19. Such circuitry and software can lock the drive frequency onto a key element (the maximum of the real admittance or the minimum of the impedance magnitude of the transducer 22 when it is loaded with the liquid-filled cone and stream; the frequency at which current through and voltage across the transducer are in phase when the transducer is loaded with the liquid- filled cone and stream; the frequency at which maximum power is monitored to transmit into the stream using effect of the loading on the electrical signal across the transducer 22) and track it as the apparatus 2 runs and warms up, and as the stream develops. This efficiency is important in reducing the heating of the transducer 22, which is encapsulated. As the transducer 22 heats up, its properties can change, and this can adversely affect the performance of the apparatus 2. The efficiency of the apparatus 2 is also important for enabling the apparatus 2 to be powered from a vehicle battery or portable battery.

[0198] For frequency tracking as described above to work, a signal is required that reflects the efficiency of performing the treatment. Acoustic receivers sensitive to the ultrasonic drive frequency of the transducer 22 can be placed in the body 4 or on the rear wall 8, or even in a test surface at the proposed location of the target, and the amplitude of the signal can be interpreted to indicate the effectiveness of the apparatus 2 in generating ultrasound. These only act as proxies for the effectiveness of the surface (e.g. wound) treatment, and as such need to be interpreted carefully to avoid the frequency tracker being misled. Other proxies include elements of the signal measured across the ultrasonic drive transducer terminals, e.g., reflecting power, current, or the voltage across the transducer, or to use a fixed voltage drive and monitor how other parameters vary under this condition as the frequency is varied.

[0199] One option for implementing the frequency following is to identify the optimum carrier frequency (and keep monitoring changes every few seconds) by maximizing the crosscorrelation signal of the returned acoustic wave from the nozzle 14 as described herein with respect to sonar ranging. The amplitude of the returned acoustic wave (cross correlation signal) will be largest close to the resonance of the system. With a simple search algorithm that varies the drive frequency, the optimal frequency can be found byPatent Application Attorney Docket No. 008634.01587VWO evaluating the cross-correlation peak of the nozzle reflection. Consumed electrical power or current may or may not be a useful proxy for effective surface treatment, depending on the number and nature of vibrational modes that are being excited in the transducer 22. If the transducer 22 and its loading cause the excitation only of modes that drive the rear wall 8 in a way that generates a strong propagating acoustical field down the stream (i.e. the acoustic particle velocity of the rear wall 8, at its interface with the liquid is always in a direction that is perpendicular to the interface between the backplate and the liquid, is in phase at all points across the interface between the backplate and the liquid), then the consumed electrical power can be used to identify the optimal frequency for driving. However, this will not be a reliable signal if other vibrational modes are excited in the rear wall 8, because electrical power that is consumed to drive modes that do not contribute significantly to the ultrasonic field in the stream (such as a radial mode in the transducer 22) does not act as a good proxy for the effectiveness of surface treatment. The rear wall 8 can be driven such that the surface in contact with the liquid moves perpendicular to the interface between rear wall 8 and the liquid, with all parts of the surface moving in phase. Multiple transducers or accelerometers on the surface can be used to detect whether the points on the surface are moving in phase, as can lasers in time of flight or Doppler mode when reflecting off an interface in the backplate. In one embodiment (see FIGS. 18 and 18A), a capacitor 31 can be formed using a conductive ring (e.g. made of copper tape) attached to the rear wall 8 (preferably on the rear side 9 of the rear wall 8 that is remote from the liquid) placing a thin insulated ring above the conductive ring, and then another copper ring on top of that, such that the compressible insulator (e.g., plastic) is sandwiched between the conductive rings, to form a capacitor 31. The capacitance of such a capacitor 31 will vary as the rear wall 8 vibrates in the preferred mode (modes that are not axisymmetric are less efficient and will generate a lower signal for the frequency follower).

[0200] The system 100 may include additional removable and reconnectable components in one embodiment, such as the liquid supply conduit 20 and / or the liquid supply 61. In the embodiment shown in FIGS. 1-2, the liquid supply conduit 20 and the connector 21, or multiple connectors (e.g., an IV spike) for connecting to the liquid supply 61 may also be replaced with each use, along with the combined unit 5. For example, the combined unit 5 may be provided as a kit with the liquid supply conduit 20 andPatent Application Attorney Docket No. 008634.01587VWO connector 21, and these components may be connected to the handset 50 and the liquid supply 61 for use, then removed and replaced for the next use. Such a kit may be sterilised and packaged in a sterile bag or other sterile container. In the embodiment shown in FIG. 2, the liquid supply conduit 20 connects to the liquid supply 61 and the control unit 60 and is removed and replaced as a single conduit. The liquid supply conduit 20 in this embodiment can be connected to the pump 64 in the embodiment of FIGS. 1-2 preferably by opening up the quick-release opening 23 to the peristaltic pump 64 (see FIG. 2), placing the liquid supply conduit 20 into the peristaltic pump 64 (e.g., into the rollers of the pump 64), and closing the quick-release opening 23. In another embodiment, the liquid supply conduit 20 may be connected to the control unit 60, such as to an outlet port, and a liquid input conduit may be connected from the liquid supply 61 to the control unit 60 as a separate conduit. The liquid input conduit may or may not be configured to be removable and replaceable with the liquid supply conduit 20 in various embodiments, and may or may not be part of the aforementioned kit with the combined unit 5. The liquid supply 61 in this embodiment, in the form of an IV bag or an irrigation bag, is also replaceable. Thus, in the embodiment of FIGS. 1-2, the entire fluid pathway between the liquid supply 61 and the outlet of the nozzle 14 are removable and replaceable. This provides improved sanitary conditions and avoids intermixing of different liquids. Portions of the handset 50, in particular the rear wall 8, may contact the liquid inside the chamber 6, but the exposed nature of the rear wall 8 facilitates cleaning between uses. For example, the rear wall 8 can be sprayed with a sanitizing fluid between uses.

[0201] As disclosed herein, the apparatus 2 is usable with various different liquid supply 61 configurations, including mains water, pumped potable water, potable bagged water, bagged sterile water, saline bags, pressurized or pumped liquid containers, etc. Whatever the source of the liquid, the performance of the apparatus 2 may be improved by avoiding buildup of excessive free bubbles of gas pockets in the cone 10. This buildup can come because of the presence of excessive bubbles in the liquid supply to the chamber 6, or too much dissolved gas in the liquid entering the chamber 6 that then exsolves (comes out of solution) by rectified diffusion or cavitation in the cone 10, or where there is too great a temperature rise between the liquid supply and the liquid in the chamber 6 (a few degrees can be sufficient, depending on the level of dissolved gas in the liquid supply), or where there is a gas pocket in the liquid supply 61 or in thePatent Application Attorney Docket No. 008634.01587VWO components along the conduit 20 between the liquid supply 61 and the chamber 6 (including in the manifold or cone itself) that, through entrainment or some other process, seeds bubbles into the flow. Filters (microporous, carbon or similar) positioned at one or more points along the liquid supply conduit 20 or elsewhere in the liquid path, can remove some bubbles before they reach the cone 10. The problem can be reduced if the liquid supply 61 (e.g. saline bags) is properly managed so that the temperature of the liquid is as close as possible to the temperature the liquid will have in the cone, e.g. by appropriate storage of the liquid supply 61 in the hours prior to use, in an environment of the correct temperature. This will allow the dissolved gas content in the liquid to attain the proper level (as per Henry’s Law) to avoid excessive exsolution eri route to, and within, the chamber 6. Gas bubbles that may compromise the performance of the apparatus 2 may therefore be avoided. Pre-heating of the liquid supply 61 may cause gas to exsolve, which causes excess gas to occur within the chamber 6 unless the gas is removed. Whether the temperature increase of the liquid prior to entering the cone is due to environmental temperature changes or artificially induced (e.g. by heating elements), the performance problems caused by such gas bubbles can be reduced by filters, appropriate gas spaces above the liquid, and / or members which separate the flow from a region of reduced pressure to pull the gas out of the liquid. Such components can be added inline with the flow and / or in a static volume of water.

[0202] If the liquid supply is provided with a gas permeable wall (as some saline bags are), this can facilitate the establishment and control of conditions within the liquid supply 61 and the conditions the liquid will encounter within the chamber 10, in terms of Henry’s Law. The liquid supply may be handled properly to avoid gas buildup, e.g., by giving enough time (as given by Fick’s Law) to allow changes in temperature to establish equilibrium conditions with respect to dissolved gas in the liquid supply 61 compared to the conditions that the liquid will encounter in the cone 10, and not handling the liquid supply 61 roughly, which may perturb and break the liquid surface and entrain bubbles within the bags. Taking measures such as gentle handling, the use of a gas permeable membrane in the wall of the liquid supply 61, and the allowance of sufficient time for the liquid supply 61 to be left at the temperature the liquid will encounter in the cone 10, can give consistent gas levels in the liquid supply 61, and therefore give consistent performance. It is also noted that a reduction in pressure asPatent Application Attorney Docket No. 008634.01587VWO the liquid travels from the liquid supply 61 to the chamber 6, or when the liquid is stored in a liquid supply 61, may also cause gas to come out of solution and cause similar problems. The processes and apparatus described herein also hold if such a reduction in pressure is the driver for gas to come out of solution. In one embodiment, the liquid supply 61 may therefore be provided using a bag design that has material gas permeability and liquid content formulation to avoid gas buildup, as well as having one or more connection ports and a volume optimized for the specific application or condition.

[0203] As disclosed herein, measures can be taken to avoid excess gas that would degrade the performance of the apparatus, caused by previously-dissolved gas coming out of solution either when the liquid is stored prior to use, or on its journey from the liquid supply 61 to the cone 10, through drivers such as an increase in temperature and / or a decreasing in ambient pressure. However, even if the dissolved gas concentration in the gas is identical in the supply and in the cone without any gas coming out of solution in transiting between the two, the ultrasonic field in the cone 10 can also cause gas to come out of solution. This can occur through the mechanism of rectified diffusion, or through the mechanism of inertial cavitation in front of the transducer 22 or at acoustic pressure antinodes within the modal acoustic field in the cone 10. The amplitude of the ultrasonic field within the chamber 6 can be tuned such that enough gas comes out of solution to seed the flow to the surface-to-be-treated with enough bubbles of the correct size, i.e., close to the pulsation resonance frequency of the sound field, and if required, at a size appropriate to stimulate surface waves on the bubble wall. It is noted that the allowed breadth of the range of effective bubbles sizes increases as the amplitude of the ultrasonic field on the surface-to-be-treated increases, so long as the bubbles are not undergoing inertial cavitation, without so much gas coming out of solution as to reduce the performance of the apparatus 2 through acoustic absorption and scattering by the bubbles. The amplitude required to do this depends on the duration of the time the liquid and bubbles spend within the cone 10, and whether the liquid in the cone 10 is oversaturated, saturated, or under-saturated with dissolved gas.

[0204] Various measures are described herein to avoid the liquid being over-saturated with dissolved gas, as gas comes out of solution readily in those circumstances (through the drivers of increased temperature, reduced pressure, or rectified diffusion in thePatent Application Attorney Docket No. 008634.01587VWO ultrasonic field). However, it is possible to pre-treat the liquid to cause an undersaturation of gas dissolved in the liquid as it enters the chamber 6, which may improve performance if excess exsolution is causing attenuation of the sound field. Such pretreatments include storing the liquid at a warmer temperature than the temperature that it will experience in the cone 10, or at a lower pressure that the pressure it will experience in the cone 10, and ensuring that all the gas that exsolves during storage is removed from the liquid, e.g. through the gas-permeable walls of a saline bag or in a gas head space. Further, in some embodiments, additives such as drugs / formulations can be added to the liquid, if necessary for a specific application or enhancement. In one embodiment, one or more additives 90 may be added to the liquid via a port 88 (or equivalent) in the liquid supply conduit 20, using a regulator 89, to allow the addition of drugs or other additives 90 to the liquid after it leaves the liquid supply 61, as shown in FIG. 66. The additive 90 in this configuration is provided in a bag, although other delivery vehicles may be used. In another embodiment, the liquid supply 61 may have a port 88 to allow addition of the additive 90 directly to the liquid supply 61. For example, the liquid supply 61 in the form of a saline bag may have a port 88 in the form of a syringe port to permit the addition of the additive 90 directly to the liquid supply 61 via a syringe as the additive delivery vehicle, as shown in FIG. 67.

[0205] The apparatus 2 in one embodiment may further include a range finding or estimating mechanism, for determining the proper range from the target to the nozzle 14 for maximum effectiveness of the apparatus 2. In one embodiment, the apparatus 2 may use sonar as a range finding mechanism. In the embodiment of FIGS. 1-17, the transducer 22 is mounted to the rear wall 8, which is in the form of a flexible plate (e.g., a glass plate). The transducer 22 vibrates at or near resonant frequency, thereby vibrating the rear wall 8. The vibrating rear wall 8 in turn sends acoustic waves through the liquid stream through the body 4 and the nozzle 14 to the target. It is important that the target is close enough to the nozzle 14 in order to maximize cleaning performance. At larger distances from the nozzle, the acoustic wave may be reflected back towards the nozzle 14 by a narrowing stream, therefore limiting the cleaning distance of the stream. In this configuration, the transducer 22 can be used as a sonar device by receiving reflected acoustic waves downstream of the transducer 22. The apparatus 2 may include a sensor (not shown) that is capable of sensing the returned acoustic waves, thereby determining the distance to the target via sonar. The use of acoustic energy inPatent Application Attorney Docket No. 008634.01587VWO this way permits the distance to the target to be measured by the length of the path of the stream (which may curve) as opposed to a straight-line distance measurement. If the sound transmitted is turned on and off, the transducer 22 can itself be used as a sensor (in addition to a generator of acoustic waves) to detect the reflected acoustic waves.

[0206] By measuring the travel time of a reflected acoustic signal and knowing the wave speed of the liquid (e.g. saline), the distance from the transducer to the reflection point can be determined. That travel time can be measured by calculating the cross correlation of the signal sent and the reflected signal received. The cross correlation will have a peak for every reflection in the acoustic path. A coded signal such as Barker code (where the signal is phase modulated) can be used to suppress sidelobes in the cross-correlation calculation.

[0207] The wave speed in the water, however, can vary with environmental factors such as temperature. In addition, it can greatly vary with the density of bubbles. Therefore, it is desirable to measure the speed of sound relevant to pulse propagation (e.g. group velocity). This is accomplished in one embodiment by measuring a reflection time at a known distance from the transducer. As the acoustic impedance changes from a velocity boundary condition to a pressure release boundary condition on the curved perimeter walls of the free stream, there is a relatively strong reflection at the nozzle of the cone. As the distance from the transducer 22 to the nozzle 14 is well known, the acoustic energy reflected at the nozzle 14 can be used to calculate the wave speed, while the cross correlation at the same time will provide the delay of the target.

[0208] Another reflection will be from the target. If the target is a solid (e.g. bone) that has a greater ‘specific acoustic impedance’ than the specific acoustic impedance of the liquid, that target will reflect the signal in a manner controlled by the acoustical boundary condition. Alternatively, if the target is mostly water (e.g., flesh) the acoustic wave will be reflected by a sudden cross sectional area change causing another impedance change. If no target is present, or the target is too far away, the acoustic wave will be reflected by the narrowing of the stream. In that case the returned signal delay will show the “target” to be too far away for cleaning.Patent Application Attorney Docket No. 008634.01587VWO

[0209] The transducer 22 may be operated to detect range through the pulses emitted for cleaning, or for pulses that are identical to those used for cleaning in one embodiment. In another embodiment, the transducer 22 may emit a different type of pulse for acoustic range finding, to distinguish them from the cleaning pulses. For example, the sonar pulses can be of shorter duration than the cleaning pulses, which may help to resolve distance better or reduce reverberation. As another example, the sonar pulses can be a different frequency to the cleaning pulses, e.g., being generated using a higher harmonic of the loaded transducer 22 to generate sonar pulses that have a frequency that is higher than the frequency of the pulses used for cleaning. In another embodiment, the apparatus 2 may include a second transducer that is used for range detection, while the primary transducer 22 is used for cleaning pulses.

[0210] In other embodiments, other types of range finding mechanisms may be used. For example, a laser beam can be projected through the glass back plate and be wave guided down the liquid stream to bounce off the target, with the “time of flight” giving the distance to the target. Use of a laser signal within the water that remains within the water stream is advantageous, because the signal internally reflects off the stream walls and ensures that the laser signal is constrained to follow the path of the stream. Accordingly, this technique permits measurement of the distance to the target as measured by the travel path of the stream (including curvature) that the acoustic energy would experience, as opposed to a straight-line distance measurement. Another possible option is to use two visible laser beams (projected through the water stream or an air path), where the beams are angled in such way that when the target to be cleaned is at the optimal distance from the end of the apparatus 2, the spots projected by the two beams on the target will be merged into one spot, showing the user that the optimal distance has been reached.

[0211] Another option to detect the range to the target includes the use of mechanical range finding devices, such as measuring sticks or brushes that project from the end of the apparatus 2. Fine flexible wires, hairs, bristles, rubber or silicone spikes used for this purpose can be made to lie along the curved wall of the water stream and reduce the formation of pearling, because of the energy required to deform these wires, hairs, or bristles and the subsequent dissipation by which they convert ultimately to heat the energy that would be used to deform the cross section of the stream.Patent Application Attorney Docket No. 008634.01587VWO

[0212] The apparatus 2 may be primed to avoid trapped gas pockets in the cone 10, manifold 40, or elsewhere in the liquid from impeding performance of the apparatus by absorbing or scattering or otherwise attenuating the ultrasonic field. In one embodiment, a priming sequence can be programmed into the action of the pump 64 that supplies the liquid to the apparatus 2. If priming by use of this pump 64 introduces excess bubbles that degrade the device’s performance by attenuating the ultrasonic field in the liquid, manual priming of the apparatus 2 can be used instead. The priming operation may be improved by controlling the relative heights of the cone 10 and the liquid supply 61. The height of the receptacle 71 for the apparatus 2 and / or the height of the liquid supply 61 may be adjustable or controllable in one embodiment. For example, as shown in FIG. 71, the liquid supply 61 may be mounted on an adjustable stand 92 that permits height adjustment of the liquid supply 61 relative to the receptacle 71, and relative to the level 99 of the liquid in the cone 10. The stand 92 may be integrated into the support 72. In one embodiment using a saline bag as a liquid supply 61, priming may include adjusting the stand 92 after spiking the bag and hanging it on the stand 92, and before putting the liquid supply conduit 20 into the peristaltic pump 64 and closing that pump’ s jaws (which will stop any liquid flow in tube whilst the rollers of the peristaltic pump are stationary), as shown in FIG. 69. A change in the relative height of the liquid level 99 in the cone 10 and the liquid supply 61 may be used to prime the cone 10, after which the user can load the tube into the jaws of the peristaltic pump 64 (i.e., via opening 23).

[0213] In one embodiment, the tube connections between the liquid supply 61 and the cone 10 should be designed to avoid the trapping and retention of bubbles during priming, e.g., by avoiding slots and crevices that are exposed to the liquid and may be imperfectly wetted. FIGS. 73 A-B and 74 illustrate an example embodiment of a spike apparatus 93 for connection to a saline bag, as well as a liquid supply conduit 20 connected to such a spike apparatus 93. The spike apparatus 93 may serve as a connector 21 for the liquid supply 61 as described herein. In this configuration, a flexible tube of the liquid supply conduit 20 is inserted into an end opening 94 of the spike 93 and may be bonded to the spike 93, e.g., by glue. For example, a UV-activated glue may be used in one embodiment. The conduit 20 and the spike 93 may be configured with the same interior dimensions (i.e., inner diameter) to provide a clear, smooth, continuous bore 98 for efficient fluid transfer and to minimise bubbles caught at the interface between the conduit 20 and the spike 93. This connection is illustrated in FIGS. 73A-B. The spikePatent Application Attorney Docket No. 008634.01587VWO93 and / or the conduit 20 may be clear so any bubbles can be observed. A similar connection configuration may be used to connect the conduit 20 to the apparatus 2 (e.g., the hollow body 4), such as at the manifold inlet 42 or another inlet if no manifold 40 is used, as shown in FIG. 74. This configuration may provide similar benefits for the connection between the conduit 20 and the hollow body 4, with a clear, smooth, continuous bore 98.

