NZ760615B2 - Cleaning, healing and regeneration of tissue and wounds - Google Patents
Cleaning, healing and regeneration of tissue and wounds Download PDFInfo
- Publication number
- NZ760615B2 NZ760615B2 NZ760615A NZ76061518A NZ760615B2 NZ 760615 B2 NZ760615 B2 NZ 760615B2 NZ 760615 A NZ760615 A NZ 760615A NZ 76061518 A NZ76061518 A NZ 76061518A NZ 760615 B2 NZ760615 B2 NZ 760615B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- liquid
- bubbles
- chamber
- acoustic
- output stream
- Prior art date
Links
- 210000001519 tissues Anatomy 0.000 title claims abstract description 108
- 238000004140 cleaning Methods 0.000 title claims description 99
- 230000035876 healing Effects 0.000 title claims description 62
- 230000008929 regeneration Effects 0.000 title claims description 7
- 238000011069 regeneration method Methods 0.000 title claims description 7
- 200000000019 wound Diseases 0.000 title description 102
- 239000007788 liquid Substances 0.000 claims abstract description 299
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 71
- 239000011780 sodium chloride Substances 0.000 claims description 71
- 239000000463 material Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 15
- 230000005284 excitation Effects 0.000 claims description 6
- 238000007789 sealing Methods 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 4
- 229920002725 Thermoplastic elastomer Polymers 0.000 claims description 3
- 229920003051 synthetic elastomer Polymers 0.000 claims description 3
- 239000005061 synthetic rubber Substances 0.000 claims description 3
- 230000003797 telogen phase Effects 0.000 claims 3
- 239000007789 gas Substances 0.000 description 122
- 230000017423 tissue regeneration Effects 0.000 description 36
- 230000000694 effects Effects 0.000 description 26
- 230000001965 increased Effects 0.000 description 19
- 230000000051 modifying Effects 0.000 description 19
- 239000012530 fluid Substances 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 238000011144 upstream manufacturing Methods 0.000 description 14
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 13
- 229940055023 Pseudomonas aeruginosa Drugs 0.000 description 13
- 238000002604 ultrasonography Methods 0.000 description 13
- 210000002950 fibroblast Anatomy 0.000 description 12
- 230000000638 stimulation Effects 0.000 description 12
- 230000003115 biocidal Effects 0.000 description 11
- 238000010191 image analysis Methods 0.000 description 11
- 238000011065 in-situ storage Methods 0.000 description 11
- 210000002510 Keratinocytes Anatomy 0.000 description 10
- 241000282898 Sus scrofa Species 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 210000000214 Mouth Anatomy 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000029663 wound healing Effects 0.000 description 9
- 230000002708 enhancing Effects 0.000 description 8
- 239000004094 surface-active agent Substances 0.000 description 8
- 210000003491 Skin Anatomy 0.000 description 7
- 230000005540 biological transmission Effects 0.000 description 7
- 239000000356 contaminant Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- WZUVPPKBWHMQCE-XJKSGUPXSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 6
- 208000005888 Periodontal Pocket Diseases 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 244000052616 bacterial pathogens Species 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000005868 electrolysis reaction Methods 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 230000001225 therapeutic Effects 0.000 description 6
- 239000011800 void material Substances 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 238000004581 coalescence Methods 0.000 description 5
- 238000011109 contamination Methods 0.000 description 5
- 201000009910 diseases by infectious agent Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002500 effect on skin Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000002055 immunohistochemical Effects 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000004936 stimulating Effects 0.000 description 5
- 231100000948 EpiDerm Skin Irritation Test Toxicity 0.000 description 4
- 206010022114 Injury Diseases 0.000 description 4
- 102000001776 Matrix Metalloproteinase 9 Human genes 0.000 description 4
- 108010015302 Matrix Metalloproteinase 9 Proteins 0.000 description 4
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 4
- WYTGDNHDOZPMIW-UHOFOFEASA-O Serpentine Natural products O=C(OC)C=1[C@@H]2[C@@H]([C@@H](C)OC=1)C[n+]1c(c3[nH]c4c(c3cc1)cccc4)C2 WYTGDNHDOZPMIW-UHOFOFEASA-O 0.000 description 4
- 230000001580 bacterial Effects 0.000 description 4
- 229940079593 drugs Drugs 0.000 description 4
- 229920000591 gum Polymers 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 230000001737 promoting Effects 0.000 description 4
- 230000002829 reduced Effects 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 102000018332 Keratin-14 Human genes 0.000 description 3
- 108010066321 Keratin-14 Proteins 0.000 description 3
- 210000003928 Nasal Cavity Anatomy 0.000 description 3
- 238000010162 Tukey test Methods 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 239000003139 biocide Substances 0.000 description 3
- 230000001419 dependent Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001317 epifluorescence microscopy Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000029774 keratinocyte migration Effects 0.000 description 3
- 230000002147 killing Effects 0.000 description 3
- 230000000813 microbial Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 210000000056 organs Anatomy 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229940064005 Antibiotic throat preparations Drugs 0.000 description 2
- 229940083879 Antibiotics FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE Drugs 0.000 description 2
- 229940042052 Antibiotics for systemic use Drugs 0.000 description 2
- 229940042786 Antitubercular Antibiotics Drugs 0.000 description 2
- 210000002615 Epidermis Anatomy 0.000 description 2
- 229940093922 Gynecological Antibiotics Drugs 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 108009000330 Matrix Metalloproteinases Proteins 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 229940024982 Topical Antifungal Antibiotics Drugs 0.000 description 2
- 230000000844 anti-bacterial Effects 0.000 description 2
- 230000000845 anti-microbial Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000003190 augmentative Effects 0.000 description 2
- 210000003969 blast cell Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000004027 cells Anatomy 0.000 description 2
- 230000001413 cellular Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 210000002249 digestive system Anatomy 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 239000001963 growth media Substances 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000000977 initiatory Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 229940079866 intestinal antibiotics Drugs 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 media Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229940005935 ophthalmologic Antibiotics Drugs 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000030439 positive regulation of keratinocyte migration Effects 0.000 description 2
- 230000001902 propagating Effects 0.000 description 2
- 230000001172 regenerating Effects 0.000 description 2
- 230000000717 retained Effects 0.000 description 2
- 230000003068 static Effects 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 210000002229 urogenital system Anatomy 0.000 description 2
- 206010000269 Abscess Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 210000000988 Bone and Bones Anatomy 0.000 description 1
- 210000001736 Capillaries Anatomy 0.000 description 1
- 210000004262 Dental Pulp Cavity Anatomy 0.000 description 1
- 210000004207 Dermis Anatomy 0.000 description 1
- 210000000613 Ear Canal Anatomy 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010043417 Therapeutic response unexpected Diseases 0.000 description 1
- 210000004746 Tooth Root Anatomy 0.000 description 1
- 206010068760 Ulcers Diseases 0.000 description 1
- 102000013127 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminum Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000006143 cell culture media Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000007374 clinical diagnostic method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000002153 concerted Effects 0.000 description 1
- 229920001940 conductive polymer Polymers 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000001079 digestive Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000003628 erosive Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000003116 impacting Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002458 infectious Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000004301 light adaptation Effects 0.000 description 1
- 230000000670 limiting Effects 0.000 description 1
- 238000011068 load Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000003287 optical Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000045947 parasites Species 0.000 description 1
- 230000000149 penetrating Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002035 prolonged Effects 0.000 description 1
- 230000001681 protective Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000007388 punch biopsy Methods 0.000 description 1
- 230000001105 regulatory Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000001340 slower Effects 0.000 description 1
- -1 sodium chloride Chemical class 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 230000036561 sun exposure Effects 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001131 transforming Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000004506 ultrasonic cleaning Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
- A61B2017/22005—Effects, e.g. on tissue
- A61B2017/22007—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C17/00—Devices for cleaning, polishing, rinsing or drying teeth, teeth cavities or prostheses; Saliva removers; Dental appliances for receiving spittle
- A61C17/02—Rinsing or air-blowing devices, e.g. using fluid jets or comprising liquid medication
- A61C17/024—Rinsing or air-blowing devices, e.g. using fluid jets or comprising liquid medication with constant liquid flow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C17/00—Devices for cleaning, polishing, rinsing or drying teeth, teeth cavities or prostheses; Saliva removers; Dental appliances for receiving spittle
- A61C17/16—Power-driven cleaning or polishing devices
- A61C17/20—Power-driven cleaning or polishing devices using ultrasonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D5/00—Instruments for treating animals' teeth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2209/00—Ancillary equipment
- A61M2209/04—Tools for specific apparatus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2250/00—Specially adapted for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B2203/00—Details of cleaning machines or methods involving the use or presence of liquid or steam
- B08B2203/007—Heating the liquid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B3/00—Cleaning by methods involving the use or presence of liquid or steam
- B08B3/04—Cleaning involving contact with liquid
- B08B3/10—Cleaning involving contact with liquid with additional treatment of the liquid or of the object being cleaned, e.g. by heat, by electricity or by vibration
- B08B3/12—Cleaning involving contact with liquid with additional treatment of the liquid or of the object being cleaned, e.g. by heat, by electricity or by vibration by sonic or ultrasonic vibrations
Abstract
apparatus for treating human or animal tissue, the apparatus comprising a conical body defining a chamber, the conical body extending between a base of the conical body and an outlet nozzle of the conical body, wherein the base has an inlet for liquid flow into the chamber and the outlet nozzle is at a conical tip of the conical body and is configured to generate an output stream of liquid flow from the chamber for treating human or animal tissue, an acoustic transducer associated with the conical body and configured to introduce acoustic energy into the liquid within the chamber whereby the acoustic energy is present in the output stream, and a gas bubble generator configured for providing gas bubbles in the output stream that are configured to be excited by the acoustic energy, wherein the conical body and the nozzle thereof are configured to have pressure amplitude reflection coefficients with respect to the acoustic energy in liquid within the chamber of from -0.95 to -1.0, a liquid supply system adapted to supply a liquid flow through the inlet at a flow rate of from 0.1 to 7 litres/minute, the outlet nozzle is configured to generate an output stream of liquid flow having an average width of from 0.25 to 20 mm, the acoustic transducer is configured to generate acoustic energy having a frequency of from 0.1 to 5 MHz and the gas bubble generator is configured to provide in the output stream bubbles having a radius of from 0.5 to 40 µm, wherein at least one of the acoustic transducer and the gas bubble generator is configured to be controlled such that the frequency of the acoustic energy generated by the acoustic transducer is sufficient to produce non-inertial cavitation on bubble walls of the gas bubbles generated by the gas bubble generator. The invention is directed at minimizing energy usage. s at a conical tip of the conical body and is configured to generate an output stream of liquid flow from the chamber for treating human or animal tissue, an acoustic transducer associated with the conical body and configured to introduce acoustic energy into the liquid within the chamber whereby the acoustic energy is present in the output stream, and a gas bubble generator configured for providing gas bubbles in the output stream that are configured to be excited by the acoustic energy, wherein the conical body and the nozzle thereof are configured to have pressure amplitude reflection coefficients with respect to the acoustic energy in liquid within the chamber of from -0.95 to -1.0, a liquid supply system adapted to supply a liquid flow through the inlet at a flow rate of from 0.1 to 7 litres/minute, the outlet nozzle is configured to generate an output stream of liquid flow having an average width of from 0.25 to 20 mm, the acoustic transducer is configured to generate acoustic energy having a frequency of from 0.1 to 5 MHz and the gas bubble generator is configured to provide in the output stream bubbles having a radius of from 0.5 to 40 µm, wherein at least one of the acoustic transducer and the gas bubble generator is configured to be controlled such that the frequency of the acoustic energy generated by the acoustic transducer is sufficient to produce non-inertial cavitation on bubble walls of the gas bubbles generated by the gas bubble generator. The invention is directed at minimizing energy usage.
Description
a radius of from 0.5 to 40 µm, wherein at least one of the acousc transducer and the gas bubble
generator is configured to be controlled such that the frequency of the acousc energy generated
by the acousc transducer is sufficient to produce non-ineral cavitaon on bubble walls of the
gas bubbles generated by the gas bubble generator. The invenon is directed at minimizing energy
usage.
CLEANING, HEALING AND REGENERATION
OF TISSUE AND WOUNDS
The present invention relates to an apparatus for, and a method of, for treating
human or animal tissue. The present invention also relates to a method of generating a
liquid stream for treating a surface. The present invention further relates to a method of
treating a wound or anatomical pocket or anatomical space or potential space in human or
animal tissue, soft or hard tissue in the oral cavity, or tissue in the nasal cavity, for example
for healing wounds and regenerating healthy tissue in a wound.
It is known from WO-A-2011/023746 to provide a cleaning method and apparatus
in which cleaning of a surface is achieved by the employment of bubble action on a surface,
or within a crevice within a surface, driven by acoustic stimulation. The method provides
gas bubbles at the surface and employs modulated acoustic energy to generate surface
waves in the bubbles to cause non-inertial cavitation of the bubbles. Such a bubble action
enhances cleaning of the surface. A stream of liquid containing gas bubbles excited by
acoustic energy is directed at the surface to be cleaned.
WO-A-20161180978 discloses a modified cleaning method and apparatus in which
cleaning of a surface is also achieved by the employment of bubble action on a surface
driven by acoustic stimulation, but rather than using a stream of liquid, a body of liquid is
retained against the surface to be cleaned, and acoustically excited gas bubbles in the body
of liquid are directed against the surface to be cleaned.
Although WO-A-201 1/023746 and WO-A-2016/180978 disclose that a wide range
of surfaces may be cleaned by acoustically excited gas bubbles, there is still a need for
further applications employing bubble action driven by acoustic stimulation to treat a
surface, or a crevice within a surface.
The present invention aims at least partially to provide this need.
The present invention provides an apparatus for treating human or animal tissue,
the apparatus comprising a conical body defining a chamber, the conical body extending
between a base of the conical body and an outlet nozzle of the conical body, wherein the
base has an inlet for liquid flow into the chamber and the outlet nozzle is at a conical tip
of the conical body and is configured to generate an output stream of liquid flow from the
chamber for treating human or animal tissue, an acoustic transducer associated with the
conical body to introduce acoustic energy into the liquid within the chamber whereby the
acoustic energy is present in the output stream, and a gas bubble generator for providing
gas bubbles in the output stream, the gas bubbles in the output stream being excited by the
acoustic energy, wherein the conical body and the nozzle thereof have a pressure amplitude
reflection coefficient with respect to the acoustic energy in water within the chamber of
from -0.95 to -1.0, a liquid supply system adapted to supply a liquid flow through the inlet
at a flow rate of from 0.1 to 7 litres/minute, the outlet nozzle is configured to generate an
output stream of liquid flow having an average width of from 0.25 to 20 mm, the acoustic
transducer is configured to generate acoustic energy having a frequency of from 0.1 to 5
MHz and the gas bubble generator is configured to provide in the output stream bubbles
having a radius of from 0.5 to 40 µm.
