HK40026448B - An apparatus for generating therapeutic shockwaves - Google Patents

Description

Apparatus for generating therapeutic shock waves

The application is a divisional application of an invention patent application with the application date of 2014, 3, 7, and the application number of 201480023497.7, and the invention name of the invention is 'fast pulse electrohydraulic shock wave generator device and cosmetic method'.

(Cross-reference to related applications)

This application claims as priority U.S. patent application No. 13/798710 filed on day 13 at 3/2013 and U.S. provisional patent application No. 61/775232 filed on day 8 at 3/2013. The contents of the above-mentioned applications are incorporated by reference in the present specification.

Technical Field

The present invention relates generally to the therapeutic use of shock or shock waves. More particularly, but not exclusively, the invention relates to apparatus for generating therapeutic shock or shock waves (shock waves of therapeutic use).

Background

Acoustic shock waves have been used for many years for some therapies. "shock waves" or "shock waves" generally refer to acoustic phenomena (e.g., from explosions and lightning) that produce sudden and intense pressure changes. These strong pressure changes may generate strong energy waves that may propagate through an elastic medium such as air, water, human soft tissue, or some solid substance such as bone, and/or induce an inelastic response in such an elastic medium. A method for generating shock waves for therapeutic use includes: (1) electro-hydraulic, or spark gap (EH); (2) electromagnetic waves or EMSE; and (3) piezoelectricity. Each based on its own unique physical principles.

A. Apparatus and system for shockwave generation

US patent application 13/574228 (national phase application published as PCT/US2011/021692 of WO 2011/091020), proposed by one of the inventors of the present invention, discloses a device for generating shockwaves at high pulse rates by using a transducer. The device includes: an acoustic wave generator configured to emit acoustic waves having at least one frequency between 1MHz and 1000 MHz; a shockwave housing coupled to the acoustic wave generator; and a shockwave medium disposed in the shockwave housing, where the apparatus is configured such that, if the acoustic wave generator emits an acoustic wave, at least some portion of the acoustic wave will travel through the shockwave medium and form a shockwave. The device may be driven to form a shockwave configured to cause particles within the patient to rupture one or more cells of the patient, and the shockwave may be directed to the cells of the patient such that the shockwave causes the particles to rupture one or more of the cells. The acoustic transducer device is capable of generating high power shockwaves at high frequencies or pulse rates.

Other systems for generating shock waves may include electro-hydraulic (EH) wave generators. EH systems may generally transmit energy at levels similar to other methods, but may be configured to transmit energy over a wider area and thus transmit more shock wave energy to the target tissue in a shorter period of time. EH systems typically incorporate electrodes (i.e., spark plugs) to initiate the shock wave. In an EH system, high-energy shock waves are generated when power is applied to electrodes immersed in the treatment water contained in an outer envelope. When the charge is fired, a small amount of water is evaporated at the tip of the electrode, and the rapid, almost instantaneous expansion of the evaporated water generates shock waves that propagate outward through the liquid water. In some embodiments, the water is contained in the outer shell of an ellipsoid. In these embodiments, the shock waves may be ejected from both sides of the ellipsoidal shell and converge at a focal point that coincides with the location of the region to be treated.

For example, U.S. patent No.7189209 (the' 209 patent) describes a method of treating pathological conditions associated with the bone and musculoskeletal environment and soft tissues by applying acoustic shock waves. The' 209 patent describes that shock waves cause local trauma and apoptosis therein, including micro-disruption, as well as osteoblastic responses such as cell recruitment, stimulating the formation of molecular bone, cartilage, tendon, fascia and soft tissue morphogenesis and growth factors, and causing neovascularization. The' 209 patent claims several specific implementations of its method. For example, the' 209 patent claims a method of treating a diabetic foot ulcer or pressure sore, the method comprising: locating a site or suspected site of a diabetic foot ulcer or pressure sore in a patient; generating an acoustic shock wave; focusing acoustic shock waves on the whole positioned part; each treatment applies more than 500 to about 2500 acoustic shock waves to the localized site to cause micro-damage and more vascularization, thereby causing or accelerating healing. The' 209 patent discloses a frequency range of about 0.5-4 Hz and the application of about 300-2500 or about 500-8000 acoustic shock waves per treatment site, which may result in an excessively long treatment time per treatment site and/or "total time per treatment" for all sites. For example, the' 209 patent discloses that the total time for each treatment for the different examples ranges from 20 minutes to 3 hours.

U.S. patent 5529572 (the' 572 patent) includes another example of the use of electro-hydraulically generated shock waves to produce a therapeutic effect on tissue. The' 572 patent describes a method of increasing the density and strength of bone (to treat osteoporosis) comprising administering to the bone a therapeutically effective amount of a composition comprising a therapeutically effective amount of a compound of formula (I)The bone is subjected to a substantially planar, collimated longitudinal shock wave having a substantially constant intensity depending on the distance to the shock wave source, and the collimated shock wave is applied to the bone at an intensity of 50-500 atmospheres. The' 572 patent describes applying an unfocused shockwave to create a dynamic repetitive loading of bone to increase the average bone density and thereby enhance the fracture resistance of the bone. As described in the' 572 patent, "preferably over a relatively large surface of the bone being treated, e.g., covering 10-150 cm²Applying unfocused shockwaves. The intensity of the shock wave may be 50 to 500 atm. Each shock wave has a duration of a few microseconds as in a conventional lithotripter and is preferably applied at a frequency of 1-10 shock waves per second for a period of 5-30 minutes per treatment. The number of treatments depends on the particular patient. "

U.S. patent application No.10/415293 (the' 293 application), also published as US 2004/0006288, discloses another embodiment for generating shock waves using EH to provide a therapeutic effect on tissue. The' 293 application discloses devices, systems, and methods for generating therapeutic acoustic shock waves for at least partially separating deposits from vascular structures. The' 293 application describes that the device is capable of generating shockwaves at pulse rates of about 50 to about 500 pulses per minute (i.e., 0.83 to 8.33Hz), with the number of pulses per treatment site (in terms of unit length of blood vessel being treated) being per 1cm²About 100 to 5000.

B. Rate of shock wave

The prior art literature shows faster pulse rates by using EH systems to provide shockwaves that can cause tissue damage. For example, in one study (Delius, Jordan, & et al, 1988) [2], a group of dogs exposed to 3000 shock waves at their kidneys were examined for the effect of shock waves on normal dog kidneys. The groups differ only in the shock wave application rates of 100Hz and 1Hz, respectively. After 24-30 hours, necropsy was performed. Visually and histologically, if the rate of shock wave application is 100Hz (as opposed to 1 Hz), then significantly more renal damage occurs in the renal parenchyma (parenchyma). The results show that kidney injury is dependent on shock wave application rate.

In another study (Madbouly & et al,2005) [7], slow shock wave fragmentation rate (SWL) was associated with significantly higher success rates with fewer total shock waves than fast shock wave fragmentation rate. In this paper, the authors discuss how our studies have also shown that when a slower rate of experimental SWL is used, the incidence of renal injury caused by SWL or the need for anesthesia is reduced.

In yet another study (gillitizer & et al,2009) [5], slowing the transmissibility from 60 to 30 shockwaves per minute also provided dramatic protection on the integrity of the actual blood vessels in the pig model. These findings support a potential strategy to reduce the pulse rate frequency to improve the safety and effectiveness of in vitro seismology lithotripsy.

C. Texture as a viscoelastic material

One reason for the sensitivity to pulse rate found in the prior art may be due in part to the relaxation time of the tissue. Cells have elastic and viscous properties and are therefore viscoelastic materials. Unlike most conventional materials, the elastic modulus of cells is highly nonlinear depending on the degree of applied or internal stress. (Kasza,2007) [6 ]. One study (Fernandez, 2006) [3] suggests that fibroblasts can be modeled as gels with a network of cross-linked actin that exhibits a transition from the linear region to power-law strain hardening.

The authors of another article (Freund, Colonius, & Evan,2007) [4] speculate that the cumulative shear of many impacts is damaging and that the mechanism may depend on whether the tissue has sufficient time to relax to a non-strained state between impacts. Their viscous fluid model showed that any deformation recovery that occurred was almost complete within the first 0.15 seconds after impact. As a result, for impact rates slower than 6Hz, their model of cellular injury mechanisms will be independent of impact rate. However, the actual viscoelasticity of the gap material with a relaxation time of about 1 second would be expected to introduce its sensitivity to shock transmission. Assuming that the gap material had a relaxation time of 1 second, the authors would expect significantly reduced damage for transmission rates below 1 Hz. Conversely, for a faster delivery rate, the damage should increase. Their model implies that both slowing the transmission rate and widening the focal zone reduce the damage.

Disclosure of Invention

For Pulse Rates (PR) of 1Hz to 10Hz, soft tissue may transition from elastic to viscous behavior. As a result, the potential damage to tissue by shock waves at PR at 1Hz to 10Hz is unpredictable when typical lithotripsy power levels are used. Perhaps as a result, the prior art teaches slower PR and greater Total Time Per Treatment (TTPT). For example, currently known EH shock wave systems typically transmit PR at less than 10Hz and require a large Total Time Per Treatment (TTPT) (e.g., a TTPT period of several minutes or even hours for even a single treatment site). When treatment requires the device to be repositioned at multiple treatment sites, which may be typical, TTPT becomes large and may not be practical for many patients and treatment requirements.

While long treatment times may be acceptable for extracorporeal shock wave lithotripsy, it is not desirable, if not impractical, to utilize shock waves to provide non-lithotripsy treatment effects on tissue in a medical setting. For example, the cost of treatment often increases with the time required to administer the treatment (e.g., due to labor, facilities, and other resource costs assigned to treatment administration). Furthermore, in addition to cost, at some point, the duration of time that treatment is provided to a patient becomes intolerable to the receiving patient and the medical personnel providing the treatment.

The present disclosure includes apparatus and methods for electrohydraulic generation of therapeutic shock waves. The present EH shockwave systems and methods are configured to transmit shockwaves to tissue to provide predictable therapeutic effects on the tissue, such as by transmitting shockwaves at higher (e.g., higher than-10 Hz) levels to reduce TTPT relative to known systems.