[0214] In one embodiment of use, the cone 10 is primed with nearly bubble free irrigation fluid prior to treatment starting. An angle detection device (not shown) can be included in the apparatus 2 to assist in priming and / or treatment, and the controller 19 may be programmed for such operation. For example, a semi-automated priming sequence may be performed manually by the user, e.g., using input from the display 54. Alternatively, the priming sequence can be fully-automatic, performed by automatic angling of the receptacle 71 just prior to treatment, when the apparatus 2 is held by the receptacle 71 and the time is correct for priming to begin, without the need for the user to be holding the handset during priming. A tray or other collection device 65 (see FIG. 2) may be used to collect liquid that comes from the cone 10 during priming. In one embodiment, the apparatus 2 may be configured with a priming sequence in which, after initiation, a specific dose of liquid will be pumped, but only when the apparatus 2 is held at the correct angle (i.e. the nozzle 14 pointing upwards at an appropriate angle), thus filling the chamber 6 but allowing any air to rise to top and escape through the nozzle 14. The treatment will then be initiated when the handset is tipped forward beyond a specific angle, automatically triggering the pump to start, and the flow rate may ramp up at a rate proportional to the change in angle. The flow rate during treatment may change dependent on the angle of the handset to optimize performance and reduce liquid use. In one embodiment, the treatment can be automatically paused at any point by angling the handset / cone upwards and above a specific angle, which may be chosen to limit liquid loss when pausing. Alternatively, a button could be used to pause or stop the treatment.

[0215] In addition to priming at the start of use, the device may require excess gas to be flushed periodically from the liquid in the cone, depending on the propensity of the liquid, to allow gas to come out of solution (e.g. by warming up from the temperature it had when its equilibrium dissolved gas content was established, such that the equilibrium shiftsPatent Application Attorney Docket No. 008634.01587VWO and previously-dissolved gas comes out of solution). This can be done in a number of ways, for example via a manual or semi-automated tipping of the nozzle towards an upwards position, e.g., using input from the display 54 or an audible or tactile vibration alarm. This will serve to remove bubbles from the liquid in the cone 10 and, via the conduit vent 33, to remove bubbles from the manifold conduit 44 and flush them into the cone 10 from which they are removed with the flow in the same way as other bubbles are removed from the cone 10 if the gas builds up within it (e.g. by tipping it, or by having a second exhaust to the exterior of the cone 10, e.g. via a pump as described in incorporated US 2021 / 0387237 Al). In another embodiment, a device may be connected to the conduit vent 33 to remove surplus gas from the conduit vent and direct the gas to the exterior of the cone 10, e.g., via a pump as described in incorporated US 2021 / 0387237 Al.

[0216] Sensors to detect the position and orientation of the device, along with timers to time the duration of a given orientation or position, correlated to the timing of the pump 64 being turned off and on and / or the flow rate being changed, can be used to completely automate the priming process when the apparatus 2 is placed on / in the stand / receptacle 71. Confirmation that apparatus 2 is correctly positioned in the stand / receptacle 71 can come from a sensor or switch in one embodiment. These features can also be used to indicate to the user of the need to change the orientation of the apparatus 2 or make some other changes. Feedback and instructions to the user may be visual, e.g., via a display, colored lights on the body, or illumination of the cone 10 (if a transparent or semitransparent material is used) and / or audible by recorded messages or alerts.

[0217] In one embodiment, any automated or semi-automated operation of the apparatus 2 may be designed to be conservative with the volume of liquid used, since the liquid supply 61 is needed for both priming and treatment. For this reason, the flow rate may be kept low to around 1.1 to 1.3 litres per minute, or 1.0 to 1.5 litres per minute, or 0.7 to 2 litres per minute, or 0.5 to 3 litres per minute, or 0.15 to 3 litres per minute. Saline bags come in standard sizes of 1 litre, 3 litres or 5 litres. In one embodiment, a single bag may be used as the liquid supply 61 and replaced when it runs low. In another embodiment, multiple bags may be connected together by appropriate structures, such as using a manifold with multiple connections to permit the bags to flow simultaneously into the device, or using a manually or automatically activating valve based on thePatent Application Attorney Docket No. 008634.01587VWO output of sensors and alarms monitoring the weight or volume of liquid in the bag to switch between bags (allowing an empty bag to be replaced with a full one with uninterrupted flow). This would allow for increased operating time, e.g., to allow the clinician to treat larger wound areas or multiple wounds. If periodic evacuation of bubbles from the cone is needed, this can be accomplished by routinely tipping the apparatus 2 upwards, so pausing the treatment and flow and allowing the gas to rise and escape from the cone 10 or manifold 40, a method that conserves the liquid. Additionally, the controller 19 may be provided with power conservation / safety features as well. For example, the current consumption may be monitored immediately and at regular intervals during operation and compared to expected levels with and without liquid in the cone 10, to avoid running the transducer 22 when there is no liquid in the chamber 6.

[0218] In another embodiment, the methods to supply and / or conserve the liquid disclosed herein could also be implemented with the liquid supply conduit 20 connected to a different type of liquid supply 61. For example, as shown in FIG. 70, the liquid supply 61 may be provided as a reservoir or tank containing saline, sterile water, or other liquid deemed suitable for the desired use. Such a reservoir or tank may be interchangeably connected to the liquid supply conduit 20 and / or refillable, and further may be provided with other features of liquid supplies 61 disclosed herein, such as a port 88. In another embodiment, a mixed model for a liquid supply 20 could be used, where a plentiful and inexpensive liquid (e.g., sterile water or saline) is used for the priming, and a more expensive liquid (e.g., one containing a drug or other additive) may be used for treatment. The system 100 may include a valve (not shown) or other device to switch between the two liquid supplies 61 at the appropriate time, which may be being triggered manually, by timer, by sensors based on the orientation and history of movements performed by the apparatus 2 (e.g., tipping the nozzle 14 upwards), etc. In another embodiment, such as where the system 100 is configured as shown in FIGS. 66-67, the additive 90 may not be added until after priming is complete.

[0219] The apparatus 2 may be configured for maximizing cleaning performance using drive signal modulation in one embodiment. Owing to the acoustic reflection at the target and at the nozzle 14, several events can happen that degrade the cleaning performance. First, the acoustic wave can introduce strong oscillatory variations in the thickness ofPatent Application Attorney Docket No. 008634.01587VWO the liquid stream (pearling) and eventually to breakup of the free stream. If the stream breaks up, no ultrasound can be transmitted beyond the breakup point because of the strong impedance mismatch between liquid and air. If the stream narrows to a diameter that makes the ultrasonic frequency lower than the cut-off frequency for that mode in the waveguide, no sound will propagate further down the stream beyond that point, and indeed acoustic energy will be reflected back up the stream (since such narrowing can be oscillatory, these restrictions in allowing the sound to propagate down the stream may be temporary but repeated at a rate associated with the rate at which the stream narrows to this extent). Second, the reflections at the various points of the stream can create a nodal point for the cleaning action near the target wound that will be only active in a very small focal point. This is remedied by spreading the drive spectrum of the apparatus 2. A spread spectrum produces multiple wave modes with different wavelengths and phase angles therefore avoiding pearling or focal points. Such a spread spectrum may be centered around the resonant frequency of the acoustic system (the transducer 22 and its loading with structure and liquid, and the sound field it creates and which, on reflecting back to the transducer 22, drives it). This spectrum has to be narrow banded enough to prevent energy loss from damping.

[0220] Two potential methods for drive signal modulation can be used in various embodiments. In one embodiment, the high frequency drive signal is pulsed at a pulse frequency rate that is significantly slower than the drive frequency, which produces side bands near the drive frequency. This amplitude modulation essentially stops the pearling of the stream. This can be understood in terms of frequency space (as above), or in terms of the timescales in which actions are driven. Simply put, the ultrasonic field operates on a rapid scale (of order 10 microseconds for a 145 kHz ultrasonic field, and of order 1 microsecond for a 1 MHz ultrasonic field). Before the ultrasound is turned on, the stream can fall without pearls (if the diameter is large, and flow speed appropriate, and the turbulence low enough), thinning as it accelerates downwards under gravity to conserve volume flux across any given cross section in the stream. When the ultrasound is first activated, the pearls form on a slower timescale than the ultrasonic wave (for example, the entire oscillatory cycle for pearls is around 10-60 ms for a stream of 10 mm diameter, and of order 5-30 ms for a stream of 2 mm diameter). A short on-time for an ultrasonic pulse therefore allows ultrasonic energy immediately to propagate from the nozzle 14 to target while any stream narrowing due to pearlingPatent Application Attorney Docket No. 008634.01587VWO has barely started. If the ultrasonic pulse duration is sufficiently short, then although there is radial momentum invested in the pearling distortion of the stream, there are also damping factors. Consequently, very short on-times can minimize the formation of pearls, and reduce their effect on the treatment, provided that the off-times between pulses are long enough for the system vibrations to dampen away. Some examples of ranges for pulsing regimes are shown in Table 1 where the pulse on-time and off-time are expressed in the number of ultrasonic cycles, for 6 protected ranges.Table 1

[0221] In Table 2, for an example ultrasonic frequency of 150 kHz, the pulse on-time and off- time are expressed in the number of microseconds, for 6 protected ranges.Table 2

[0222] In Table 3, for an example ultrasonic frequency of 500 kHz, the pulse on-time and off- time are expressed in the number of microseconds, for 6 protected ranges.Patent Application Attorney Docket No. 008634.01587VWOTable 3

[0223] In Table 4, for an example ultrasonic frequency of 1 MHz, the pulse on-time and off- time are expressed in the number of microseconds, for 6 protected ranges.Table 4

[0224] The duty cycle of the transducer 22 operation may be calculated as a percentage based on the following calculation:100% x (On-time) / (on-time + off-time) where on-time is the duration of a single ultrasonic pulse sent out in the signal controller (e.g., the signal generator) and off-time is the duration of the “silent” time between ultrasonic pulses.Patent Application Attorney Docket No. 008634.01587VWO

[0225] In one embodiment, the transducer 22 may be operated at a duty cycle of 1% to 100%. In another embodiment, the transducer 22 may be operated at a duty cycle of 5% to 80%. In a further embodiment, the transducer 22 may be operated at a duty cycle of 5% to 60%. In a still further embodiment, the transducer 22 may be operated at a duty cycle of 10% to 50%. One purpose of these duty cycles is the same as the pulse lengths and off times: to maximize the cleaning and / or therapeutic effects while reducing the pearling on the stream that prevents the ultrasound travelling to an effective distance down the stream, and while also reducing the power consumption of the transducer 22 (within the bounds of maintaining good cleaning and / or healing) so that the transducer 22 does not overheat and the apparatus 2 is suitable for powering by vehicle or battery if required. These pulse lengths and duty cycles are configured for ultrasonic cleaning using a stream. Although the apparatus 2 is frequently described herein for use in wound treatment and regeneration, the use of acoustic energy passed down a stream may be used to clean surfaces in general, from windscreens to lettuces to surgical instruments to silicon chips.

[0226] In another embodiment, phase modulation can be used, which may be random or pseudo-random, and one embodiment uses Barker code. Barker code is easy to implement as only phase inversion is necessary in the drive signal. In addition, Barker code can also be used for sonar ranging to reduce sidelobes in the cross correlation. If both the pulsing and phase modulations are used together, the same signal can be used for both cleaning and sonar ranging at the same time. Otherwise, the method would alternate between cleaning with amplitude modulation and sonar ranging. Chirps can also be used to broaden the spectrum to achieve the purposes mentioned above.

[0227] The pulsing of the ultrasonic signal can be optimized, both in terms of carrier signal and in terms of the pulse duration. In one embodiment, short pulses can be used, with the awareness that the carrier frequency for the ultrasonic signal that is created by the signal generation software, may not necessarily be the frequency of the signal that drives the transducer 22, because of the effect on the spectrum of similar pulses separated by an off-time (for example, if the pulses are identical, then the time-averaged spectrum over many pulses is an array of discrete narrow-band peaks underneath a Lorentzian envelope, and the intended drive frequency might not coincide with the frequency at which one of those peaks falls). The time series is a series of short pulsesPatent Application Attorney Docket No. 008634.01587VWO with gaps in between, repeated, and so the signal in frequency space is a series of peaks. The spacing of those peaks in frequency space is dependent on the interval between pulses, whereas the envelope is controlled by the carrier frequency. The interval between pulses can be set as a multiple of the carrier frequency, so that no peak occurs at the peak of the envelope. Hence it may be important to ensure that, when the particular carrier frequency is set (for example to generate the maximum efficiency for transmitting power into the ultrasonic stream from the transducer), the spacing between pulses is adjusted to ensure that the peak of maximum amplitude occurs at the frequency designed to drive the transducer 22. An alternative measure for dealing with this would be to add some jitter or variation of about 10% in the spacing between pulses which would allow a continuing frequency to be filled in between the peaks with the frequency spectrum, or incrementing the carrier frequency between pulses, or both.

[0228] In view of the above, in order to maximize cleaning, a number of potential options exist:(i) Keep a fixed frequency and pulse interval for all ultrasonic pulses, while ensuring the interval between pulses places a convolution spike at the desired frequency. This has the benefits of containing high energy within a narrow frequency spike at the desired frequency, being easy to program into the software, and not needing to tune every transducer 22 individually. The disadvantage is that the frequency must be correctly calculated, and a frequency tracker may be needed to keep the spike at the correct frequency.(ii) Jitter the interval between pulses. This enables achieving a continuum within a spectral peak, so there is no concern of putting zero energy in at the assumed frequency, and is also easy to program into the software, and may not require tuning every transducer 22 individually. The disadvantage is that there is less actual energy in the desired frequency because the energy is spread over many frequencies in the continuum.(iii) Frequency- step the carrier frequency. This has the advantages of ensuring that the right frequency will eventually be used for a short period, and is also easy to program, and may not require tuning every transducer 22 individually. The disadvantage is that significant energy may be expended into frequencies that are inferior for cleaning.(iv) A combination of the above, e.g., a combination of (ii) and (iii).Patent Application Attorney Docket No. 008634.01587VWO

[0229] The apparatus 2 may be configured to provide user input during, before, and / or after operation, such as using a display 54 or other methods described herein. For example, the apparatus 2 can indicate to the user that it is in an appropriate condition to commence an activity (such as priming or treatment); alert the user to the apparatus 2 entering a particular condition (such as coming into or out of range for treating the wound with respect to the distance from the nozzle down the stream to the wound; to give alerts of faults associated with overheating; to provide information on the activities conducted so far such as the total duration of the treatment and the exposure of the patient). In one embodiment, a light can be generated within the chamber 6 and travel down the stream, or light up the transparent cone, in order to send signals to the user. If the rear wall 8 is made of glass or some other transparent material, then the light can be projected through the rear wall 8 from a source (for example a ring source) on the rear side 9 of the rear wall 8 where it is more conveniently accessible by the electrical power, electronics and control circuitry. In another embodiment, a light can also be used in this way to illuminate the wound to facilitate treatment through the visual observation of the clinician. In a further embodiment, the display 54 can also be used to provide the user with information such as whether the device is within the appropriate range for treating the wound, and whether it is within acceptable operating parameters. In yet another embodiment, different colored lights can be used to indicate various parameters and operating conditions (as can lights flashing in a coded manner). Still further, the user interface can include an audible component. Information that can be communicated in this manner also includes the time to clean a wound, the volume of liquid required, when to change over the liquid or empty the waste container, and other critical factors. An algorithm may be used (e.g., in the controller 19) to enable the user to input the size of the wound and get feedback and instruction from the apparatus 2 as to how long the cleaning should take and what volume of liquid to supply. The system may also include a video device (e.g., a camera 36 as in FIG. 30) with video memory to record the image as the target is cleaned and to monitor the area cleaned for the purpose is advising the user as to how much the treatment has been completed, weather a region of the wound has been cleaned for long enough at the appropriate cleaning range, and to avoid unnecessary repeat of the same area of wound, among other messages. All this information can be fed back to the user using technologies mentioned above. Such a video device may be located on the apparatus 2 or separate therefrom.Patent Application Attorney Docket No. 008634.01587VWO

[0230] The system 100 may be provided with a device for collecting the run-off from a wound treatment, for disposal or for further analysis, for example via qPCR (Quantitative Polymerase Chain Reaction) to detect and quantify the number of cells that are in the run-off of each species, and identify whether they are in a fragmented state, whether nucleus material has escaped its membrane, living, dead, or viable but not culturable (VBNC). A number of options are available for collecting the waste run-off such as buckets, bags in frames, or specialized chairs or beds adapted to accommodate wastewater collection. If there is concern of particularly hazardous or infectious runoff, the waste receptacle can have a seal to prevent spread of infection and / or may be equipped with suction. The waste receptacle can also detect the quantity of waste by monitoring the weight of the collected run-off or having a level meter within (e.g. ultrasonic or ballcock). Either separately or together, the meter(s) can be used to ensure that the liquid supply 61 is renewed at an appropriate time, and the waste receptacle changed over for a new one when it gets too full. Wired or wireless communication can be used for this purpose.

[0231] The apparatus 2 of FIGS. 1-17 and other apparatuses described herein may additionally include one or more bubble generators in one embodiment, e.g., positioned within or proximate to the nozzle 14, such as in International Publication Nos. WO 2018 / 228848 and WO 2011 / 023746, both of which are incorporated herein by reference, and / or in incorporated US 2021 / 0387237 Al. FIGS. 19B and 27-28 illustrate embodiments that optionally include a bubble generator 24, but it is understood that any embodiment disclosed herein may be provided with such a bubble generator 24. The use of a bubble generator can assist in keeping the acoustic propagation path, as much as is feasible, clear of bubbles when the transducer 22 is on. This use also assists in producing a beneficial effect on the target by acoustically activating bubbles there, because if the bubbles are acoustically activated anywhere else in the apparatus 2 (except for the purpose of bubble generation), they attenuate the acoustic field and are detrimental to the acoustic energy reaching the bubbles when they are in close proximity to the target. Such a bubble generator (not shown) may be configured to produce bubbles predominantly of a size to be considered resonant bubbles and not unwanted bubbles, so that they generate the desired beneficial effects on the target. It is also important not to produce resonant sized bubbles in too high of numbers that may cause attenuation of the acoustic waves. Additionally, the bubble generator may be configured to producePatent Application Attorney Docket No. 008634.01587VWO bubbles in clouds or boluses that are timed so that as they are convected into the stream to produce regions of relatively bubble-free water. Further, the timing of the bubble generation and transducer 22 activation can be coordinated (taking into account their different propagation speeds in the stream) to ensure that the stream contains either bubbles, or acoustic waves, but not both at the same time (except for the location at the target where the timings of bubble generation and ultrasonic wave generation are timed to make sure that the bubbles and ultrasonic waves occur at the same time on the target). Various range-finding mechanisms described herein may be used for this purpose. The timing of bubble generation may be timed to generate bubbles that propagate similarly to the bubbles produced by acoustic energy within the body 4, or the operation of the transducer 22 can be controlled such that the acoustic energy does not produce bubbles, so that the apparatus relies on bubbles produced by the bubble generator alone. In other embodiments, no bubble generator may be used, or the vibrating rear wall 8 may function as a bubble generator.