The present invention further provides an apparatus for treating human or animal
tissue, the apparatus comprising a conical body defining a chamber, the conical body
extending between a base of the conical body and an outlet nozzle of the conical body,
wherein the base has an inlet for liquid flow into the chamber and the outlet nozzle is at a
conical tip of the conical body and is configured to generate an output stream of liquid
flow from the chamber for treating human or animal tissue, an acoustic transducer
associated with the conical body to introduce acoustic energy into the liquid within the
chamber whereby the acoustic energy is present in the output stream, a gas bubble
generator for providing gas bubbles in the output stream, the gas bubbles in the output
stream being excited by the acoustic energy, and a cup member having a closed end fitted
to the outlet nozzle of the conical body, the cup member defining a second chamber and
being configured to receive the output stream into the second chamber from the closed
end, the cup member having an open end with an annular rim configured to form an annular
contact against human tissue.
The present invention further provides an apparatus for producing a liquid
including acoustically excited gas bubbles, the apparatus comprising a body defining a
chamber, the body having an inlet for liquid flow into the chamber and an outlet for liquid
including acoustically excited gas bubbles, an acoustic transducer associated with the
body to introduce acoustic energy into the liquid within the chamber, a gas bubble
generator for providing gas bubbles in the liquid within the chamber, the gas bubbles in
the liquid being excited by the acoustic energy, and a gas removal device coupled to the
inlet for removing gas from a liquid supply to the apparatus, the gas removal device
comprising a casing having a input for liquid and an output for liquid, and a plurality of
compartments serially located between the input and output which define a serpentine path
therebetween, at least one of the compartments including a headspace at an upper part
thereof for collecting gas released from liquid flowing along the serpentine path
The present invention further provides a method of generating a liquid stream for
treating a surface, the method comprising the steps of:
a. providing a conical body defining a chamber, the conical body extending between
a base of the conical body and an outlet nozzle at a conical tip of the conical body;
b. inputting a flow of aqueous liquid into the chamber through an inlet at the base and
generating an output stream of liquid flow from the chamber through the outlet
nozzle, the output stream having a liquid flow rate of from 0.1 to 7 litres/minute,
and the output stream having an average width of from 0.25 to 20 mm;
c. providing gas bubbles in the output stream, the gas bubbles having a radius of from
0.5 to 40 µm;
d. introducing acoustic energy having a frequency of from 0.1 to 5 MHz into the
liquid within the chamber whereby the acoustic energy is present in the output
stream and excites the gas bubbles; and
e. directing the output stream comprising the acoustically excited gas bubbles and
acoustic energy towards a surface to be treated.
[1O] The present invention further provides a method of generating a liquid stream for
treating a surface, the method comprising the steps of:
a. providing a conical body defining a chamber, the conical body extending between
a base of the conical body and an outlet nozzle at a conical tip of the conical body,
wherein a closed end of a cup member is fitted to the outlet nozzle of the conical
body, the cup member defines a second chamber, and the cup member has an open
end with an annular rim which is disposed against a surface to be treated;
b. inputting a flow of aqueous liquid into the chamber through an inlet at the base and
generating an output stream of liquid flow from the chamber through the outlet
nozzle and into the second chamber from the closed end;
c. providing gas bubbles in the output stream;
d. introducing acoustic energy into the liquid within the chamber whereby the
acoustic energy is present in the output stream and excites the gas bubbles; and
e. directing the output stream comprising the acoustically excited gas bubbles and
acoustic energy towards a surface to be treated.
The present invention further provides a method of treating human or animal tissue,
the method comprising the step of: i. directing a stream of an aqueous liquid comprising
gas bubbles excited by acoustic energy towards a wound or anatomical pocket in human
or animal tissue, or towards an anatomical space or potential space in human or animal
tissue, or towards soft or hard tissue in an oral cavity or elsewhere in the human or animal
body, or towards tissue in a nasal cavity, or towards tissue associated with sinuses, eye,
ear, digestive and genito-urinary systems, thereby to treat the human or animal tissue with
the stream.
The present invention yet further provides an aqueous liquid comprising gas
bubbles excited by acoustic energy for use in wound healing in human or animal tissue.
Optional or preferred features are defined in respective dependent claims.
The present invention is at least partly predicated on the finding by the present
inventors that a stream of liquid containing gas bubbles excited by acoustic energy can be
provided with specific parameters, such as liquid flow rate, average width of the stream of
liquid flow, acoustic energy frequency and gas bubble radius, to enable the stream of liquid
containing the acoustically excited gas bubbles to be applied to human or animal tissues
with the effect that therapeutic effects are achieved.
In particular, it has been found by the present inventors that such a liquid stream
can provide the technical effect of cleaning wounds and anatomical pockets or anatomical
space or potential space in human or animal tissue. The present invention can also clean
soft and hard tissue in the oral cavity and tissue in the nasal cavity. In this context, the term
'cleaning' in this specification encompasses both the removal of inactive contaminants,
such as small particles, and the removal of active contaminants, such as microbes,
biofilms, and chemicals that interact with tissue. Most particularly, it has been found that
such a liquid stream can provide the technical effect of the disruption of biofilms on human
or animal tissue, particularly within wounds and anatomical pockets or anatomical space
or potential space.
Furthermore, it has been surprisingly found by the present inventors that there is
additional healing of tissue and wounds over and above that healing which follows from
cleaning. That is to say, whilst the presence of a contaminant (such as a biofilm) hinders
healing and this hindrance is reduced if the contaminant level is reduced, there is additional
healing over and above that which comes from the removal of such a hindrance. That is to
say, wounds and injured tissues that are kept free of contamination, heal better when
treated by the device than control tissue that has been similarly kept free of contamination.
Furthermore, it has been found by the present inventors that such a liquid stream
can provide the technical effect of promoting the healing of wounds in human or animal
tissue and the formation of/return to normal healthy tissue and tissue regeneration. It has
surprisingly been found that the output stream heals the wound by stimulating blast cells
in tissue in the wound, and modulating biochemical mediators of wound healing,
optionally wherein the wound is a wound in skin and the output stream heals the wound
by stimulating dermal fibroblasts and keratinocytes in epidermal tissue in the wound and
modulating mediators of tissue repair. For a wound in skin, the output stream heals the
wound by causing, promoting or enhancing re-epithelialisation of epidermal tissue in the
wound, and this may be achieved optionally by stimulating dermal fibroblasts and
keratinocytes in epidermal tissue in the wound and modulating mediators of tissue repair.
It has been surprisingly found by the present inventors that although it is known in
the prior art that ultrasound can be applied to certain classes of injury, such as bone
microfractures, to achieve a therapeutic healing effect, the combination of ultrasound
within a cleansing stream of liquid provides the ability to both clean and promote the
formation of healing and tissue regeneration, as well as having the ability to disrupt and
remove biofilm and can optionally have a direct bactericidal action, preventing biofilm
reformation, which can be combined into a single treatment.
[J 9] The present invention has particular application to wounds that have become
infected, for example by bacteria or other micro-organism (e.g. fungi, parasites). The
technology can clean away, and at times have a killing effect on, such microbes.
In this specification, the term 'wound' is herein defined as including (but is not
restricted to) sites formed by the removal or transformation or inflammation of the normal
human or animal tissue (epidermis, gum 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, disease (including gum disease) are all
included. Specific circumstances would be abrasion or cutting or burning or solar exposure
of the epidermis to expose the dermis; or damage to the gum.
In this specification, the term 'anatomical pocket' is herein defined as including
(but is not restricted to) periodontal pockets, and cavities associated with the eye, the
urinary-genital system, ears, and oral, nasal and digestive systems.
In some preferred embodiments of the present invention, 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 (i.e. by which, in this specification, is meant
typically 'normal saline', 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 water or a
saline solution reduces the risk of adverse reactions in tissue that can have been severely
traumatized (e.g. burns), and also reduces the provision in waste of dilute forms of
pharmaceuticals (such as antibiotics) which are known to contribute to the development
of antibiotic resistance.
In alternative preferred embodiments of the present invention, gene therapy agents
or chemical agents, for example biocides, antimicrobials, pharmacological agents to
promote healing, and/or biochemical modulators, may optionally be added to the liquid,
e.g. as agents in the bulk liquid, or the bubble, e.g. as agents carried in the bubble wall or
gas. By combining such agents with the delivery system of the stream of liquid containing
gas bubbles excited by acoustic energy, the penetration of such agents into a difficult-to-
penetrate target region, for example crevices, contoured surfaces, biofilms and anatomical
spaces such as dental root canals, an exemplar but not exhaustive list of the structures that
are covered by the term 'difficult-to-penetrate target region', is increased when the bubbles
are drawn into these surfaces by radiation forces. The penetration of the agents is further
increased because the bubbles induce liquid convection by generating bubble-induced
liquid motions associated with the wakes, boundary layer, and local circulations including
microstreaming. This would, for example, 'pump' agents into regions such as 'difficult-
to-penetrate target region' where normally the concentration of that species is lower than
desirable, or takes a greater amount of time to penetrate, because it has previously relied
upon diffusion. Inthis way, the bubbles employed in accordance with the present invention
increase the penetration of these agents into the 'difficult-to-penetrate target region'.
The result is that greater and quicker penetration of the agents into the 'difficult- to-
penetrate target region' can be achieved using the same concentration of the original
agents, or the same concentration as before can be achieved at the base of the 'difficult-to-
penetrate target region' using less of the agent at the source. As an example of the latter,
if an agent is present in aqueous solution, and previously relied simply on diffusion to
achieve the target concentration at a 'difficult-to-penetrate target region' (e.g. the base of
a crevice), then the present invention allows the same concentration at the same
inaccessible location to be achieved using a lower concentration of the agent in the bulk
liquid outside of the 'difficult-to-penetrate target region'.
In the preferred embodiments of the present invention, the method and apparatus
provide that the treatment of the human or animal tissue can be carried out during
conventional medical procedures and does not require extensive additional medical
training. In the method, a stream of liquid is directed towards the area of tissue to be
treated, and this technique can be employed simply to replace the time taken for the
clinician to conduct one action, such as a flush, rinse or wash, with an very similar amount
of time conducted in a very similar manner, namely to direct a stream of liquid towards
the area of tissue to be treated. However, it has been found by the present inventors that
by providing the stream of liquid containing the acoustically excited gas bubbles which is
applied to human or animal tissues, unexpected therapeutic effects are achieved. The
incorporation into a stream of aqueous liquid of acoustically excited gas bubbles
transforms a conventional flush, rinse or wash from a sometimes ineffective procedure, to
a highly effective one, both in terms of cleaning and in terms of healing.
The preferred embodiments of the present invention provide an apparatus and
method adapted to achieve treatment of human or animal tissue by the employment of
bubble action on a surface, or within an anatomical pocket, such as a crevice, within a
surface, driven by acoustic stimulation. This avoids inertial collapse at the surface and
hence the associated erosion mechanisms of known ultrasonic cleaning systems and
methods.
For the apparatus of the preferred embodiments of the present invention, the nozzle
material and shape, and the driving acoustic frequency, may be chosen such that at least
one mode is not evanescent in the liquid stream. The nozzle may be designed to prevent
a strong impedance mismatch between the sound field in the conical body and the sound
field in the liquid stream. When the liquid stream is surrounded by gas, such as atmospheric
air, once it leaves the nozzle, it is preferred that material of the nozzle, and the conical
body, are either exactly (or nearly) able to produce pressure-release reflection of sound
from the liquid that is incident upon the material, or acoustically transparent (no reflection
or attenuation) so that the sound field encounters a pressure-release condition when in
contact with the atmospheric air. Furthermore, it is preferred if the shape of the cone and
nozzle allows the perimeter of the pressure-release boundary to transition from the end of
the cone that is remote from the nozzle, towards the nozzle, in a smooth manner without
sudden changes in cross section; and furthermore, at the tip of the nozzle where the stream
exits the nozzle, for the perimeter for the pressure-release boundary in the nozzle to match,
as closely as possible, the perimeter of the stream where it exits the nozzle. The flow rate
and nozzle design may be chosen so that the liquid stream does not lose integrity before it
reaches the target surface to be cleaned and healed (e.g. break up into drops, entrain
unwanted bubbles, etc.) to the extent that it hinders the transmission of sound from the
nozzle to the target surface. The shape of the conical body may be designed to assist the
transmission of sound from the cone to the liquid stream and subsequently through the
nozzle. An amplitude or frequency modulated sound field may dramatically improve
pressure transmission within the fluid flowing through the apparatus to the target surface.
Without being bound by theory, it is believed that in accordance with the preferred
aspects of the present invention, the motion of the bubble process is dominated by the
dynamic balance and imbalance of the oscillating pressure in the liquid and the oscillating
pressure within the gas phase which results in non-inertial cavitation, rather than the
converging momentum and inertia of the liquid which results in inertial collapse. The
cleaning, healing and tissue regeneration can be further enhanced by the establishment of
surface waves on the bubble wall (also sometimes referred to as bubble shape oscillations,
of which the Faraday wave is the surface wave which, when the bubble is in pulsation
resonance, requires the least acoustic pressure to stimulate). Therefore the apparatus and
method of the present invention are preferably adapted to generate bubbles in the device
at a location remote from, but close to, the solid/liquid interface of the surface to be treated
and then to drive them against that surface with an appropriate sound wave sufficient to
produce non-inertial cavitation and, if applicable, surface waves on the bubble wall. In
addition to the stream flow, acoustic radiation forces may be effective at moving bubbles
towards the tissue, and in particular can be effective at causing bubbles to penetrate
crevices which other treatment methods (flow, wipes, brushes, etc.) can find difficult to
penetrate.
A further feature of the preferred embodiments of the present invention is to deliver
such treatment of human or animal tissue, using non-inertial cavitation, through a liquid
stream, which avoids the need for immersion, and so makes the apparatus portable. This
may be achieved by a suitable adaptation of existing cleaning systems which currently
deliver a flow of liquid to generate cleaning, and healing and tissue regeneration. A
portable apparatus may be battery driven. Such an apparatus of the preferred embodiments
of the present invention system may also conserve water and/or power compared to a
known immersion system.
In particular, the present invention is at least partly based on the findings by the
present inventors that surface treatment (tissue cleaning, healing and regeneration) may be
achieved through the generation of bubble oscillation (including surface waves) driven by
appropriate acoustic excitation. Also, crevice cleaning may be achieved through bubble
capture into pores and other surface features, including, but not restricted to, capture
through processes of flow, hydrodynamic effects, or acoustic radiation forces. These
bubbles oscillate and remove material from the crevice, and promote tissue regeneration
and healing.
In the preferred embodiments of the present invention, the bubbles are generated,
and then the bubbles flow, together with the flowing stream, towards a target tissue
surface; the bubbles are not excited whilst they are in the stream, but only when the bubbles
are on the tissue surface. If the bubbles are excited in the stream, they attenuate the sound
field in the stream, and prevent the sound field effectively reaching the target tissue
surface. Furthermore, if the sound field hits the bubbles when they are in the stream, before
they reach the target, the sound field can cause the bubbles to coalesce with each other in
the stream, which can prevent the combination of tissue cleaning, tissue regeneration and
healing being effectively achieved.
Itis well known that effective irrigation I cleansing of 'dirty' wounds (such as those
caused by trauma) presents a particular challenge compared to simple wounds, due to the
increased microbial contamination, tissue debris and irregularity of the wound shape
(including small crevices).
Bubble population effects may be harnessed to allow transmission of sound down
through the liquid to the surface to be cleaned, healed and regenerated. The flow
apparatus, geometry, materials and acoustic characteristics of the bubble population (as
well as its distribution in the liquid and how this varies in space and time) may allow
efficient acoustic transfer to the surface to be cleaned, healed and regenerated.