The present embodiments of electro-hydraulic (EH) devices may be configured to generate high frequency shock waves in a controlled manner (e.g., by using an electro-hydraulic spark generator and a capacitive/inductive coil spark generation system). The present pulse generation (e.g., electro-hydraulic spark circuit) may include one or more EH tips and, with the present capacitive/inductive coil spark generation system, spark pulse rates of 10 Hz-5 MHz may be generated. The shockwave can be configured to apply sufficient mechanical stress to target cells of the tissue to rupture the target cells and can be transmitted to certain cellular structures of the patient for medical and/or cosmetic treatment applications.

The present high Pulse Rate (PR) shock wave therapy can be used to provide predictable therapeutic effects on tissue while having a practical Total Time Per Treatment (TTPT) at the site of treatment. The present high PR shockwave therapy can be used to provide predictable therapeutic effects on tissue if the viscoelastic nature of the tissue is considered. Specifically, shockwave therapy with PR greater than 10Hz and even greater than 100Hz may be used to provide predictable therapeutic effects on tissue because, at those PR, tissue is, for the most part, predictably viscous in nature and generally does not change between elastic and viscous states. Given that tissue behaves as a viscous material with a sufficiently large PR, the PR and power level can be adjusted to account for the viscosity of the tissue. When dealing with the viscous nature of tissue by using a higher PR, a lower power level can be used to achieve a therapeutic effect. One benefit of using higher PR in combination with low power levels is a reduction in cavity formation, which further improves the predictability of the present shock wave treatment. Embodiments of the present EH devices and methods can provide targeted disruption of specific cells without damaging side effects such as cavitation or thermal degradation of surrounding non-target cells.

Some embodiments of the present apparatus (for generating therapeutic shock waves) include: a housing defining a chamber and a shock wave outlet; a liquid disposed in the chamber cavity; a plurality of electrodes configured to be disposed in the chamber to define one or more spark gaps; and a pulse generation system configured to apply voltage pulses to the plurality of electrodes at a rate of 10Hz to 5 MHz; wherein the pulse generation system is configured to apply voltage pulses to the plurality of electrodes such that the liquid partially evaporates to propagate the shock wave through the liquid and the shock wave outlet.

Some embodiments of the present apparatus (for generating therapeutic shock waves) include: a housing defining a chamber and a shock wave outlet, the chamber configured to be filled with a liquid; a plurality of electrodes disposed in the chamber to define a plurality of spark gaps; wherein the plurality of electrodes are configured to receive voltage pulses from the pulse generating system at a rate of 10Hz to 5MHz such that the liquid is partially vaporized to propagate the shockwave through the liquid and the shockwave outlet.

Some embodiments of the present apparatus (for generating therapeutic shock waves) include: a housing defining a chamber and a shock wave outlet, the chamber configured to be filled with a liquid; a plurality of electrodes disposed in the chamber to define one or more spark gaps; wherein the plurality of electrodes are configured to receive a voltage pulse from the pulse generating system such that the liquid partially vaporizes to propagate the shockwave through the liquid and the shockwave outlet, and wherein the housing comprises a translucent or transparent window configured to allow a user to view a region of the patient containing the target cells.

In some embodiments of the present device, the plurality of electrodes are not visible to a user viewing an area through the window and the shockwave outlet. Some embodiments further comprise: an optical shield disposed between the window and the plurality of electrodes. In some embodiments, the plurality of electrodes are offset from an optical path extending through the window and the shockwave exit. Some embodiments further comprise: an acoustic mirror configured to reflect the shockwave from the plurality of electrodes toward the shockwave exit. In some embodiments, the acoustic mirror comprises glass. In some embodiments, the one or more spark gaps include a plurality of spark gaps. In some embodiments, the plurality of electrodes are configured to be removably coupled with the pulse generation system. In some embodiments, the housing is replaceable.

Some embodiments of the apparatus further comprise: a spark module, the spark module comprising: a side wall configured to releasably couple the spark module with the housing; wherein the plurality of electrodes are coupled to the sidewall such that the plurality of electrodes are disposed in the chamber cavity if the spark module is coupled to the housing. In some embodiments, the sidewall comprises a polymer. In some embodiments, the side wall of the spark module is configured to cooperate with the housing to define a chamber cavity. In some embodiments, the sidewall defines a spark chamber with a plurality of electrodes disposed therein, the spark chamber is configured to be filled with a liquid, and at least a portion of the sidewall is configured to transmit a shockwave from the liquid in the spark chamber to the liquid in the chamber of the housing. In some embodiments, the side wall of the spark module includes at least one of a pin, a groove, or a thread, and the housing includes at least one of a corresponding groove, pin, or thread to releasably couple the spark module and the housing. In some embodiments, the housing includes a first liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the housing, and the sidewall of the spark module includes a second liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the housing. In some embodiments of the present device, the housing further comprises two fluid connectors. Some embodiments further comprise: a liquid reservoir; and a pump configured to circulate liquid from the reservoir to the chamber of the housing through the two liquid connectors.

In some embodiments of the apparatus, the pulse generation system is configured to apply the voltage pulses to the plurality of electrodes at a rate of between 20Hz and 200 Hz. In some embodiments, the pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate of 50Hz to 200 Hz. In some embodiments, the pulse generation system comprises: a first capacitive/inductive coil circuit, the first capacitive/inductive coil circuit comprising: an induction coil configured to discharge to apply at least some of the voltage pulses; a switch; and a capacitor, wherein the capacitor and the switch are coupled in parallel between the induction coil and the current source. In some embodiments, the pulse generation system comprises: a second capacitive/inductive coil circuit similar to the first capacitive/inductive coil circuit; and a timing unit configured to coordinate discharge of the induction coil of each of the first and second capacitive/induction coil circuits.

Some embodiments of the present apparatus include: a spark module, the spark module comprising: a sidewall configured to releasably couple the spark module with the probe; a plurality of electrodes disposed on a first side of the sidewall and defining one or more spark gaps; and a plurality of electrical connectors in electrical communication with the plurality of electrodes and configured to releasably connect the electrodes with the pulse generation system to generate a spark across the one or more spark gaps. In some embodiments, the sidewall comprises a polymer. In some embodiments, the sidewall includes a liquid connector configured to communicate liquid through the sidewall. In some embodiments, the sidewall defines a spark chamber with a plurality of electrodes disposed therein, the spark chamber is configured to be filled with a liquid, and at least a portion of the sidewall is configured to transmit a shockwave from the liquid in the spark chamber to the liquid in the chamber of the housing. In some embodiments, the spark module further includes one or more liquid connectors in fluid communication with the spark chamber cavity such that the spark chamber cavity can be filled with a liquid. In some embodiments, the one or more fluid connectors include two fluid connectors that can circulate fluid through the spark chamber cavity. In some embodiments, the sidewall is configured to releasably couple the spark module with a probe having a chamber such that the electrode is disposed within the chamber of the probe. In some embodiments, the sidewall and the probe cooperate to define a chamber cavity. In some embodiments, the spark module further includes one or more liquid connectors in fluid communication with the chamber of the probe, such that the chamber of the probe can be filled with liquid through the one or more liquid connectors. In some embodiments, the one or more fluid connectors comprise two fluid connectors via which fluid can be circulated through the chamber cavity of the probe. In some embodiments, the spark module includes a first liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the probe, and the probe includes a second liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the probe.

In some embodiments of the present apparatus including a spark module, the one or more spark gaps include a plurality of spark gaps. In some embodiments, the plurality of electrodes includes three or four electrodes defining two spark gaps. In some embodiments, the three or four electrodes include a first peripheral electrode, a second peripheral electrode spaced apart from the first electrode, and one or two central electrodes configured to reciprocate between the peripheral electrodes. In some embodiments, the spark module further comprises: an elongated member coupled to the one or two central electrodes and configured to move to reciprocally carry the one or two central electrodes between the peripheral electrodes. In some embodiments, the one or two central electrodes comprise two central electrodes in electrical communication with each other and disposed on opposite sides of the elongated member. In some embodiments, the elongated member is configured to self-adjust the spark gap between the peripheral electrode and one or both of the center electrodes over a desired range of operating frequencies. In some embodiments, the desired range of operating frequencies is from 10Hz to 5 MHz. In some embodiments, the elongated member is pivotally coupled to the sidewall and is biased toward the initial position by one or more spring arms. In some embodiments, the elongated member and the one or more spring arms are configured to determine a pulse rate of the spark module over a desired range of operating frequencies. In some embodiments, the desired range of operating frequencies is from 10Hz to 5 MHz. In some embodiments, the device is configured to discharge an electrical pulse between the electrodes while the electrodes are submerged in the liquid such that movement of the elongated member automatically and alternately adjusts a spark gap between one or both of the central electrodes and each of the peripheral electrodes. In some embodiments, the elongated member comprises a spring beam having a base coupled in fixed relation to the sidewall. In some embodiments, the spring beam is configured to determine a pulse rate of the spark module under desired operating conditions. In some embodiments, the device is configured to discharge an electrical pulse between the electrodes while the electrodes are submerged in the liquid, such that movement of the resilient beam automatically and alternately adjusts a spark gap between one or both of the central electrodes and each of the peripheral electrodes.

In some embodiments of the present apparatus including a spark module, a sidewall of the spark module includes at least one of a pin, a groove, or a thread and is configured to couple with a probe including at least one of a corresponding groove, pin, or thread to releasably couple the spark module with the housing. Some embodiments further comprise: a probe configured to couple with the spark module such that the plurality of electrodes are disposed in the liquid-fillable chamber and such that a shockwave originating at the electrodes travels through a shockwave outlet of the device. In some embodiments, the chamber is filled with a liquid. In some embodiments, the probe does not define additional chamber cavities, such that the spark chamber cavity is the only chamber cavity through which the shockwave originating at the electrode propagates. In some embodiments, the probe defines a second chamber cavity within which the spark chamber cavity is disposed if the spark module is coupled to the probe. In some embodiments, the probe includes a plurality of electrical connectors configured to couple with a plurality of electrical connectors of the spark module. In some embodiments, the probe includes one or more liquid connectors configured to couple with one or more liquid connectors of the spark module. In some embodiments, the probe includes two fluid connectors configured to couple with two fluid connectors of the spark module. In some embodiments, the spark module is configured to couple with the probe such that, when the spark module is coupled with the probe, the electrical and liquid connectors of the spark module are simultaneously connected with the corresponding electrical and liquid connectors of the probe. In some embodiments, the probe includes one or more liquid connectors configured to couple with one or more liquid connectors of the spark module. In some embodiments, the probe includes a combination connection having two or more electrical conductors and two lumens for communicating a liquid, the combination connection configured to couple with a combination tether or cable having two or more electrical conductors and two lumens for communicating a liquid. In some embodiments, the combination connection is configured to be removably coupled with a combination tether or cable.