[0232] The apparatus 2 may include a controller 19, which is shown schematically in FIGS. 1- 2 and 4. The apparatus 2 may require electronics to perform a number of tasks, including but not limited to: providing the signal that will drive the transducer 22, and any additional signal required for bubble generation if a separate bubble generator is used; electrical power amplification of those signals; control of the liquid supply, which in one embodiment (e.g., FIGS. 1-17) can be turned on and off by activating and deactivating the pump 64. Various other electronic devices described herein (e.g., sensors) can also be used in automatically activating or deactivating the liquid flow. These can communicate to the switches, transducer, display, and other necessary components via wired or wireless connection. Some or all of these electronic devices can be incorporated within the casing 55 if space and electrical safety considerations allow, and / or at least some of these electronic devices may be located outside the casing 55, in various embodiments, such as in the control unit 60. These electronic devices may be collectively considered to constitute the controller 19, and may include at least a memory, a processor, and one or more electronic interfaces for transmitting and / or receiving signals from other devices and components. In one embodiment, the controller 19 may be configured to perform at least one or all of the following functions: generate drive signals to the power amplifier for driving the transducer 22; turn the flow of liquid on and off, and potentially control the flow rate, by controlling the pump 64;Patent Application Attorney Docket No. 008634.01587VWO monitor the liquid flow; monitor the temperature at one or more locations; respond to button presses to control the liquid flow and the transducer 22; operate a range finding mechanism, and report operation status by providing input to the operator, among other operations described herein. It is understood that the controller 19 may include additional functionality as well, including communication with one or more devices external to the apparatus 2.

[0233] FIGS. 24A and 24B illustrate inner and outer profiles of an example embodiment of a cone 10 for use with an apparatus 2 as disclosed herein and shown in FIGS. 1-17. In FIGS. 24A-B, the “Radius” and “Distance” values represent the vertical and horizontal coordinates, respectively, in meters of the inner surface of the cone 10, assuming the axis of rotational symmetry is horizontal and lies on the axis defined by r = 0. The diamonds signify the points where the radius and slope are defined. These profiles are defined by piece-wise third-order polynomial expressions based on the radius and slope at various distances, as shown in Table 5. These profiles are defined by lookup tables, or by inserting appropriate values into piece-wise third-order polynomial expressions based on the radius and slope at four distances:is the radius of the cone curve along the 7thpolynomial, x is the continuous coordinate along the length of the cone, dmidis the average of the two endpoints (d(j) and d(j + 1)) of each polynomial segment, and Atis the coefficient found through the solution of:where / ?( / ) and S(j) are the discrete values from the table that correspond to the jthrow.

[0234] By inserting particular parameter values for d, R and S, particular profiles can be defined for inner and outer walls of the cones. If a cone of a smaller or larger size needs to be defined, then the selected profile calculated below can be scaled into the desired one,Patent Application Attorney Docket No. 008634.01587VWO by use of a scaling factor based on the desired outflow orifice radius divided by the outflow orifice of the curves shown in FIGS. 24A-B.

[0235] For the inner cone profile shown in FIG. 24 A, the maximum deviation of the polynomial estimate from the look-up table (Table 6) is 0.12 mm. For the outer cone profile, shown in FIG. 24B, the maximum deviation of the polynomial estimate from the look-up table (Table 7) is 0.10 mm.Table 5: Basis Data for FIGS. 24A-BTable 6: Lookup Table for Inner Curve Profile (FIG. 24A)Patent Application Attorney Docket No. 008634.01587VWOTable 7: Lookup Table for Outer Curve Profile (FIG. 24B)

[0236] In one embodiment, the two curves in FIGS. 24A-B define the outer and inner walls of the same cone 10. Other cone shapes and / or cones with straight walls, can also be made to work, e.g., with only one of the two profiles shown. The curves of the cone 10 may be chosen, at least in part, to ease removal of the cone from a casting mold. Other shapes for the cone 10 may be used as well. If there is a desire to make a smaller or larger cone that has the same general profile of either of the above for one of the walls, then such a scaling can be made by application to the values in Tables 5-7 or FIGS. 24A-B of a scaling factor calculated from the ratio of the relevant desired radius at the outlet orifice to the corresponding radius in Tables 5-7 or FIGS. 24A-B.

[0237] In some embodiments, the apparatus 2 may have a cone 10 with a nozzle 14 and / or an orifice 12 that is rectangular (including potentially square), which may also be referred to herein as a “slot-shaped” nozzle 14 and / or orifice 12. An apparatus 2 with a slotshaped nozzle 14 could be used for a wide variety of applications. As stated above, wound cleaning and treatment is important. The combined cleansing and healing stimulation are beneficial for a wide range of wounds, both acute (for example, for cleaning and stimulating healing before transit to clinic or battlefield injuries) and chronic (include venous leg ulcers, diabetic foot ulcers, bums, pressure sores) and other infections typically found in surface tissue (such a surgical site infections and acne). Certain anatomical regions are particularly prone to contamination and infection, such as the gut cavity, and a cleaning stream would be beneficial, particularly if it promotes tissue regeneration and the equipment can be made portable, such as in embodiments described herein. The slot-shaped nozzle 14 will cover a broad breadth of the woundPatent Application Attorney Docket No. 008634.01587VWO in one direction, and the narrow breadth in the other direction can reduce overall stream volume and reduce liquid usage (for example, if supplied by a saline bag). If the narrow length of the shorter edge of the orifice 12 is 1-2 mm to conserve liquid by reducing flow rate (e.g. to 1 litre per minute or less), then the ultrasonic frequency will need to be sufficiently high (i.e. greater than about 1 MHz, depending on the sound speed in the liquid) to be above the cut-off frequency of the acoustic waveguide that the stream represents. This might come with advantages for the clinician, in that it allows a greater range of operating distances (0.5 - 5 cm from the nozzle) at which the wound can be from the nozzle, decreasing the need for the clinician to be trained to keep the nozzle to a specific distance, with little tolerance for deviation, from the nozzle.

[0238] As with other nozzles 14, for nozzles 14 with rectangular or similarly slot-shaped outflow orifices 12, the lengthscales and timescales can be scaled as per the dimensions suggested in the earlier tables, where the determining lengthscale from which everything else follows (the ultrasonic frequency, the pulsing off-time and on-time, etc.) is the narrowest dimension of the slot-shaped outlet orifice. The examples tested later in this patent are all operating at around 1 MHz, because the shortest lengthscale of the outlet orifice is of millimetre order, which was chosen to conserve water by keeping the volume flow rate low. Great flow rates can produce cleaning to longer ranges since, at any given range, the percentage increase in stream speed as a result of the acceleration due to gravity is less.

[0239] For nozzles 14 with rectangular or similarly slot-shaped outflow orifices 12, foods (meat, salad, etc.), electronics (e.g. silicon), optical components (lenses, contact lenses optical fibres, etc.) and elements on conveyor belts and production lines, are all suitable for cleaning. The apparatus 2 could be mounted on a handheld unit, a movable robotic arm, or at a stationary position over a conveyor belt 35 (see FIG. 28) or production line in various embodiments.

[0240] One advantage of nozzles 14 with rectangular or similarly slot-shaped outflow orifices 12, is that it issues a slot-shaped stream of liquid, enabling a broader line of cleaning and treatment to be swept, mapped, or painted over the surface to be cleaned. This can, in one sweep, clean a larger area of the surface than the streams issuing from the nozzle with a round cross-section. Consequently, the treatment of the whole area that needs to be cleaned, can in some embodiments take less time and consume less liquid and lessPatent Application Attorney Docket No. 008634.01587VWO electrical energy (the power integrated over the time for which the power is on, including off-times between pulses) if done by a stream issuing from the slot-shaped nozzle 14 compared to a stream issuing from a round nozzle. Conserving liquid and electrical energy can be important if the supplies of both are limited (e.g. the device is being used in a vehicular, emergency, home, battlefield or portable setting). It also reduces the amount of contaminated run-off produced, which can be important if the setting has limited means of disposing of that run-off.

[0241] As with round nozzles 14, with nozzles 14 with rectangular or similarly slot-shaped outflow orifices 12, there comes a number of advantages to using smaller orifice dimensions (i.e. reducing the size of the narrower dimension of a slot-shaped orifice, or reducing the diameter of a circular orifice) at the orifice 12 from which the stream issues. The use of smaller dimensions at the orifice 12 can increase the range to which cleaning occurs, and reduce the size and weight of the transducer and overall device (e.g. by using a smaller nozzle 14, eliminating the need for large head and tail mass in the transducer 22, reducing the size of the electronic components, etc.). The volume flux of liquid from the orifice 12 is reduced, which reduces the volume of liquid needed for supply (especially important if the device is used in a portable setting such as vehicle or personal, as discussed herein).

[0242] However, because the stream acts as an acoustical waveguide, the ultrasonic frequency must be increased in line with the smallest dimension, because it is the smallest dimension that controls the acoustic cut-off frequency of the waveguide. Hence a nozzle with a slot-shaped outflow orifice measuring 5 cm by 2 mm, would have its cut-off frequency determined primarily by the 2 mm dimension and require signals of at least several hundred kHz (depending on the liquid) and likely 1 MHz or above. It is because of this change that a smaller orifice 12 makes it possible to reduce the size and weight of the transducer by eliminating the need for large head and tail mass in the transducer, and reducing the size of the electronic components, the water reservoir etc.

[0243] FIGS. 25A-D show four illustrative examples of cones 10 having nozzles 14 with rectangular outflow orifices (labelled SI, S2 S3, and S4). FIGS. 38A-41C also show depictions of the cones 10 S1-S4. These examples of nozzles 14 with rectangular outflow orifices 12 were tested in this experiment reported herein. All cones have 1 mm thick walls and a height of 45.5 mm from base to tip. Cones 10 labelled S1-S3 (FIGS.Patent Application Attorney Docket No. 008634.01587VWO25A-25C) have a rectangular inlet throat (the end of the cone 10 opposite the orifice 12 and adjacent to the base 11) of 20 mm by 40 mm and are constructed of PLA (Polylactic acid). The dimensions of the rectangular outflow orifices are: (a) 1.4 mm x 10 mm for SI, (b) 1.4 mm x 20 mm for S2, and (c) 2.8 mm x 10 mm for S3. Cone SI takes the form of a rectangular pyramid, with an outflow orifice measuring 1.4 mm x 10 mm, a throat measuring 20 mm x 40 mm, a length of 45.5 mm, and a wall thickness of 1.0 mm. Cone S2 takes the form of a rectangular pyramid, with an outflow orifice measuring 1.4 mm x 20 mm, a throat measuring 20 mm x 40 mm, a length of 45.5 mm, and a wall thickness of 1.0 mm. Cone S3 takes the form of a rectangular pyramid, with an outflow orifice measuring 2.8 mm x 10 mm, a throat measuring 20 mm x 40 mm, a length of 45.5 mm, and a wall thickness of 1.0 mm. Cone S4 has a square throat of 10 mm x 10 mm, with parallel walls on the shorter sides, an outflow orifice measuring 1.4 mm x 10 mm, and a uniform wall thickness of 1 mm, and is constructed from an ABS- like material (ACCURA BLACK 7820).

[0244] The cones SI, S2, S3 and S4 illustrated in FIGS. 25A-D and FIGS. 38A-41C are examples from a range of different configurations for a body 4 and cone 10 that are usable with an apparatus 2 and system 100 as disclosed herein. Such cone 10 profiles may provide enhanced cleaning ability in some applications and may be particularly useful in connection with an apparatus 2 or a system 100 for cleaning items 34 or other matter (e.g., organic vegetable matter) on a conveyor 35 passing beneath the nozzle 14 (see FIG. 28) in one embodiment, or in wound cleaning as described herein. For example, such items 34 or other matter may include organic vegetable matter (lettuce, basil, etc.), contact lenses, prepared matter (e.g., potato chips / slices), or various other items / matter disclosed herein. The bodies 4 in FIGS. 25A-C and 38A-40C have cones 10 (SI -S3) that are pyramidal in shape, with a first pair of surfaces 80 and a second pair of surfaces 81 that are tapered inward from the base 11 to the orifice 12. Each of the cones 10 (S1-S3) in FIGS. 25A-C and 38A-40C is rectangular at the base 11 and at the orifice 12. The first and second pairs of surfaces 80, 81 in FIGS. 25A-C and 38A-40C are flat, but one or both of the surfaces 80, 81 may have some curvature in another embodiment. This configuration creates a nozzle 14 with a rectangular orifice 12 having a slot or “letterbox” shape as described herein. The body 4 in FIG. 25D and 41A-C has a cone 10 (S4) that has a first pair of surfaces 80 that are flat and parallel, and a second pair of angled or tapered surfaces 81, creating a nozzle 14 with an orificePatent Application Attorney Docket No. 008634.01587VWO12 having a slot or “letterbox” shape. The cone 10 in FIG. 25D and 41 A-C is square at the base 11 and rectangular at the orifice 12. The surfaces 80, 81 in this embodiment are flat, but curved surfaces 80, 81 may be used in one embodiment, including an embodiment where the second surfaces 81 have a cross-sectional profile similar to that of the cone 10 in FIGS. 1-17 (e.g., as shown in FIGS. 24A-B) , as shown in FIGS. 27- 30. Such curved wall shapes can be made to optimize the acoustics and hydrodynamics (e.g. to minimize turbulence and vorticity within the cone 10). The size of the nozzle 14 can be scaled up or down, or in either direction in the plane of the orifice 12. In another embodiment with one pair of tapered surfaces 81 and one pair of parallel surfaces 80 (not illustrated), the width of the nozzle 14 is 1.4 mm, the width of the cone 10 at the base 11 is 20 mm, the width of the cone 10 (between the parallel surfaces 80) is 10 mm, and the length of the cone 10 is 45.5 mm. Thus, the outflow orifice 12 is 10 mm x 1.4 mm. In another embodiment, the cone 10 may be designed (potentially by scaling) to have an orifice 12 that is 2 mm x 1-4 cm. Effective transducer frequencies usable with the cones 10 (S1-S4) in FIGS. 25A-D and 38A-41C are in the range 0.5-5 MHz or 1-3 MHz. Each body 4 in FIGS. 25A-D and 38A-41C, in one embodiment, has a base 11 that is configured for connection to an apparatus 2 as disclosed herein, which may be in the form of a handset 50 or another structure. It is understood that any components and features (including operation) described herein with respect to other embodiments may be used in connection with the cone 10 and body 4 in such an example embodiment, with appropriate structural modifications.

[0245] FIGS. 27-30 illustrate schematically some methods of use of the cones 10 in that have rectangular or similarly slot-shaped outflow orifices (the near side of the cone is not shown for clarity), in treating or cleaning a patient’s hands (FIG. 27) and in cleaning items 34 or other matter on a conveyor belt 35 (FIG. 28). FIG. 29 illustrates the handheld apparatus 2 being used in treating a wound on a patient’s knee. FIG. 30 illustrates a different type of apparatus 2 that includes an arm 82 using the cone 10 in treating a surface, e.g., a patient’s leg. This arm 82 may be robotic and could be controlled manually, or controlled remotely by a clinician, or controlled to a predetermined program, or be partially or fully computer controlled to achieve a specific objective. The robotic arm 82 may be configured to connect to the handle 56 of a handset-based apparatus 2, or may otherwise include a user input / output, such as one or more buttons 59 and / or a display 54, which may be provided at location 37 in FIG.Patent Application Attorney Docket No. 008634.01587VWO30. A camera 36, e.g., a mono or stereo camera, and / or appropriate sensor devices may be used to provide a video feed for targeting, monitoring, and / or ranging. The arm 82 may be provided as an articulating arm in one embodiment, e.g., an articulating robotic arm. The arm 82 may also be configured to hold and / or contain conduits (not shown) for electrical and / or fluid communication with the apparatus 2, such as an electrical cord 62, a liquid supply conduit 20, and / or wires / cables for electrical control and data transmission purposes, such as for the transducer 22, the camera 36, etc. These conduits may run alongside the arm 82 and / or through the arm 82, and at least some of them may be incorporated into a common umbilical 87 as disclosed herein.

[0246] For the three example nozzles (SI, S2 and S3) shown in FIGS. 25A-C, the slanted sides of the nozzle are in this case flat and angled, although curved wall shaped can be made to optimise the acoustics and hydrodynamics (e.g. to minimise turbulence and vorticity within the nozzle). To produce the same optimized acoustics and hydrodynamics, curved wall shapes could also be added to a cone made from an ABS-like material (e.g., ACCURA BLACK 7820), such as cone S4. The size of the cone 10 and / or the orifice 12 can be scaled up or down, or in either direction in the plane of the orifice 12.

[0247] FIG. 42 A illustrates an example manifold 40 for use with cones 10 such as the cones S1-S3 or other cones 10 with rectangular nozzles 14 and / or orifices 12. FIG. 42B illustrates an example manifold 40 for use with cones 10 such as the cone S4 or other cones 10 with rectangular nozzles 14 and / or orifices 12. The manifolds 40 in FIGS. 42A-B are configured for separate connection to the base 11 of each cone 10, such as via bolts or other fasteners, although in another embodiment, the manifold 40 may be integrally connected to the cone 10 to form a combined unit 5 as described herein, which may achieve benefits including reducing the number of separate parts that need to be connected together during assembly. The manifolds 40 in FIGS. 42A-B each have a liquid inlet 42 (shown at the base of each image) connected to the liquid inlet conduit 44, and cone vent 43 (shown at the top of each image) from which excess gas can be expelled. The size of the cone 10, the nozzle 14, and / or the orifice 12 can be scaled up or down, or in either direction in the plane of the orifice 12. The nozzle 14 can point in any direction if the water volume flow rate is sufficient to produce a stream, however it is noted that the testing reported herein is performed with a nozzle 14 in the downwards facing direction. The base 11 of each of the cones 10 in FIGS. 25A-D mayPatent Application Attorney Docket No. 008634.01587VWO be fixed to a manifold 40 supplying the liquid as described herein, such as the manifolds 40 in FIGS. 42A-B, or to a reservoir from which the liquid exudes. The cones 10 in FIGS. 25A-D may be used with an apparatus 2 and a system 100 as described herein (or components thereof), and may use any source of liquid described herein. The cone vent 43 in these embodiments is a conduit that permits excess gas from the region of liquid adjacent to the rear wall 8 to exit the chamber 6, and the cone vent 43 may be connected to a device to assist gas removal, such as a siphon venturi or pump, as described in incorporated US 2021 / 0387237 Al. Another embodiment could include a conduit vent as described herein.