Relatively low flow rates may be deployed, minimising cleaning solution wastage,
and making the ingress of liquid more acceptable to the patient (e.g. dental patient),
simplifying management of the run-off (e.g. in hospital wards), and reducing the dilution
of the run-off. A run-off with a generally higher concentration of contaminants (e.g.
microbes) is more facilitated for use in detecting the contaminants present in the run-off
on a time scale that is rapid enough to allow for targeted therapy. The targeted therapy
may, for example, comprise detecting the bacterial species that was present in the biofilm
in an infected wound, and detecting any antibiotic resistances in that bacteria, so that a
targeted and effective antibiotic can be delivered to the disrupted biofilm within the
window (e.g. 24 hours) after disruption when the biofilm is particularly susceptible to the
correct antibiotic, before the protective effect of the biofilm is re-established. However, it
has been demonstrated that biofilm removed by the device fails to re-establish for over 24
hours following a single treatment.
Embodiments of the present invention will now be described by way of example
only, with reference to the accompanying drawings, in which:
Figure 1 is a schematic side view, not to scale, of a cleaning, healing and tissue
regeneration apparatus in accordance with a first embodiment of the present invention;
Figure 2 is a schematic side view of a cleaning, healing and tissue regeneration apparatus
in accordance with a second embodiment of the present invention;
Figure 3 is a schematic perspective view of a cleaning, healing and tissue regeneration
apparatus in accordance with a third embodiment of the present invention;
Figure 4 shows images of a pig trotter wound model used in Example 1;
Figure 5 illustrates micrographs which show direct EDIC/EF micrographs of SYT0-9 pre-
stained E-MRSA-16 accumulation/early biofilm within the pig trotter wounds used in
Example 1;
Figure 6 illustrates micrographs which show Pseudomonas aeruginosa pMF230 in situ
detection in direct EDIC/EF micrographs of GFP tagged Pseudonwnas aeruginosa
pMF230 accumulation/early biofilm within the pig trotter wounds used in Example l ;
Figure 7 is a graph which shows Pseudomonas aeruginosa pMF230 in situ detection
image analysis, in particular image analysis (ImageJ) of EDIC/EF micrographs
demonstrating the percentage coverage of GFP tagged Pseudomonas aeruginosa pMF230
accumulation/early biofilm within the pig trotter wounds used in Example 1;
Figures 8(a) and 8(b) are graphs which show the percentage coverage of GFP tagged
Pseudonwnas aeruginosa pMF230 in situ detection from image analysis in wound models
used in Example 1, Figure 8(a) showing the coverage immediately after cleaning and
Figure 8(b) showing the coverage 24 hours after cleaning;
18079711_1 (GHMatters) P112816.NZ
Figure 9 illustrates micrographs which show wound healing in Epiderm full thickness
wound models used in Example 2;
Figure 10 is a graph which shows wound healing in the Epiderm full thickness wound
models used in Example 2;
Figure 11 illustrates micrographs which show Haematoxylin and Eosin (H&E) stained
sections from the Epiderm full thickness wound models used in Example 2;
Figure 12 illustrates micrographs which show the re-epithelialisation in the Epiderm full
thickness wound models used in Example 2;
Figures 13(a) and (b) demonstrates the increased migration of keratinocytes across a
wound bed seven days post-treatment with a cleaning, healing and tissue regeneration
apparatus in accordance with an embodiment of the present invention, Figure 13(a)
showing micrographs and Figure l 3(b) showing a graph illustrating increased migration
of keratinocytes;
Figure 14 illustrates micrographs showing immunocytochemical staining for cytokeratin
14 demonstrating stimulation of keratinocyte migration across a wound after treatment
with a cleaning, healing and tissue regeneration apparatus in accordance with an
embodiment of the present invention;
Figure 15(a) and (b) illustrate the increased fibroblast activity observed in the dermo-
epidermal junction of Epiderm full thickness (EFT) tissue samples seven days post-
treatment with a cleaning, healing and tissue regeneration apparatus in accordance with an
embodiment of the present invention, Figure 15(a) showing micrographs and Figure 15(b)
showing a graph illustrating increased fibroblast numbers in the dermo-epidermal
junction;
Figure 16 is a graph showing modulation of matrix metalloproteinases, to demonstrate
modulation of mediators to improve healing, after treatment with a cleaning, healing and
tissue regeneration apparatus in accordance with an embodiment of the present invention;
Figure 17 shows micrographs of Pseudornonas aeruginosa removal from stainless steel
after treatment with a cleaning, healing and tissue regeneration apparatus in accordance
with an embodiment of the present invention;
Figure 18 is a graph which shows killing of Pseudomonas aeruginosa after treatment with
a cleaning, healing and tissue regeneration apparatus in accordance with an embodiment
of the present invention;
18079711_1 (GHMatters) P112816.NZ
Figure 19 illustrates a control protocol for the transducer when there is a separate bubble
generator (e.g. by electrolysis, venturi, gas injection, ozone generation, rnicrofluidics etc.)
in an apparatus according to a further embodiment of the present invention; and
Figure 20 illustrates a control protocol for the transducer when the transducer additionally
functions as the bubble generator in an apparatus according to a further embodiment of the
present invention.
Referring to Figure 1, there is shown a cleaning, healing and tissue regeneration
apparatus in accordance with a first embodiment of the present invention.
The cleaning, healing and tissue regeneration apparatus, designated generally as 2,
comprises a hollow conical body 4 defining a central chamber 6. The body 4 has a rear
wall 8 in a base 11 and a substantially conical wall 10 extending forwardly away therefrom
which terminates in a forwardly-located orifice 12 in an outlet nozzle 14 of the conical
body 4. The rear wall 8 also contains one or more vents 9 through which liquid containing
any gas pockets can leave. Although use of an outgasser, as described below, should reduce
the build-up of gas within the conical body 4, certain circumstances (for example,
prolonged use, air leaks in the pump, insufficiently smooth pumping, variation in the gas
content of the water coming from the source etc.) can cause gas to build up in the cone,
and if this happens this needs to be periodically vented, most conveniently if the vent is
place at the uppermost point of the liquid in the conical body 4 (e.g. in Figure 1 that would
be in the rear wall 8). Typically, both the substantially conical wall 10 and the outlet
nozzle 14 are rotationally symmetric, i.e. circular, although other geometric shapes may
be employed. In this specification the term 'substantially conical' should be interpreted
broadly to encompass 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,
having a concave inner wall as seen from inside, or have a constant half-angle as shown,
or are horn-like and have a convex inner wall as seen from the inside.
The nozzle 14 is at a conical tip 15 of the conical body 4 and defines a liquid outlet
16 in the form of an orifice. The base 11 has a liquid inlet 18 which is located at or adjacent
to the rear wall 8. A liquid supply conduit 20, typically in the form of a flexible hose,
communicates with the inlet 18 and comprises part of a liquid supply system 21. An
acoustic transducer 22 is mounted on the rear wall 8. A controller 23 controls the operation
of the transducer 22. Typically, the transducer 22 is mounted on an outer surface of the
wall 8 and extends over a substantial proportion of the surface area of the wall 8.
18079711_1 (GHMatters) P112816.NZ
Alternatively, the transducer 22 may be embedded into the chamber 6 on or through 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.
The rear wall 8 comprises a plate, for example of plastic, such as polycarbonate, or
a metal such as aluminium or stainless steel, having the liquid inlet 18 therein and on which
the acoustic transducer 22 is mounted. The conical body 4 extends forwardly of the rear
wall 8 and forms an integral nozzle 14. The walls of the conical body 4 and the nozzle 14
are composed of a material selected to achieve a pressure-release condition at any point
between and including the inner and outer boundaries of the walls as experienced by the
sound field in the liquid. Preferentially that is done by ensuring that the acoustical space
in the conical body 4 and the nozzle 14 which has the characteristics close to the liquid (in
terms of both the real and imaginary parts of the acoustical impedance that an infinite
volume of the material would have), has a perimeter from which acoustical signals in the
liquid are reflected with a pressure amplitude reflection coefficient (R) close to -1, -0.95
to -1.0, preferably from -0.99 to -1.0. That is to say, almost all the incident energy is
reflected back into the liquid, with a 180 degree phase change occurring in the pressure
waveform on reflection. That perimeter can be at the interface between the liquid and the
solid wall, or in the wall, or at the interface between the wall and the outer atmosphere,
depending on the choice for the real and imaginary parts of the specific acoustic impedance
of the material(s) which make up the wall. This pressure-release condition is achieved by
providing that the conical body 4 and the nozzle 14 thereof have a pressure amplitude
reflection coefficient (R) with respect to the acoustic energy in the aqueous liquid, i.e.
water or a saline solution, within the chamber 9 of from -0.95 to -1.0, preferably from -
0.99 to -1.0.
When the liquid stream containing acoustically excited gas bubbles leaves the
nozzle 14, there is an interface between the liquid stream and air. The pressure amplitude
reflection coefficient (R) with respect to the acoustic energy in a semi-infinite volume of
aqueous liquid, i.e. water or a saline solution, at the water/air interface, would be -0.999.
That is to say, in general there is an acoustic impedance mismatch (i.e. poor impedance
matching) between aqueous liquid and air. However when a material is bounded in a shape
and size, with walls of a certain material and thickness, that volume of itself has an acoustic
18079711_1 (GHMatters) P112816.NZ
impedance. It is very important not to confuse these different impedances. The objective
of the device is to avoid impedance mismatches between the sound fields in the conical
body 4, the nozzle 14 and the stream, so that energy propagates from transducer 22 into
the liquid within the conical part 5 of the central chamber 6 and thence into the nozzle part
7 of the central chamber 6 defined by the nozzle 14 and thence into stream, with minimal
losses, notably at the interfaces between these three acoustical compartments. One way of
matching them is to ensure that the specific acoustic impedance of the material that houses
the sound field, and the acoustical boundary conditions at the perimeter of that sound field,
and the shape and size of that acoustical perimeter, match. If an acoustical modal structure
exists, that modal structure must be appropriate to the transmission of energy from
transducer 22 to conical part 5 to nozzle part 7 to stream to target.
Consequently, in order to provide that the acoustic energy in the stream, and in the
gas bubbles in the stream, is not absorbed by the conical wall or nozzle, the pressure-
release boundary condition of the sound field in the cone (either the liquid in the cone
alone or the combination of the liquid and the cone) must match the pressure-release
boundary condition between the liquid and atmospheric air. This means that one of three
cases needs to be satisfied. The first case that satisfies the required conditions is that in
which the boundary between the liquid and the wall material has a reflection coefficient
(R) of approximately zero, the wall material does not attenuate acoustic waves
significantly, and the reflection coefficient (R) between the wall material and the
atmospheric air is the same as that between the liquid and atmospheric air. The second
case that satisfies this condition is when the pressure amplitude reflection coefficient (R)
with respect to the liquid and the nozzle wall material is substantially the same as the
pressure amplitude reflection coefficient (R) with respect to the acoustic energy in the
aqueous liquid at the liquid/air interface. Performance in this second case is augmented if
the pressure amplitude reflection coefficient (R) with respect to the liquid and the cone
wall material is substantially the same as the pressure amplitude reflection coefficient (R)
with respect to the acoustic energy in the aqueous liquid and the nozzle wall material. The
third case that satisfies this condition is when the nozzle material is engineered in such a
way as to provide a pressure amplitude reflection coefficient (R) at some intermediate
location between the inner and outer wall that is substantially the same as the pressure
amplitude reflection coefficient (R) with respect to the acoustic energy in the aqueous
liquid at the liquid/air interface. Performance in this third case is augmented if the cone
18079711_1 (GHMatters) P112816.NZ
material is engineered in such a way as to provide a pressure amplitude reflection
coefficient (R) at some intermediate location between the inner and outer wall (which
smoothly transitions to the respective location of the corresponding boundary in nozzle)
that is substantially the same as the pressure amplitude reflection coefficient (R) with
respect to the acoustic energy in the aqueous liquid at the liquid/air interface.
Consequently, the conical body 4 and the nozzle 14 provide a pressure amplitude reflection
coefficient (R) with respect to the acoustic energy in the aqueous liquid, i.e. water, at some
point within boundary of chamber 9 which is as close to -1 as possible, in particular from
-0.95 to -1.0, preferably from -0.99 to -1.0.
The conical wall and nozzle are shaped such that, at the tip of the nozzle where the
stream leaves the nozzle, the perimeter of the pressure release boundary in the nozzle is
identical to the perimeter of the outer radius of the liquid stream at the moment that it
leaves the nozzle.
The substantially conical element may be geometrically conical, or alternatively
may have a non-geometric shape, such as being horn-shaped or bell shaped. The
substantially conical element may be formed, for example, of cellular foam, plastic,
rubber, or a composite of materials. Cellular foam, if its specific acoustic impedance is
much less than that of the liquid (which is likely if it much less dense than the liquid), will
place a pressure release reflection coefficient (as seen by the acoustic energy that is
propagating in the liquid towards that interface) at the inner boundary of the cone and
nozzle, where the liquid meets the solid. Alternatively, if the substantially conical element
has a specific acoustic impedance that is similar to that of the liquid, then the pressure
release boundary will occur between the solid wall and the outer atmosphere. Note that
this requires that the solid material used does into absorb too much acoustical energy, or
this will violate the condition that the acoustical energy which returns to the liquid after
reflection is substantially the same as the acoustical energy which attempted to propagate
out of the liquid. Other materials, including glasses and plastic, may be used provided they
also satisfy the following criteria (i.e. that an acoustic wave heading towards the material
from the water eventually (i.e. from the inner surface of the wall, the outer surface of the
wall, or some structure embedded within the wall) produces a reflection back into the water
that substantially contains all the energy present in the original waveform, but with the
pressure wave inverted by 180 degrees in phase. The choice of material is determined by
the requirement to match (as closely as practicable) the acoustic wall boundary conditions
18079711_1 (GHMatters) P112816.NZ
at the edge of the ultrasonic field within the cone to those at the edge of the acoustic field
in the nozzle and those at the edge of the ultrasonic field in the liquid stream once it leaves
the nozzle, so as to avoid sharp impedance mismatches between cone, nozzle and liquid
stream that would hinder the passage of acoustic energy along the stream from the
transducer, through the cone and into the nozzle, through the nozzle and into the stream.
Therefore, a design principle employed by the conical body 4 and the nozzle 14
used in the preferred embodiments of the present invention is that the acoustic boundary
condition at the edge of the acoustic field in the cone and nozzle (which will be at the inner
wall if the wall material is, say, much less dense that the liquid; and at the outer wall if the
specific acoustic impedance of the wall is sufficiently similar to that of water and the wall
materials do not significantly absorb the sound) should match the acoustic boundary
condition that will occur in the stream of liquid once it leaves the nozzle. Other materials,
including glasses and plastic, may be used provided they also satisfy the following criteria
i.e. that an acoustic wave heading towards the material from the liquid eventually (i.e. from
the inner surface of the wall, the outer surface of the wall, or some structure embedded
within the wall) produces a reflection back into the water that substantially contains all the
energy present in the original waveform, but with the pressure wave inverted by 180
degrees in phase.