In some embodiments of the present device that include a spark component, the probe includes a housing having a translucent or transparent window configured to allow a user to view a region of a patient containing target cells. In some embodiments, if the spark module is coupled to the probe, the plurality of electrode pairs are not visible to a user viewing an area through the window and the shockwave outlet. Some embodiments further comprise: an optical shield disposed between the window and the plurality of electrodes. In some embodiments, the optical shield comprises a photosensitive material that darkens or increases opacity in the presence of bright light. In some embodiments, the plurality of electrodes are offset from an optical path extending through the window and the shockwave exit. Some embodiments further comprise: an acoustic mirror configured to reflect the shockwave from the plurality of electrodes toward the shockwave exit. In some embodiments, the acoustic mirror comprises glass.

Some embodiments of the present apparatus include: a probe configured to couple with a spark module having a plurality of electrodes defining one or more spark gaps such that the plurality of electrodes are disposed in a chamber cavity that can be filled with a liquid. In some embodiments, the chamber is filled with a liquid. In some embodiments, the probe is configured to cooperate with the spark module to define a chamber cavity. In some embodiments, the probe includes a first liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the probe, and is configured to be coupled with the spark module including a second liquid connector configured to be in fluid communication with the chamber when the spark module is coupled with the probe.

In some embodiments, the spark module contains a spark chamber in which the plurality of electrodes are disposed, and the probe does not define additional chambers, such that the spark chamber is the only chamber through which shock waves originating at the electrodes will propagate. In some embodiments, the spark module includes a sidewall defining a spark chamber in which the plurality of electrodes are disposed, wherein if the spark module is coupled with the probe, the probe defines a second chamber in which the spark chamber is disposed. In some embodiments, the probe includes a plurality of electrical connectors configured to couple to a plurality of electrical connectors of a spark component in electrical communication with the plurality of electrodes. In some embodiments, the probe includes one or more liquid connectors configured to couple with one or more liquid connectors of the spark module. In some embodiments, the probe includes two fluid connectors configured to couple with two fluid connectors of the spark module. In some embodiments, the spark module is configured to couple with the probe such that, when the spark module is coupled with the probe, the electrical and liquid connectors of the spark module are simultaneously connected with the corresponding electrical and liquid connectors of the probe.

In some embodiments of the present devices comprising a stylet, the stylet comprises a combination connection having two or more electrical conductors and two lumens for communicating a liquid, the combination connection being configured to couple with a combination tether or cable having two or more electrical conductors and two lumens for communicating a liquid. In some embodiments, the combination connection is configured to be removably coupled with a combination tether or cable. In some embodiments, the probe includes a housing having a translucent or transparent window configured to allow a user to view a region of a patient containing target cells. In some embodiments, if the spark module is coupled to the probe, the plurality of electrode pairs are not visible to a user viewing an area through the window and the shockwave outlet. Some embodiments further comprise: an optical shield disposed between the window and the plurality of electrodes. In some embodiments, the plurality of electrodes are offset from an optical path extending through the window and the shockwave exit. Some embodiments further comprise: an acoustic mirror configured to reflect the shockwave from the plurality of electrodes toward the shockwave exit. In some embodiments, the acoustic mirror comprises glass.

Some embodiments of the present apparatus comprising a probe further comprise: a pulse generation system configured to repeatedly store and discharge an electrical charge, the pulse generation system configured to couple with an electrical connector of the spark module to discharge the electrical charge through an electrode of the spark module. In some embodiments, the pulse generation system is configured to apply the voltage pulses to the plurality of electrodes at a rate of 20Hz to 200 Hz. In some embodiments, the pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate of 50Hz to 200 Hz. In some embodiments, the pulse generation system includes a single charge/discharge circuit. In some embodiments, the pulse generation system includes a plurality of charge/discharge circuits and a timing unit configured to coordinate charging and discharging of the plurality of charge/discharge circuits. In some embodiments, each of the charge/discharge circuits includes a capacitance/induction coil circuit. In some embodiments, each capacitive/inductive coil circuit comprises: an induction coil configured to discharge to apply at least some of the voltage pulses; a switch; and a capacitor, wherein the capacitor and the switch are coupled in parallel between the induction coil and the timing unit. Some embodiments further comprise: a liquid reservoir; and a pump configured to circulate liquid from the reservoir to the chamber of the housing.

Some embodiments of the present apparatus include: a pulse generation system comprising a plurality of charge/discharge circuits and a timing unit configured to coordinate charging and discharging of the plurality of charge/discharge circuits at a ratio between 10, wherein the pulse generation system is configured to couple with a plurality of electrodes of the spark module to discharge the charge/discharge circuits through the electrodes. Some embodiments further comprise: each of the configured charge/discharge circuits includes a capacitance/induction coil circuit. Each capacitor/inductor circuit includes: an induction coil configured to discharge to apply at least some of the voltage pulses; a switch; and a capacitor, wherein the capacitor and the switch are coupled in parallel between the induction coil and the timing unit. The pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate of 20Hz to 200 Hz. The pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate of 50Hz to 200 Hz. Some embodiments further comprise: a liquid reservoir; and a pump configured to circulate liquid from the reservoir to the chamber of the housing.

Some embodiments of the method include: positioning the shockwave outlet of one of the devices in proximity to a region of a patient containing target cells; and activating the pulse generating system to propagate the shockwave through the fluid toward the target cell. In some embodiments, at least a portion of the plurality of shock waves is transmitted to a portion of an epidermal layer of the patient that contains a tattoo. In some embodiments, the housing and/or probe of the apparatus comprises a translucent or transparent window configured to allow a user to view a region of the patient containing the target cells; the method further comprises the following steps: the region is viewed through the window while the device is positioned. In some embodiments, the apparatus comprises a spark module (the spark module comprising a sidewall releasably coupling the spark module with the housing; wherein the plurality of electrodes are coupled with the sidewall such that, if the spark module is coupled with the housing, the plurality of electrodes are disposed in the chamber cavity), the method further comprising: the spark module is coupled to the probe prior to activating the pulse generation system.

Some embodiments of the method include: generating a plurality of shock waves electro-hydraulically at a frequency between 10; transmitting at least a portion of the plurality of shock waves to at least one cellular structure comprising at least one region of heterogeneity; and disrupting the at least one cellular structure by the continuous transmission of the plurality of shock waves. In some embodiments, the at least one region of heterogeneity comprises an effective density greater than an effective density of the at least one cellular structure. Some embodiments further comprise the step of varying the frequency of the acoustic wave. In some embodiments, at least a portion of the plurality of shock waves are delivered to an epidermal layer of the patient. In some embodiments, the portion of the epidermis layer that receives the shock wave includes cells that contain tattoo pigment particles. Some embodiments further comprise: identifying the disrupted at least one target cellular structure prior to transmitting at least a portion of the shock wave to the at least one target cellular structure.

Some embodiments of the method include: transmitting a plurality of electrohydraulically-generated shock waves to at least one cellular structure comprising at least one region of heterogeneity until the at least one cellular structure ruptures. In some embodiments, at least a portion of the plurality of shock waves is delivered to a portion of an epidermal layer of the patient that includes cells containing tattoo pigment particles. In some embodiments, the shock wave is transmitted to the at least one cellular structure for no more than 30 minutes within a 24 hour period. In some embodiments, the shock wave is transmitted to the at least one cellular structure for no more than 20 minutes within a 24 hour period. In some embodiments, 200 to 5000 shockwaves are delivered between 30 seconds and 20 minutes at each of a plurality of locations of the shockwave outlet. Some embodiments further comprise: while transmitting the shock wave, a portion of the patient's skin is tensioned. In some embodiments, the tensioning is performed by pressing the convex outlet member against a portion of the patient's skin. Some embodiments further comprise: transmitting laser light to at least one cellular structure; and/or delivering a chemical or biological agent to at least one cell.

Any embodiment of any of the present systems, devices, and methods may include or consist essentially of, rather than include/contain/house/have any of the described steps, elements, and/or features. Thus, in any of the claims, the term "comprising" or "substantially comprising" may be replaced by the above-mentioned extensible linking verb in order to alter the scope of a given claim by the extensible linking verb.

Details and others relating to the above-described embodiments are given below.

Drawings

The following drawings are given by way of example and not limitation. For purposes of simplicity, each feature presented as a structure is not always labeled in every drawing in which the structure appears. The same reference numerals do not necessarily denote the same structures. And the same reference numerals may be used to denote similar features or features having similar functions, or different reference numerals may be used. The figures are drawn to scale (unless otherwise indicated) and thus mean that, at least for the embodiments shown in the figures, the dimensions of the elements shown are exact to each other.

FIG. 1 shows a block diagram of a first embodiment of the present electro-hydraulic (EH) shock wave generation system.

Figure 2 illustrates a cross-sectional side view of a hand-held probe of some embodiments of the present EH shockwave generating system.

FIG. 2A shows a cross-sectional side view of a first embodiment of a removable spark head that may be used with embodiments of the present hand-held probe, such as that of FIG. 2.

FIG. 2B shows a cut-away side view of a second embodiment of a removable spark head that may be used with embodiments of the present hand-held probe, such as that of FIG. 2.

FIG. 2C shows a cut-away side view of a third embodiment of a removable spark head that may be used with embodiments of the present hand-held probe, such as that of FIG. 2.

Fig. 3A-3B show timing diagrams of one example of the timed application of energy cycles or voltage pulses in the system of fig. 1 and/or the hand-held probe of fig. 2.

Fig. 4 illustrates waveforms that may be launched into target tissue by the system of fig. 1 and/or the handheld probe of fig. 2.

FIG. 5 illustrates a schematic diagram of one embodiment of a multi-gap pulse generation system for use in or with some embodiments of the present system.

Fig. 6 illustrates a block diagram of an embodiment of a Radio Frequency (RF) power acoustic ablation system.

Fig. 7A-7B show perspective and cross-sectional views of a first prototype spark chamber housing.

Fig. 8 shows a cross-sectional view of a second prototype embodiment of a spark chamber housing.