[0248] FIGS. 26A-E and 43A-47B illustrate example embodiments of bodies 4 having cones 10 with cones with small round orifices 12 (< 10 mm diameter). The components of these embodiments are generally the same as described herein with respect to other cones 10 disclosed herein, such as in FIGS. 1-17, and such similar components may not be described again herein for the sake of brevity. In the embodiments of FIGS. 26A-E and 43 A-47B, the base 11 of each body is in the form of a mounting plate configured for connection to a manifold, similar to the cones S1-S4 illustrated in FIGS. 25A-D and 38A-41C. The cones R1-R3 all have curved walls that have convex and concave curvatures, as described herein with respect to the cone 10 in FIGS. 1-17. The cones R4-R5 both have straight conical walls. U.S. Patent Application Publication No. 2020 / 0164194 Al, which is incorporated by reference herein, introduced the use of small round nozzles. Further details and results using cones with such orifices are disclosed herein. Cones with small round (or in the family of having curved walls in the outflow orifice of the cone, e.g. oval or elliptical) outflow orifices offer some advantages:• They can operate with low volume flow rates (conserving fluid use, and so not rapidly depleting the reservoir, which might be a bag of saline or sterilized or potable water),• They produce low volumes of contaminated run-off, making disposal of this easier;• They can accurately target small items to clean (e.g. contact lenses and silicon chips);Patent Application Attorney Docket No. 008634.01587VWO• For the same volume flow rate as a larger nozzle, the smaller nozzle has a greater flow speed as the liquid exits the nozzle. This means that when acceleration due to gravity adds the same increment of speed for a given vertical drop to nozzles of differing cross-sectional outflow areas but the same volume flow rate, the percentage increase in speed is less for the nozzle that has smaller area but the same volume flow rate (so long as the stream remains intact). Therefore, the proportional narrowing of the time-averaged cross- sectional area of the stream at any given range from the nozzle, as it drops under gravity, is less for the narrow stream (provided the volume flow rate is the same for the larger and small orifices under consideration). It is about this mean cross-sectional area that any instabilities cause thinner areas of the stream. Therefore, if both the larger and smaller orifices emit ultrasound that is close to the cut-off frequency on emission, the stream that does not narrow rapidly with increasing distance from the nozzle remains wide enough to prevent the ultrasound frequency dropping below the local cut-off frequency for the local diameter of stream. This means that, under these specific circumstances of having the same volume flow rate and both having ultrasound just above the cut-off frequency when the stream leaves the orifice, the stream from the narrower nozzle can travel further. Of course, if these constraints are relaxed (e.g. both wider and narrower streams use the same ultrasonic frequency that is above the cutoff frequency in the narrow stream as it leaves the nozzle), then the wider stream might also clean to long distance. The same is true if the volume flow rate is increased, but this then comes with the disadvantage of producing more run-off and depleting the liquid supply more rapidly.

[0249] The first of these advantages is very important, as it supports the larger advantage of portability (e.g. devices for carrying by persons or vehicles). As the volume flux of liquid from the orifice is reduced, there is a reduction in the volume of liquid needed to be carried for the liquid supply. This is important if the device is used in a vehicular setting, such as in an ambulance, motorbike, boat or car, or by a person carrying the liquid supply (e.g. bottled or bagged water or saline, or an aqueous solution).Patent Application Attorney Docket No. 008634.01587VWO

[0250] The power requirements from the ultrasonic device and its associated control, monitoring and data acquisition, is low (under 10 W to the transducer in many circumstances). More power is needed to pump the supply, although there are many options for replacing this.

[0251] FIGS. 56A-D shows four potential embodiments of methods and systems 100 for use of an apparatus 2 according to aspects of the present disclosure, which may incorporate a cone 10 having a small, round orifice 12 as shown in FIGS. 26A-E and 43A-47B. It is understood that other cones 10 disclosed herein may be used in connection with the systems 100 and apparatuses 2 of FIGS. 56A-D. The apparatuses 2 in FIGS. 56A-D could all be entirely manual, or could, optionally, be supplemented by electronic systems that are easily within the capability of a vehicular supply. Such configurations would be options for use in circumstances, access to a reliable mains electricity supply might not be practical (in some Low / Middle income countries), or for mountain or at- sea rescue, or in catastrophe zones, or the battlefield. In those circumstances, the power required of the apparatus 2 (and its associated data acquisition, control and monitoring systems) is low enough to be supplied by a vehicle (car, ambulance, motorcycle etc.) and suitable electrical connections for these power supplies are practical. For example, assuming the vehicle battery generates 12 V, a DC / DC converter is used to boost the voltage to the required level (currently about 36 V to 48 V), and where this converter is selected to be capable of handling the required current, this being either an external product or integrated into the device electronics using an appropriate chip. Connection to a motorcycle is shown in FIGS. 56A-D as an example, but other alternatives to mains electricity are possible (other vehicles, batteries, generators, solar and wind sources etc.). The systems 100 in FIGS. 56A-D have a control unit 60 connected to a vehicle 83 to provide power, with different liquid supply configurations.

[0252] If the pump requirements can also be supplied by such a power source, then that can be used. However, the pump can use more power than the ultrasonics, such that in some circumstances, the use of a liquid pump might not be practical. For example, it might not be affordable in some Low / Middle income countries, or the power requirements of the pump may be too great, or too heavy to carry by a person, or power may be inaccessible in remote areas. In those circumstances the required liquid flow rate could be provided by:Patent Application Attorney Docket No. 008634.01587VWO• a suitable hydrostatic head between the liquid supply 61 (e.g., bag) and the nozzle 14, as shown in FIG. 56A;• squeezing a liquid supply 61 (e.g., a bag or other compressible container) manually or by a mechanical device such as a clamp or a plunger as shown in FIG. 56B;• applying a weight 84 to a liquid supply 61 (e.g., a bag or other compressible container) as shown in FIG. 56C;• placing a liquid supply 61 (e.g., a bag or other compressible container) in a box or other container 85, and pumping up the fluid (gas or liquid) pressure in the box, such as by using a manual or foot pump, or an electrical (e.g., battery operated, including vehicle battery) pump to provide the correct liquid flow to the apparatus 2 as shown in FIG. 56D. Note that the design in FIG. 56D avoids the possibility of the high pressure gas outside the bag passing into the bag (such as by using a second, impermeable bag if the first bag is permeable), because this would cause the liquid to be saturated or super-saturated with gas when it enters the cone, leading to excessive bubble generation there, attenuating the sound field and preventing treatment of the target. For the same reason, directly pressurizing the bag containing the liquid by pumping gas directly into it should be avoided. Thus, the system of FIG. 56D prevents gas entering the liquid bag.

[0253] Regulators (passive, manually-controlled or electronic) could be added to ensure that the liquid flow was correct in any of these embodiments. Whilst these measures would make the provision of electrical power suitable for vehicle and possibly personal use suitable for streams of any size, it is by using streams of small cross-section and / or streams that leave the nozzle with low flow speeds (which tend to reduce the downstream range to which cleaning can occur) that it is possible to reduce the total volume of fluid used for the treatment, thereby reducing the weight and volume of fluid that must be carried by the vehicle or person. Thus, cones 10 with small orifices 12 (e.g., cones R1-R5) may be particularly useful in such systems 100.

[0254] Note that these measures would make the electrical power supply and the liquid supply portable, which would mean that this cleaning technology could be fitted to an ambulance or other portable service (e.g. community nursing), or for cleaning otherPatent Application Attorney Docket No. 008634.01587VWO targets using a portable service, or by a mountain-rescuer, catastrophe zone worker, or battlefield medic (using an appropriate battery), all situations where the power requirement can be reduced by replacing the pump with one of the systems 100 of FIGS. 56A-D. Use of a lower volume flow rate also reduces the likelihood of the liquid flooding any macroscopic cavity in which the cleaning is occurring (e.g., the mouth during dental cleaning, a body cavity, a mechanical space etc.), and reduces the total volume of run-off, which may be important if the user has difficulties in disposing of contaminated run-off (e.g. from treatment in a hospital ward bed, or if the run-off has nuclear or chemical contamination after cleaning some radioactive or chemical item).

[0255] FIGS. 48A-C illustrate potential embodiments of a manifold 40 useable with a cone 10 with a circular opening, such as cones R1-R5 shown in FIGS. 26A-E and 43A-47B. In one embodiment, a scaling factor is used, so that the circular space at the center of the manifold has a diameter that matches the diameter of the inlet throat of the cone 10, which was 40 mm for cones R1-R5. Thus, of the three manifolds shown in FIGS. 48 A- C, only the manifold shown in FIG. 48A meets the criterion of matching the throat diameter without scaling. The manifolds 40 in FIGS. 48B-C are designed to fit a scaled version of a cone 10 with a round orifice 12, such as scaled versions of the cones Rl- R5 shown in FIGS. 26A-E and 43A-47B. The manifolds 40 in FIGS. 48A-C are configured for separate connection to the base 11 of each cone 10, such as via bolts or other fasteners, although in another embodiment, the manifold 40 may be integrally connected to the cone 10 to form a combined unit 5 as described herein, which may achieve benefits including reducing the number of separate parts that need to be connected together during assembly. The manifolds 40 in FIGS. 48A-B each have one liquid supply inlet 42 (the wider passage), and one cone vent 43 (the narrower passage), as described herein. The liquid supply inlet 42 is connected to an inlet conduit 44 that feeds the liquid directly into the cone 10. The manifold 40 in FIG. 48C has a semicircular lower inlet conduit 44 that distributes the liquid flow to a plurality of inlet ports (not visible in FIG. 48C) around the inner annular surface 46, as disclosed herein with respect to the embodiment of FIGS. 1-17. The size of the cone 10, the nozzle 14, and / or the orifice 12 can be scaled up or down, or in either direction in the plane of the orifice 12. The nozzle 14 can point in any direction if the water volume flow rate is sufficient to produce a stream. The base 11 of each of the cones 10 in FIGS. 26A-E and FIGS. 43 A-47B may be fixed to a manifold 40 supplying the liquid as described herein, suchPatent Application Attorney Docket No. 008634.01587VWO as the manifolds 40 in FIGS. 42A-C, or to a reservoir from which the liquid exudes. The cones 10 in FIGS. 26A-E and FIGS. 43A-47B may be used with an apparatus 2 and a system 100 as described herein (or components thereof), and may use any source of liquid described herein. The type of vent shown in FIG. 48 is a cone vent 43, as described herein and in incorporated US 2021 / 0387237 Al . Another embodiment could include a conduit vent 33 as described herein.

[0256] FIGS. 35-37 illustrate three potential sidewall profiles for a body 4 having a cone 10 with a concave portion and a convex portion, for use with an apparatus 2 as shown and described in incorporated US 2021 / 0387237 Al. The profiles shown in FIGS. 35-37 are profiles of the inner surface of the cone 10. These inner wall cone profiles may be used with a range of outer wall thicknesses (which can be constant, or vary with distance from the backplate), the efficiency depending on material and the scaling factor chosen to transform each profile into a scale-down or scaled-up version for manufacture. These profiles present particular advantages by minimizing the amount of standing water in the chamber 6 and transmitting maximum acoustic energy into the liquid stream. In FIGS. 35-37, the “Radius” and “Distance” values represent the vertical and horizontal coordinate axes as plotted in the graph, respectively, in meters of the inner surface of the cone 10, assuming the axis of rotational symmetry is horizontal and lies on the axis defined by r = 0 (where r is the radial coordinate). The diamonds signify the points where the radius and slope are defined. These profiles are defined by piece-wise third- order polynomial expressions based on the radius and slope at various distances, as shown in Table 8. These profiles are defined by lookup tables, or by inserting appropriate values into piece-wise third-order polynomial expressions based on the radius and slope at four distances:where is the radius of the cone curve along the 7thpolynomial, x is the continuous coordinate along the length of the cone, dmjdis the average of the two endpoints (d(j) and d(j + 1)) of each polynomial segment, andis the coefficient found through the solution of:Patent Application Attorney Docket No. 008634.01587VWOwhere / ?( / ) and S(j) are the discrete values from the table that correspond to the jthrow.

[0257] By inserting particular parameter values for d, R and S, particular profiles can be defined for inner and outer walls of the cones. If a cone of a smaller or larger size needs to be defined, then the selected profile calculated below can be scaled into the desired one, by use of a scaling factor based on the desired outflow orifice radius divided by the outflow orifice of the curves shown in FIGS. 35-37.

[0258] For cone profiles 1-3, the lookup tables for the curves are shown in Tables 9-11. For cone profile 1, shown in FIG. 35, the maximum deviation of the polynomial estimate from the look-up table (Table 9) is 0.21 mm. For cone profile 2, shown in FIG. 36, the maximum deviation of the polynomial estimate from the look-up table (Table 10) is 0.18 mm. For cone profile 3, shown in FIG. 37, the maximum deviation of the polynomial estimate from the look-up table (Table 11) is 0.17 mm.Patent Application Attorney Docket No. 008634.01587VWOTable 8: Basis Data for FIGS. 35-37Patent Application Attorney Docket No. 008634.01587VWOTable 9: Lookup Table for Curve Profile 1 (FIG. 35)Patent Application Attorney Docket No. 008634.01587VWOTable 10: Lookup Table for Curve Profile 2 (FIG. 36)Patent Application Attorney Docket No. 008634.01587VWOTable 11: Lookup Table for Curve Profile 3 (FIG. 37)

[0259] It is understood that, for rotationally symmetric cones, the two-dimensional profiles shown in FIGS. 35-37 are symmetrically rotated about the length (d-axis) to define the shape of the body 4, and that these shapes do not include additional structure of the body 4 such as mounting structures (e.g., flange 5). It is also understood that the outer surface of the body 4 may be dimensioned using a constant wall thickness (e.g., 2 mm or other thickness described herein) based on the internal wall shape. Alternatively, the wall thickness may vary with distance from the backplate, e.g. to produce a tapered effect to improve the transmission of sound from the cone to the stream, to reduce the amount of material used in manufacture, and to facilitate the removal of an injection- moulded cone from the mould.Patent Application Attorney Docket No. 008634.01587VWO

[0260] Stating the internal volumes to 1% accuracy or better, the body 4 corresponding to Profile 1 in FIG. 35 has a volume of 99,000 mm3or 99.0 mL. The volume of the chamber produced by Profile 2 in FIG. 36 has a smaller volume of 64,300 mm3or 64.3 mL, which presents some advantages. For example, the chamber 6 empties more quickly, which assists in flushing gas out of the chamber 6. Additionally, if the transducer 22 is operated in a pulsing manner as described herein, and the time between pulses is configured to flush bubbles out of the chamber 6 and nozzle 14 as described herein, then the use of a smaller chamber 6 means that bubbles can be more rapidly cleared from the propagation path between the transducer 22 and the target. This facilitates complete flushing of the bubbles in the off-time between pulses if the volumes of the chamber 6 and the nozzle 14 are smaller. Smaller chambers also allow more rapid priming, and less loss of liquid during priming if the volume of the liquid supply is limited (e.g. for portable devices) or if it is desirable to minimize the volume of run-off to be disposed of. The volume of the chamber produced by Profile 3 in FIG. 37 has a volume of 69,400 mm3or 69.4 mL.

[0261] EXAMPLE 1

[0262] The ability of the cone shown in FIG. 18 (the outflow orifice of which has an inner diameter of 10 mm) to remove biofilm from tissue is shown in FIGS. 20A-D. FIGS. 20A-D demonstrate the efficacy of the apparatus 2 of FIGS. 1-17 compared to a standard saline wash and a commercially available silver dressing, on ex vivo porcine skin explant wound models infected with single-species bacterial biofilms of Acinetobacter baumannii, Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus or Methicillin-sensitive Staphylococcus aureus and singlespecies fungal biofilm (Candida albicans'). Furthermore, the efficacies of the same treatments were tested against porcine skin explant wound models infected with a dual species biofilm of Methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. The cleaning efficacy was evaluated by comparing the microbial bioburden (expressed as colony forming units (CFU) / ml remaining on the explants post treatment in FIGS. 20A and 20C, and in percentage removal based on CFUs in FIGS. 20B and 20D over and above the saline rinse baseline for each microbe species, such that samples washed with only a saline rinse would score 0% in FIGS. 20B and 20D). The treatment methods included: a 5 ml saline rinse (“Saline”), which was delivered over 2Patent Application Attorney Docket No. 008634.01587VWO s from a 5 ml pipette and used as a control group to compare the cleaning performance in terms of percentage removal (FIGS. 20 A and 20C); commercially available silver dressing applied onto the porcine explants for 6 hours (“Silver Dressing”), followed by a 5 ml saline rinse; treatment by the apparatus 2 for 10 seconds (“LAWS (Liquid Acoustic Wound Stream) 10s”); 30 seconds (“LAWS 30s”); or 60 seconds (“LAWS 60s”), all followed by a 5 ml saline rinse. The apparatus was operated at a driving frequency of 145.05 kHz, pulse-on time of 180 microseconds and pulse-off time of 600 microseconds, duty cycle of 23.1% and time-average mean power of around 7.5 W. The distance between the tip of the LAWS device nozzle and the top surface of the porcine explant was set at 15 mm. The data shown is the mean where the error bars represent the Standard Error of the Mean (SEM - 9 sample repeats, obtained from 3 biological repeats).

[0263] Single species biofilm treatment

[0264] FIGS. 20 A and B show the effectiveness of the apparatus 2 at removing microbial biofilm from explant porcine skin explant ex vivo. Since the porcine tissue used in the test is dead, no healing efficacy of the apparatus 2 can be tested in this way, but the ability of the apparatus 2 to remove microbial biofilm is demonstrated. FIG. 20A shows that, compared to washing with saline alone and treatment with silver dressing, treatment using the apparatus 2 is many times more effective at removing the bioburden (note the logarithmic scale used to quantify the colony forming units in FIGS. 20 A and C).

[0265] Dual species biofilm treatment

[0266] FIGS. 20 A and B are for tests where one microbial species at a time infects the porcine tissue. However, in real wounds or oral cavities, more than one unwanted microbial species can colonize the tissue at the same time, creating a multi-species biofilm. FIGS. 20C and D test the efficacy of the apparatus 2 on tissue that is simultaneously infected with two species of microbes, in a multi-species biofilm. This can be more representative of infected wounds or oral cavities. It is particularly important because if one species alone is used to convey the effectiveness of a treatment, then the results can be misleading: for example, if the efficacy of the silver dressing in FIG. 20C were advertised by tests on Acinelobacler baumannii along in a single-species test, one mightPatent Application Attorney Docket No. 008634.01587VWO think that the silver dressing is highly effective, because the silver dressing drops the CFU count by around two orders of magnitude. However, FIG. 20C shows that the resources (e.g. space, nutrients etc.) that have been freed up by the reduction in Acinetobacter baumannii caused by the silver dressing, stimulates a large increase in the population of MRS A, so that the total CFU count in the dual species biofilm does not decrease (the mean actually increases as a result of the application of silver dressing). In contrast, treatment using the apparatus 2 reduces the CFUs for all the microbial species present in the biofilm in FIG. 20C, as expected because its mechanical mode of operation is not species-specific (i.e. not reliant of a chemical pathway or a drug sensitivity).

[0267] Summary of biofilm removal tests

[0268] The apparatus 2 outperformed the standard saline wash and commercially available silver dressings in terms of logio CFU / ml removal and percentage of total bioburden. The average percentage removal achieved using the apparatus 2 on all the species (both single and dual species) tested exceeded 80% removal, higher than that of silver dressing, i.e. a conventional treatment widely used in clinical environment.

[0269] Furthermore, the effectiveness of silver dressing was not as consistent in efficacy against different bacterial / fungal species compared to treatment by the apparatus 2. This could be caused by the difference in bacterial susceptibility to antibiotics, as observed in samples inoculated with MSSA and MRSA (FIG. 20B). Another factor could be the difference in biofilm structure which can affect the penetration of the silver through the biofilm layer for effective microbial inactivation. This is further highlighted in the dualspecies experiment where the silver dressing was effective against the Acinetobacter baumannii but not the MRSA, which led to an increase in the MRSA following silver treatment, this effect was not apparent following treatment by the apparatus 2 where both pathogens were removed equally.

[0270] Similarly, the effectiveness of treatment using the apparatus 2 can vary when treating different bacterial species because of the difference in the degree of bacterial adhesion and biofilm structure. However, during such treatment, the surface waves on acoustically activated bubble walls produce shear and flow in the liquid close to the bubble, which penetrate or disrupt the biofilm layer and then detach the microbes fromPatent Application Attorney Docket No. 008634.01587VWO the porcine skin explant. Depending on species, such variation could be overcome by increasing the cleaning duration.