In use, liquid flows continuously through the supply conduit 20 into the central
chamber 6 and then outwardly through the outlet 16 of the nozzle 14 to form a stream 24
of liquid which is directed against the surface 26 of tissue 28 to be treated. The surface 26
may, in particular, be provided with three dimensional surface features, such as a crevice
shown in an exaggerated form in Figure 1, which forms an anatomical pocket.
A bubble generator 32 may be located within the conical body 4 upstream, in the
direction of fluid flow, of the outlet nozzle 14 and the orifice 12 therein. The bubble
generator 32 generates gas bubbles within the liquid stream so that the liquid stream
impacting on the surface 26 includes not only acoustic energy from the transducer 22 but
also gas bubbles which have been acoustically excited by the acoustic energy from the
transducer 22. Preferably a bolus of bubbles is formed in each of a series of treatment
cycles. In each treatment cycle, the respective bolus of bubbles is directed to the target
surface, and then, when located at the target surface, is acoustically excited. In this
specification the term "bolus of bubbles" is intended to mean a plurality of bubbles that
are close together, and form a small, tight cloud of bubbles in the liquid.
18079711_1 (GHMatters) P112816.NZ
There are several options for seeding gas bubbles into the liquid flow, including
gas injection and in situ electrochemical gas bubble generation by electrochemical
in situ electrochemical gas bubble generation,
decomposition of water in the liquid. For
the incorporation of electrodes, for example 10-100 µm diameter Pt wires, into the liquid
flow allows controlled seeding. Alternatively, small bubbles of selected gases, such as
oxygen or ozone, are generated close to the nozzle 14 by electrolysis, microfluidic
injection, radiation, or ultrasonic or flow cavitation, etc. Electrolysis and microfluidic
injection are preferred for achieving gas bubbles with the desired and controlled bubble
size, in particular to prevent or restrict the formation of excess bubble dimensions.
Electrolysis is particularly convenient if the aqueous solution contains salt to give it
standard conductivity, as might be used in aqueous medical saline. A short electrical pulse
can produce the spatially restricted bolus of small bubbles of a size that is roughly resonant
with the sound field to be used for treatment of the target surface. Periodically reversing
the current will reduce the decrease in electrode performance over time. Ifthe conductivity
of the liquid is low, conductivity (e.g. pol ymer) membranes between the electrodes can
assist with electrolysis.
In the illustrated embodiment, the bubble generator 32 is located within the conical
body 4. The liquid flow into the conical body 4 is pre-treated to remove gas bubbles from
the liquid flow so that the bubbles controllably generated within the conical body 4 are the
only bubbles present in the liquid stream to be acoustically excited. The pre-treatment also
can remove solid particles from the liquid flow, and also some dissolved or suspended
chemicals.
The liquid supply is a supply of clean water or saline solution. Throughout this
specification, whether the skilled person wishes to use sterile liquid is a clinical decision
in line with guidance: for example, sterile liquids are not usually used in the oral cavity,
and in certain circumstances there are justifiable reasons for using clean but not sterile
liquids in wound irrigation. Throughout this specification, where the liquid is mentioned,
it should be understood that the assessment of whether to use sterile or simply clean liquid
will be a clinical decision. This also includes whether the liquid contains drugs or
antimicrobial ingredients. The temperature of the liquid supply may be regulated, and the
liquid may have been degassed. The liquid supply is pumped to a desired pressure by a
pump 27. Alternatively the liquid feed can be gravity fed from an elevated container, so
that pump 27 is not needed: this can be particularly is resources are limited (e.g. pump
18079711_1 (GHMatters) P112816.NZ
facilities are not available), or if the skilled person wishes to reduce the possibility of a
pump entraining unwanted large bubbles into the flow, and/or if the skilled person wishes
to use pre-prepared (possibly sterile) bags of bottles of rinse, which could optionally have
been degassed prior to sealing to reduce the need for an outgasser, as described below.
The pump outlet 29 passes to a venturi 31 which decreases the dissolved gas
concentration within the liquid, by application of suction by the venturi and bubble
buoyancy and coalescence. The degassed liquid is then fed to a liquid pressure control 33
which provides a sufficient liquid pressure to enable the liquid to flow at a desired flow
rate through a subsequent outgasser 34 which is located upstream of the inlet 18 of the
conical body 4. The outgasser 34 is configured to remove gas bubbles from the liquid
flow.
The outgasser 34 comprises a casing 35 having an input 36 and an output 37. A
plurality of compartments 38 are serially located between the input 36 and output 37 which
define a serpentine path 39 therebetween. In the illustrated embodiment, the serpentine
path 39 is vertically oriented, although other non-vertical orientations may be employed.
The input 36 is, in the figure, a downwardly oriented pipe 92 (although a horizontal
inlet point would work equally as well) located at an upstream central part 93 of the
outgasser 34 and the output 37 is located at a lower part 94 of the downstream end wall 95
in communication with a lower portion of a compartment 38. Inthe illustrated embodiment
each compartment 38 is either circular, for the central first compartment 38, or annular,
for the remaining radially outward second, third, etc compartments 38. The serpentine path
39 is annular, and extends radially outwardly.
By providing successive compartments 38 of increasing radius, the cross-sectional
area of the flow from the compartments 38 along the outgasser 34 increases, which
progressively slows down the flow rate along the outgasser 34, and correspondingly
enhances the ability of larger bubbles to rise within the liquid flow and be separated from
the liquid flow.
The annular arrangement is particularly attractive because each wall need only
support a fraction of the overall pressure drop between input 36 and output 37, meaning
the likelihood of leaks and overall weight and cost of materials can be reduced.
In an alternative configuration, the outgasser 34 comprises a linear array of the
compartments 38; the input 36 is a downwardly oriented pipe located at an upstream
central part of the outgasser and there are two outputs, each output being located at a lower
18079711_1 (GHMatters) P112816.NZ
part of respective opposite downstream end walls at opposite sides of the outgasser 34.
There are two serpentine paths 39 extending in opposite linear directions. Each output 37
connects to a respective inlet 18 of the conical body 4, or connects to a common manifold
which then connects to the inlet 18 of the conical body 4.
The apparatus may further comprise, at a location upstream of the input 36, in the
direction of liquid flow into the casing, a venturi device for removing from the liquid gas
in solution in the liquid. This venturi will increase the volume of gas required to be
removed by the outgasser 34, but will ensure a lower dissolved gas content which will
cause any bubbles that escape the outgasser to dissolve more quickly.
A heating device for heating the liquid may be located at a location upstream of
the input 36, in the direction of liquid flow into the casing 35, and upstream of the venturi
device if present. A cooling device for cooling the liquid may be additionally or
alternatively located at a location downstream of the output, in the direction of liquid flow
from the casing 35. By heating the aqueous liquid more gas comes out of solution, so this
can enhance the performance by heating the water just before it enters the venturi or
outgasser. By cooling the water, more gas tends to dissolve, so cooling the aqueous liquid
as it exits the outgasser reduces uncontrolled gas bubble formation in the conical chamber.
The serpentine path 39 is, in use, filled with the liquid flow from the input 36 to
the output 37. Each compartment 38 of the series of compartments 38 comprises an
upstream chamber 40 and a downstream chamber 41. Each upstream chamber 40 defines
an upward flow path 42 therealong and each downstream chamber 41 defines a downward
flow path 43, with alternating upward flow paths 40 and downward flow paths 43 in
combination forming the serpentine path 39.
Each pair of adjacent upstream and downstream chambers 40, 41 of each
compartment 38 is separated by a respective first wall element 44 which extends upwardly
from a bottom wall 45 of the casing 35. An upper edge 25 of the first wall element 44 is
located lower than a top wall 46 of the casing 35 to define a headspace 47 thereabove.
Each pair of adjacent compartments 38 is separated by a respective second wall
element 48 which extends downwardly from the top wall 46 of the casing 35. A lower
edge 49 of the second wall element 48 is located above the bottom wall 45 of the casing
to define a fluid connection 90 between the adjacent compartments 38.
A filter element 91 is located within the fluid connection 90. The filter element 91
may be held in place by shaping of the lower edge 49 of the second wall element 48 and/or
18079711_1 (GHMatters) P112816.NZ
the bottom wall 45 of the casing 35, for example to define a channel for receiving the filter
element 91 or to provide tooth elements which are embedded into the filter element 91.
The filter element 91 typically comprises a porous open cell foam or sponge, for
example composed of a synthetic polymer, which may optionally be supported within a
cage or by a framework. Alternatively, the filter element 91 comprises a porous ceramic
or stone or plastic or fabric, or a metal mesh. The filter element 91 is configured to function
to filter out gas bubbles exceeding a desired dimension. In addition, the filter element 91
is configured to filter out unwanted solid particles and dissolved or suspended chemicals
in the liquid flow.
Baffle members 96, defining an array of parallel linear channels, may be provided
within one or more of the compartments 38 to enhance laminar flow of the liquid through
the outgasser 34 and reduce turbulence.
The serpentine path 39 extends from the input 36 upwardly into the first upstream
chamber 40, over the upper edge 45 of the first wall element 44, downwardly into the first
downstream chamber 41, through the first fluid connection 90 and the filter element 91
located therein, and thereby into the adjacent second compartment 38. This sequence is
repeated for the series of compartments 38 until the output 37 is reached.
In use, the casing 35 is filled with liquid so that the liquid level extends above the
upper edge 45 of each first wall element 44 but is below the top wall 46 of the casing 35
to provide a headspace 47 in each compartment 38 which contains gas and is free of liquid.
Each headspace 47 is vented to provide an outlet for excess gas pressure within the
headspace 47, for example by providing a gas conduit 97 connected to a common manifold
pipe 98.
The liquid flow from the input 36 is caused to rise within the first upstream
chamber 40, and passes over the upper edge 25 of the first wall element 44, then is caused
to descend downwardly into the first downstream chamber 41, and through the first fluid
connection 90 and the filter element 91 located therein, and thereby into the adjacent
second compartment 38. This sequence is repeated for the series of compartments 38 until
the output 37 is reached.
Inthe compartments 38, bubbles have greater buoyancy than liquid. Consequently,
any bubbles tend to rise more rapidly than the liquid when the liquid is caused to rise
within each first upstream chamber 40. When the liquid is caused to descend within each
downstream chamber 41, the bubbles tend to descend more slowly than the liquid. The
18079711_1 (GHMatters) P112816.NZ
resultant effect is that the bubbles reach the liquid upper surface and then accumulate in
the headspace 47 beneath the top wall 46, and the accumulated gas is vented away by the
gas conduits 97.
Each compartment 38 may optionally be provided with a capillary tube outlet in
the top wall 46 to permit excess gas pressure venting but which prevents leakage of liquid.
A liquid sensor may be provided to detect the liquid level in the compartment 38 to warn
of actual or potential liquid leakage or overfilling of the compartments 38, or to activate a
vent when the gas content in the headspace exceeds a pre-determined limit, as monitored
via liquid level sensing, ballcock, conductivity sensor, optical sensor, ultrasonic level
meter or equivalent. The headspaces 47 may be in fluid communication to ensure gas
pressure equalisation within the outgasser 34. However some embodiments have
advantages in isolating each headspace 47 one from another, for example if there is a
possibility that the outgasser 34 might be tipped at an angle. At least one wall of the casing
may be transparent, e.g composed of a transparent polymer sheet, to permit viewing of the
liquid levels to check correct operation of the outgasser 34. The casing 34 may be at least
partially disassembled for cleaning, maintenance or filter replacement. An additional filter
may be located within the output 37.
Accordingly, the outgasser 34 functions to remove gas bubbles from the liquid flow
so that within the liquid flow entering the conical body 4 for formation of gas bubbles of
a controlled size and excitation of the gas bubbles by the acoustic transducer 22, there are
substantially no gas bubbles of an undesired excess dimension, and the void fraction of
bubbles smaller than this is so low as to not noticeably reduce the performance of the
device for example by absorbing or scatter the sound field in the cone and nozzle.
Consequently, the liquid stream exiting the nozzle 14 has a gas bubble population having
a controlled size distribution and in particular a threshold for the maximum bubble size,
so that the flow contains only bubbles smaller than this, and furthermore has a controlled
void fraction that is not so large as to degrade the performance of the device. Furthermore
it is advantageous to restrict the spatial spread of bubbles to a small bolus of bubbles that
travels down the stream, with substantially bubble-free water flowing in front of and
behind this bolus as it travels towards the target tissue.
The operation of the outgasser 34 can readily be tuned to control the threshold for
the maximum bubble size of any bubbles present in the liquid flow entering the conical
body 4 by adjusting the liquid flow rate through the outgasser 34 (which can be done by
18079711_1 (GHMatters) P112816.NZ
choice of the way the widening of the annuli reduces the flow), or alternatively it can be
done by stacking outgassers in series so that the outflow of one enters a second as its
inflow.
Therefore in the illustrated embodiment, the venturi 31 and the outgasser 34 are
employed to prevent large bubbles from being present in the liquid stream, and to ensure
that the void fraction of bubbles entering the stream (other than bubbles purposefully
placed in the stream by the bubble generator) is not so great as to impede the liquid flow
and acoustic transmission in the path of the ultrasound from the transducer to the target
tissue via the cone, nozzle and stream.
However, in some embodiments of the present invention in which the diameter of
the liquid stream is selected to be large, for example greater than approximately 10 mm,
and the ultrasonic frequency is lower than approximately 200-300 kHz, this in turn permits
a resonant gas bubble size to be selected so that larger bubbles sizes that may be
inadvertently present in the liquid flow into the conical body do not significantl y reduce
the effectiveness of the cleaning, healing and tissue regeneration effect of the acoustically
excited bubbles (depending on the gassiness of the liquid flow provided e.g. by water
mains, bagged or bottled liquid, etc.). In such embodiments, either or both of the venturi
31 and the outgasser 34 may be omitted. However, when small resonant bubble
dimensions are required for an effective cleaning, healing and tissue regeneration effect of
the acoustically excited bubbles, for example with a low volume flow rate of the stream
and a low stream width, then at least one of, and preferably both of, the venturi 31 and the
outgasser 34 may be required to pre-treat the aqueous liquid stream, the likelihood of their
being needed as the frequency increases, and the likelihood being reduced if other steps
are taken to reduce the likelihood of bubbles in the liquid feed (e.g. sealed bottles or bags
of degassed fluid are sufficiently elevated to provide a gravity fed supply without the need
for a pump).
In an alternative embodiment, the bubble generator 32 is located upstream, in the
direction of fluid flow, of the liquid supply conduit 20.
In an alternative embodiment, the conical body 4 and nozzle 14 are composed of
material that can function as a pressure release boundary when aqueous fluid is
thereagainst, so that acoustic energy in the aqueous fluid is effectively and efficiently
reflected with a phase change transmitted back into the flowing liquid at the inner surface
of the conical body 4 and nozzle 14. The aim of the apparatus of this embodiment is to
18079711_1 (GHMatters) P112816.NZ
introduce acoustic energy into the flowing fluid stream and then to direct that stream
through the outlet onto the surface to be treated by using the conical shape and outlet to
concentrate both the acoustic energy and the fluid flow while minimising acoustic losses
or frictional loses against the conical and outlet surfaces.