Fig. 9 shows a schematic diagram of the circuitry of a prototype pulse generation system.

FIG. 10 illustrates a conceptual flow diagram of one embodiment of the present method.

Fig. 11 shows an exploded perspective view of another prototype embodiment of the present probe with a spark head or module.

Fig. 12A and 12B illustrate portions of the components of the probe of fig. 11.

Fig. 13A and 13B show perspective and side cross-sectional views, respectively, of the probe of fig. 11.

FIG. 13C shows an enlarged side cross-sectional view of the spark gap of the probe of FIG. 11.

Fig. 14 shows a schematic diagram of a second embodiment of the circuit of the prototype pulse generation system.

Detailed Description

The term "coupled" is defined as connected, although not necessarily directly, and not necessarily mechanically; two items that are "coupled" may be separate from each other; the terms "a" and "an" are defined as one or more unless the disclosure explicitly requires otherwise. As understood by those skilled in the art, the term "substantially" is defined as being substantially, but not necessarily completely, specified (and inclusive of the specified; e.g., substantially 90 degrees includes 90 degrees, and substantially parallel includes parallel). In any disclosed embodiment, the terms "substantially", "about" and "approximately" may be substituted with the stated "… [ percent ], where the percentages include.1, 1, 5 and 10%.

The terms "comprising" (and any form of comprising, such as "including" and "comprising"), "having" (and any form of having, such as "having" and "owning") and "containing" (and any form of containing, such as "containing" and "containing") are open-linked verbs. Thus, a system or device that "comprises," "has," "includes" or "contains" one or more elements possesses those one or more elements, but is not limited to possessing only those elements. Similarly, a process that "comprises," "has," "includes," or "contains" one or more steps possesses those one or more steps, but is not limited to possessing only those one or more steps.

Also, structures (e.g., components of a device) that are configured in a certain way are configured in at least that way, but may also be configured in other ways than those specifically described.

Certain embodiments of the present systems and devices are configured to generate high frequency shock waves in a predictable and consistent manner. In some embodiments, the generated EH shockwaves may be used in medical and/or cosmetic treatment applications (e.g., when directed and/or transmitted to a target tissue of a patient). Examples of medical and/or cosmetic treatment applications in which the present system may be used are disclosed in (1) U.S. patent application No.13/574228, published as US 2013/0046207, and (2) U.S. patent application No.13/547995, published as US 2013/0018287, the entire contents of which are incorporated herein by reference. EH shock waves generated by the present system may be configured to apply sufficient mechanical stress to rupture cells of the target tissue (e.g., through membrane deterioration damage).

When target cells (cells of a target tissue) are exposed to the generated high PR shock waves, the cells experience large gradients of mechanical stress due to spatial heterogeneity parameters of the cells such as density and shear elastic modulus of different components of the cells. For example, dense and/or inelastic components within a cell experience greater mechanical stress when subjected to shock waves than do lighter components. In particular, the acceleration of higher density particles or components within the cellular structure prior to exposure to the impact is generally very large. At the same time, the impact on low density biological structures that make up the cellular structure is significantly reduced when exposed to such large gradients of stress, since the elasticity of the low density biological structures allows them to function generally as low compliance materials. The difference in mechanical stress results in movement of dense and/or inelastic components within the cell.

When cells are exposed to repeated shock waves of a certain frequency and energy level, the dense and/or inelastic components move repeatedly until they disrupt the cells, thereby rupturing the cells. In particular, the mismatch in the properties of the cellular structure and the ability of the cells to undergo deformation before exposure to an impact leads to the cell destruction described above. One possible theory to explain the phenomenon of disrupting cellular structures can be found in (Burov, v.a.,2002), which is incorporated herein by reference in its entirety.

Such as Burov [1 ]]As discussed, while cells oscillate as an integral unit when subjected to these pre-pressure shocks, large gradients of mechanical stress can be generated within the cell as a result of the spatially heterogeneous parameters (i.e., density and shear elastic modulus). Can be obtained by modeling a biological structure to have a mass m₁And m₂Shows the concept and at a speed mu_o(t) the density (p) of the liquid oscillating around the ball₀) Clearly different from the density of the ball (difference in p, respectively)₁And ρ₂). If only the resistance to the undercurrent is considered, the force applied to the link is calculated as shown in equation 1:

in [1 ]]Additional discussion of formula (1) and its variants is provided further in. For example, if the sphere radius (R) is about 10 μm and the difference between the densities of the spheres is 0.1 ρ₀Then stress 10 results⁹dyne/cm²F/(π R)²) And m is selected. This is sufficient to rupture the cell membrane. Embodiments of the present device generate shock waves in a controlled manner that can be used to cause targeted damage to certain cells, which has medical and/or cosmetic treatment applications as discussed further below.

Another possible theory to explain the phenomenon of cell rupture is the cumulative shear stress of denser materials in the cell structure. In heterogeneous media, such as cells with particles (e.g., pigment particles), shock waves cause cell membrane failure through a progressive (i.e., cumulative) shear mechanism. On the other hand, in a homogenous medium, the compression of the shock wave causes minimal, if any, damage to the membrane. The microscopic focusing and defocusing of the shock wave as it passes through heterogeneous media can result in local strengthening or weakening of the shock wave, which leads to an increase in local shear. Relative shear movement of the cell membrane occurs on the scale of heterogeneity in the cellular structure. It is believed that when a shock wave impacts a region of heterogeneity (e.g., a cell containing a particle), particle movement out of phase with the incoming wave generates a cell disruption energy transfer (e.g., shear stress). The different phase movements (e.g., shear stress) cause microscopic damage to the cell membrane, which can grow progressively into cell membrane failure with additional continuous accumulation of shear stress.

The progressive shear mechanism of repeated exposure to shock waves can be seen as dynamic fatigue of the cell membrane. The damage caused by dynamic fatigue depends on three factors: (1) applied stress or strain; (2) a rate of strain application; and (3) cumulative strain cycle number. These three factors can be manipulated to cause cells with heterogeneity to experience severe cell membrane failure as compared to the relatively more homogeneous properties at a particular applied strain, strain rate, and strain cycle.

Manipulation of the factors may be accomplished by providing EH shock waves of certain properties, such as the number of shock waves, the amount of time between shock waves, and the intensity of the shock wave applied. As described above, if there is too long time between shock waves for the tissue to relax to its unstrained state, the cells will become more resistant to failure. Thus, in a preferred embodiment for an EH system, shock waves at PR greater than 5Hz, preferably greater than 100Hz and most preferably greater than 1MHz are transmitted to the target cellular structure to achieve dynamic fatigue of the tissue and not allow time for relaxation of the tissue.

At a sufficiently high PR, the tissue behaves as a viscous material. As a result, PR and power levels may be adjusted to account for the viscous properties of the tissue.

A third possible theory is that EH shock waves cause direct movement of particles contained in cellular structures and fine particlesThe effect of dynamic fatigue of cell rupture. While cells comprising particles are typical examples of cellular structures exhibiting heterogeneity, this description is not intended to limit the scope of the disclosure. While the embodiments disclosed herein may be used to disrupt or cause damage to other cellular structures exhibiting heterogeneity, such as cellular structures having regions of different effective densities. Parameters of shockwaves generated according to the disclosed aspects can be adjusted based at least on regions of different effective densities (e.g., heterogeneity) to cause cell damage as described herein. Heterogeneity may be regions within a single cell, regions of different types of cells, or a combination of both. In certain embodiments, the region of heterogeneity within the cell comprises a region having an effective density greater than the effective density of the cell. In one particular example, the effective density of fibroblasts is about 1.09g/cm³The region of heterogeneity in the cell will be that contained within the cell with greater than 1.09g/cm³Of particles having an effective density, such as 2.25g/cm³Graphite of density (2). In certain embodiments, the region of cellular heterogeneity between cells comprises a region with different types of cells, wherein each cell type has a different effective density, such as fibroblasts and adipocytes or hair follicles. The present disclosure provides further examples of cellular structures that include heterogeneity hereinafter.

Referring now to the drawings, and more particularly to FIG. 1, designated and designated herein by the reference numeral 10 is a block diagram of one embodiment of the present device or system for the electro-hydraulic generation of shock waves in a controlled manner. In some embodiments such as shown, the apparatus 10 includes a hand-held probe (e.g., having a first housing, such as in fig. 2) and a separate controller or pulse generation system (e.g., in or having a second housing coupled to the hand-held probe by a flexible cable or the like). In other embodiments, the system includes a single handheld device disposed in a single housing.

In the illustrated embodiment, the apparatus 10 includes: a housing 14 defining a chamber 18 and a shock wave outlet 20; a liquid (54) disposed in the chamber 18; a plurality of electrodes configured to be disposed in the chamber to define one or more spark gaps (e.g., in a spark head or module 22); and a pulse generation system 26 configured to apply voltage pulses to the electrodes at a rate of 10Hz to 5 MHz. In this embodiment, the pulse generation system 26 is configured to apply a voltage pulse to the electrodes such that the liquid partially evaporates to propagate the shock wave through the liquid and the shock wave outlet.

In the illustrated embodiment, the pulse generation system 26 is configured for use with an ac power source (e.g., a wall outlet). For example, in the present embodiment, the pulse generation system 26 includes a plug 30 configured to be plugged into a 110V wall outlet. In the illustrated embodiment, pulse generating system 26 comprises a capacitive/inductive coil system, an example of which is described later with reference to FIG. 6. In other embodiments, the pulse generation system 26 may include any suitable structure or component configured to apply a high voltage to the electrodes in a periodic manner to generate an electrical spark of sufficient power to vaporize the liquid in each spark gap, as described in this disclosure.

In the illustrated embodiment, the pulse generation system 26 is (e.g., removably) coupled with the spark head or electrodes in the module 22 by a high voltage cable 34, which high voltage cable 3 may, for example, contain two or more electrical conductors and/or be heavily shielded from electrical shock by rubber or other types of electrically insulating material. In some embodiments, the high voltage cable 3 is a combination tether or cable that further includes one or more (e.g., two) liquid lumens through which the chamber cavity 18 may be filled with a liquid and through which the liquid may be circulated through the chamber cavity 18 (e.g., through the combination connection 36). In the illustrated embodiment, the device 10 includes a handpiece or probe 38, and the high voltage cable 34 is removably coupled with the probe 38 by a high voltage connector 42, the high voltage connector 42 being coupled with the spark head or module 22 by two or more electrical conductors 44. In the illustrated embodiment, probe 38 includes a head 46 and a handle 50, and probe 38 may include a polymer or other electrically insulating material to enable an operator to grasp handle 50 to position probe 38 during operation. For example, the handle 50 may be formed from plastic and/or may be coated with an electrically insulating material such as rubber.