[0271] EXAMPLE 2

[0272] Example 2 illustrates a comparison of the abilities of a scaled version of a cone 10 as shown in FIGS. 3-17 (scaled down so that the internal diameter of the nozzle 14 is 4.2 mm) (R4) as shown in FIGS. 26D and 46A-B and a cone with the slot-shaped orifice (SI) as shown in FIGS. 25 A and 38A-C, to remove MRS A from a wound in porcine tissue, all driven at the same frequency. The results are shown in FIG. 23 and Table 12. All tissue samples were subjected to a rinse with saline, delivered over 2 s from a 5 ml pipette. This saline rinse formed the baseline. Prior to this saline rinse, some samples were first subjected to a pre-wash by either cone SI or cone R4, at a flow rate of 0.75 L / min of ultrasonically-activated fresh water. The water and the saline for all tests was kept at a temperature of 20 + / - 1 degrees Celsius. Both cones R4 and cone SI were driven at the same frequency, 1.037 MHz. For both cones, the signal was pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. For cone R4, the time- averaged electrical power to the transducer was 6.3 + / - 0.2 W. For cone SI, the time- averaged electrical power to the transducer was 6.4 W.

[0273] FIG. 23 shows the microbial bioburden, expressed as the number of colony forming units (CFU) / ml, remaining post treatment following single-species infection (Methicillin-resistant Staphylococcus aureus) of ex vivo porcine skin explant wound models. After 48 hours infection, the porcine explants were treated with one of the following treatments:(i) The column on the far left of FIG. 23 shows the colony -forming units measured on samples that were subjected to the ‘saline baseline rinse’ only (it is labelled ‘saline’).(ii) The second column from the left of FIG. 23 shows the colony-forming units measured on samples that were given a pre-wash for 10 seconds using fresh water flowing through cone SI (labelled “SI (10s)”), with ultrasound, before they were then given the ‘saline baseline rinse’.Patent Application Attorney Docket No. 008634.01587VWO(iii) The third column from the left of FIG. 23 shows the colony-forming units measured on samples that were given a pre-wash for 5 seconds using fresh water flowing through cone R4 cone (labelled “R4 (5s)”), with ultrasound, before they were then given the ‘saline baseline rinse’.(iv) The column on the right of FIG. 23 shows the colony-forming units measured on samples that were given a pre-wash for 10 seconds using fresh water flowing through cone R4 (labelled “R4 (10s)”), with ultrasound, before they were then given the ‘saline baseline rinse’.

[0274] The data in FIG. 23 show the mean where the error bars represent the Standard Error of the Mean between three sample repeats. The microbial bioburden was log- transformed into units of log CFU / ml and the differences between all sample groups were analyzed using one way Analysis of Variance (ANOVA) followed by post-hoc Tukey pairwise comparisons, where ** = P < 0.01 and non-significance (ns) = P > 0.05.

[0275] Results

[0276] Compared to the saline baseline, a 10 s ultrasonically-activated pre-wash with fresh water through cone SI resulted in 0.8 log reduction of MRSA bioburden, if assessed by comparing the mean CFUs only. However, the mean difference between both groups was insufficient to show statistically significant difference (p = 0.085). On the other hand, when comparing between the saline baseline and cone R4, both 5 s and 10 s cleaning achieved a significant log reduction of 1.4 log (p = 0.004) and 1.5 log (p = 0.006) respectively.

[0277] Discussion and Conclusions

[0278] At 4.2 mm diameter, the stream diameter as it leaves the outflow orifice for the R4 tests is much greater, compared to the wavelength, than the narrowest dimension of the SI orifice (which measures 10 mm x 1.4 mm), and so the narrowing of the mean diameter of the stream (as it accelerates under gravity) and the temporary yet periodic narrowing of the stream as a result of instabilities, must be greater in R4 to cause the propagating ultrasound field to become evanescent. Therefore, the R4 cone is likely to transmit the sound to distance better than the SI cone.Patent Application Attorney Docket No. 008634.01587VWO

[0279] The mean difference between the SI cone and R4 cone was insufficient to show statistical difference between the performance of both cones in FIG. 23. But when compared against the saline control group, cone R4 performed significantly better. The large error bars reflect the small number of data points (n=3) that went into the analysis and hence the levels of significance that can be determined at this stage. It is expected that with more data, these uncertainties can be reduced, and greater confidence attributed to the differences that are subsequently measured.

[0280] Comparisons between circular and rectangular orifices allows identification of the relative importance of the ultrasound and the flow speed. If the same volume flow rate issues from two nozzles of different cross-sectional areas, then the nozzle with the smaller cross-sectional area at the outflow orifice has the greater flow speed, since the volume flow rate (Q) is the product of the flow speed through the nozzle (vn) and the cross-sectional nozzle area (An), assuming the flow is perpendicular to the area An and uniform across the stream (an idealized situation). If these idealized conditions were to hold, the flow speeds at the nozzles SI and R4 would be as shown in Table 23. Although the flow speeds vary by less than 1%, the cleaning performance differs by an order of magnitude (FIG. 23). This proves that in this flow regime, the ultrasonic effect is far stronger than the flow speed effect when it comes to cleaning these biofilms.

[0281] Table 12 below reports calculations of the flow velocity at the outflow orifice, using the cross-sectional area of the orifice and the volume flow rate, under the assumptions of perpendicular uniform flow.Table 12

[0282] EXAMPLE 3

[0283] Time-resolved performance of nozzle R2 with round opening of 4 mm internal diameter at two different ranges from outflow orifice to targetPatent Application Attorney Docket No. 008634.01587VWO

[0284] FIGS. 32A-33F show the cleaning result from cone R2 (FIGS. 26B and 44A-C), which is a scaled version of a cone 10 (having a circular outflow orifice) as shown in FIGS. 3-17 (scaled down so that the internal diameter of the nozzle is 4 mm; Table 14).

[0285] FIGS. 32A-33F illustrate cleaning tested by the ability of the stream to remove a standard pink contaminant from CHEMDYE® TERRAGENE® Ultrasonic Cleaning Indicator test strips, as the strip moves under the stream. For the data in FIG. 32, the target is 30 mm from the outflow orifice, and for the data in FIG. 33, the target is 90 mm from the outflow orifice. The cone cleans effectively at both ranges.

[0286] The ultrasonic frequency was 1.037 MHz. The signal was pulsed with an on-time of 48.2 microseconds (50 cycles) and an off-time of 201.8 microseconds. The pulse repetition frequency was 4 kHz. The volume flow rate was 1 litre / minute. The electrical power to the transducer was 10 W. The final form of the target is shown on the right of the stills taken at times (t) of 2, 3, 4, 5, 6 s from the start of the experiment. The stream begins to touch the pink contaminant at about time t = 3 s. The nozzle was angled 15 degrees from the vertical.

[0287] At 30 mm range the stream cleaned a strip 2.6 mm wide. At 90 mm range the stream cleaned a strip that varied between 2.7 mm and 4.7 mm wide. The device showed excellent cleaning from 1 mm to 90 mm range of the target from the outlet of the nozzle (examples from ranges of 30 mm and 90 mm are shown in FIGS. 32A-33F). For this flow rate, there was reduced cleaning after 90 mm (bearing in mind that the maximum effective cleaning distance depends on a range of factors such as pulsing, turbulence, nozzle orientation and flow speed from the nozzle).

[0288] In this example, and in each example shown below, there is a maximum distance to which the apparatus will clean effectively. This maximum distance depends on a number of factors. If the stream is propagating downwards (i.e. the nozzle points downwards from the horizontal, or was pointing upward but the stream has begun its downwards arc under gravity) then the cross-section in general reduces if the stream accelerates under gravity, as a result of conservation of mass in the accelerating stream. The higher the flow rate, the further the distance at which effective cleaning can be achieved (one reason being that the acceleration due to gravity adds proportionately small increments in speed per second, because it is normalized to the exit speed fromPatent Application Attorney Docket No. 008634.01587VWO the nozzle), provided the flow rate does not become so high that turbulence and air entrainment / stream breakup become problematic. Changing the pulsing can also be used to extend the cleaning distance, as can other technology (e.g. turbulence tamers). Turbulence tamers are separate items from pulse dampeners disclosed herein, although they can be combined into the same system 100 or apparatus 2. Turbulence tamers are used to create laminar flow, and to stop vortices that can trap bubbles within one part of the equipment (e.g., the cone 10) without releasing the bubbles out into the flow.

[0289] EXAMPLE 4

[0290] Slot-shaped nozzle with target at various ranges from outflow ori fice

[0291] FIGS. 25A-D and 38A-41C show a range of cones 10 with outflow orifices 14 that have a rectangular slot-shaped outlet from which the cleaning liquid issues, as described herein. Cone S4 (FIGS. 25D and 41A-C) is used in this experiment. Cone S4 has a square throat of 10 mm x 10 mm, with parallel walls on the shorter sides, an outflow orifice measuring 1.4 mm by 10 mm, and a uniform wall thickness of 1 mm, and is constructed from an ABS-like material (ACCURA BLACK 7820). The nozzle can point in any direction if the water volume flow rate is sufficient to produce a stream, but in the results below it is used in the downwards facing direction. The base 11 from which the nozzle protrudes could be fixed to a manifold supplying the cleaning liquid, or to a reservoir from which the cleaning liquid exudes. The cleaning liquid itself could be saline, tap water from mains, or some other source. In this instance, the liquid was originally mains tap water, which was used to fill a reservoir that supplied the flow through the action of a peristaltic pump (other types of pumps have also been used successfully).

[0292] For the example given below, the carrier frequency of the ultrasonic wave is 1.037 MHz. The ultrasonic signal is pulsed, with an on-time of 48.2 microseconds (50 cycles), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. The volume flow rate of the liquid is 1 litre per minute. The time-average electrical power supplied to the transducer is 34 W. The exposure time was 1 s.

[0293] The results (examples from ranges of 8 mm, 15 mm and 20 mm are shown in FIGS. 31A-C) illustrate excellent cleaning for 1 s exposure, from 1 mm to 15 mm, where the cleaned area reflects the slot-like shape from the nozzle. Very often, the stream andPatent Application Attorney Docket No. 008634.01587VWO target move in relation to each other (e.g. with the target on a conveyor belt, or one or other on an automated control arm or rotatory or linear motion rig). Usually, the motion is perpendicular to the longer side of the slot, to clean a broad path on the target as the motion occurs. As the target moves further from the nozzle 14, the stream loses its slotlike cross-section, and becomes more rounded (in part because of the effect of surface tension). The cross-section in general reduces if the stream accelerates under gravity, as a result of conservation of mass in the accelerating stream. The results show limited cleaning at 15 - 40 mm.

[0294] EXAMPLE 5Time-resolved performance of cone R1 which has a circular outflow orifice of 2.0 mm internal diameter

[0295] FIGS. 34A-B show the cleaning result from cone R1 (FIGS. 26A and 43A-C), a scaled version of a cone 10 as shown in FIGS. 3-17 (scaled down so that the internal diameter of the nozzle is 2.0 mm). In this case, using a thicker wall than that required by scaling still works but eases manufacturing. The ultrasonic carrier frequency to take the data of FIGS. 34A-B was 1.037 MHz. The nozzle was angled 15 degrees from the downwards vertical direction. The signal was pulsed with an on-time of 48.2 microseconds (50 cycles) and an off-time of 201.8 microseconds, with a pulse repetition frequency of 4 kHz. This arrangement generated good cleaning from 1 mm to 30 mm. A lower flow rate enables the technology to be used when the volume of water available for treatment is restricted (e.g. if it is carried by a drone or a mountain rescue worker), or if it is inconvenient or unsafe to flood the treatment area with excessive cleaning liquid (such as when cleaning a body cavity or the mouth when cleaning in the oral cavity), or when the volume of run-off needs to be minimized (e.g. in a clinic or home setting, where the run-off liquid must be collected in a container that is smaller than ideal, and far from a suitable liquid waste drain), or to enable what liquid there is (or run-off that will be made) to be practicable over a longer time (e.g. when the liquid supply is carried by a vehicle such as an ambulance or car / motorbike of a community / field practitioner) or to treat more or larger targets (e.g. wound surface area). It is also convenient to reduce the volume flow rate when the cleaning fluid is an exotic, rare, expensive or hazardous liquid (e.g. mercury). The technology can also be convenient when the target is smallPatent Application Attorney Docket No. 008634.01587VWO(such as the removal of excess solder from circuitry, or the cleaning of small electronic or silicon components).

[0296] The apparatus 2 showed excellent cleaning from 1 mm to 30 mm range of the target from the orifice of the nozzle (examples from ranges of 8 mm and 20 mm are shown in FIGS. 34A-B). For this flow rate, there was reduced cleaning after 30 mm (bearing in mind that the maximum effective cleaning distance depends on a range of factors such as pulsing, turbulence, nozzle orientation and flow speed from the nozzle). It is noted that the test rig did not allow the stream to move across the right side of the target area in FIG. 34A.

[0297] EXAMPLE 6

[0298] Comparing salad cleaning using ultrasonic cleaning baths with cleaning by ultrasonically-activated streams

[0299] Example 6 illustrates performance of the apparatus 2 in cleaning biofilm from delicate tissue (salad) without harming that tissue, which was demonstrated in a number of experiments. It is noted that by 2050, there may be an additional 2 billion people on the planet, and extending food shelf-life is critical to the providing sufficient food. Currently 25% of the world’s food calories, and up to 50% by weight, are wasted before consumption) (Smil, V. (2004) Improving Efficiency and Reducing Waste in Our Food System, Environmental Sciences, 1(1), 17-26, DOI: 10.1076 / evms.l .l. l7.23766; Kader, A. A. (2005) Increasing food availability by reducing postharvest losses of fresh produce. Acta Horticulturae . 682, 2169-2175; Parfitt J., Barthel M. and Macnaughton S. (2010) Food waste within food supply chains: quantification and potential for change to 2050. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1554), 3065-3081). Cleaning can extend shelf life, and also reduce the risk of illness from consumption of contaminated food, for example, ready-to-eat salad, that is rarely cooked to sterilize it before consumption.

[0300] The cleaning performance of three ultrasonic cleaning devices, i.e., a commercial ultrasonic bath (its electrical power is rated at 400 W and its nominal operating frequency ranges from 32 kHz to 38 kHz), and two apparatuses 2 as disclosed herein (a handheld embodiment, and a version where the ultrasonic nozzle is incorporated into a gooseneck faucet-like embodiment as described in incorporated US 2021 / 0387237 Al).Patent Application Attorney Docket No. 008634.01587VWOIn each case, the degree of cleaning during a treatment time of 2 minutes was evaluated on unprocessed spinach leaves. Both the handheld and gooseneck ultrasonic apparatuses were operated at around 133 kHz and at a flow rate of 2 + / - 0.1 L / min. The ultrasound signal used in the handheld device was a continuous sine wave, whereas the signal used in gooseneck device was a pulsed sine wave at a pulse repetition frequency of 30 Hz and duty cycle of 50%. The mean power (calculated by coherently multiplying the voltage and current waveforms) consumed by the handheld and gooseneck ultrasonic apparatuses were around 110 W and 17 W respectively. Both ultrasonic streams (from the handheld and gooseneck apparatuses) used water supply directly from mains tap water.

[0301] FIGS. 21-22E illustrate the results of this experiment. FIG. 21 illustrates the cleaning performance (evaluated by comparing the microbial load of treated samples against control samples and expressed as log reduction) achieved using ultrasonic bath at 50% power and 100% power (labelled UB50 and UB100, respectively), the handheld ultrasonic stream device (labelled SS-UAS), and the gooseneck ultrasonic stream device (labelled ARI-UAS), at a cleaning duration of 2 minutes. The CFU measurements were taken on day 0 and day 6 post cleaning. Data shown is the mean log reduction where the error bars represent the Standard Error of the Mean (SEM - 6 sample repeats, obtained from 3 biological repeats). Statistical differences were evaluated using one-way ANOVA followed by a post-hoc pairwise comparison using Holm-Sidak method, where *** =p < 0.001, ** =p < 0.01 and non-significance (ns) = p > 0.05. FIGS. 22A-E show episcopic differential interference contrast (EDIC) micrographs acquired at 400X magnification showing the adaxial (left) and abaxial (right) surface of (A) uncleaned spinach leaf sample as a control group, and spinach leaf samples cleaned using ultrasonic bath at (B) 50% and (C) 100% power; (D) the handheld ultrasonic stream device and (E) the gooseneck ultrasonic stream device for 2 minutes. The scale bar in FIGS. 22A-E represents 100 micrometer.

[0302] The cleaning performance was evaluated by comparing the microbial load (in units of colony forming units (CFU) / g) on the cleaned samples against that of uncleaned control samples and expressing all the cleaned samples as a log reduction compared to the control (Tog reduction’ quantified as log CFU / g as shown in FIG. 21). The initialPatent Application Attorney Docket No. 008634.01587VWO microbial load of the spinach leaf samples consists of endogenous bacteria that naturally reside on the spinach leaf surface.

[0303] Both the handheld and gooseneck ultrasonic stream devices achieved a significantly higher log reduction in CFUs as compared to ultrasonic bath (which was tested at both nominal power settings on the bath of 50% and 100%) on day 0 and day 6. The bath achieved low log reduction (0.5 log at 50% power setting and 0.6 log at 100% power setting) compared to both ultrasonic stream devices, and a negative log reduction on day 6. The negative log reduction on day 6 indicated that the microbial loads of the cleaned samples were higher than the uncleaned control samples. This is because of the surface damage (FIGS. 22B-C) caused by the cleaning action of the ultrasonic cleaning bath which led to rapid proliferation of bacteria on the wounds over time. When cleaning with the ultrasonic bath, during the cleaning process, the inertial cavitation used to clean the bubbles (and associated high speed liquid microjets and evolution of a bubble torus, with associated effects on the leaf) impinge on the leaf surface and dislodge microbes from the leaf surface to the wash water. After cleaning, as the leaves were being removed from the wash water, microbes could also be redeposited onto the leaf surface, leading to ineffective cleaning and further contamination.

[0304] When cleaning with handheld and gooseneck ultrasonic stream devices, microbes were detached from the leaf surfaces through the convection and shear forces generated by bubbles hosting surface wave activities and then removed through the rinsing action of the stream (Chong, W. Y., Seeker, T. J., Dolder, C. N., Keevil, C. W. and Leighton, T. G. (2021) The possibilities of using Ultrasonically Activated Streams to reduce the risk of foodborne infection from salad. Ultrasound in Medicine and Biology, 47(6), 1616- 1630). The whole cleaning process did not involve the inertial collapse of bubbles, therefore the risk of creating surface damage on the leaves could be minimized (FIGS. 22D-E). These results demonstrated that non-immersive ultrasonic cleaning using ultrasonic stream devices is more suitable for salad leaf cleaning as the risk of cross contamination between the products and the washwater could be reduced since the cleaning process does not require salad leaves to be kept immersed in the washwater. Furthermore, a reduction of more than 1.5 log CFU / g on day 6 also demonstrated the potential of ultrasonic stream devices in increasing product shelf life.Patent Application Attorney Docket No. 008634.01587VWO

[0305] EXAMPLE 7

[0306] Comparisons of slot-shaped nozzles (S1-S3) as a function of range to target

[0307] Depending on the usage and scenario, there can be a number of advantages to using cones with rectangular or similarly slot-shaped outflow orifices, using cones SI -S3 shown in FIGS. 25A-C and 38A-40C. The power supply could be mains electricity, but power supply from a battery or a vehicle power unit could alternatively be used, e.g. for a field- or battle-field treatment (as it can for any geometry of ultrasonically- activated liquid stream, although combining portable power supplies with the streams that are made more portable by having lower volume flow rates, is particularly attractive). With any stream geometry, the liquid used could be, for example, sterile water or potable water, either bagged, pumped or from a mains or pressurized supply. However, it is particularly convenient to use bagged saline because this is available in clinical settings, sterile and sealed until use making it suitable for transport, (e.g. in a vehicle for treatment in the field or battlefield or community setting, or to bedside locations that are not close to suitable sources of liquid such as bedside locations in wards). Although they may be added if preferred, no chemicals, drugs or additives are necessary to generate the cleansing and healing. This is particularly important in terms of reducing the rise of Anti-Microbial Resistance (AMR).