The rear wall 8 functions as a backplate which serves the acoustical purpose of
transmitting the ultrasound from the transducer 22 into the liquid in the cone. It also puts
distance between the edge of the transducer 22 and the pressure release bou ndary where
the net pressure fluctuation is zero (because the incident acoustic wave is added to the
phase inverted reflected pressure wave). Bringing that pressure release boundary close to
the transducer 22 degrades the amplitude of the sound field that can be generated in the
liquid close to the transducer 22.
A faceplate of the transducer 22 can be bonded onto the rear wall 8. Alternatively
the transducer faceplate can be in direct contact with the liquid if the transducer accesses
directly the liquid via a water-tight aperture in the backplate, so that if the transducer
faceplate is flush with the side of the backplate in contact with the liquid, the backplate
acts as a rigid acoustical baffle, amplifying the sound field in the liquid. Contact of the
transducer with the liquid in this way can help the water to cool the transducer, as can the
backplate if it has sufficient thermal conductivity. This can also work if the transducer is
bonded onto the backplate without an aperture, as can the addition of a cooling coil to take
the water supply, or a diverted offshoot from it, in a cooling coil which wraps around the
transducer and is thermally connected to it. Measures to prevent the transducer heating up
assist in keeping its performance stable,
The embodiment discussed above is directed to the specific application of
introducing sound energy into the liquid stream when the liquid is surrounded by air after
leaving the nozzle. The nozzle and the outlet are shaped and dimensioned to allow for
acoustic transmission along the fluid stream. It is advantageous to form a smooth flow of
the stream. It is well within the abilities of a person skilled in the art to produce a suitable
combination of shape and dimensions for the conical body and nozzle outlet to achieve the
desired smooth flow of liquid containing acoustic energy from the transducer.
In the embodiment of Figure 2, the liquid stream 50 containing the acoustically
excited gas bubbles is directed into a periodontal pocket 52 between a tooth 54 and gum
tissue 56. The liquid stream typically clean water or clean saline solution for most oral
procedures, except those where infection risk must be minimized commensurate with the
18079711_1 (GHMatters) P112816.NZ
current level of contamination and infection by bacteria or other micro-organism, and the
susceptibilities of the tissue and patient. In this embodiment, the liquid stream 50 cleans
the periodontal pocket 52 and promotes tissue healing and regeneration in the periodontal
pocket. Therefore the liquid stream 50 can clean, and therapeuticall y treat, soft tissue. The
liquid stream 50 can also clean hard tissue, such as the surface of the tooth 54, for example
by removal or disruption of a biofilm on the tooth surface. Other dental sites such as root
canals can also be cleaned and the soft tissue therein regenerated. Conventional dental
tools or implements may optionally be used to open up the periodontal pocket 54 for
cleaning and treatment.
Conventional dental suction devices may be employed to remove the run-off of the
liquid stream, and to suck the liquid from the periodontal pocket and the oral cavity after
the liquid has performed a cleaning/treating function against the soft and hard tissue
surfaces to be treated. The removed liquid run-off may be stored for disposal or subsequent
analysis. For example, the removed liquid run-off from the oral cavity may be analysed to
determine the composition of the liquid, for example to target subsequent therapeutic
treatment, such as drug or pharmaceutical therapy. Other anatomical structures that would
be similarly treated include sinuses, ear canal, the digestive and the genito-urinary systems,
and anatomical spaces or potential spaces in general or particular (e.g. as in the eye).
Referring to the embodiment of Figure 3, the apparatus is modified as compared to
the apparatus of Figures 1 and 2 by providing a cup member 60 having a closed end 62
fitted to the outlet nozzle 64 of the conical body 66. The cup member 60 defines a second
chamber 68. The cup member 60 is configured to receive the output stream 70 from the
outlet nozzle 64 into the second chamber 68 from the closed end 62. The outlet nozzle 64
typically has a circular outlet orifice. The cup member 60 has an open end 72 with an
annular rim 74 configured to form an annular contact against human tissue 76. Typically,
the annular rim 74 is adapted to form an annular seal against the human tissue 76, and the
annular rim 74 may, for example, include an annular groove, chamber or pocket 78 therein
to provide an annular suction device 80 for sealing against the tissue 76.
The cup member 60 and outlet nozzle 64 are configured so that an orientation of
the outlet nozzle 64 relative to the cup member 60 is modifiable thereby to modify the
direction of the output stream 70 within the second chamber 68. Typically, the cup member
60 is composed of a flexible material, optionally a thermoplastic elastomer, or inert
synthetic rubber. In one preferred configuration, additionally or alternatively, outlet nozzle
18079711_1 (GHMatters) P112816.NZ
64 is translationally movable within the cup member 60. Typically, the outlet nozzle 64
and the cup member 60 are connected by a seal 82 therebetween.
The cup member 60 includes at least one outlet port 86 for liquid which
communicates with, and extends away from, the second chamber 68.
In the embodiment of Figure 3, the liquid stream 70 containing the acoustically
excited gas bubbles is directed at a desired direction though the second chamber 68 of the
cup member 60 and against a wound that is at least partially covered by the cup member
60. The liquid stream 70 typicall y comprises sterile water or a sterile saline solution. The
cup member 60 allows the direction of the liquid stream 70 to be aimed at a desired region
of the tissue to be treated, by orienting the outlet nozzle 64 at a desired angle and
translationally moving the outlet nozzle 64 within the cup member 60. The annular rim 74
of the cup member 60 forms and maintains a seal between the cup member 60 and the
skin/tissue/organ surface which reduces, minimises or prevents loss of liquid from the
treatment site covered by the cup member 60. The annular rim 74 may be held against the
skin by suction, for example using the annular groove/pocket 78 to provide annular suction
for sealing against the tissue 76. Additionally or alternatively, the entire cup member 60
can be subjected to an underpressure, or a pressure which is less than atmospheric pressure,
for example by using a suction pump to reduce pressure within the second chamber 68, so
that atmospheric pressure applies a holding pressure on the cup member 60 against the
tissue 76. In such circumstances flow control (e.g. valves, pressure differentials and
gradients) would be needed to ensure satisfactory forward flows, and no backflows,
through orifice 86 and the nozzle outlet 64.
Inthis embodiment, the liquid stream 70 cleans the soft tissue and the wound. The
liquid stream 70 can clean the wound by removing at least one of a contaminant, unwanted
particulate matter, a microbe, a biofilm, and a chemical from the wound. The liquid stream
70 can also clean the wound by disrupting a tissue-bound biofilm in the wound or
anatomical pocket. Furthermore, the liquid stream 70 treats the wound by healing the
wound, such as by stimulating blast cells in tissue in the wound, for example by causing,
promoting or enhancing re-epithelialisation of epidermal tissue in the wound, such as by
stimulating dermal fibroblasts and keratinocytes in epidermal tissue in the wound and
modulating mediators of tissue repair, or similarly regenerating an organ to replace the
normal tissue that would have occupied that location when the organ was healthy.
18079711_1 (GHMatters) P112816.NZ
The run-off of the liquid stream 70 is removed though the outlet port(s) 86. The
run-of may passively flow through the outlet port(s) 86. Alternatively, suction from a
suction pump may be applied to remove the liquid run-off though the outlet port(s) 86.
The removed liquid run-off may be discarded directly, stored for disposal or subsequent
analysis, or be taken for immediate analysis. For example, the removed liquid run-off from
the wound treatment may be analysed to determine the composition of the liquid, for
example to detect microbial species, to detect biofilm components or composition, or to
target subsequent therapeutic treatment, such as drug or pharmaceutical therapy.
The outflow from the cup can be disposed of; or alternatively sent for measurement
tests to provide a rapid diagnosis. Such a rapid diagnosis would be extremely valuable,
because if the injury contains a bacterial biofilm, then if an effective treatment can be
applied within 24 hours of the ultrasonic disruption of the biofilm (indeed, the sooner the
better within that 24 hour window), it can be far more effective at healing the wound and
combatting the infection than if the same treatment is applied after the 24 hour window
after disruption of biofilm. Ironically, guidelines which insist on rapid treatment of
infection in order to save lives in the short term, might indeed put lives in danger in the
longer term by promoting the use of broad-spectrum antibiotics, if the guideline window
for treatment does not allow sufficient time to identify the microbe present and any
resistances it has. A rapid diagnosis based on the run-off from the wound would reduce
this hazard. Similar comments apply for other forms of microbe.
When the apparatus of the preferred embodiments of the present invention is
employed to treat human or animal tissue, the liquid supply system 21 is adapted to supply
a liquid flow through the inlet at a flow rate of from 0.1 to 7 litres/minute, optionally from
0.1 to 0.75 litres/minute, for example from 0.25 to 0.5 litres/minute. Typically, the outlet
nozzle 14 is configured to generate an output stream of liquid flow having an average
width of from 0.25 to 20 mm, optionally from 0.25 to 10 mm, further optionally from 0.25
to 4 mm, for example from 0.5 to 2 mm. The acoustic transducer 22 is configured to
generate acoustic energy having a frequency of from 0.1 to 5 MHz, for example from 0.5
to 5 MHz. The gas bubble generator 32 is configured to provide in the output stream
bubbles having a radius of from 0.5 to 40 µm, optionally from 0.6 to 20 µm for example
from 0.75 to 4 µm. Note however that the flow rate, stream diameter, frequency, optimal
and maximum permissible bubble sizes and void fractions, and the amplitude of the sound
field at the target tissue, cannot be independently selected, and instead the choice of one
18079711_1 (GHMatters) P112816.NZ
of these (starting with the front of this list and working forwards) narrows down the
possible range of values from which one might select items later in the list.
For example, in human dental or for wound treatment on a hospital ward, the
volume flow rate, or flux, of liquid to the site of interest may advantageously not exceed
0.3 litres/min. If, for example, the site were the mouth, then greater flow rates would
generate acceptance problems with dental patients. If the treatment site is a wound, for
example on human skin, greater flow rates would produce volumes of run-off that would
be inconvenient to handle. Moreover, there may be an enhanced risk of spillage of
infectious material with increasing flow rates. However flow rates up to much higher
values, for example 5 litres per minute, might be acceptable for wound treatment in large
animals in a zoo situation.
Furthermore, one advantage of having low flow rates is that the run-off may be
collected and used for subsequent diagnostic analysis. For example, the analysis may be
for an infection by bacteria or other micro-organism, such as with an objective to meet a
24 hour time window within which a correct antibiotic would be effective against a
disrupted biofilm. When such an analysis is employed, the volume of post-rinse run-off
liquid should not be inconveniently large, resulting in the microbial load being
inconveniently dilute, which would mitigate against easy handling, analysis and
diagnostics.
For a given liquid flow rate, this parameter correspondingly impacts on the
dimensions of the width or cross-section of the liquid stream. Since the flow speed cannot
fall below a minimum speed without the stream breaking up and preventing the sound
passing down it to reach the wound, to meet the criterion of the selected flow rate the width
dimension, for example the average width, which is the diameter for a circular cross-
section stream, of the liquid stream must be selected to provide the desired flow rate
without the risk of breaking up the stream. With a flow rate of about 0.3 Litres/min, the
diameter is typically around 1 mm. Larger flow rates allow for commensurately wider
streams.
For a given average width of the liquid stream, this parameter in turn
correspondingly impacts on the ultrasonic frequency of the acoustic energy. The average
width corresponds to a minimum threshold for the ultrasonic frequency otherwise the
ultrasound would be evanescent in the liquid stream, and the acoustic energy would not
propagate in the liquid stream to the target tissue/wound/pocket. For a stream average
18079711_1 (GHMatters) P112816.NZ
diameter which is typically around 1 mm, the ultrasonic frequency is preferably at least 1
MHz.
For a given ultrasonic frequency of the acoustic energy, this parameter in tum
correspondingly impacts on the gas bubble radius. The ultrasonic frequency corresponds
to the dimensions of the bubbles on which the Faraday waves and other surface waves on
the bubble wall need to be stimulated. For an ultrasonic frequency which is at least l MHz,
typically the effective gas bubbles are about 1 µm in radius. The actual optimal bubble
size is that which experiences resonance pulsation with the sound field frequency, which
can be calculated once the gas and liquid parameters are known (e.g. liquid density, static
pressure etc.) noting that once the bubbles are smaller than about 30 microns in radius, it
is important for most bubbles not to neglect the influence of surface tension in determining
the pulsation resonance bubble size for a given ultrasonic frequency. Significantly larger
bubbles than this optimal bubble size (e.g. bubbles having radii more than 10% greater
than the radius of the bubble that is in pulsation resonance with the ultrasonic frequency)
would tend to degrade the sound field.
For a given bubble dimension, it should be provided that bubbles larger than the
desired radius (the radius that is resonant with the sound field, i.e. 1 micron radius for a
sound field of, say, 3 MHz), are absent from the liquid stream, while at the same time
ensuring, for example by microfluidic or electrolytic bubble generation, that there are
bubbles of the desired radius, for example 1 µm, present in order to host the surface waves.
For example, the liquid flow may be treated to remove bubbles larger than a selected
radius.
This combination of parameters provides the advantage that small bubbles can,
through the action of flow and acoustic radiation forces, penetrate smaller crevices than
can larger bubbles.
Bubbles of pulsation resonance size are useful for cleaning, healing and tissue
regeneration, but larger bubbles degrade the cleaning/healing/regeneration effect, because
they scatter and absorb the sound field without contributing to the cleaning, healing and
tissue regeneration. This attenuates the acoustic power that would otherwise reach the
resonant bubbles, and so hinders cleaning, healing and tissue regeneration. Therefore it is
vital to remove such larger bubbles from the flow. This can be achieved by a Venturi, an
outgasser, and/or the use of degassed water. Any or all can be used, though if not all can
18079711_1 (GHMatters) P112816.NZ
be used, the outgasser is preferred unless the skilled person has access to adeqate supplies
of degassed water which can be fed into the device without entraining bubbles.
For a selection of an ultrasonic frequency and bubble dimension, the acoustic
driving pressure can be increased to enhance the achievement of surface waves at the
bubble wall. Furthermore, salts, such as sodium chloride, and surfactants may be provided
in the liquid stream to selected to modify the surface properties, for example the surface
tension, of the bubble wall and enhance the achievement of surface waves at the bubble
wall.
Furthermore, the flow speed of the liquid stream will have an influence on the
existence and effect of Rayleigh perturbations in the liquid stream, which tend to generate
narrowing in the stream. The cut-off frequency for the stream waveguide is determined by
the dimension of the narrowest part of the stream, and so such Rayleigh perturbations
would tend to reduce the ability of ultrasonic acoustic energy in the MHz range to travel
down the stream. The option of increasing the ultrasonic frequency, to be above the cut-
off frequency for the narrowest part of the stream, is not an option, because that would
require a commensurate decrease in the bubble size (from 1 µm to, for example, 0.1 µm
radius), and this would produce difficulties in generating Faraday surface waves at the
bubble wall. Consequently, the ultrasonic frequency cannot be freely increased, and so the
generation of the Rayleigh perturbations in the stream must be controlled by providing a
selection of flow rate, flow speed and stream width as discussed above.
Various example scenarios showing how maximum and minimum parameters may
be calculated are shown in Table 1. Some of these parameters are dictated by the laws of
physics, and some of these parameters may, for example, constitute preferred practical
upper or lower limits. These examples employ calculations for a variety of wound
cleaning, healing and tissue regeneration applications. The example calculations are made
assuming air bubbles in clean water with no added salts at room temperature under 1 bar
of static pressure.