In the illustrated embodiment, a liquid 54 (e.g., a dielectric liquid such as distilled water) is disposed in (e.g., substantially fills) the chamber cavity 18. In the present embodiment, the spark head 22 is located in the chamber cavity 18 and surrounded by liquid such that the electrodes may receive voltage pulses from the pulse generating system 26 (e.g., at a rate of 10 Hz-5 MHz) causing the liquid to partially evaporate to propagate the shockwave through the liquid and the shockwave outlet 20. In the illustrated embodiment, the probe 38 includes an acoustic delay chamber cavity 58 between the chamber cavity 18 and the shock wave outlet 20. In the present embodiment, the acoustic delay chamber cavity is substantially filled with a liquid 62 (e.g., the same liquid as liquid 54) and has a length 66 sufficient to allow a shockwave to form and/or be directed toward shockwave outlet 20. In some embodiments, the length 66 may be 2 millimeters (mm) to 25 mm. In the illustrated embodiment, the chamber cavity 18 and the acoustic delay chamber cavity 58 are separated by a layer of acoustically transparent (sound permeable) material that allows sound waves and/or shock waves to travel from the chamber cavity 18 into the acoustic delay chamber cavity 58. In other embodiments, the liquid 62 may be different from the liquid 54 (e.g., the liquid 62 may include bubbles, water, oil, and/or mineral oil, etc.). Certain features, such as bubbles, may induce and/or improve non-linearity in the acoustic behavior of the liquid 54 to increase shock wave formation. In other embodiments, the chamber cavity 18 and the acoustic delay chamber cavity 58 may be uniform (i.e., may contain a single chamber cavity). In other embodiments, the acoustic delay chamber cavity 58 may be replaced by a solid member (e.g., a solid cylinder of elastomeric material such as polyurethane). In the illustrated embodiment, probe 38 also includes an outlet member 70 removably coupled to the housing at the end of the acoustic delay chamber cavity as shown. The exit piece 70 is configured to contact tissue 74 and may be removed and optionally sterilized or replaced between patients. The outlet member 70 comprises an acoustically transparent polymer or other material (e.g., low density polyethylene or silicone rubber) that allows the shock waves to exit the acoustic delay chamber cavity 58 through the shock wave outlet 20. Tissue 74 may be, for example, human skin to be treated by device 10, and may, for example, contain a tattoo, a scar, a subcutaneous lesion, or a basal cell abnormality. In some embodiments, an acoustic coupling gel (not shown) may be disposed between the exit piece 70 and the tissue 74 to lubricate and provide additional acoustic transmission to the tissue 74.

In the illustrated embodiment, probe 38 includes an acoustic mirror 78, which acoustic mirror 78 comprises a material (e.g., glass) configured to reflect a substantial portion of the acoustic and/or shock waves incident on the acoustic mirror. As shown, the acoustic mirror 78 may be angled to reflect sound waves and/or shock waves (e.g., originating from the spark head 22) toward the shock wave exit port 20 (through the acoustic delay chamber cavity). In the illustrated embodiment, the housing 14 may include a window 82, the window 82 configured to allow a user to view (through the window 82, the chamber cavity 18, the acoustic delay chamber cavity 58, and the exit member 70) a region of the patient (e.g., tissue 74) containing target cells (e.g., during application of the shockwave or prior to application of the shockwave to position the shockwave exit port 20 on the target tissue). In the illustrated embodiment, the window 82 comprises an acoustically reflective material (e.g., glass) configured to reflect a majority of the acoustic and/or shock waves incident on the window. For example, the window 82 may comprise a transparent glass having sufficient thickness and strength to withstand the high energy acoustic pulses generated at the spark head 22 (e.g., a tempered sheet glass having a thickness of about 2mm and a light transmission efficiency of greater than 50%).

In fig. 1, the human eye 86 indicates that the user is viewing the target tissue through the window 82, but it is understood that the target tissue may be "viewed" through the window 82 by a camera (e.g., a digital still and/or video camera). By direct or indirect viewing, and by indication of acoustic energy, such as a change in color of tissue, acoustic energy may be located, applied, and repositioned according to a target tissue, such as an existing tattoo. However, if the spark head 22 is positioned where the user may view the spark head 22, the resulting brightness of the spark from the spark head 22 may be too bright for the user to look uncomfortable, and, in the illustrated embodiment, the probe 38 is configured such that the plurality of electrodes are not visible to the user viewing the area (e.g., of the target tissue) through the window 82 and the shockwave outlet 20. For example, in the illustrated embodiment, the probe 8 includes an optical shield 90 disposed between the spark head 22 and the window 82. The optical shield 90 may, for example, have a width and/or length that is less than a corresponding width and/or length of the window 82, such that the optical shield 90 is large enough to substantially block light from the spark head 22 from directly entering the user's eye, but not to unnecessarily interfere with the field of view through the window 82 and the shock wave exit 20 to block the light. The optical shield 90 may, for example, comprise a thin metal plate, such as stainless steel or other opaque material, or may comprise solder glass (e.g., an LCD darkened by a photocell or other light sensitive material) that is optically activated and darkened by the brightness of the spark across the spark gap. In order to maintain the effect of the point source from the spark head 22 and the resulting desired planar wavefront, consideration must be given to masking the resulting acoustic effect of the spark from the spark gap head. If the optical shield 90 comprises an acoustically reflective material, then, to prevent pulse widening, the distance between the shield and the spark gap between the electrodes in the spark head 22 may be selected to minimize (e.g., with minimal disruption) interference between the acoustic and/or shock waves reflected from the shield and the acoustic and/or shock waves originating from the spark head 22. The distance between the spark head and the shield can be calculated as 1/2 and 3/4 wavelengths from the source by the velocity of the acoustic wave in a medium such as distilled water of about 1500 m/sec.

The spark head 22 (e.g., an electrode in the spark head 22) may have a limited life that may be extended by limiting the duration of activation. In the illustrated embodiment, the apparatus 10 includes a switch 94 coupled to the pulse generation system 26 by the connector 40 via a switch wire or other connection 98 such that the switch 94 may be actuated to apply voltage pulses to the electrodes in the spark head 22.

FIG. 2 illustrates a cross-sectional side view of a second embodiment 38a of the present probe for use with some embodiments of the present EH shock wave generating system and apparatus. The probe 38a is substantially similar in some respects to the probe 38 and therefore only the differences will be primarily described herein. For example, probe 38a may also be configured such that a plurality of electrode pairs of spark head 22a are not visible to a user viewing an area (e.g., of a target tissue) through window 82a and shockwave outlet 20. However, rather than including an optical shield, the probe 38a is configured such that the spark head 22a (and the electrode of the spark head) is offset from the optical path through the window 82a and the shock wave exit 20. In the present embodiment, an acoustic mirror 78a is positioned between the spark head 22a and the outlet 20a as shown to define the boundary of the chamber 18a and direct sound and/or shock waves from the spark head 22a to the outlet 20 a. In the illustrated embodiment, window 82a may comprise a polymer or other acoustically transparent or permeable material because acoustic mirror 78a is disposed between window 82a and chamber cavity 18a, and sound and/or shock waves are not directly incident on window 82 (i.e., because the sound and/or shock waves are primarily reflected by acoustic mirror 78 a).

In the illustrated embodiment, the spark head 22a includes a plurality of electrodes that define a plurality of spark gaps. The use of multiple spark gaps may be advantageous because it may double the number of pulses that may be transmitted in a given time. For example, after the pulse has evaporated a certain amount of liquid in the spark gap, the vapor must arbitrarily return to its liquid state or must be replaced by a different portion of the liquid still in the liquid state. In addition to the time required for the spark gap to refill with water before a subsequent pulse can evaporate additional liquid, the spark also heats the electrodes. Thus, for a given sparking rate, increasing the number of spark gaps reduces the rate at which each spark gap must be fired and thereby extends the life of the electrodes. Thus, ten spark gaps potentially increase the possible pulse rate and/or electrode life by a factor of 10.

As mentioned above, high pulse rates can generate large amounts of heat that can increase fatigue on the electrodes and/or increase the time required for the vapor to return to a liquid state prior to evaporation. In some embodiments, this heat may be managed by circulating a liquid around the spark head. For example, in the embodiment of FIG. 2, as shown, the probe 38a includes conduits 104 and 108 that extend from the chamber cavity 18a to respective connectors 112 and 116. In this embodiment, connectors 112 and 116 may be coupled with a pump to circulate liquid through the chamber (e.g., through a heat exchanger). For example, in some embodiments, pulse generation system 26 (fig. 1) may include a pump and a heat exchanger in series and configured to couple with connectors 112 and 116 through conduits or the like. In some embodiments, a filter may be included in the probe 38a, in the pulse generation system (e.g., 26), and/or between the probe and the pulse generation system to filter liquid circulating through the chamber cavity.

Additionally, some embodiments of the present probe may be disposable due to the limited lifetime of the electrode 100 at high pulse rates. Alternatively, some embodiments are configured to allow a user to replace the electrodes. For example, in the embodiment of FIG. 2, the spark head 22a is configured to be removable from the probe 38 a. For example, the spark head 22a may be removed by the handle 50a, or the handle 50a may be removably coupled with the head 46a (e.g., by threads, etc.), such that when the handle 50a is removed from the head 46a, the spark head 22 may be removed from the head 46a and replaced.

As shown in FIG. 2, applying each shock wave to the target tissue includes the wavefront 118 propagating from the shock wave exit port 20 and traveling outward through the tissue 74. As shown, the wavefront 118 curves according to its expansion as it moves outward and, in part, according to the shape of the outer surface of the exit component 70a that contacts the tissue 74. In other embodiments, such as that of FIG. 1, the external shape of the contact member may be planar or otherwise shaped to affect certain properties of the wave front as it passes through the outlet 20a and propagates through the target tissue.