[0308] FIGS. 49-51 illustrate various embodiments of systems 10 including some example options for supplying liquid (e.g., water) and electricity to an apparatus 2 having a cone 10 with a rectangular orifice, such as the cones S1-S4 described herein. It is understood that the features shown in FIGS. 49-51 and disclosed herein may be used with other embodiments of apparatuses 2 and / or cones 10, including other embodiments disclosed herein. FIG. 49 illustrates a system 100 that uses a bagged or bottled liquid supply 61 (e.g., a saline bag) as shown in FIGS. 1-2, which offers portability, among other advantages. The embodiment of FIG. 49 may use a slotted cone in a configuration (with a twist-on / off slotted nozzle with integrated manifold) that allows for such a portable liquid supply, and a twist-on / off slotted nozzle with integrated manifold. FIG. 50 illustrates another embodiment of a system 100 that uses a pressurized liquid supply 61, such as mains tap water 200, or a reservoir (e.g. pressurized or pumped), which is delivered to a liquid conditioning unit 201 (e.g. containing filters to remove bubbles and particulates) through a tube 199, and then delivered to the apparatus 2 via the liquidPatent Application Attorney Docket No. 008634.01587VWO supply conduit 20. In both FIGS. 49 and 50, the slotted cone 10 and manifold 40 are provided as a combined unit 5 as disclosed herein, making it easily removable so that a contaminated cone 10 can be replaced (for example, between patients). The combined unit 5 in any embodiment herein may be a treatment unit that is removable and replaceable, such as an interchangeable, single-use or multi-use treatment unit. FIG. 51 illustrates an embodiment of a system 100 similar to that of FIG. 50, in which the apparatus has a manifold 40 that is separate from the cone 10 and remains part of the handset 50 when the cone 10 is interchanged. In this configuration, prior to reaching the handset 50, the electrical cord 62 and the liquid supply conduit 20 run parallel in a common umbilical 87 for a length, and the liquid supply conduit 20 may run into and through a portion of the casing 55 to reach the manifold 40. For example, as shown in FIGS. 19A and 29, the electrical cord 62 and the liquid supply conduit 20 may run through the handle 56. This configuration might be suitable for a handset cleaning application, e.g., of tools, where contamination of the nozzle is not such a problem, but a reduction in the number of tubes and wires in the work environment is seen to be advantageous.

[0309] Example applications of the systems 100 illustrated in FIGS. 49-51 might be for wound cleaning and treatment such as shown in FIG. 29 or handwashing as shown in FIG. 27, which are shown in these figures being deployed using a handheld unit. However, deployment of an apparatus 2 including a cone 10 with a rectangular orifice 12 using an arm 82 (e.g. an articulated positioning system, a robotic arm) is also feasible, as shown in FIG. 30 for use of cleaning hardware such as engine parts, the interior of a nuclear facility, etc. In the above examples, the nozzle 14 is moved by the operator over the surface that is to be treated. However, the converse geometry is also feasible, such as in the movement of items 34 on a conveyor belt 35 through the slot-like stream from a fixed nozzle as shown in FIG. 28.

[0310] In one embodiment using a cone 10 with a rectangular orifice 12, the relative motion of the item to be cleaned, and the slot-like stream, are configured such that the direction of relative motion is perpendicular to the long side of the orifice 12, in order to paint out a large area with each pass. Alternatively, it is also possible to use a cone 10 with a rectangular orifice 12 in a manner such that the direction of relative motion is parallel to the long side of the orifice 12. This would only apply the liquid in a thin strip of areaPatent Application Attorney Docket No. 008634.01587VWO with each pass, but the treated area would stay under the stream for far longer, and these long treatment times per unit area of target may be preferential in some clinical environments.

[0311] A wide range of cone 10 shapes can be provided that have rectangular or square outflow orifices. The cones S1-S4 illustrated herein all have straight side-walls, but it is possible to construct functioning devices with a number (e.g., two or four) curved side walls, modelled for example on a scaled version of the shapes defined in FIGS. 8, 18, 24, 35, 36, 37 and Tables 5-11.

[0312] As described above, FIGS. 25A-D and FIGS. 38A-41C show examples of cones 10 with rectangular outflow orifices 12, which are each connected to a base 11 in the form of a mounting plate configured to connect to a manifold 40 or other liquid inlet configuration (e.g. from a reservoir or supply without using a manifold), e.g., by fasteners. In other embodiments, the manifold 40 and the cone 10 may be provided as a single-part combined unit 5 as disclosed herein, thereby reducing the number of separate parts that need to be connected together during assembly. The examples of manifolds shown in FIGS. 42A-B may all be made from PLA in one embodiment, although a wide range of options are available (metal, plastics, glass). In general, stiffer materials work better than flexible materials for such an application. The bodies 4 and / or at least the cones 10 thereof can be made of a transparent material, which:• Aids the user in seeing the target (e.g. enables the clinician to see the wound, or the cleaner to see a small component);• Enables the user to see inside the nozzle and cone in order to assess how completely the cone is filled with water and the bubble population there (incomplete filling and an excess of bubbles in the cone / nozzle can reduce the efficacy of treatment);• Enable the lights to be mounted to shine into the cone / nozzle as disclosed herein. These lights can illuminate the target (e.g. wound) and / or the water (e.g. target to help assess the bubble population present). The lights can also be used to signal the operational efficiency to the user, so that the user receives a visual cue without taking their eyes off the target. For example, use of different colors or flashing sequences and timings can be used to indicate if the device is in range to clean / treat the target efficiently, orPatent Application Attorney Docket No. 008634.01587VWO whether the cone needs venting of excess gas. The use of lights within the eyesight of the user (e.g. illuminating the cone by shining lights through a transparent (e.g. glass) rear wall 8, has the advantage over using sounds in that it works for hearing impaired users, and when there is significant background noise.

[0313] This example uses the following test protocols. The technology can be made to work for various sizes and shapes of cones 10. In each of the examples shown in this section, cleaning is tested by the ability of the stream to remove a standard pink contaminant from CHEMDYE® TERRAGENE® Ultrasonic Cleaning Indicator test strips. The performances of these cones were compared. The performances of cones SI, S2, and S3 are shown in FIGS. 52A-G (SI), FIGS. 53A-G (S2), and FIGS. 54A-F (S3). For scale, the black circle in the test strips is 10 mm diameter. Image analysis was used to determine the areas that were completely cleaned in the test strip, and the areas that were partially cleaned, which are indicated in the graphical data (FIGS. 52H, 53H, 54G, 62) produced. “Complete” as used in describing such testing herein indicates that all the dye in the area is removed. “Partial” as used in describing such testing herein indicates partial removal of the dye in a given area (above an arbitrary brightness threshold) . The zero-to-peak voltage (Vpeak) across the transducer was 120 V. The liquid flow rate was 0.75 litre / minute for cone SI, 1.5 litre / minute for cone S2, and 1.0 litre / minute for cone S3. The time-average power to the transducer was 6.3 + / - 0.2 W. The error bars represent the 95% Confidence Interval of the Mean with N > 3. All the tests were for 1 second of cleaning, where the target and nozzle stationary with respect to each other (clearly, in many practical applications, one would be in motion relative to the other), and with the nozzle angled 15 degrees from the vertical. For the examples given below, the carrier frequency of the ultrasonic wave is 1.037 MHz. The ultrasonic signal is pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. For cone SI, the absence of data for ranges greater than 50 mm should not be used to infer the cone could not clean beyond 50 mm range as some cleaning was seen at these longer ranges, but not enough repeats were taken to include data in this plot for ranges exceeding 50 mm. For cone S2, the absence of data for ranges greater than 70 mm should not be used to infer the cone could not clean beyond 70 mm range: some cleaning was seen at these longer ranges, but not enough repeats were taken to include data inPatent Application Attorney Docket No. 008634.01587VWO this plot for ranges exceeding 70 mm. For cone S3, the absence of data for the 2 mm range should not be used to infer the cone could not clean at 2 mm range: the cone was able to clean at 2 mm but not enough repeats were taken at that range to include data on the 2 mm range in this plot. The absence of data for ranges greater than 70 mm should not be used to infer the cone could not clean beyond 70 mm range: some cleaning was seen at these longer ranges, but not enough repeats were taken to include data in this plot for ranges exceeding 70 mm.

[0314] The test results for this example are as follows. FIGS. 52A-H show cleaning as a function of range (in mm) from outlet of nozzle to the target for Cone SI held over the target, with the nozzle angled 15 degrees from the vertical (a phrase which herein means 75 degrees below the horizontal). In FIG. 52H, the shaded column indicates the area that is completely cleaned (i.e. white on the tested pink strips) and the hashed column indicates the area that is partially cleaned (i.e. a lighter pink on the tested pink strips). A horizontal line is used to indicate the area of the nozzle. FIGS. 53 A-H similarly show cleaning as a function of range (in mm) from outlet of nozzle to the target for Cone S2 held over the target (the nozzle was angled 15 degrees from the vertical). FIGS. 54A- G similarly show cleaning as a function of range (in mm) from outlet of nozzle to the target for Cone S3 held over the target (the nozzle was angled 15 degrees from the vertical).

[0315] The conclusions from this example test are as follows. All the cones in this example (for cones with slot-shaped outflow orifices) cleaned well over a wide (and continuous, though that is not shown from the way the data is plotted here) variety of outflow-to- target distances (ranges), from millimetres to centimetres. This gives the advantage of tolerance in positioning (particularly if the device is being handled manually, or the target shape is structured to present a variety of outflow-to-target distances (ranges).

[0316] These slotted cones all demonstrated cleaning in a water sheet, producing a line of cleaning in the range of at least 3 mm - 50 mm, a distance that would increase if the cone size were scaled up, and / or the flow rate were increased appropriately, so long as instabilities on the stream surface and stream break-up were avoided (note that the “zero” entries in columns outside of this range in FIGS. 52H, 53H and 54G does not indicate an absence of cleaning, but rather insufficient repeats to warrant plotting). As the range increases, the cross-sectional area of the stream becomes more circular as aPatent Application Attorney Docket No. 008634.01587VWO result of surface tension and the damped resolution of instabilities on the wall of the stream, such that the cleaned area tends to be more circular for this static arrangement with the nozzle above the target (the nozzle was angled 15 degrees from the vertical). If the stream is angled such that it is not travelling perpendicular to the target when impact occurs, the shape of the cleaned area becomes non-circular as the target cuts through the cross-section of the stream at a non-normal angle, and gravity pulls the runoff downwards.

[0317] Because the ultrasonic frequency is selected to be above a cut-off frequency that is determined by the narrowest dimension of the slot outflow orifice, it continues to be well above the cut-off frequencies associated with the circular stream for a long range (until the stream has narrowed as a result of gravity). This gives this stream extra ability to clean to long range.

[0318] Relative motion between the nozzle and the target, when the two are within the 2 mm - 6 mm range, would result in a sheet of liquid passing over the target, cleaning out a ‘stripe’ across the target.

[0319] In each example shown, there is a maximum distance to which the apparatus will clean effectively. This maximum distance depends on a number of factors. If the stream is proceeding downwards, it accelerates under gravity. If the stream is propagating downwards (i.e., the nozzle points downwards from the horizontal, or was pointing upward but the stream has begun its downwards arc under gravity) then the crosssection in general reduces if the stream accelerates under gravity, as a result of conservation of mass in the accelerating stream. This reduction in cross-section can take the frequency of the ultrasound below the cut-off frequency of a part of the stream (particularly if instabilities on the stream wall cause excessive stream narrowing in places), thereby forming a limit on effective cleaning distance.

[0320] The higher the flow rate, the further the distance at which effective cleaning can be achieved (one reason being that the acceleration due to gravity adds proportionately small increments in speed per second, because it is normalized to the exit speed from the nozzle), provided the flow rate does not become so high that turbulence and air entrainment / stream breakup become problematic. Changing the pulsing can also be used to extend the cleaning distance, as can other technology (e.g., turbulence tamers)Patent Application Attorney Docket No. 008634.01587VWO mentioned in incorporated U.S. Patent Application Publication No. 2021 / 0387237 Al. The cleaning distance can be increased by increasing the volume flow rate within the bounds of keeping the stream intact

[0321] EXAMPLE 8

[0322] Cleaning with slot-shaped nozzles at other flow rates, drive parameters, and nozzle shape and materials

[0323] To demonstrate that these cleaning abilities are not restricted to the materials and parameters shown in Example 7, data is here presented from a cone S4 as shown in FIGS. 25D and 41A-C that has a square throat of 10 mm by 10 mm, has parallel walls on the shorter sides, and is constructed from an ABS-like material (ACCURA BLACK 7820). The outflow orifice has dimensions 1.4 mm by 10 mm. The wall thickness was 1 mm. The cone S4 was tested with a liquid volume flow rate (Q) = 1.0 litre / minute, a time-average electrical power to the transducer (W) of 34 W, and a zero-to-peak voltage across transducer (Vpeak) of 275 V. The ultrasonic frequency was f= 1.037 MHz. The ultrasound was pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. The cleaning duration was 1 second. FIGS. 55A-F illustrate the cleaning performance of the cone S4. As with the previous nozzles, cleaning retains the slot shape close to the nozzle, but loses that shape as the range increases (see FIGS. 55A-F).

[0324] EXAMPLE 9

[0325] The use of round nozzles of less than 10 millimetres diameter

[0326] In this experiment, the cones R1-R5 shown in FIGS. 26A-E and 43A-47B were tested. The test method for this example was as follows. The technology can be made to work for various nozzle / cone sizes and shapes. In each of the examples shown in this section, cleaning is tested by the ability of the stream to remove a standard pink contaminant from CHEMDYE® TERRAGENE® Ultrasonic Cleaning Indicator test strips.

[0327] The first two experiments of Example 9 were conducted as described in Example 3 above, as preliminary look-see experiments to show how, as the target tracks underneath that stream, the stream is able to create a stripe of cleaned area. The results are a sequence of stills taken from a movie that begins before the target comesPatent Application Attorney Docket No. 008634.01587VWO underneath the stream, and ceases when the stream has traversed approximately across the target, and are reported in FIGS. 32A-F and FIGS. 33A-F as discussed above.

[0328] FIGS. 32A-F and 33A-F show the cleaning results from cone R2, where the target moves under the cone so that the stream traverses over the target. The ultrasonic carrier frequency to take the data of FIGS. 32A-33F was 1.037 MHz, the signal being pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. The volume flow rate was 1 litre / minute, and the time-average electrical power to the transducer was 10 W.

[0329] The device showed excellent cleaning from 1 mm to 90 mm range of the target from the orifice of the nozzle (examples from ranges of 30 mm and 90 mm are shown in FIGS. 32A-F and 33A-F respectively). At 30 mm range, the stream cleaned a strip 2.6 mm wide (FIGS. 32A-F). At 90 mm range the stream cleaned a strip that varied between 2.7 and 4.7 mm wide (FIGS. 33 A-F). For this flow rate, the device was able to clean to greater distances than 90 mm, but not with the same efficiency that it demonstrated at 30 mm (bearing in mind that the maximum effective cleaning distance depends on a range of factors such as pulsing, turbulence, nozzle orientation and flow speed from the nozzle as discussed above).

[0330] The second experiment undertaken in Example 9 was of the cleaning ability of a nozzle with circular opening of 2.0 mm internal diameter as target moves under stream, as described in Example 5 above. The specification for the test was to measure the cleaning result from cone R1 where the target moves under the cone so that the stream traverses over the target. The ultrasonic carrier frequency to take the data of FIG. 34 was 1.037 MHz, the signal being pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. The electrical power to the transducer was 12 W. The small size of the outflow orifice allows a low flow rate (200 millilitres per minute) which is advantageous in that it can reduce the liquid reservoir that needs to be carried (facilitating person- or vehicle- borne deployments) and reduce the volumes of contaminated liquid run-off. The results are shown in FIGS. 34A-B, discussed above.

[0331] The device showed excellent cleaning from 1 mm to 30 mm range of the target from the orifice of the nozzle (examples from ranges of 8 mm and 20 mm are shown in FIGS.Patent Application Attorney Docket No. 008634.01587VWO34A-B). For this flow rate, the device was able to clean to greater distances than 30 mm, but not with the same efficiency that it demonstrated at 30 mm (bearing in mind that the maximum effective cleaning distance depends on a range of factors such as pulsing, turbulence, nozzle orientation and flow speed from the nozzle, as discussed above).

[0332] For the third experiment of Example 9, the tests are conducted for 1 second of cleaning, where the target and nozzle are stationary with respect to each other. The third experiment of Example 9 consisted of controlled examination of the cleaning results of cones R1 to R5 (the specifications of which are given in Table 14, and which are shown in FIGS. 26A-E and 43A-47B) when the cone and target are stationary for 1 s of cleaning. FIGS. 57-61 compare the results, for cleaning from CHEMDYE® TERRAGENE® Ultrasonic Cleaning Indicator test strips using cones R1 to R5. For each target-to-outflow orifice distance, the area of the test strip that is completely cleaned, and the area that is partially cleaned, are shown by two separate bar columns. These areas are judged using image analysis of the colour distribution remaining on the strip after cleaning.

[0333] For the tests documented in FIGS. 57-61, the ultrasonic frequency was 1.037 MHz, and the signal was pulsed with an on-time equivalent to 50 cycles (48.2 microseconds), and an off-time of 201.8 microseconds, and a pulse repetition frequency of 4 kHz. The volume flow rate and the time-averaged electrical power to the transducer are as follows: 0.17 litre / minute and 6.3 + / - 0.2 W for cone Rl; 0.68 litre / minute and 6.3 + / - 0.2 W for cone R2; 0.68 litre / minute and 6.3 + / - 0.2 W for cone R3; 0.75 litre / minute and 6.3 + / - 0.2 W for cone R4; and 1.0. litre / minute and 6.3 + / - 0.2 W for cone R5. For cone Rl (FIG. 57), the absence of data for ranges greater than 50 mm should not be used to infer the cone could not clean beyond 50 mm range: some cleaning was seen at these longer ranges, but not enough repeats were taken to include data in this plot for ranges exceeding 50 mm.

[0334] The results shown in FIGS. 57-61 allow a number of conclusions to be drawn, as follows: In terms of the apparatus and operating conditions, there are a wide range of cone shapes and outflow orifice sizes that can induce treatment of a surface, although they vary in performance. FIG. 62 presents a comparison of cleaning data from all of cones S 1 -S3 and Rl -R5 when the target was a range of 10 mm from the outflow orifice,Patent Application Attorney Docket No. 008634.01587VWO and the stream was held stationary above the target for 1 second. The first five pairs of columns in FIG. 62 compare the cleaning of the cones with small circular outflow orifices (R1-R5). These cones with small circular outflow orifices (R1-R5) were all tested at an ultrasonic frequency of 1.037 MHz, which is a frequency high enough to be above the cut-off frequency for the smallest diameter nozzle tested (R1 at 2 mm inner diameter). For the rectangular nozzles S1-S3, the ultrasonic frequency that can propagate down the stream is determined by the smaller of the dimensions at the outflow orifice, and so the group of cones SI to S3 (with rectangular outflow orifices) were also tested at the same frequency. Hence, FIG. 62 also shows the performance of three cones that have rectangular outflow orifices (SI -S3), at the same range between outflow orifice and target of 10 mm.