18079711_1 (GHMatters) P112816.NZ
Table 1
Column Column
1 3 4 5 6 7 8 9
operating operating
operating Max
Volume Optimal Max
Flow Min bubble bubble
(L/min)
In the column marked Column l , a number of different aqueous liquid flow rates
are indicated. In the method of the invention, a flow rate is selected to match the particular
application, for example an oral care application for a human patient in which the liquid
stream is applied into the mouth at a flow rate which is sufficiently low to avoid flooding
the mouth with the aqueous liquid.
Column 2 specifies the minimum width or radius of the stream (note this is the
radius, i.e. half the diameter if the stream perimeter is circular). The minimum radius of
the stream is calculated from the flow rate. The minimum stream radius follows from the
requirement to avoid the production of a high pressure jet, since a low pressure stream of
aqueous liquid is desired in the method of the invention, for example having a maximum
stream pressure of 50 kPa, which substantially corresponds to 0.5 atm pressure. Here we
refer to the pressure generated by the flow of the stream itself on the target (which must
18079711_1 (GHMatters) P112816.NZ
not be confused with the acoustic pressure of the ultrasonic field, or the radiation pressure,
or the pressure within the bubble, or the pressure waves radiated by a cavitation event).
Such pressures in the flow exceed 50 kPa in the least powerful pressure/power washers,
where the pressure and flow in the stream are the mechanism used in cleaning. The present
invention seeks to avoid unwanted damage to the wanted tissue from such pressures, and
instead generate cleaning, healing and tissue regeneration using the effects of non-inertial
cavitation.
Column 3 specifies the maximum radius of the stream, based on the requirement
for stream stability, to avoid it breaking up into drops or undergoing narrowing and
distortion by large instabilities, as discussed above.
For each stream radius, there is a minimum and maximum operating frequency.
The minimum operating frequency shown in Column 4 is based upon the acoustic cut-off,
below which sound will not travel down a stream with pressure-release walls as seen from
the sound field in the water, as discussed above.
There is no firm basis for stating a maximum operating frequency, and the values
given in Column 5 are based on a practical solution of multiplying the minimum frequency
by a factor of 5. Unlike the minimum operating frequency (Column 4), these maximum
operating frequency values are not constraining, or based on the laws of physics, but are a
practical solution a single transducer is used to drive the sound field, placing a limit of the
energy at roughly the 5th harmonic of the fundamental (note that an integer of 5 here only
roughly represents the actual frequency multiplier for this circular stream, because the
actual multiplier would be based on the appropriate Bessel function). Because these values
are not based on the laws of physics, for illustrative purpose the values in Column 5 are
placed in brackets.
Column 6 shows the optimal bubble radius, for the corresponding frequency stated
in the same row in Column 4 or Column 5). This parameter is dependent on the pulsation
resonance of the bubble for the frequency in question. An operating frequency between
the upper and lower frequencies stated in Columns 4 and 5 may be chosen, but note that
there are there are 2 upper and 2 lower frequencies for each value of the flow rate initially
selected in Column 1 at the start of the parameter determination process. Therefore by
stating an optimal bubble size, it is important to note that that optimal size is a one-to-one
mapping that directly follows from the frequency used. If a mode frequency between the
upper and lower limits is chosen, then the optimal bubble size will be some value between
18079711_1 (GHMatters) P112816.NZ
those limits stated in Table 1, directly as a consequence of the operating frequency being
changed, for example to suit the choice of an optimal acoustic field in the cone, or the
transducer resonance, or (most likely) both.
Column 7 shows the maximum bubble radius, which is a calculated approximation.
The optimal bubble radius is given by the pulsation resonance of the bubble for the
frequency in question. Bubbles significantly larger than this will degrade the sound field
by scattering. Therefore it is an advantage to ensure that no bubbles larger than 110% of
the resonance bubble radius (which would correspond to 100% on this scale) are present.
However the extent to which large bubbles degrade the sound field depends on their void
fraction (the proportion by volume of bubbly water that is free gas), and a very low void
fraction might enable bubbles as large as 140% to be present and still allow operation of
the device. Just as with Column 6, if the operating frequency takes a value between the
maximum and minimum values allowed in Table 1 for a given flow rate and stream radius,
then the maximum bubble radius will change accordingly.
The optimal bubble size (Column 6) is in pulsation resonance with the sound field,
and that conditions corresponds to there being a minimum acoustic pressure of that
resonant sound field that will be required to simulate Faraday waves on that optimally-
sized bubble. This minimum acoustic pressure at the target tissue is given in Column 8 and
can be calculated. If the surface to be treated is a delicate but desirable structure (e.g.
healthy tissue to be retained undamaged, which is often the case but not necessarily if a
surgeon wishes to generate debridement), then it is desirable to avoid inertial cavitation,
and that places an upper acoustic pressure on the sound field at the target tissue, as listed
in Column 9. As with Columns 6 and 7, if the ultrasonic frequency is selected to be some
intermediate value between the minimum (Column 4) and maximum (Column 5) values
(in order to tune the transducer resonance to the frequency of a desirable sound field mode,
for example), then the optimal bubble size will vary between the limits shown for the
stream in question, and the minimum (Column 8) and maximum (Column 9) acoustic
pressure amplitudes will need to be calculated within the ranges shown.
[l 07] From Table 1, some desired parametric combinations for the aqueous liquid stream
and entrained acoustically excited bubbles can be specified for different given ranges of
volume flow rate of the liquid stream. These are shown in Table 2.
18079711_1 (GHMatters) P112816.NZ
Volume
to 4
I .5 to
3 to
>2 to 4
>4 to 6 3.5 to
As an additional preferred mechanism to generate bubbles, electrochemical bubble
seeding technology has been developed. Pulsed bubble generation (creating a bubble
swarm) in tandem with pulsed acoustic excitation may generate 'active' bubbles on the
surface to be cleaned, healed and regenerated. An amplitude or frequency modulated
sound field, coupled with the acoustic energy optionally being switched on and off, may
be employed to maximise the acoustic pressure delivered by the apparatus to the surface
to be treated in the presence of a suitable bubble swarm. Such independent control can
vary the bubble pulses and the acoustic energy pulses independently so that at the surface
to be treated the bubbles and the acoustic energy pulse can be incident on, or in the vicinity
of, the surface substantially simultaneously to enable efficient treatment of the substrate
by the acoustic energy causing non-inertial cavitation of the bubbles at or in the vicinity
of the surface.
Such pulsing of the acoustic energy does not need necessarily to turn the sound
field off between pulses, but instead may modulate the acoustic energy, by amplitude or
frequency modulation, it to provide high energy acoustic pulses separated by low energy
background.
In some embodiments, the sound is turned off as the bubble swarm travels down
the stream (to prevent acoustically-induced bubble coalescence), and then the sound is
turned on to provide a modulated acoustic energy pulse once the bubble swarm reaches
the surface to be treated. Once these bubbles have undertaken some treatment and started
to disperse in the flow, the sound is turned off and another swarm of bubbles is generated
at the nozzle and the process is repeated.
18079711_1 (GHMatters) P112816.NZ
It is critically important to ensure that pulsing of the sound field and the bubble
generation are coordinated to satisfy the following two rules:
The sound is not activated to achieve cleaning or healing when the bubbles are anywhere
(in nozzle, stream etc.) except at, or very close to, the location where it is intended to treat
the tissue. Otherwise bubbles in the water (even optimally-sized bubbles) attenuate the
passage of the sound from the transducer to the target tissue; and the sound field causes
the bubbles to coalesce to a size that is greater than the maximum allowed bubble radius.
This means that the off-time of the pulsed acoustic field corresponds to the time taken for
the tight bolus of bubbles produced by the bubble generator to travel in the flow from the
bubble generator to the target tissue (e.g. 30-600 ms, where greater cleaning ranges require
longer times, but faster flow speeds reduce this).
The sound to achieve cleaning or healing is timed to come on just as the bolus of bubbles
reaches the location where it is expected that the target tissue is located, and to persist until
the bubbles have largely stopped delivering beneficial effects to the target tissue. This
means that the sound pulse intended to achieve cleaning or healing persists for around 50
The independent control can be achieved by taking into account the fact that sound
travels down the liquid stream at a different speed to the bubbles. The timing of the current
supplies used to generate bubbles and sound is such as to ensure both bubble swarm and
ultrasound arrive at the surface at the same time. Given this criterion, the different transit
times of bubbles and sound down the tube dictate the timing for the activation of the
currents which generate sound and bubbles, such that their activations may be staggered if
the timing so dictates. The underlying technical concept is to utilise their different transit
times down the liquid stream to ensure that the bubbles and acoustic energy occur at the
same time at the surface which is to be treated.
[1 13] A preferred control protocol for the transducer 22 and bubble generator 32 is
illustrated in Figure 19. In Figure 19, the relationship between voltage supplied to the
transducer and to the bubble generator (the electrolysis wires; the pump or solenoid for
introducing bubbles into the flow by microfluidics or Venturi) are shown on a common
time axis for a pair of successive treatment cycle, each cycle providing a pulse of
acoustically excited bubbles against the target surface.
In a first phase 100, the voltage is off and the transducer is not activated. In a
second phase 102, a short signal l 04 activates the bubble generator to produce a tight bolus
18079711_1 (GHMatters) P112816.NZ
(i.e. a small cloud) of bubbles that can then travel down the flow with relatively bubble-
free water before and after it.
In a third phase 106, no ultrasound or bubbles are generated. This third phase 106
ensures that no sound propagates down the stream while bubbles are propagating down
the liquid in the flow towards the target tissue. In this third phase 106 the liquid flow
carries the bubbles towards the target surface located downstream of the nozzle outlet.
In a fourth phase 108, which is initiated at the moment the bubbles reach the target
surface, the ultrasound is activated. In Figure 19, the envelope l l 0 of the nearly sinusoidal
signal emitted by the transducer is shown as the fourth phase 108. The transducer 22 is
activated at a frequency which is close to the resonant frequency of the bubbles and close
to a resonance of the transducer. The acoustic energy acoustically excites the bubbles at
the target surface to be treated, and preferably generates surface waves in the bubble walls.
The bubbles exhibit non-inertial cavitation at the target surface, providing the desired
effects on the surface as discussed above.
Then the cycle of first to fourth phases is repeated to providing a successive cycle
in which a further bolus of bubbles is generated and travels in the flow towards target
surface. After the fourth phase 108, there is a successive first phase 100 during which the
transducer is not activated which allows the bubbles and tissue to be flushed away from
the wound/tissue.
By increasing the time period of the third phase 106, prior to initiation of the
acoustic excitement of the bubbles at the target surface, targets at greater range from the
transducer can be effectively treated. If the target surface is at a variety of ranges from the
nozzle outlet, for example from 1 to 10 cm, then the time period for the third phase 106
can be correspondingly varied, either to provide a selected fixed time period for the third
phase 106 or to provide a progressively changing time period for the third phase 106 over
successive cycles. For example, in a sequence of cycles, the third phase 106 may have a
progressively increasing time period to accommodate treatment at progressively
increasing distances away from the nozzle outlet.
Note that it is particularly appealing to use one transducer to serve both functions,
of generating the bubbles and undertaking cleaning and healing. In such circumstances
there is no need of a bubble generator placed at location 32 in the nozzle, and that item 32
can be omitted as a separate item in the nozzle, because the transducer 22 now takes on its
function, as well as retaining its former function of generating ultrasound to cause both
18079711_1 (GHMatters) P112816.NZ
cleaning and healing. This simplifies construction, though the off-times of the pulses that
precede the pulses intended to cause cleaning and healing must be longer, because the
bubbles must traverse not only the length of the liquid stream (as they did when the bubble
generator was in the nozzle), but also the length of the nozzle and cone. The voltage
applied to the transducer 22 to conduct both the bubble generation function and the
cleaning and healing functions, is shown in Figure 20. The preferred control protocol for
the transducer 22 if it serves both as the bubble generator and as the source of the pulse
for cleaning and healing, is illustrated in Figure 20. In Figure 20, the relationship between
voltage supplied to the transducer and time is shown for a pair of successive treatment
cycle, each cycle providing a pulse of acoustically excited bubbles against the target
surface. Note that the line plotted in Figure 20 is the envelope of nearly sinusoidal signals
(or a summation of nearly sinusoidal signals).
Referring to Figure 20, in a first phase 200, the voltage is off and the transducer is
not activated. In a second phase 202, a short period high amplitude voltage pulse 204
activates the transducer. This generates a small cloud of bubbles. The frequency of the
transducer activated in the second phase 202 may be at a lower frequency than the resonant
frequency of the bubbles, and at a lower frequency than the resonant frequency of the
transducer, because the purpose of the ultrasound in the second phase 202 is to generate
bubbles rather than to acoustically excite the bubbles.
In a third phase 206, the transducer is not activated, and no ultrasound is generated.
This third phase 206 ensures that no sound propagates down the stream while bubbles are
in the chamber of the conical body or the nozzle. In this third phase 206 the liquid flow
carries the bubbles towards the target surface located downstream of the nozzle outlet.
In a fourth phase 208, which is initiated at the moment the bubbles reach the target
surface, the ultrasound is activated. In Figure 19, the envelope 210 of the nearly sinusoidal
signal emitted by the transducer is shown as the fourth phase 208. The voltage, and
correspondingly the amplitude of vibration, may be different, e.g. lower, than in the second
phase 202. The transducer is activated at a frequency which is close to the resonant
frequency of the bubbles and close to a resonance of the transducer. The acoustic energy
acoustically excites the bubbles at the target surface to be treated, and preferably generates
surface waves in the bubble walls. The bubbles exhibit non-inertial vibration at the target
surface, providing the desired effects on the surface as discussed above.
18079711_1 (GHMatters) P112816.NZ
Then the cycle of first to fourth phases is repeated to providing a successive cycle
in which a further pulse of acoustically generated bubbles is directed against the target
surface. After the fourth phase 208, there is a successive first phase 200 during which the
transducer is not activated.
By increasing the time period of the third phase 206, prior to initiation of the
acoustic excitement of the bubbles at the target surface, targets at greater range from the
transducer can be effectively treated. Ifthe target surface is at a variety of ranges from the
nozzle outlet, for example from I to 10 cm, then the time period for the third phase 206
can be correspondingly varied, either to provide a selected fixed time period for the third
phase 206 or to provide a progressively changing time period for the third phase 206 over
successive cycles. For example, in a sequence of cycles, the third phase 206 may have a
progressively increasing time period to accommodate treatment at progressively
increasing distances away from the nozzle outlet.
In any of the embodiments, the inlet 18 may be provided with an acoustic isolation
device which prevents acoustic energy being transmitted back along the liquid supply
conduit 20. The acoustic isolation device may comprise an acoustic filter, optionally
having a selected frequency range, and/or a narrowing or expansion in the conduit 20,
and/or an expansion chamber, and/or by control of the diameter of the conduit to provide
that the driving frequency is below the cut-off frequency of all modes for the inlet (as
would happen for sufficiently small-bore manifold inlets made of pressure-release
material).