Fig. 2A shows an enlarged cross-sectional view of a first embodiment of a removable spark head 22A. In the illustrated embodiment, the spark head 22a includes a sidewall 120 defining a spark chamber 124 and a plurality of electrodes 100a, 100b, and 100c disposed in the spark chamber. In the illustrated embodiment, spark chamber 124 is filled with a liquid 128, which may be similar to liquid 54 (FIG. 1). At least a portion of the sidewall 120 comprises an acoustically transparent or sound permeable material (e.g., a polymer such as polyethylene) configured to allow acoustic waves and/or shock waves generated on the electrodes to travel through the sidewall 120 and through the chamber cavity 18 a. For example, in the illustrated embodiment, the spark head 22a includes a cup member 132 that may be configured as an acoustically reflective and acoustically transmissive cup member 136. In this embodiment, the cup member 136 is a cone shaped to approximate the curved shape of the expanding wavefront originating from the electrodes and compress the skin when a moderate pressure is applied. Cup member 136 may be coupled with cup member 132 by an O-ring or gasket 140 and a collar 144. In the illustrated embodiment, the cup-shaped member 132 has a cylindrical shape with a circular cross-section (e.g., having a diameter of 2 inches or less). In the present embodiment, the cup-shaped member includes bayonet-type pins 148, 152 configured to align with corresponding grooves in the head 46a of the probe 38a (FIG. 2) to lock the position of the spark head 22a relative to the probe.

In the illustrated embodiment, the electrode core 156 has conductors 160a, 160b, 160c and extends through the aperture 164 such that there is an interface between the aperture 164 and the electrode core 156 that is sealed by a gasket 168. In the illustrated embodiment, the center conductor 160a runs through the center of the electrode core 156 and serves as a ground point for the respective center electrode 100 a. The peripheral conductors 160b, 160c communicate with the peripheral electrodes 100b, 100c to generate sparks across the spark gaps between the electrodes 100a and 100b and between the electrodes 100a and 100 c. It should be appreciated that while two spark gaps are shown, any number of spark gaps may be used and may be limited by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps.

Fig. 2B shows an enlarged cut-away side view of a second embodiment of a removable spark head or module 22B. In the illustrated embodiment, the spark head or module 22b includes a sidewall 120a defining a spark chamber 124a and a plurality of electrodes 100d-1, 100d-2, 100f disposed in the spark chamber. In the illustrated embodiment, spark chamber 124a is filled with a liquid 128a similar to liquid 128 and/or 54. At least a portion of the sidewall 120a includes an acoustically transparent or sound permeable material (e.g., a polymer such as polyethylene) configured to allow acoustic and/or shock waves generated on the electrodes to travel through the sidewall 120a and/or through the chamber 18a (fig. 2). For example, in the illustrated embodiment, the spark head 22b includes a cup-shaped member 132a that may be configured as an acoustically reflective and acoustically transmissive cup member 136 a. In this embodiment, cup component 136a is a cone shaped to approximate the curved shape of the expanding wavefront originating from the electrodes and compress the skin when a moderate pressure is applied. Cup member 136a may be coupled to cup member 132a by an O-ring or gasket (not shown, but similar to 140) and collar 144 a. In the illustrated embodiment, the cup-shaped member 132a has a cylindrical shape with a circular cross-section (e.g., having a diameter of 2 inches or less). In some embodiments, the cup-shaped member may also include bayonet-type pins (not shown, but similar to 148, 152) configured to align with corresponding grooves in the head 46b of the probe 38a (fig. 2) to lock the position of the spark head 22b relative to the probe.

In the illustrated embodiment, the conductors 160d, 160e, 160f extend through the rear portion of the sidewall 132a (opposite the outlet cap member 136a) as shown. In this embodiment, the center conductor 160b and the peripheral conductors 160a, 160c may be shaped as the sidewall 120a such that gaskets or the like are not required to seal the interface between the sidewall and the conductors. In the illustrated embodiment, center conductor 160d serves as a ground point for the respective center electrodes 100d-1 and 100d-2, which are also in electrical communication with each other. Peripheral conductors 160e, 160f communicate with peripheral electrodes 100e, 100f to generate a spark across the spark gap between electrodes 100d-1 and 100e and between electrodes 100d-2 and 100 f. It should be appreciated that while two spark gaps are shown, any number of spark gaps may be used and may be limited only by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps.

In the illustrated embodiment, the center electrodes 100d-1 and 100d-2 are carried by and may be integral with a member 172 that extends from the sidewall 120a into the cap member 136a into the spark chamber 124 a. In this embodiment, the member 172 is mounted on a hinge 176 (fixed relative to the sidewall 120 a) to allow the distal ends of the members (adjacent electrodes 100d-1, 100d-2) to rotate back and forth between the electrodes 100e and 100f as indicated by arrow 180. In the illustrated embodiment, the distal portion of member 172 is biased toward electrode 100e by spring arm 184. In the present embodiment, spring arm 184 is configured to position electrode 100d-1 at an initial spark gap distance from electrode 100 e. Applying an electrical potential across the electrodes 100d-1 and 100e (e.g., by a pulse generation system described elsewhere in this disclosure) will generate a spark arc between the two electrodes to release an electrical pulse to vaporize the liquid between the two electrodes. The expansion of the vapor between the two electrodes drives the component 172 and the electrode 100d-2 downward toward the electrode 100 f. During the time period that the component 172 is traveling down, the pulse generation system may recharge and apply an electrical potential between the electrodes 100d-2 and 100f such that, when the distance of the electrodes 100d-2 and 100f becomes sufficiently small, a spark arc will be generated between the two electrodes to release an electrical pulse to evaporate the liquid between the two electrodes. The expansion of the vapor between electrodes 100d-2 and 100f then drives member 172 and electrode 100d-1 upward toward electrode 100 e. During the time period that the component 172 is traveling upward, the pulse generation system may recharge and apply an electrical potential between the electrodes 100d-1 and 100e such that, when the distance between the electrodes 100d-1 and 100e becomes sufficiently small, a spark arc will be generated between the two electrodes to release an electrical pulse to evaporate the liquid between the two electrodes, resulting in the cycle beginning again. In this manner, the member 172 oscillates between the electrodes 100e and 100f until the application of the potential to the electrodes is stopped.

Exposure to high rates and high energy electrical pulses, particularly in liquids, subjects the electrodes to rapid oxidation, corrosion, and/or other degradation that can alter the spark gap distance between the electrodes if the electrodes remain in a fixed position (e.g., requiring replacement and/or adjustment of the electrodes). However, in the embodiment of FIG. 2B, rotation of the electrodes 100d-1, 100d-2 between the member 172 and the electrodes 100e and 100f effectively adjusts the spark gap for each spark. In particular, the distance between the electrodes at which the current arc occurs between the electrodes is a function of the electrode material and the potential. Thus, the closest surfaces (even if eroded) of some adjacent electrodes (e.g., 100d-1 and 100e) reach the spark gap distance for a given embodiment, creating a spark between the electrodes. Thus, the component 172 is configured to self-adjust the respective spark gaps between the electrodes 100d-1 and 100e and between 100d-2 and 100 f.

Another example of the advantages of the present movable electrode, as in fig. 2B, is that multiple coils are not required as long as the electrodes are positioned such that only one pair of electrodes is within arc distance at any given time, and such a single coil or coil system is configured to recharge in less time than the time it takes for the component 172 to rotate from one electrode to the next. For example, in the embodiment of FIG. 2B, an electrical potential may be applied to electrodes 100e and 100f simultaneously with electrodes 100d-1 and 100d-2 acting as a common ground point, the electrical potential being such that, when member 172 is rotated upward relative to horizontal (in the orientation shown), a spark arc will only be generated between electrodes 100d-1 and 100e, and, when member 172 is rotated downward relative to horizontal, a spark arc will only be generated between electrodes 100d-2 and 100 f. Thus, when the component 172 is rotated up and down as described above, a single coil or coil system may be connected with the peripheral electrodes 100e, 100f and alternately discharged through each of the peripheral electrodes. In such an embodiment, the pulse rate may be adjusted by selecting the physical properties of member 172 and spring arm 184. For example, the properties of the member 172 (e.g., mass, stiffness, cross-sectional shape and/or length, etc.) and the properties of the spring arms 184 (e.g., spring constant, shape and/or length, etc.) may be varied to adjust the resonant frequency of the system and, thus, the pulse rate of the spark head or module 22 b. Similarly, the viscosity of the liquid 128a may be selected or adjusted (e.g., increased to reduce the travel speed of the component 172, or decreased to increase the travel speed of the component 172).

As with fig. 2B, another example of an advantage of the present movable electrode is that the performance (e.g., shape, cross-sectional area, depth, etc.) of the electrode may be configured to achieve a known useful or useful life (e.g., one 30 minute treatment) for the spark head, such that the spark head 22B is inoperative or limited in effectiveness after the specified useful life. Such features may be used to ensure that the spark head is disposed after a single treatment, such as, for example, ensuring that a new, sterilized spark head is used for each patient or treatment area to minimize potential cross-contamination between patients or treatment areas.

Fig. 2C shows an enlarged cut-away side view of a third embodiment of a removable spark head or module 22C. The spark head 22c is substantially similar to the spark head 22b, except as noted below, and therefore like reference numerals are used to identify the structure of the spark head 22c that is similar to the corresponding structure of the spark head 22 b. The primary difference with the spark head 22b is that the spark head 22c includes a beam 172a that has no hinge, such that, as described above for the spark head 22b, deflection of the beam itself provides movement of the electrodes 100d-1 and 100d-2 in the up-down direction indicated by arrow 180. In the present embodiment, the resonant frequency of the spark head 22c is particularly dependent upon the physical properties of the beam 172a (e.g., mass, stiffness, cross-sectional shape and area, and/or length, etc.). As described for spring arm 184 of spark head 22b, beam 172a is configured to be biased toward electrode 100e as shown, such that electrode 100d-1 is first positioned at an initial head gap distance from electrode 100 e. The function of the spark head 22c is similar to that of the spark head 22b, except that the beam 172a bends upon itself and provides some resistance to movement, such that the hinge 176 and spring arm 184 are not necessary.