[0335] The use of a high frequency such as 1.037 MHz affords the opportunity to use smaller, lighter and more compact transducers that are difficult to achieve with lower frequencies, like 145 kHz. Furthermore, sound with a frequency of 145 kHz would not propagate down a stream so narrow, such that it placed 145 kHz below the cut-off frequency for that stream (and so 145 kHz would not propagate down a stream 2 mm inner diameter). However, the lower frequency, if it can propagate down the stream, activates surface waves on bubbles that are too large (e.g. 20 micrometres radius) for the ~ 1 MHz ultrasound of the same low amplitude to stimulate surface waves. Instead, higher amplitude ultrasound would be needed, and if- 1 MHz ultrasound is to stimulate surface waves, it needs to be on much smaller bubbles. Furthermore, if the water contains many bubbles having radii around 1 micrometre, then the - 1 MHz ultrasound field might be absorbed before it reaches the target. Hence, the choice of ultrasonic frequency and stream size depends on optimizing a number of factors (ultrasonic absorption, ultrasonic scattering, the device size and weight that can be tolerated, the area of the stream that the defined target requires) alongside knowledge of the maximum distance between the target and the outflow orifice that is needed.

[0336] In terms of the ability of devices to clean to distance, the third experiment of Example 9 showed that there is a maximum distance to which the device will clean effectively (this being at a range greater than the maximum range shown for each nozzle in FIGS. 57-61 for the round nozzles; and larger than the maximum range shown in FIGS. 52A- 55F for the slot-shaped nozzles, there being a shorter range for each at which the streamPatent Application Attorney Docket No. 008634.01587VWO loses its slot-shaped cross-section as it evolves into a stream of more circular crosssection). This maximum distance at which cleaning and effective target treatment occurs depends on a number of factors. If the stream is proceeding downwards, it accelerates under gravity. If the stream is propagating downwards (i.e. the nozzle points downwards from the horizontal, or was pointing upward but the stream has begun its downwards arc under gravity) then the cross-section in general reduces if the stream accelerates under gravity, as a result of conservation of mass in the accelerating stream. The higher the flow rate, the further the distance at which effective cleaning can be achieved (one reason being that the acceleration due to gravity adds proportionately small increments in speed per second, because it is normalized to the exit speed from the nozzle), provided the flow rate does not become so high that turbulence, vorticity and air retention in the cone, air entrainment in the stream and stream breakup become problematic. Changing the pulsing can also be used to extend the cleaning distance, as can other technology (e.g. turbulence tamers) mentioned in incorporated US 2020 / 0164194 A.

[0337] In terms of the ability to use low volume flow rates, the example shown in FIGS. 34A- B exhibited a case when good cleaning was achieved with a volume flow rate of 200 millilitre / minute. A lower volume flow rate enables the technology to be used when the volume of water available for treatment is restricted (e.g. if it is carried by a drone or a mountain rescue worker), or if it is inconvenient or unsafe to flood the treatment area with excessive cleaning liquid (such as when cleaning a body cavity or the mouth when cleaning in the oral cavity), or when the volume of run-off needs to be minimized (e.g. in a clinic or home setting, where the run-off liquid must be collected in a container that is smaller than idea, and far from a suitable liquid waste drain), or to enable the liquid supply (or run-off that will be made) to be usable over a longer time (e.g. when the liquid supply is carried by a vehicle such as an ambulance or car / motorbike of a community / field practitioner) or to treat more or larger targets (e.g., wound surface area). It is also convenient to reduce the volume flow rate when the cleaning fluid is an exotic, rare, expensive or hazardous liquid (e.g. mercury). The technology can also be convenient when the target is small (such as the removal of excess solder from circuitry, or the cleaning of small electronic or silicon components).Patent Application Attorney Docket No. 008634.01587VWO

[0338] In terms of the general requirement to produce good cleaning and target treatment, then the general trend (to which there can be exceptions in specific circumstances) is that, so long as the stream stays intact and the cone liquid does not overfill with bubbles produced by transducer activity (to the extent that the ultrasound is absorbed such that its amplitude at the target is insufficient to generate treatment), then larger electrical powers and higher volume flow rates and higher flow speeds at the nozzle improve the treatment. However, the risk of generating stream breakup and overpopulating the cone water with bubbles will becoming limiting factor. Furthermore, low volume flow rates and low electrical power requirements are advantageous for many scenarios, particularly those that favour portability, as well as reducing the volume of problematic contaminated run-off that must be disposed of.

[0339] Table 13 summarises the dimensions of the cones used in these examples, that have rectangular outflow orifices.Table 13

[0340] Table 14 summarises the dimensions of the cones used in these examples, that have circular outflow orifices.Patent Application Attorney Docket No. 008634.01587VWOTable 14METHODOLOGIES FOR EXAMPLES 10-14

[0341] Methodology: Ethical approvals. All ex vivo human skin tissues were sourced from Genoskin (France) where they were harvested under their ethical approvals, inclusive of, informed consent and anonymisation. Experiments carried out on the sourced ex vivo skin were done so following the Declaration of Helsinki principle under favorable ethical approval from the London - South East Research Ethics Committee (24 / PR / 0075).

[0342] Methodology: WoundSkin culture and treatment. Surgically salvaged ex vivo skin samples sourced from Genoskin (France, WoundSkin 11mm) were cultured using their proprietary culture media and gel matrix that holds the skin samples at the air-liquid interface. Throughout all experimentation, apart from during treatments on day 0 (DO), the skin samples were incubated at 37 degrees Celsius within a 5% (v / v) CO2 supplemented and humid environment. Pre-warmed, fresh culture media was replaced under the suspended tissues every 24 hours. After the tissues had reached equilibrium following 24 hours of incubation, they were either treated for 5 seconds with an apparatus as shown in FIGS. 3-17 with a 10 mm contact distance (“apparatus treated” or “LAWS”), treated with the apparatus with no ultrasound activated (“saline treated”), or not treated (“untreated control”). The day of treatment for each sample was classed as DO.

[0343] Methodology: Methicillin Resistant Staphylococcus Aureus (MRSA) culture and infection of ex vivo human skin wound models. Methicillin Resistant StaphylococcusPatent Application Attorney Docket No. 008634.01587VWOAureus (MRS A - NCTC 11940, UKHSA) was grown in nutrient broth overnight at 37 degrees Celsius. The following day, the overnight culture was normalized to between 0.800 and 1.000 OD600 (~lxl06cells / ml). The human skin samples were inoculated with 8 pL of the normalised MRSA culture directly onto the wound bed of each skin sample. The skin samples were then incubated at 37 degrees Celsius within a 5% (v / v) CO2 supplemented and humid environment for 24 hours prior to treating by either saline (5 s) or the apparatus with ultrasound (5 s).

[0344] Methodology: Tissue harvest, fixation, and processing. On the specified days post treatment, the skin samples were removed from the incubator and, within a microbiological safety cabinet, each tissue was removed from the 12-well plate, the skin was carefully removed from the Transwell inserts, the supporting gel matrix was removed using sterile forceps, then the tissues were fixed in 10% Neutral Buffered Formalin for 24 hours at room temperature. After fixation, the skin tissues were transferred to 70% (v / v) Ethanol and stored until tissue processing. Tissue processing was carried out using a Sakura VIP-5 automatic vacuum-based tissue processing machine using the following protocol (Table 15). After processing, all skin samples were embedded into paraffin wax blocks using a Rankins Basics embedding console and cryo-plate. Tissue sections were cut on a Leica RM-2125 microtome at 5 pm thickness and captured on SuperFrost+ glass microscope slides.Patent Application Attorney Docket No. 008634.01587VWOTable 15

[0345] Methodology: Hematoxylin and Eosin (H&E) staining. Prior to dewaxing and rehydration, all tissue sections were baked onto the glass slides by placing the unstained slides into a dehydration oven at 65 degrees Celsius for 30 minutes. Straight after baking, the slides were dewaxed and rehydrated through the wash stages described in Table 16 (all steps were carried out at room temperature). Once dewaxed and rehydrated, slides were stained with Hematoxylin and Eosin following a established protocol. Briefly, slides were stained in Mayers hematoxylin for 3 minutes followed by washing and bluing in running hard tap water, followed by a second wash in Phosphate Buffered Saline (PBS) for 2 minutes. Slides were then stained in 1% (v / v) Eosin solution for 2 minutes, flowed by a brief wash in 95% (v / v) Ethanol prior to dehydration (graded Ethanol concentrations), clearing (Histoclear II), and coverslipping in Omnimount (National Diagnostics, US) for 2 minutes.Patent Application Attorney Docket No. 008634.01587VWOTable 16

[0346] Methodology: Masson Trichrome staining. Prior to dewaxing and rehydration, all tissue sections were baked onto the glass slides by placing the unstained slides into a dehydration oven at 65 degrees Celsius for 30 minutes. Straight after baking, the slides were dewaxed and rehydrated through the wash stages described in Table 17 (all steps were carried out at room temperature). Slides were then stained using a trichrome stain kit (Abeam, UK) following the manufacturer’s specific protocol. Briefly, Bouin’s fluid was preheated in a water bath to 56-64°C in a fume hood. Once heated, slides were incubated in the Bouin’s fluid for 60 minutes, followed by a 10-minute cooling period. When cooled, the slides were washed in tap water until the tissue sections were clear of the yellow mordant from the Bouin’s fluid. Slides were then rinsed with deionized water before staining in the working stock of Weigert’ s Iron Hematoxylin for 5 minutes, followed by a 2 minute wash in running tap water. Biebrich Scarlet / Acid Fuchsin Solution was then applied to the slides for 15 minutes, followed by a 2-minute wash in deionized water. The stains are then differentiated in Phosphomolybdic / Phosphotungstic Acid Solution for 10-15 minutes or until the collagen is no longer red. Aniline Blue solution was directly applied (without rinsing) to the slides and allow to stain for 5-10 minutes. Finally, the slides were washed in deionized water, followed by Acetic Acid Solution (1% v / v) for 3-5 minutes, thenPatent Application Attorney Docket No. 008634.01587VWO dehydrated (through graded Ethanol), clear (Histoclear II), and the stained tissue sections were coverslipped in Omnimount (National Diagnostics, US) for 2 minutes.Table 17

[0347] Methodology: Microscopy and Image analysis. All microscopy was carried out using the brightfield capabilities of a Nikon Eclipse NiU upright microscope, with all images being captured using a cooled CCD camera (Euromex). Images were either captured as multiple fields of view stitched together to produce X / Y scans or taken as single fields of view. Image analysis was conducted to either take measurements of wound morphology, or to determine the integrated density of dermal collagen, and was carried out using ImageJ software (NIH). All image analysis was carried out on the raw microscopy images, and all measurements and scale bars were standardized to a calibrated graticule measurement.EXAMPLE 10

[0348] This experiment demonstrates the improvements in wound healing observed following a 5 second treatment using an embodiment of the apparatus and method described herein. FIGS. 75A-F are example micrographs of X / Y scans (lOOx total magnification) of the wounded area of the ex vivo human skin tissue sections following H&E staining. The example micrographs were taken from tissues 7 days post treatment (D7) with two examples from each treatment group: untreated controls (A and B), 5 second salinePatent Application Attorney Docket No. 008634.01587VWO treated (C and D), and 5 second apparatus treated (E and F). The scale bars on all images represent 200 pm.

[0349] The H&E stained tissues sections in FIGS. 75A-B show two examples of the negative control tissues that were cultured for 7-days following no treatment (baseline healing). These example images demonstrate both the initial reepithelialisation, shown by the migrating epithelial tongue, and in both sets of images, the remodeling of the dermal matrix has also begun, but the extent at which the dermal matrix has matured is variable between repeat samples as shown by differences in dermal matrix coverage and density (under the wound bed) in FIGS. 75A-B.

[0350] The example H&E sections in FIGS. 75C-D show skin tissues harvested at 7 days following treatment of a 5 second saline treated (0.9% NaCl) wash at 1.5 litres per minute. The healing observed in this set of tissues was again variable, some of the tissues showed complete reepithelialisation across the wound as shown in in FIG. 75C, whereas in both examples, the dermal matrix remodeling was very poor compared to the negative controls and those treated with an embodiment of the apparatus and method described herein.

[0351] The example H&E stained skin sections in FIGS. 75E-F show two examples of tissues 7 days following a 5 second apparatus treatment (at 1.5 litres per minute) with an embodiment of the apparatus and method described herein. In all samples, complete reepithelialisation had occurred and consistent dermal matrix remodeling can be seen. No damage, for example, breakdown of the epidermal or dermal tissue, thinning of the epidermis, and / or removal of the stratus corneum were observed 7 days following treatment with an embodiment of the apparatus and method described herein.EXAMPLE 11

[0352] This experiment demonstrates both the safety and efficacy to stimulate healing in human skin, summarized with the example H&E stained skin sections and associated image analysis in FIGS. 76A-K and 77A-B, using an embodiment of the apparatus and method described herein. Tissues were harvested on Day-0 (DO) immediately after treatment to study the effects of treatment on the integrity and morphology of the skin tissue. Tissues were also harvested on Day-3 (D3) and Day-5 (D5) post treatment toPatent Application Attorney Docket No. 008634.01587VWO determine the healing response and trajectory following treatment with either a saline wash or with an embodiment of the apparatus and method described herein.

[0353] FIGS. 76A-K are example micrographs of X / Y scans (lOOx total magnification) of the wounded area of the ex vivo human skin tissue sections following H&E staining. The images were from tissues harvested immediately after treatment (DO), 3 days post treatment (D3), and 5 days post treatment (D5). The example micrographs were taken from untreated controls (A, B, C, and D), 5 second saline treated (E, F, and G), and 5 second apparatus (LAWS) treated (H, I, J, and K). To note, no samples were harvested at DO following saline treatment. The scale bars on all images represent 200 pm. FIGS. 77A-B are graphs showing image analysis measurements comparing wound width (from the inner edge of the epithelial tongue of each wound side) and wound depth (from the position of the epithelial layer to the leading point of complete extracellular matrix) at DO, D3, and D5 from each treatment group: untreated control, 5 second saline treated, and 5 second apparatus treated tissues. To note, no samples were harvested at DO following saline treatment, hence no bar is present for this timepoint and treatment. The error bars represent the Standard Error of the Mean (SEM, n = 3-5 measurements).

[0354] From the example, skin sections taken at DO for the negative untreated control (FIG. 76A) and the skin treated with an embodiment of the apparatus and method described herein (FIG. 76H), no damage to the thickness of the epidermal tissue, no removal of the stratus corneum, and no breakdown of the dermal matrix can be observed. The integrity of the skin following treatment with an embodiment of the apparatus and method described herein is no different than skin that has had no treatment. The untreated control skin samples harvested at D3 and D5 (FIGS. 76B-D) showed a small migrating epithelial tongue and minimal dermal matrix remodeling at D3 post treatment, whereas a small increase in the distance of the migrating epithelial tongue occurred between D3 and D5 post treatment. Minimal difference in the remodeling of the dermal matrix was observed between D3 and D5 in the untreated control samples.

[0355] In all examples of the saline wash (1.5 litres per minute) treated skin tissues taken at D3 and D5 post treatment (FIGS. 76E-G), only a small amount of reepithelialisation was observed, with a subtle increase between D3 and D5 post treatment. The dermal matrix was shown to increase in maturity at D5 post treatment but not to the extent thatPatent Application Attorney Docket No. 008634.01587VWO is observed following a 5 second treatment with an embodiment of the apparatus and method described herein.

[0356] For the skin tissues treated with an embodiment of the apparatus and method described herein (LAWS) at D3 post treatment (FIG. 761), the extent of reepithelialisation is similar to that observed in the untreated controls and the saline wash treated tissues. However, the density of the dermal matrix at the same time point was observed to be denser and already filling the space below the wound bed. The biggest difference was observed at D5 post treatment of the apparatus treated skin tissues (FIGS. 76J-K), where almost complete or complete reepithelialisation was observed in all tissues. More apparent was the remodeling of the dermal matrix, where complete remodeling was observed following treatment with an embodiment of the apparatus and method described herein, which was not observed to the same extent in the untreated or saline wash treated skin tissues.

[0357] The image analysis measurements shown in FIGS. 77A-B confirm the observations of the skin sections in FIGS. 76A-K, with a clear reduction in both the wound width (measured between the inner edges of the migrating epithelial tongues) and depth (measured between the position of epithelial growth and the top-most point of the remodeling dermis) at D5 post treatment.EXAMPLE 12

[0358] This experiment investigates if there was any therapeutic effect following shorter (below 5 seconds) treatments of skin tissue with an embodiment of the apparatus and method described herein. FIGS. 78A-F are example micrographs of X / Y scans (lOOx total magnification) of the wounded area of the ex vivo human skin tissue sections following H&E staining. The images were from tissues harvested 5 days post treatment (D5) from the following treatment groups: untreated controls (A and D), 1 second apparatus treated (B and E), and 3 second apparatus (LAWS) treated (C and F). The scale bars on all images represent 100 pm. The representative H&E stained skin sections in FIGS. 78A-F show two examples from each treatment group harvested at D5. Both the untreated skin samples (FIGS. 78 A and D) and the samples treated for 1 second with an embodiment of the apparatus and method described herein (FIGS. 78B and E) showed similar healing trajectories, with varying extents of reepithelialisation and dermal matrix remodeling between repeat samples. The extent of reepithelialisationPatent Application Attorney Docket No. 008634.01587VWO and dermal remodeling in the apparatus treated samples treated for 1 second were slightly improved compared to the untreated controls, but still variable between repeat samples. The skin tissues treated for 3 seconds with an embodiment of the apparatus and method described herein (FIGS. 78C and F) all showed complete reepithelialisation across the wound, and were in the process of dermal matrix remodeling, but not to the extent of the dermal matrix remodeling observed in tissues treated for 5 seconds with an embodiment of the apparatus and method described herein (FIGS. 76J-K). As demonstrated previously, no damage, for example, breakdown of the epidermal or dermal tissue, thinning of the epidermis, removal of the stratus corneum, were observed following treatment with an embodiment of the apparatus and method described herein.EXAMPLE 13

[0359] This experiment was conducted to study dermal matrix remodeling and to measure the density of the dermal collagen formation within skin samples treated with an embodiment of the apparatus and method described herein. FIGS. 79A-F are example micrographs of X / Y scans (lOOx total magnification) of the wounded area of the ex vivo human skin tissue sections following Masson-Trichrome staining. The images were from tissues harvested 3 days post treatment (D3), and 5 days post treatment (D5). The example micrographs were taken from untreated controls (A and D), 5 second saline treated (B and E), and 5 second apparatus (LAWS) treated (C and F). The scale bars on all images represent 200 pm. FIG. 80 is a graph showing image analysis quantification of the density (integrated density) of Masson-Trichrome stained dermal collagen in the sections of human skin harvested 3 days post treatment (D3), and 5 days post treatment (D5) from untreated controls, 5 second saline treated, and 5 second apparatus treated samples. To note, no samples were harvested at DO following saline treatment, hence no bar is present for this timepoint and treatment. The units of integrated density are arbitrary units (AU.), and the error bars represent Standard Error of the Mean (SEM, n = 3-5 sections).

[0360] The Masson-Trichrome stained sections taken from untreated skin samples at D3 and D5 showed minimal difference in collagen density (blue staining) in the dermal matrix (FIGS. 79A and D). The image analysis (FIG. 80) quantified no difference in collagen density from D0-D3, and a slight increase at D5 in the untreated control samples.Patent Application Attorney Docket No. 008634.01587VWO

[0361] The 5 second saline treated samples (FIGS. 79B and E) showed similar density of collagen in the dermal matrix at D3 and D5 post treatment, with an increase in dermal matrix remodeling directly under the wound bed and the advancing epithelial tongue at D5 compared to D3. The similar collagen density at these two timepoints following a saline wash treatment was confirmed with the image analysis results of FIG. 80.