In these embodiments, the apparatus size can be varied to provide varying volumes
of the liquid stream. Smaller or larger volumes can be achieved by scaling the flow rate,
nozzle size and the driving acoustic frequency, thereby to provide an aqueous liquid stream
impacted onto the surface accompanied by a suitable sound field and active bubbles.
The bubble generator 32 is adapted to generate gas bubbles which are then
acoustically excited and impact on the surface to be cleaned, healed and regenerated. The
bubbles are driven into oscillation by the acoustic energy and can get into crevices and
pores on the substrate to be cleaned, healed and regenerated, so that they effectively clean,
and stimulate healing and regeneration in, the substrate.
The bubble generator 32 may act directly to inject gaseous bubbles into the fluid
flow, for example through a needle, the needle optionally vibrating. Other options for
bubble generation include through use of cavitation (hydrodynamic or acoustic) or free-
18079711_1 (GHMatters) P112816.NZ
surface bubble entrainment, or chemical gas production, or by a more preferred route of
electrochemical in situ generation of gas bubbles by electrolytic decomposition of the
water in the liquid flow. If the liquid has low conductivity, conductive polymers can be
placed between the electrodes. The bubble generator 32 adapted for electrochemical
bubble generation comprises an electrode comprising an array of electrically conductive
wires, for example platinum wires having a diameter of 50 µm, extending across the outlet,
for when bubbles of around 20-30 µm radius are required. Commensurately smaller
bubbles in general demand thinner wires, depending on the surface tension of the liquid.
The electrode is connected to a source of electrical energy (not shown) and, when
electrically powered, the electrical energy electrolytically decomposes water in the fluid
flow to generate bubbles of both oxygen and hydrogen gas which are entrained in the
flowing fluid and directed towards the target surface to be cleaned, healed, regenerated.
Ozone generators can similar be operated and incorporated in this way.
The bubble generator may be controlled by a controller so that bubbles are formed
intermittently to form boluses (intermittent swarms or waves) of bubbles which
successively impact against the surface to be cleaned, healed, and regenerated. When the
bubbles impact the surface to be cleaned/healed/regenerated, the bubbles are driven to
oscillate by the acoustic energy, thereby penetrating crevices which are
cleaned/healed/regenerated by the acoustic energy and the effect of the bubble non-inertial
cavitation, particularly the surface waves on the bubble wall and the local shear and
secondary waves that they generate in the surrounding local medium. It is particularly
beneficial not to produce such swarms or boluses independent of the acoustic pulsing, but
rather to coordinate the timing of the pulsing to the bubble generation and bubble
generation systems as shown in Figure 19, in order to ensure that:
One does not activate the sound to achieve cleaning or healing when the bubbles are
anywhere (in nozzle, stream etc.) except at, or very close to, the location where one hopes
to treat the tissue. Otherwise bubbles in the water (even optimally-sized bubbles) attenuate
the passage of the sound from the transducer to the target tissue; and the sound field causes
the bubbles to coalesce to a size that is greater than the maximum allowed bubble radius.
This means that the off-time of the pulsed acoustic field corresponds to the time taken for
the tight bolus of bubbles produced by the bubble generator to travel in the flow from the
bubble generator to the target tissue (e.g. 30-600 ms, where greater cleaning ranges require
longer times, but faster flow speeds reduce this).
18079711_1 (GHMatters) P112816.NZ
The sound to achieve cleaning or healing is timed to come on just as the bolus of bubbles
reaches the location where one expects the target tissue to be, and to persist until the
bubbles have largely stopped delivering beneficial effects to the target tissue. This means
that the sound pulse intended to achieve cleaning or healing persists for around 50 ms.
The amplitude or frequency modulated acoustic energy from the transducer may
be pulsed intermittently. This produces pulses of acoustic energy, which interact with the
intermittent bubble swarms described above, in a concerted manner.
The acoustic energy of the pulse activates the bubbles of the swarm at the surface
to effect enhanced cleaning, and the stimulation of healing and tissue regeneration
mechanisms, by non-inertial vibration of the bubbles at the surface, and optionally
generating surface waves in the bubbles. This completes a cleaning (and the stimulation
of healing and tissue regeneration mechanisms) cycle for a single bubble swarm. A next
cleaning and therapy cycle for a subsequent bubble swarm is then initiated by generation
of the subsequent bubble swarm.
At the nozzle there is a particular phase relationship between the generation of the
sound pulse and the generation of the pulse of bubbles. The phase relationship changes
as the sound and bubbles are transmitted away from the nozzle through the liquid since the
acoustic energy and the bubbles are transmitted at different velocities through the liquid
towards the surface to be cleaned, and in which healing and tissue regeneration processes
are to be stimulated. The aim is to provide a phase relationship, which typically involves
a delay time tct between bubble generation and generation of the pulse of the acoustic
energy, so that the acoustic energy and the bubbles reach the surface to be cleaned (and in
which healing and tissue regeneration processes are to be stimulated) in phase and at the
same time.
Therefore by employing pulsed bubble generation and pulsed generation of
acoustic energy in a coordinated manner, bubbles are excited at the surface so that bubbles
are present at the surface when the acoustic energy is also at the surface, and furthermore
the cleaning impact (and the stimulation of healing and tissue regeneration processes)
achieved by both the bubbles and the acoustic energy is increased by additionally
providing that the acoustic energy is amplitude or frequency modulated at a higher
frequency that the pulses, greatly improving cleaning efficacy (and the stimulation of
healing and tissue regeneration processes). The presence of a bubble swarm formed
between a pair of acoustic energy pulses separates those acoustic energy pulses. Each
18079711_1 (GHMatters) P112816.NZ
bubble swarm is independently impacted on the surface to be treated and independently
excited by the acoustic energy of the succeeding acoustic energy pulse.
In accordance with a further aspect of the apparatus and method of the present
invention, it has been found that the addition of a surfactant to the liquid can affect the
bubble size achievable without bubble coalescence. Sufficient surfactant may be added,
if necessary, to prevent coalescence of bubbles as they flow down the stream if, without
surfactant, such coalescence produces bubbles too large for appropriate cleaning (and the
stimulation of healing and tissue regeneration processes); but not so much surfactant that
the bubbles are too small for cleaning (or the stimulation of healing and tissue regeneration
processes) when they reach the site.
The particular total surfactant and surfactant concentration values to achieve the
desired bubble activity may be dependent on the type of surfactant employed.
The present invention will now be described in greater detail with reference to the
following non-limiting Examples.
Example 1
In this example, the cleaning of bacteria from a wound in animal and human tissue
was investigated using the method and apparatus of the present invention.
In order to examine the therapeutic effect of an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention on biofilm in biological
soft tissue, a series of in vitro experiments were performed.
Two wound models were used: pig trotters obtained from a butcher (and so
containing no remaining healing property); and a pre-wounded cultured human skin model
(EpidermTM FT, Mattek Inc, USA). The EpiDerm models were maintained in an antibiotic
free medium under standard cell culture conditions at 37°C and 5% C02. Early stage
biofilms were cultured within the wounds using fluorescent-tagged Pseudomonas
aeruginosa pMF230 and SYT0-9 pre-stained E-MRSA-16.
Once established with biofilm, the wound models were rinsed with either a
conventional saline wash (2 I/min) or an ultrasonically activated gas bubble-containing
saline stream in accordance with the present invention (2 l/min), and residual bacteria
within the wounds before and after treatments was visualised by direct in situ
epifluorescence microscopy.
Following a one-minute or two-minute treatment (the text states which) with an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
18079711_1 (GHMatters) P112816.NZ
invention, a significant amount of biofilm was seen to have been removed from both
models.
Figure 4 shows images of the pig trotter wound model having -2 cm diameter
wounds produced within frozen/thawed pig trotters, before inoculation (A), post
inoculation of Pseudomonas aeruginosa pM F230 and incubation at 37°C for 5 hours (B)
and post and wound beds post 2 min treatment by an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention (C). Scale bars represent
2 cm.
Figure 5 shows direct EDIC/EF micrographs of SYT0-9 pre-stained E-MRSA-16
accumulation/early biofilm within the pig trotter wounds after 5 hour incubation at 37°C.
This figure shows E-MRSA-16 in situ detection. Figure 5 shows the results with no
treatment (A), after a 1 min saline wash at a flow rate of 2 L/min (B) and after a 1 min
treatment by an ultrasonically activated gas bubble-containing saline stream in accordance
with the present invention at a flow rate of 2 L/min (C). Scale bars represent lOµm.
Figure 6 shows Pseudomonas aeruginosa pMF230 in situ detection in direct
EDIC/EF micrographs of GFP tagged Pseudomonas aeruginosa pMF230
accumulation/early bipfilm within the pig trotter wounds after 5 hour incubation at 37°C;
with no treatment (A), after a 1 min saline wash at a flow rate of 2 L/min (B), after a l min
treatment by an ultrasonically activated gas bubble-containing saline stream in accordance
with the present invention at a flow rate of 2 L/min (C) and after a 2 min treatment by an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention at a flow rate of 2 L/min (D). Scale bars represent l Oµm.
Figure 7 shows Pseudomonas aeruginosa pMF230 in situ detection image analysis,
in particular image analysis (ImageJ) of EDIC/EF micrographs demonstrating the
percentage coverage of GFP tagged Pseudomonas aeruginosa pMF230
accumulation/early biofilm within the pig trotter wounds after 5 hour incubation at 37°C;
with no treatment (Control), after a 1 or 2 min saline wash at a flow rate of 2 L/min (Saline)
and after a l or 2 min treatment by an ultrasonically activated gas bubble-containing saline
stream (i.e. an ultrasonically activated stream (UAS) in accordance with the present
invention at a flow rate of 2 L/min (DAS/Saline). Error bars represent the standard error
of the mean (N=3), One way ANOVA/Tukey post hoc test demonstrated *** = p :S 0.001
when compared to the non-treated controls.
18079711_1 (GHMatters) P112816.NZ
Figure 8 shows Pseudomonas aeruginosa pMF230 in situ detection image analysis,
in particular image analysis (ImageJ) of EDIC/EF micrographs demonstrating the
percentage coverage of GFP tagged Pseudomonas aeruginosa pMF230 biofilm within the
EpidermFT (Epiderm full thickness tissues (EFT), MatTek, USA) wound models after 24
hour incubation at 37°C. Data demonstrates % coverage straight (a) after treatment and (b)
24 hours post cleaning with no treatment (Control), after a 2 min saline wash at a flow rate
of 2 L/min (Saline) and after a 2 min treatment by an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention at a flow rate of 2 L/min
(UAS/Saline). Error bars represent the standard error of the mean (N=3), One way
ANOVA/Tukey post hoc test demonstrated = p :S 0.001 when compared to the non-treated
controls.
These results illustrated in Figures 4 to 8 demonstrate that a wound treatment by
an ultrasonically activated gas bubble-containing saline stream in accordance with the
present invention is highly effective in removing bacterial biofilm from a living human
cell wound model, without causing damage as shown by the normal microscopic
architecture of the EFT skin model after treatment.
There is also an enhanced effect, with biofilm showing no regrowth at 24 hours
post treatment.
This data suggests that wound treatment by an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention is superior to
conventional low frequency ultrasound (LFUS) systems used in wound care, where
repeated applications and the use of biocides is often required to achieve lower levels of
biofilm disruption than observed with the method of the present invention.
Example 2
[ l 50] To explore whether wound treatment by an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention had any effect on the
rate of wound healing, a series of EpiDerm models, pre-wounded using a 3mm punch
biopsy, were treated with either a single plain saline wash or a single saline wash using an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention.
The wounds were maintained under standard cell culture conditions, and samples
of the culture media taken at day 0 and day 7 for analysis of matrix metalloproteinases
(MMP l , 3, and 9) by enzyme immunoassay, as biochemical markers of fibroblast and
18079711_1 (GHMatters) P112816.NZ
keratinocyte activity in wound healing. At 7 days post treatment the wound sizes were
calculated and the EpiDerm models were fixed in formalin and paraffin embedded.
Transverse sections were prepared and stained with haematoxylin and eosin to permit basic
histological examination Additional sections were prepared for immunohistochemical
examination of fibroblast and keratinocyte activity and wound healing markers.
A reduction in wound diameter was seen in all EpiDerm models, showing that the
models had remained viable throughout the time course of the experiment. No difference
was observed between untreated control wounds and those treated with a plain saline wash.
However the wounds treated with an ultrasonically activated gas bubble-containing
saline stream in accordance with the present invention showed a significant (p = ::; 0.01)
reduction in wound size, demonstrating a direct stimulation of healing.
Figure 9 shows wound healing in the Epiderm full thickness wound models. These
are example micrographs taken using a dissection microscope demonstrating the wound
sizes 7 days post rinsing; with no treatment (A), after a 2 min saline wash at a flow rate of
2 L/min (B) and after a 2 min treatment by an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention at a flow rate of 2 L/min
(C). Scale bars represent lmm.
Figure 10 shows wound healing in the Epiderm full thickness wound models, and
is an image analysis results demonstrating the wound diameters 7 days post rinsing; with
no treatment (Control), after a 2 min saline wash at a flow rate of 2 L/min (Saline) and
after a 2 min wound treatment by an ultrasonically activated gas bubble-containing saline
stream in accordance with the present invention at a flow rate of 2 L/min (DAS/saline).
Error bars represent the standard error of the mean (N=3). One way ANOVA/Tukey post
hoc test demonstrated ** = p ::; 0.01 when compared to the non-treated controls.
Figure 11 shows Haematoxylin and Eosin (H&E) stained sections from the
Epiderm full thickness wound models, in particular H&E stained sections (4µm) taken
from the EFT wounds 7 days post rinsing ; with no treatment (A), after a 2 min saline wash
at a flow rate of 2 L/min (B) and after a 2 min treatment by an ultrasonically activated gas
bubble-containing saline stream in accordance with the present invention at a flow rate of
2 L/min (C and D). The arrows highlight the re-epithelialization across the wound bed.
Scale bars represent 500 µm.
Figure 12 shows the re-epithelialisation in the Epiderm full thickness wound
models, the image analysis results demonstrating the distance of re-epithelialisation from
18079711_1 (GHMatters) P112816.NZ
the wound edge 7 days post rinsing; with no treatment (Control), after a 2 min saline wash
at a flow rate of 2 L/min (Saline) and after a 2 min treatment by an ultrasonically activated
gas bubble-containing saline stream in accordance with the present invention at a flow rate
2 L/min (DAS/Saline). Error bars represent the standard error of the mean (N=3), T-test
demonstrated * = p :S 0.05 when compared to the non-treated controls.
Histological examination confirmed no tissue damage following treatment by an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention, and an increase in re-epithelization in wounds treated with treatment by an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention compared to controls. Furthermore, immunohistochemistry showed stimulation
of fibroblasts and keratinocyte migration in the wound models treated with an
ultrasonically activated gas bubble-containing saline stream, as illustrated in Figures 13,I 4
and15. Analysis of the cell culture medium showed modulation of matrix
metalloproteinase activity in the wound models treated with an ultrasonically activated gas
bubble-containing saline stream, particularly in the case of MMP9, demonstrating a direct
action on dermal fibroblasts and keratinocyte migration to heal the wound, as illustrated
in Figure 16.