In the illustrated embodiment, spark head 22b also includes fluid connectors or ports 188, 192 through which fluid may be circulated through spark chamber cavity 124 b. In the illustrated embodiment, the proximal end 196 of the sparking head 22b serves as a combined connection having two lumens for liquid (connectors or ports 188, 192) and two or more (e.g., three, as shown) electrical conductors (connectors 160d, 160e, 160 f). In such embodiments, the combined connection of the proximal end 196 may be coupled (directly or through a probe or handpiece) with a combined tether or cable having two fluid lumens (corresponding to the connectors or ports 188, 192) and two or more electrical conductors (e.g., a first electrical conductor for connecting the connector 160d and a second electrical conductor for connecting the peripheral connectors 160e, 160 f). Such a combination tether or cable may couple a spark head (e.g., and a probe or handpiece coupled to the spark head) with a pulse generating system having a liquid reservoir and a pump such that the pump may circulate liquid between the reservoir and the spark chamber cavity. In some embodiments, the cap member 136a is omitted such that the connectors or ports 188, 192 may allow for circulation of liquid through a larger chamber (e.g., 18a) of a handpiece to which the spark head is coupled. Similarly, the probe or handpiece to which the spark head 22a is configured to be coupled may include electrical and fluid connectors corresponding to the respective electrical (160d, 160e, 160f) and fluid connectors (188, 192) of the spark head, such that when the spark module is coupled to the handpiece (e.g., by pressing the spark head and probe together and/or wrapping or rotating the spark head relative to the probe), the electrical and fluid connectors of the spark head are simultaneously connected with the respective electrical and fluid connectors of the probe or handpiece.

In this embodiment, a pulse rate of a few Hz to many KHz (5 MHz maximum) can be used. Since fatigue events generated by multiple pulses or shock waves generally accumulate at higher pulse rates, treatment time can be significantly reduced by using many moderate power shock waves in rapid succession rather than several higher power shock waves separated by long dwell durations. As described above, at least some of the present embodiments (e.g., those having multiple spark gaps) enable electro-hydraulic generation of shock waves at higher rates. For example, fig. 3A shows a timing diagram enlarged to represent only two sequences of voltage pulses applied to the electrodes of the present embodiment, and fig. 3B shows a timing diagram representing more voltage pulses applied to the electrodes of the present embodiment.

In additional embodiments similar to any of the spark modules 22a, 22b, 22c, a portion of each sidewall (120, 120a, 120b) may be omitted such that each spark chamber (124, 124a, 124b) is also omitted or left open such that liquid in the larger chamber (e.g., 18 or 18a) of the respective handpiece may freely circulate between the electrodes. In such embodiments, the spark chamber cavity (e.g., sidewalls 120, 120a, 120b) may contain a liquid connector, or the liquid may be circulated through a liquid port that is independent of the spark chamber cavity (e.g., shown in fig. 2).

The portion of the pulse train or sequence 200 shown in fig. 3A includes groups of pulses 204 and 208 having a delay period 212 therein. A pulse group (e.g., 204, 208) may contain as few as 1 or 2, or as many as several thousand pulses. In general, each pulse set 204, 208 may include several voltage pulses applied to the electrodes to trigger an event (i.e., a spark across the spark gap). The duration of the delay period 212 may be set to allow the electrodes to cool across the respective spark gaps and to allow for the recharging of electrons. As with embodiments of the present disclosure, pulse rate refers to the rate at which groups of voltage pulses (each having one or more pulses) are applied to an electrode; as shown in fig. 3A-3B, meaning that individual pulses within a pulse group having two or more pulses are applied at a greater frequency. Each of these pulse groups may be configured to generate a shock wave or shock waves.

The series of events (sparks) initiated by the multiple pulse sets 204 and 208 transmitted by the present system and apparatus may include a higher Pulse Rate (PR) that may reduce treatment time compared to a lower PR that may need to be applied over many minutes. For example, tattoos may contain wide areas and are therefore time consuming to treat unless rapid cell destruction is achieved (e.g., within the higher PR of the present disclosure). In contrast to the prior art systems described above, the present embodiments may be configured to transmit shockwaves at a relatively high PR 216 of 10-5000 or more pulses per second (e.g., greater than or between any of 10Hz, 30Hz, 50Hz, 1000Hz, 10000Hz, 100000Hz, 500000Hz, and/or 5000000).

Fig. 4 shows a waveform that may be launched into a tissue volume by any of the probes 38 or 38a, and which has a form that can be used to eliminate tattoos. The pulse 300 has the typical shape of a pulse generated by the present EH spark head at a relatively high voltage pulse. For example, pulse 300 has a rapid rise time, a short duration, and a fall period. The vertical axis V is displayed on an oscilloscope_aThe unit of (c) is arbitrary. The actual acoustic pulse amplitude may be as low as 50 μ Pa, up to several MPa in various embodiments, at least because the cumulative energy transfer may be effective as discussed above. Due to their sharpness and short rise and fall times, the individual time periods 304 may be 100 nanoseconds respectively, in contrast to short pulses known in the art as "shock wave" pulsesThe length corresponds. For example, for the purposes of this disclosure,<a rise time of 30 nanoseconds, considered a shock wave, is particularly effective for rapidly generating a relatively large pressure-time pressure gradient across small cellular-scale structures in tissue (e.g., dermis). The rapid compression and decompression of dermal structures containing tattoo "ink" which is in fact particulate pigment, leads to fatigue and destruction of pigment-containing cells over time and is considered to be an underlying mechanism of the present method described above. For example, when applied at a high pulse rate over a relatively short period of time, agitation of the tissue with such a shock wave is shown to be effective and generate ruptured pigment cells at a sufficient energy level to liberate the captured microparticles and subsequently disperse the pigment particles within the body, thereby reducing the appearance of a tattoo. It is believed necessary to have a pulse 300 with a short waveform that the pulse 300 with a short waveform can be applied to the treated area multiple times, and preferably several hundred to several million times, to generate the fatigue required for tattoo "ink" removal.

Fig. 5 shows a schematic diagram of one embodiment 400 of a pulse generation system for use in or with some embodiments of the present system. In the illustrated embodiment, the circuit 400 includes a plurality of charge storage/discharge circuits having magnetic storage or induction type coils 404a, 404b, 404c, respectively (e.g., similar to those used in auto-ignition systems). As shown, each of the coils 404a, 404b, 404c may be grounded through a resistor 408a, 408b, 408c to limit the current allowed to flow through each coil, similar to certain aspects of the auto-ignition system. The resistors 408a, 408b, 408c may each comprise a dedicated resistor, or the length and performance of the coil itself may be selected to provide a desired level of resistance. Using components of the type used in auto-ignition systems may reduce cost and improve completeness compared to custom components. In the illustrated embodiment, the circuit 400 includes a spark head 22b similar to the spark head 22a, except that the spark head 22b includes three spark gaps 412a, 412b, 412c instead of two, and each of the three spark gaps is defined by a separate pair of electrodes instead of a common electrode (e.g., 100a) that cooperates with a plurality of peripheral electrodes. It should be appreciated that the present circuit may be coupled with the peripheral electrodes 100b, 100c of the spark head 22A to generate a spark across the spark gap defined with the common electrode (e.g., 100a), as shown in fig. 2A. In the illustrated embodiment, the circuits are configured to function similarly. For example, the coil 404a is configured to collect and store current for a short time such that, when the circuit is opened at the switch 420a, the magnetic field of the coil disappears and a so-called electromotive force or EMF is generated, which causes the capacitor 424a to rapidly discharge across the spark gap 412 a.

The RL or resistor of the coil 404 a-the inductance time constant-may be affected by factors such as the size and inductive reactance of the coil, the resistance of the coil windings, and other factors-generally corresponds to the time taken to overcome the resistance of the wire of the coil and the time to build the magnetic field of the coil and overcome the resistance of the circuit, followed by a discharge that is in turn controlled by the time taken for the magnetic field to disappear and release energy. The RL time constant generally determines the maximum charge-discharge cycle rate of the coil. If the charge-discharge cycle rate is too fast, the current available in the coil may be too low and the resulting spark pulse is weak. The use of multiple coils may overcome this limitation by firing multiple coils in rapid succession for each pulse set (e.g., 204, 208 shown in fig. 3A). For example, two coils may double the actual discharge rate by doubling (combining) the current and resulting spark pulses, and three (as shown) may effectively triple the effective charge-discharge cycle rate. When multiple spark gaps are used, timing can be very important to properly generate the spark pulses and the resulting liquid evaporation and shock waves. Thus, a controller (e.g., a microcontroller, processor, and/or FPGA, etc.) may be coupled with each of the control points 428a, 428b, 428c to control the timing of the opening of the switches 420a, 420b, 420c and the resulting discharging of the capacitors 424a, 424b, 424c and generation of the shockwave.

FIG. 6 shows a block diagram of an embodiment 500 of a Radio Frequency (RF) power acoustic shockwave generating system. In the illustrated embodiment, the system 500 includes a nonlinear medium 504 (e.g., as in the acoustic delay chamber cavity 58 or nonlinear component described above) that provides an acoustic path from the transducer 508 to the target tissue 512 to generate the actual harmonic or acoustic energy (e.g., shock waves). In the illustrated embodiment, the transducer 508 is powered and controlled by a bandpass filter and tuner 516, an RF power amplifier 520, and a control switch 524. The system is configured such that actuation of the control switch 524 activates the pulse generator 528 to generate timed RF pulses that drive the RF power amplifier 520 in a predetermined manner. A typical drive waveform may comprise, for example, a sine wave train (e.g., a plurality of sine waves in rapid succession). For example, in some embodiments, a typical string may have a string length of 10 milliseconds and contain a sine wave having a period of 0.1 (frequency of 100 MHz) to greater than 2 microseconds (frequency of 50 kHz).

The embodiment of the method comprises the following steps: positioning an embodiment of the present device (e.g., 10, 38a, 500) near a region of a patient containing target cells (e.g., tissue 74); and activating a spark generation (e.g., capacitive/inductive coil) system (e.g., 26, 400) to propagate the shockwave toward the target cell. In some embodiments, the region is viewed through a window (e.g., 82a) while the device is positioned and/or while the shockwave is generated and transmitted to the region. Some embodiments further include a housing that couples the removable spark head or module (e.g., 22a, 22b) with the apparatus prior to activating the pulse generation system.