[0362] The collagen density in the apparatus (LAWS) treated skin samples treated for 5 seconds with an embodiment of the apparatus and method described herein (FIGS. 79C and F) also showed a similar density of collagen in the dermal matrix at D3 and D5 post treatment; however, an increase in dermal matrix remodeling directly under the completely epithelialized wound was observed at D5 post treatment. The collagen density in the dermal matrix following treatment with an embodiment of the apparatus and method described herein was observed to be denser than that of the untreated or saline wash treated control samples at a given timepoint, which was confirmed with the image analysis data in FIG. 80.EXAMPLE 14

[0363] This experiment was used to demonstrate the superior microbial cleaning efficacy of a saline wash using an embodiment of the apparatus and method described herein, compared to a standard saline wash at the same flow rates, against an MRSA infection (24-hour culture) of living, and wounded human skin explants. FIG. 81 is an example micrograph of an X / Y scan (600x total magnification) of the whole wound bed of an MRSA infected ex vivo human skin section following a 5 second saline treatment. The inlays (FIGS. 81A-D) are lOOOx total magnification micrographs, to assist in visualizing the residual MRSA (Dark purple cocci cells) present within different morphological regions across the wound bed. The scale bar represents 200 pm. FIG. 82 is an example micrograph of an X / Y scan (600x total magnification) of the whole wound bed of an MRSA infected ex vivo human skin section following a 5 second apparatus treatment. The inlays (FIGS. 82A-D) are lOOOx total magnification micrographs to assist in visualizing the residual MRSA (Dark purple cocci cells) present within different morphological regions across the wound bed. The scale bar represents 200 pm.

[0364] Following a 5 second saline wash, the gross microbial contamination (as observed macroscopically) was removed from the skin. However, when magnified to 600xPatent Application Attorney Docket No. 008634.01587VWO magnification (and lOOOx magnification in the inlays FIGS. 81A-D), it is clear that there is still MRSA contamination, as demonstrated by the dark purple Hematoxylin stained cocci of the MRSA cells, especially within the wounded area of the skin samples. The MRSA cells continue to reside at the surface of the wound bed (inlay FIG. 81 A) but also penetrate deeper (>200 pm) into the dermis and between the collagen fibrils as demonstrated in inlays FIGS. 81B-C. MRSA bacterial cells were also observed deep into the crevices of the skin tissue around the undermining region of the advancing epithelial tongue as observed in inlay FIG. 8 ID.

[0365] Following a 5 second treatment with an embodiment of the apparatus and method described herein (LAWS) it is clear from both the 600x magnified (FIG. 82), and 1000 times magnified inlays FIGS. 82A-D, that there is minimal MRSA contamination remaining across the wounded skin. When studying similar morphological locations, as was observed in the saline washed samples, it is clear to see that the MRSA contamination has been removed from the undermining edge of the advancing epithelial tongue (inlay FIG. 82A) and from deep within the collagen of the dermal matrix (inlays FIGS. 82B-D). Following a 5 second treatment with an embodiment of the apparatus and method described herein, only a small number of singular MRSA cells remained, even in areas that were not reached or cleaned when treating the skin with a saline wash alone.

[0366] The apparatus and method described herein produces numerous technical advantages over existing cleaning technologies, in particular, over ultrasound baths in which the target is immersed in the cleaning liquid. One such advantage is that the liquid stream can be directed to a particular location as desired, and can be directed onto an object of any size, where a cleaning bath can only be used to clean within the bath itself, which is unable to accept any object larger than the dimensions of the bath. This is enabled by the ability of the apparatus to propagate resonant bubbles and acoustic energy sufficient for energizing those resonant bubbles down a stream to a distant target. Another such advantage is that the liquid is not retained for a subsequent cleaning, reducing the risk of cross-contamination. A further advantage is the potential for the apparatus to be portable. Yet another advantage is the capability of the apparatus to be used along with other similar apparatuses in a large-scale cleaning system.Patent Application Attorney Docket No. 008634.01587VWO

[0367] Preclinical data suggests the apparatus 2 can halve healing times for a single treatment, whilst fitting into the standard-of-care by replacing current cleaning stages, compared to a wound that is already on a healing trajectory. Furthermore, if the wound is chronic, and stalled in the inflammatory phase, the treatment can reactivate the healing process and cause a non-healing wound that would persist for months or years, into healing wound. Furthermore, by reducing the number of repeat treatments (typically 2 or 3 per week for a VLU), it is hoped that the number of clinic bookings and amount of staff time consumed in the treatment program of a patient, will be reduced. This is one of the most significant drains on medical treatment organizations in terms of wound treatment. In this way, individual treatments are of comparable length to the current standard-of- care, but the number of treatments, week-in and week-out, to heal the wound is greatly reduced, saving over the lifetime of the wound in staff and clinic time, consumable usage and patient suffering. In addition, any reduction in the use of anti-microbial agents (antibiotics, anti-fungals, anti-virals, and anti-parasite treatments) reduces the contribution to the environmental load (e.g. in the waste run-off) and so reduces a driver to anti-microbial resistance, whilst providing a tool for good anti-microbial stewardship.

[0368] The apparatus and method described herein may be used for a variety of purposes described herein, in particular the treatment of chronic wounds such as venous leg ulcers and diabetic foot ulcers. It is also applicable to burns, pressures ulcers, surgical site infections, and acute wounds such as produced by trauma, accident and battlefield injuries. The treatment also removes biofilms from spaces during surgery or physical interventions (such as the abdominal cavity or genital-urinary tract), and from the oral cavity where the saline may readily be replaced by potable water (from a bagged source, tank, or mains etc.). Further, the apparatus 2 of FIGS. 1-17 fits within the current standard of care for chronic wounds. FIG. 63 illustrates an example of a typical process of caring for wounds, which might typically last around 30 minutes and almost always incorporates a saline rinse. This might be for an initial cleansing or following some procedures such as debridement. FIG. 64 illustrates an embodiment of a process of caring for wounds using the apparatus 2 to replace this saline rinse in order to cleanse more effectively and to add the second mode of operation, which is to simulate regeneration within the wound. The process illustrated in FIG. 64 might also typically last around 30 minutes, but would provide improved cleaning and additional benefitsPatent Application Attorney Docket No. 008634.01587VWO as described herein (e.g., stimulating regeneration) within a similar time frame. Fitting within the current standard of care means that the treatment is far more easily accepted by the clinician and the clinic administrators, since it requires less training than a novel specialized procedure, and requires no change to the booking times of the clinic or the expectations of the patient. Other non-wound treatment uses are envisioned, including cleaning other organic matter, or other cleaning and / or treatment applications. Still other benefits and advantages are disclosed herein and / or readily recognized by those skilled in the art.

[0369] For example, the apparatus and methods disclosed herein may be used in a production process, including cleaning containers, tools, surfaces, etc., associated with the production process, as well as cleaning the product itself. This is particularly important in batch production, since batch contamination is a large production hurdle in such industries, sometimes resulting in a whole batch being destroyed. Specific applications include those associated with cleaning of tools, surfaces, containers and (if relevant) product, in the production of products by fermentation, cultured cells or cultured produce, in food and beverage production and brewing, and in the cleaning of fresh produce. Other applications include cleaning in industries where filling requires cleanliness and the removal of old or spilled product and reducing the potential for contamination (e.g., in the filling of food, beverage, and personal hygiene containers prior to retail). This includes processes where the filling occurs with the product as a liquid which then solidifies (e.g. margarine, ice cream, deodorant, soap, pharmaceuticals, etc.). Other applications where the cleaning of equipment, tools and surfaces is a critical and expensive stage in the production process, include instances where contamination or cross-contamination can be expensive and dangerous (e.g., in the production of pharmaceuticals and food / beverages), particularly if materials can degrade over time and become more hazardous (e.g. abattoirs, hospitals, and morgues) or less useful.

[0370] The apparatus and methods disclosed herein may be usable in any applications disclosed herein, including in the stream (i.e. non-immersion) applications such as testing of run-off and the clean-in-place utility. Such applications of use need not be restricted to specific embodiments described...

Claims

Patent Application Attorney Docket No. 008634.01587VWOCLAIMSWhat is claimed is:

1. An apparatus comprising: a combined unit comprising: a body defining a chamber configured to contain a liquid and having a nozzle located at a front end of the body and configured to discharge a stream of the liquid from the chamber toward a surface; and a manifold located at a rear of the body, wherein the manifold is configured for connection to a liquid supply conduit to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber, wherein the body and the manifold are integrally formed together as a single piece; and a base unit releasably connected to the combined unit, comprising: an acoustic transducer positioned and configured to generate acoustic energy and to introduce the acoustic energy into the liquid contained in the chamber; and a casing containing the acoustic transducer and having a mounting piece engaged with the combined unit to releasably connect the combined unit to the base unit.

2. The apparatus of claim 1, wherein the base unit further comprises: a rear wall connected to the casing and positioned at the rear of the body to at least partially define the chamber when the combined unit is connected to the base unit, wherein the acoustic transducer is positioned behind the rear wall and configured to transmit the acoustic energy through the rear wall into the chamber.

3. The apparatus of claim 1 or claim 2, wherein the mounting piece comprises a tab releasably engaging the combined unit to releasably connect the combined unit to the base unit.

4. The apparatus of claim 3, wherein the combined unit has a slot, and the tab is received in the slot to releasably connect the combined unit to the base unit.

5. The apparatus of claim 3, wherein the combined unit has a flange, and the tab has a front surface engaged with a rear surface of the flange to releasably connect the combined unit to the base unit.Patent Application Attorney Docket No. 008634.01587VWO6. The apparatus of any preceding claim, wherein the combined unit is molded as the single piece including the body and the manifold.

7. The apparatus of any preceding claim, wherein the manifold has a manifold inlet configured for connection to the liquid supply conduit, and an internal conduit in fluid communication with the liquid supply conduit and the plurality of ports and configured to permit the inlet stream to flow from the manifold inlet to the plurality of ports.

8. The apparatus of claim 7, wherein the internal conduit of the manifold is open on a rear side of the manifold, and the base unit engages the rear side of the manifold to define the internal conduit when the combined unit is engaged with the base unit.

9. The apparatus of claim 7 or claim 8, wherein the manifold has an inner annular surface having an annular shape and positioned to be in communication with the chamber, with the ports extending through the inner annular surface, and the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface.

10. The apparatus of any of claims 7-9, wherein the manifold further comprises a vent at a top of the manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.

11. The apparatus of any of claims 1-2 and 6-10, wherein the combined unit further comprises a connecting structure configured to engage the mounting piece on the base unit to releasably connect the combined unit to the base unit, and the connecting structure is integrally formed as part of the single piece with the body and the manifold.

12. A system comprising the apparatus of any preceding claim, the liquid supply conduit connected to the manifold, a liquid supply connected to the liquid supply conduit, and a pump configured to pump the liquid from the liquid supply through the liquid supply conduit and to the manifold.

13. A treatment unit configured for releasable connection to a base unit of an apparatus for treating a surface with a stream of a liquid, the treatment unit comprising: a body having a base at a rear of the body, a cone extending forward from the base and defining a chamber configured to contain the liquid when connected to the base unit, and a nozzle located at a front end of the cone and configured to discharge the stream of the liquid from the chamber toward the surface;Patent Application Attorney Docket No. 008634.01587VWO a manifold comprising a manifold body connected to the base of the body, a manifold inlet configured for connection to a liquid supply conduit to receive an inlet stream of the liquid, a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber, and an internal conduit in fluid communication with the liquid supply conduit and the plurality of ports and extending through the manifold body to permit the inlet stream to flow from the manifold inlet to the plurality of ports; and a connecting structure configured to engage a complementary connecting structure on the base unit to releasably connect the treatment unit to the base unit, wherein the body, the manifold, and the connecting structure are integrally formed together as a single piece.

14. The treatment unit of claim 13, wherein the connecting structure comprises a slot configured to receive a tab on the base unit to releasably connect the treatment unit to the base unit.

15. The treatment unit of claim 13, wherein the connecting structure comprises a flange having a rear surface configured to engage a tab on the base unit to releasably connect the treatment unit to the base unit.

16. The treatment unit of any of claims 13-15, wherein the treatment unit is molded as the single piece including the body, the manifold, and the connecting structure.

17. The treatment unit of any of claims 13-16, wherein the internal conduit of the manifold is open on a rear side of the manifold, and the rear side of the manifold is configured to engage the base unit to define the internal conduit when the treatment unit is engaged with the base unit.

18. The treatment unit of any of claims 13-17, wherein the manifold body has an annular configuration with an inner annular surface positioned to be in communication with the chamber, with the ports extending through the inner annular surface.

19. The treatment unit of claim 18, wherein the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface.

20. The treatment unit of any of claims 13-19, wherein the manifold further comprises a vent at a top of the manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.Patent Application Attorney Docket No. 008634.01587VWO21. A system comprising the treatment unit of any of claims 13-20, the base unit connected to the treatment unit, the liquid supply conduit connected to the manifold inlet, a liquid supply connected to the liquid supply conduit, and a pump configured to pump the liquid from the liquid supply through the liquid supply conduit and to the manifold.

22. An apparatus comprising: a handset configured for user manipulation by hand, comprising: an acoustic transducer configured to generate acoustic energy; a user input device in electronic communication with the acoustic transducer and configured to receive user input to control the acoustic transducer; and a casing containing the acoustic transducer and supporting the user input device, wherein the casing has a handle configured for gripping by the user; a body releasably connected to the handset at a rear of the body and defining a chamber configured to contain a liquid, the body having a nozzle located at a front end of the body and configured to discharge a stream of the liquid from the chamber toward a surface, wherein the acoustic transducer is positioned to introduce the acoustic energy into the liquid contained in the chamber when the body is connected to the handset; and a manifold located at a rear of the body and releasably connected to the handset, wherein the manifold has a manifold inlet configured for connection to a liquid supply conduit to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber and an internal conduit extending from the manifold inlet to the plurality of ports to place the ports in fluid communication with the manifold inlet.

23. The apparatus of claim 22, wherein the handset further comprises: a rear wall connected to the casing and positioned at the rear of the body to at least partially define the chamber when the body is connected to the handset, wherein the acoustic transducer is positioned behind the rear wall and configured to transmit the acoustic energy through the rear wall into the chamber.

24. The apparatus of claim 22 or claim 23, wherein the casing has a tab releasably engaging the manifold to releasably connect the manifold to the handset.

25. The apparatus of claim 24, wherein the manifold has a slot, and the tab is received in the slot to releasably connect the manifold to the handset.Patent Application Attorney Docket No. 008634.01587VWO26. The apparatus of claim 24, wherein the manifold has a flange, and the tab has a front surface engaged with a rear surface of the flange to releasably connect the manifold to the handset.

27. The apparatus of any of claims 22-26, wherein the body and the manifold are connected together by being formed of a single, integral piece including the body and the manifold, such that the body is connected to the handset by connecting the manifold to the handset, thereby connecting the single, integral piece to the handset.

28. The apparatus of claim 27, wherein the manifold further comprises a connecting structure configured to engage the handset to releasably connect the manifold to the handset, and the connecting structure is integrally formed as part of the single, integral piece with the body and the manifold.

29. The apparatus of any of claims 22-28, wherein the internal conduit of the manifold is open on a rear side of the manifold, and the handset engages the rear side of the manifold to define the internal conduit when the manifold is engaged with the handset.

30. The apparatus of any of claims 22-29, wherein the manifold has an inner annular surface having an annular shape and positioned to be in communication with the chamber, with the ports extending through the inner annular surface, and the internal conduit extends in diverging directions away from the manifold inlet and forms an annular or semi-annular shape that extends around at least a majority of the inner annular surface.

31. The apparatus of any of claims 22-30, wherein the manifold further comprises a vent at a top of the manifold and in communication with the internal conduit, to permit ejection of bubbles from the internal conduit.

32. The apparatus of any of claims 22-31, wherein the user input device is further configured for controlling flow of the liquid into the manifold and out through the nozzle to discharge the stream.

33. A system comprising the apparatus of any of claims 22-32, the liquid supply conduit connected to the manifold, a liquid supply connected to the liquid supply conduit, and a pump configured to pump the liquid from the liquid supply through the liquid supply conduit and to the manifold.

34. A method for treatment of a surface, comprising:Patent Application Attorney Docket No. 008634.01587VWO providing an apparatus comprising a base unit having an acoustic transducer configured to generate acoustic energy and a casing containing the acoustic transducer, and a first treatment unit releasably connected to the base unit and comprising a first body defining a first chamber configured to contain a liquid and having a first nozzle located at a front end of the first body and a first manifold integrally formed with the first body and connected to a liquid supply conduit in fluid communication with a liquid supply, the first manifold having a plurality of first ports in communication with the first chamber; operating the apparatus to discharge a first stream of liquid through the first nozzle to the surface, such that the liquid flows from the liquid supply through the liquid supply conduit and to the first manifold, and then flows through the first ports into the first chamber and out through the first nozzle, further comprising activating the acoustic transducer to direct the acoustic energy into the first chamber and down the first stream to the surface; removing the first treatment unit from the base unit and connecting a second treatment unit to the base unit in place of the first treatment unit; and operating the apparatus to discharge a second stream of liquid through a second nozzle of the second treatment unit to the surface, further comprising activating the acoustic transducer to direct the acoustic energy into a second chamber of the second treatment unit and down the second stream to the surface.

35. The method of claim 34, wherein the base unit comprises a tab selectively and releasably engaging the first treatment unit or the second treatment unit to releasably connect the first treatment unit or the second treatment unit to the base unit, and wherein removing the first treatment unit and connecting the second treatment unit includes rotating the first treatment unit and the second treatment unit with respect to the base unit.

36. The method of claim 34 or claim 35, wherein the second treatment unit is connected to a second liquid supply conduit, and the method further comprises removing the liquid supply conduit along with the first treatment unit.

37. The method of claim 36, wherein the second liquid supply conduit is connected to a second liquid supply, and the method further comprises removing the liquid supply along with the first treatment unit and the liquid supply conduit.

38. The method of claim 36 or claim 37, wherein operating the apparatus includes activating a pump connected to the liquid supply conduit to force the liquid through the liquid supply conduit into the first manifold and out through the first nozzle to discharge the firstPatent Application Attorney Docket No. 008634.01587VWO stream, and the method further comprises disconnecting the liquid supply conduit from the pump along with removing the first treatment unit and connecting the second liquid supply conduit to the pump along with connecting the second treatment unit to the base unit.

39. The method of any of claims 34-38, further comprising removing the liquid supply conduit from the first treatment unit and connecting the liquid supply conduit to the second treatment unit.

40. The method of any of claims 34-39, wherein the second treatment unit is identical to the first treatment unit.

41. The method of any of claims 34-40, further comprising adding an additive to the liquid supply before operating the apparatus to generate the first stream.

42. The method of any of claims 34-41, wherein operating the apparatus includes providing user input to a user input device in electronic communication with the acoustic transducer and a pump connected to the liquid supply conduit to control the acoustic transducer and to activate the pump to force the liquid through the liquid supply conduit into the first manifold and out through the first nozzle to discharge the first stream.

43. The method of claim 42, wherein the base unit comprises a handset having a handle for gripping by a user to direct the apparatus at the surface, and the user input device comprises a button on the handle of the handset.

44. The method of any of claims 34-43, further comprising priming the apparatus prior to operating the apparatus to discharge the first stream to the surface, comprising operating the apparatus while the first nozzle is pointed upward to cause the liquid to discharge upward through the first nozzle.

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