Figure 13 illustrates micrographs showing immunohistochemical staining for
cytokeratin 14 demonstrating stimulation of keratinocyte migration across wound
following treatment by an ultrasonically activated gas bubble-containing saline stream in
accordance with the present invention. Image analysis in graphical form demonstrates
statistically significant increase in keratinocyte migration across the wound bed of the
VAS treated epiderm models. Scale bars represent 500 µm and the error bars represent the
standard error of the mean (SEM).
Figure 14 illustrates micrographs of scans of the full wound bed demonstrating
immunohistochemical staining of Cytokeratin 14 expressing keratinocytes. Full migration
of the keratinocytes demonstrated in Epiderm full thickness tissues (EFT) samples 7 days
post treatment with the UAS system.
Figure 15(a) shows micrographs of immunohistochemical staining of fibroblasts
with vimentin and Figure 15(b) shows image analysis of the counts of
immunohistochemical staining of fibroblasts in the dermo-epidermal junction of the
treated EFT samples.
18079711_1 (GHMatters) P112816.NZ
Figure 16 is a graph showing modulation of matrix metalloproteinase 9 (MMP9)
in the wound model culture medium, demonstrating modulation of MMP9 in models
treated by an ultrasonically activated gas bubble-containing saline stream in accordance
with the present invention.
These results show that that wound treatment by an ultrasonically activated gas
bubble-containing saline stream in accordance with the present invention is able to
stimulate human dermal fibroblasts, keratinocytes and modulate mediators of tissue repair.
Example 3
To explore whether treatment by an ultrasonically activated gas bubble-containing
saline stream in accordance with the present invention had any effect on the viability of
biofilm causing bacteria, P. aeruginosa was inoculated onto stainless steel coupons, dried
and then washed with saline or a saline wash using an ultrasonically activated gas bubble-
containing saline stream in accordance with the present invention. Eluate was sampled,
plated on agar and visualised using microscopy. Similarly, inoculated steel coupons were
visualised using epifluorescence microscopy.
Examination of the steel coupons by epifluorescence microscopy showed no
difference between uninoculated controls and inoculated coupons treated with an
ultrasonically activated gas bubble-containing saline stream, demonstrating the ability to
significantly remove bacterial contamination.
Further examination showed that the majority of P. aeruginosa removed by the
ultrasonically activated gas bubble-containing saline stream were killed, demonstrating a
bactericidal action.
Figure 17 shows EDIC/EF micrographs demonstrating removal of P. aeruginosa
from stainless steel coupons following washing with saline or a saline wash using an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention (A = control, B = saline, C = ultrasonically activated gas bubble-containing
saline stream).
Figure 18 is a graph which shows killing of Pseudomonas aeruginosa using an
ultrasonically activated gas bubble-containing saline stream in accordance with the present
invention.
18079711_1 (GHMatters) P112816.NZ
Claims (41)
1. An apparatus for treating human or animal tissue, the apparatus comprising a conical body defining a chamber, the conical body extending between a base of the conical body and an outlet nozzle of the conical body, wherein the base has an inlet for liquid flow into the chamber and the outlet nozzle is at a conical tip of the conical body and is configured to generate an output stream of liquid flow from the chamber for treating human or animal tissue, an acoustic transducer associated with the conical body and configured to introduce acoustic energy into the liquid within the chamber whereby the acoustic energy is present in the output stream, and a gas bubble generator configured for providing gas bubbles in the output stream that are configured to be excited by the acoustic energy, wherein the conical body and the nozzle thereof are configured t o have pressure amplitude reflection coefficients with respect to the acoustic energy in liquid within the chamber of from -0.95 to -1.0, a liquid supply system adapted to supply a liquid flow through the inlet at a flow rate of from 0.1 to 7 litres/minute, the outlet nozzle is configured to generate an output stream of liquid flow having an average width of from 0.25 to 20 mm, the acoustic transducer is configured to generate acoustic energy having a frequency of from 0.1 to 5 MHz and the gas bubble generator is configured to provide in the output stream bubbles having a radius of from 0.5 to 40 µm, wherein at least one of the acoustic transducer and the gas bubble generator is configured to be controlled such that the frequency of the acoustic energy generated by the acoustic transducer is sufficient to produce non-inertial cavitation on bubble walls of the gas bubbles generated by the gas bubble generator.
2. An apparatus according to claim 1 wherein the liquid supply system is adapted to supply a liquid flow through the inlet at a flow rate of from 0.1 to 0.75 litres/minute, optionally from 0.25 to 0.5 litres/minute.
3. An apparatus according to claim 1 or claim 2 wherein the outlet nozzle is configured to generate an output stream of liquid flow having an average width of from 0.25 to 10 mm, optionally from 0.25 to 4 mm, further optionally from 0.5 to 2 mm.
4. An apparatus according to any one of claims 1to 3 wherein the acoustic transducer is configured to generate acoustic energy having a frequency of from 0.5 to 5 MHz.
5. An apparatus according to any one of claims 1 to 4 wherein the gas bubble generator is configured to provide in the output stream gas bubbles having a radius of from 0.6 to 20 µm, optionally from 0.75 to 4 µm.
6. An apparatus according to any one of claims 1 to 5 wherein the conical body and 18079711_1 (GHMatters) P112816.NZ 46 the nozzle thereof are adapted to have pressure amplitude reflection coefficients with respect to acoustic energy in the liquid within the chamber of from -0.99 to -1.0.
7. An apparatus according to any one of claims 1 to 6 further comprising a cup member having a closed end fitted to the outlet nozzle of the conical body, the cup member defining a second chamber and being configured to receive the output stream into the second chamber from the closed end, the cup member having an open end with an annular rim configured to form an annular contact against human tissue.
8. An apparatus according to claim 7 wherein the cup member and the outlet nozzle are configured so that an orientation of the outlet nozzle relative to the cup member is modifiable thereby to modify the direction of the output stream within the second chamber.
9. An apparatus according to claim 7 or claim 8 wherein the cup member is composed of a flexible material, optionally a thermoplastic elastomer or inert synthetic rubber.
10. An apparatus according to any one of claims 7 to 9 wherein the outlet nozzle is translationally movable within the cup member.
11. An apparatus according to any one of claims 7 to 10 wherein the outlet nozzle and the cup member are connected by a seal therebetween.
12. An apparatus according to any one of claims 7 to 11 wherein the annular rim is adapted to form an annular seal against human tissue.
13. An apparatus according to claim 12 wherein the annular rim includes an annular groove or chamber therein to provide an annular suction device for sealing against tissue.
14. An apparatus according to any one of claims 7 to 13 wherein the cup member includes at least one outlet port for liquid which communicates with, and extends away from, the second chamber.
15. An apparatus according to any one of claims 1 to 14 wherein the outlet nozzle has a circular outlet orifice.
16. An apparatus according to any one of claims I to 15 wherein the acoustic transducer is arranged to function as the gas bubble generator for providing gas bubbles in the output stream by acoustic cavitation.
17. An apparatus according to claim 16 further comprising a controller for the acoustic transducer, wherein the controller is adapted to provide a plurality of sequential operating phases for the acoustic transducer, the phases comprising a bubble generating phase in which the acoustic transducer is activated to generate bubbles in liquid within the chamber, a subsequent rest phase in which the acoustic transducer is inactive to allow the generated bubbles to flow together with the stream out of the nozzle, and a subsequent acoustic excitation phase in which the acoustic transducer is activated to acoustically excite the 18079711_1 (GHMatters) P112816.NZ 47 bubbles which have flowed out of the nozzle, that activation occurring at the moment when the bubbles reach the surface to be cleaned, healed or regenerated.
18. An apparatus according to any one of claims 1 to 14, further comprising a Venturi or an outgasser configured to remove gas bubbles having radii more than 10% greater than a bubble radius configured to be in pulsation resonance with the frequency of the acoustic energy.
19. A method of generating a liquid stream for treating tissue other than human tissue, the method comprising the steps of: a. providing a conical body defining a chamber, the conical body extending between a base of the conical body and an outlet nozzle at a conical tip of the conical body; b. inputting a flow of aqueous liquid into the chamber through an inlet at the base and generating an output stream of liquid flow from the chamber through the outlet nozzle, the output stream having a liquid flow rate of from 0.1 to 7 litres/minute, and the output stream having an average width of from 0.25 to 20 mm; c. providing gas bubbles from a bubble generator in the output stream, the gas bubbles having a radius of from 0.5 to 40 µm; d. introducing acoustic energy from an acoustic transducer having a frequency of from 0.1 to 5 MHz into the liquid within the chamber whereby the acoustic energy is present in the output stream and excites the gas bubbles, wherein the conical body and the outlet nozzle have pressure amplitude reflection coefficients with respect to the acoustic energy in the liquid within the chamber of -0.95 to -1.0; and e. directing the output stream comprising the acoustically excited gas bubbles and acoustic energy towards a surface to be treated; and f. controlling at least one of the acoustic transducer and the gas bubble generator such that the frequency of the acoustic energy generated by the acoustic transducer is sufficient to produce non-inertial cavitation on bubble walls of the gas bubbles generated by the gas bubble generator.
20. A method according to claim 19 wherein the flow rate is from 0.1 to 0.75 litres/minute, optionally from 0.25 to 0.5 litres/minute.
21. A method according to claim 19 or claim 20 wherein the output stream has an average width of from 0.25 to 10 mm, optionally from 0.25 to 4 mm, further optionally from 0.5 to 2 mm.
22. A method according to any one of claims 19 to 21 wherein the acoustic energy has a frequency of from 0.5 to 5 MHz. 18079711_1 (GHMatters) P112816.NZ 48
23. A method according to any one of claims 19 to 22 wherein the gas bubbles have a radius of from 0.6 to 20 µm, optionally from 0.75 to 4 µm.
24. A method according to any one of claims 19 to 23 wherein the conical body and the nozzle thereof have a pressure amplitude reflection coefficient with respect to acoustic energy in the aqueous liquid within the chamber of from -0.95 to -1.0, optionally from - 0.99 to -1.0.
25. A method according to any one of claims 19 to 24 wherein the output stream has a circular cross-section.
26. A method according to any one of claims 19 to 25 wherein a closed end of a cup member is fitted to the outlet nozzle of the conical body, the cup member defines a second chamber, and the cup member has an open end with an annular rim which is disposed against, and forms an annular contact against, a surface to be treated, and in step b the output stream is directed into the second chamber from the closed end.
27. A method according to claim 26 wherein the cup member and outlet nozzle are configured so that an orientation of the outlet nozzle relative to the cup member is modifiable thereby to modify the direction of the output stream within the second chamber.
28. A method according to claim 26 or claim 27 wherein the cup member is composed of a flexible material, optionally a thermoplastic elastomer or inert synthetic rubber.
29. A method according to any one of claims 26 to 28 wherein the outlet nozzle is translationally movable within the cup member.
30. A method according to any one of claims 26 to 29 wherein the outlet nozzle and the cup member are connected by a seal therebetween.
31. A method according to any one of claims 26 to 30 wherein the annular rim forms an annular seal against the surface to be treated.
32. A method according to claim 31 wherein the annular rim includes an annular groove or chamber therein to provide an annular suction device for sealing against the surface.
33. A method according to any one of claims 26 to 32 wherein the cup member includes at least one outlet port for liquid which communicates with, and extends away from, the second chamber.
34. A method according to any one of claims 19 to 33 wherein the aqueous liquid comprises or consists of water, optionally comprising saline.
35. A method according to any one of claims 19 to 34 wherein the acoustically excited gas bubbles have a surface wave generated at the bubble wall.
36. A method according to any one of claims 19 to 35 wherein the acoustically excited gas bubbles are configured to release acoustic energy, shear and microstreaming convection 18079711_1 (GHMatters) P112816.NZ 49 flows at and close to the surface to be treated by non-inertial cavitation of the bubbles.
37. A method according to any one of claims 19 to 36 wherein steps c and d are carried out by an acoustic transducer which is arranged to function as a gas bubble generator for providing gas bubbles by acoustic cavitation and to function to provide the acoustic energy which is present in the output stream and acoustically excites the gas bubbles when the bubbles reach the target surface in order to stimulate the cleaning, healing and regeneration processes.
38. A method according to any one of claims 19 to 37 wherein the acoustic transducer additionally functioning as a bubble generator, or the combination of an alternative bubble generator and the acoustic transducer, is controlled to provide a plurality of sequential operating phases, the phases comprising a bubble generating phase in which the bubble generator is activated to generate the bubbles within the chamber, a subsequent rest phase in which the acoustic transducer is inactive to allow the generated bubbles to flow together with the stream out of the nozzle, and a subsequent acoustic excitation phase in which the acoustic transducer is activated to acoustically excite the bubbles which have flowed out of the nozzle, that activation occurring at the moment when the bubbles reach the surface to be cleaned, healed or regenerated.
39. A method according to claim 38 wherein in the acoustic excitation phase the acoustic transducer is activated to acoustically excite the bubbles which are in the vicinity of the surface to be treated.
40. A method according to claim 38 or claim 39 wherein in the bubble generating phase a bolus of bubbles is generated.
41. A method according to claim 40 wherein in the rest phase the bolus of bubbles is flowed into the vicinity of the surface to be treated. 18079711_1 (GHMatters) P112816.NZ 50
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1708901.2 | 2017-06-05 | ||
GB1708901.2A GB2563212B (en) | 2017-06-05 | 2017-06-05 | Cleaning, healing and regeneration of tissue and wounds |
PCT/EP2018/064659 WO2018228848A2 (en) | 2017-06-05 | 2018-06-04 | Cleaning, healing and regeneration of tissue and wounds |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ760615A NZ760615A (en) | 2021-11-26 |
NZ760615B2 true NZ760615B2 (en) | 2022-03-01 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2018285022B2 (en) | Cleaning, healing and regeneration of tissue and wounds | |
US20230311171A1 (en) | Cleaning apparatus and method, and monitoring thereof | |
JP4504183B2 (en) | Device for treating biofilm attached to a catheter | |
US10806544B2 (en) | Systems and methods for removing foreign objects from root canals | |
US7522955B2 (en) | Method and apparatus for the ultrasonic cleaning of biofilm coated surfaces | |
CN106456300B (en) | Apparatus and method for cleaning teeth and root canals | |
EP1976477B1 (en) | System for treating a wound using ultrasonic debridement | |
US20060241533A1 (en) | Apparatus and method for treatment of damaged tissue | |
CN101505706A (en) | Ultrasound wound care device and method | |
CN113164226A (en) | Apparatus and method for treating teeth | |
CN101528306A (en) | Apparatus and method for wound care with ultrasound and pressure therapy device | |
US10201651B2 (en) | Systems and methods for destroying cancer cells in blood | |
EP3294469A1 (en) | Cleaning apparatus and method using an acoustic transducer | |
US20210387237A1 (en) | Apparatus, System, and Method for Cleaning, Healing, and Tissue Regeneration | |
NZ760615B2 (en) | Cleaning, healing and regeneration of tissue and wounds | |
CN108941048A (en) | A kind of ultrasonic cleaning chlorination equipment | |
KR20190062839A (en) | Parasite removal system for fish farm including ultrasonic-microbubble system | |
CN208960513U (en) | A kind of ultrasonic cleaning chlorination equipment | |
Sluis et al. | Disinfection of the root canal system by sonic, ultrasonic, and laser activated irrigation |