Results of the experiment

Experiments were performed on tattooed skin specimens obtained from dead primates to observe the effect of shock waves generated by EH on the tattooed skin. Fig. 7A-7B and 8 show two different prototype spark chamber housings. The embodiment of fig. 7A-7B illustrates a first embodiment 600 of a spark chamber housing used in the described embodiments. The housing 600 is similar in some respects to the portion of the housing 14a defining the head 46a of the probe 38 a. For example, the housing 600 includes fittings 604, 608 that allow fluid to circulate through the spark chamber 612. In the illustrated embodiment, the housing 600 includes electrode supports 616 and 620 insertable into the electrodes 624 to define a spark gap 628 (e.g., 0.127 mm or 0.005 inch in the experiments described below). However, the enclosure 600 has an elliptical inner surface shaped to reflect the shock wave traveling first rearward from the spark gap into the wall. This has the advantage that for each shock wave generated at the spark gap, a first or primary shock wave is generated which propagates from the spark gap to the shock wave exit 640, followed by a secondary shock wave which first propagates towards the inner wall of the ellipse and then reflects back to the shock wave exit 640.

In this embodiment, the electrode supports 616 and 620 are not aligned with the fittings 604, 608 (rotated about 30 degrees relative thereto about the spark chamber 612). In the illustrated embodiment, housing 600 has a hemispherical shape and electrodes 624 are positioned such that angle 632 between central axis 636 through the center of shock wave outlet 640 and periphery 644 of spark chamber 612 is about 57 degrees. Other embodiments may be configured to limit this angular sweep and thereby direct the acoustic and/or shock waves through a smaller exit. For example, FIG. 8 shows a cross-sectional view of a second embodiment 600a of a spark chamber housing. The housing 600a is similar to the housing 600 except that the fittings 604a, 608a are rotated 90 degrees relative to the supports 616a, 620 a. The housing 600a also differs in that the chamber cavity 612a comprises a hemispherical rear or proximal portion and a frustoconical forward or distal portion. In this embodiment, the electrode 624a is positioned such that the angle 632a between the central axis 636a through the center of the shockwave outlet 640a and the periphery 644a of the chamber 612a is about 19 degrees.

Fig. 9 shows a schematic diagram of the circuitry of a prototype pulse generation system used with the spark chamber housing of fig. 7A-7B during the present experiment. The schematic diagram includes symbols known in the art and is configured to implement pulse generation functionality similar to that described above. The illustrated circuit is capable of operating in a relaxation discharge mode with the present embodiments of the shockwave head (e.g., 46a, etc.). As shown, the circuit includes a 110V Alternating Current (AC) power supply, an on-off switch, a timer ("control block"), a step-up transformer having a secondary voltage of 3kV or 3000V. The secondary AC voltage is rectified in a full-wave configuration by a pair of high-voltage rectifiers. These rectifiers charge a pair of opposite polarity 25mF capacitors, respectively protected by a parallel pair of resistors (100k Ω and 25k Ω), all together temporarily storing high voltage energy. When the impedance of the shockwave chamber cavity is low and the voltage charge is high, discharge by means of ionization switches is initiated, which are large spark gaps that conduct when the threshold voltage is achieved. Positive and negative voltages flow to each of the electrodes, and thus the potential between the electrodes can rise to about 6kV or 6000V. The resulting spark between the electrodes causes a portion of the liquid to evaporate into a rapidly expanding bubble, which generates a shock wave. In a spark, the capacitor discharges and becomes ready to be recharged by the transformer and rectifier. In the experiments described below, the discharge is about 30Hz, which is regulated only by the discharge and the natural rate of the discharge-hence the term "relaxation oscillations". In other embodiments, the discharge rate may be higher (e.g., up to 100Hz, such as for the multi-gap configuration of fig. 5).

A total of 6 tattoo excised tattoo primate skin specimens were obtained, separated, mounted on a substrate and placed in a water bath. A total of 4 tattoo specimens and 4 non-tattoo specimens were separated such that each of the tattoo specimens and the non-tattoo specimens served as a control group. The impulse chamber housing 600 is placed over each excised specimen and voltage pulses are applied at full power to the electrodes 624 for various durations. The shock wave is generated at a voltage of about 5-6 kV and about 10mA, which results in a power level of about 50W per pulse, and is transmitted at a rate of about 10 Hz. For the experiments described, multiple cycles of exposure were used, and the results observed after the cumulative period of exposure (e.g., cumulative total time of 10-20 minutes) were used as an indication of exposure period at long exposure periods and/or large pulse rates. Direct results observed in the water bath indicated the formation of coagulum around the edges of the specimen, which is believed to indicate that repeated shock waves cause residual blood flow. All specimens were subjected to histopathological examination. Histopathologists report the observation that cell membrane disruption and tattoo particles of macrophages containing tattoo pigments dispersed into the treated tissue. No changes in adjacent tissues were observed-such as thermal damage, rupture of basal cells, or vacuole formation. Specimens exhibiting the most significant damage readily visible through the untrained eye had the highest duration of shock wave exposure time in the group. This strongly suggests a threshold effect, which can be further explained as power and/or time increases.

Additional in vitro and in vivo monkey and pig experiments were then performed using another embodiment 38b of the present (e.g., handheld) probe for use with some embodiments of the present EH shock wave generation system and apparatus shown in fig. 11-13C. Probe 38b is similar in some respects to probes 38 and 38a, and therefore differs primarily from that described herein. In the present embodiment, the probe 38b includes: a housing 14b defining a chamber 18b and a shock wave outlet 20 b; a liquid (54) disposed in the chamber cavity 18 b; a plurality of electrodes configured to be disposed in the chamber to define one or more spark gaps (e.g., in a spark head or module 22 d); and is configured to be coupled to a pulse generation system 26, which pulse generation system 26 applies voltage pulses to the electrodes at a rate of 10Hz to 5 MHz.

In the illustrated embodiment, the spark head 22d includes a sidewall and body 120d and a plurality of electrodes 100g defining a spark gap. In the present embodiment, as shown, the probe 38b is configured to allow circulation of fluid through the chamber cavity 18b via fluid connectors or ports 112b and 116b, one of the fluid connectors or ports 112b and 116b being coupled to the spark head 22d and the other of the fluid connectors or ports being coupled to the housing 14 b. In the present embodiment, the housing 14b is configured to receive the spark head 22d as shown such that the housing 14b and the body 120d cooperate to define the chamber 18b (e.g., such that the spark head 22d and the housing 14b include complementary parabolic surfaces that cooperate to define the chamber). In this embodiment, the housing 14b and the spark head 22d include acoustically reflective liners 700, 704 covering their respective surfaces that cooperate to define the chamber cavity 18 b. In this embodiment, the body 120d of the spark head 22d includes a passage 188b (e.g., along a central longitudinal axis of the spark head 22 d) extending between the fluid connector 112b and the chamber 18b and aligned with the spark gap between the electrodes 100g so that circulating water will flow adjacent and/or through the spark gap. In the illustrated embodiment, the housing 14b includes a channel 192b extending between the port 116b and the chamber cavity 18 b. In this embodiment, the body 120d includes a groove 708 configured to receive a resilient gasket or O-ring 140a to seal the interface between the spark head 22d and the housing 14b, and the housing 14b includes a groove 712 configured to receive the resilient gasket or O-ring 140b to seal the interface between the housing 14b and the cap member 136b when the cap member 136b is secured to the housing 14b by the ring 716 and the collar 144 a.

In the illustrated embodiment, as shown, the electrode 100g includes a strip portion 724 and a cylindrical portion 728 (e.g., comprising tungsten for durability) respectively in electrical communication with (e.g., unitary with) the strip portion 724 such that the cylindrical portion 728 may extend into the chamber cavity 18b through a corresponding opening in the spark head 22 d. In some embodiments, portions of the sides of the cylindrical portion 728 may be covered by an electrically insulating and/or resilient material (e.g., a shrink wrap) such as, for example, to seal the interface between the cylindrical portion 728 and the housing. In this embodiment, the housing further includes a longitudinal groove 732 configured to receive the strip portion 724 of the electrode 100 g. In the illustrated embodiment, the housing 14b also includes a set screw 736 positioned to align with the cylindrical portion 732 of the electrode 100g when the spark head 22d is disposed in the housing 14b, such that the set screw 736 can be tightened to press the cylindrical portion 728 inward to adjust the spark gap between the cylindrical portions of the electrode 100 g. In some embodiments, the spark head 22d is permanently attached to the housing 14 b; however, in other embodiments, the spark head 22d may be removed from the housing 14b, such as, for example, to allow for replacement of the electrode 100g alone or as part of a new or replacement spark head 22 d.

Fig. 14 shows a schematic diagram of a second embodiment of the circuit of the prototype pulse generation system. The circuit of fig. 14 is substantially similar to the circuit of fig. 9 except that the circuit of fig. 14 includes an arrangement of triggering spark gaps instead of ionization switches, and contains certain components (e.g., 200k Ω resistors instead of 100k Ω resistors) that have different performance than the corresponding components in the circuit of fig. 9. In the circuit of fig. 14, block "1" corresponds to a primary controller (e.g., a processor) and block "2" corresponds to a voltage timer controller (e.g., an oscillator), both of which may be combined in a single unit in some embodiments.

In additional in vitro monkey experiments, the probe 38b of figures 11-13C was placed on a tattoo of each subject and energized through the circuit of figure 14. In monkey experiments, voltage pulses were applied to electrode 100g at different frequencies (30-60 Hz) for different durations of 1 minute to 10 minutes. At maximum power, shock waves are generated at a voltage of about 0.5kV (between about +0.4kV maximum and about-0.1 kV minimum) and a current of about 2300A (between about 1300A maximum and about-1000A minimum), which results in a total power of about 500kW per pulse and a transmitted energy of about 420mJ per pulse, and the shock waves are transmitted at a rate of about 30 Hz. As with the previous in vitro experiments, the histopathologist reported that cell membrane disruption was observed and that tattoo particles of macrophages containing tattoo pigments dispersed into the treated tissue. No changes in adjacent tissues were observed-such as thermal damage, rupture of basal cells, or vacuole formation. The specimens that showed the most significant damage were those with the highest power and duration of shock wave exposure time. These results suggest that increasing power and increasing the number of impacts (resulting in an increase in total transmitted power) results in increased pigment destruction, consistent with earlier in vitro experiments.

In vivo experiments, the probe 38b of fig. 11-13C was placed on a tattoo of each subject and energized by the circuit of fig. 14. In monkey experiments, voltage pulses were applied to electrode 100g at full power for a duration of two minutes, repeated 6 weeks, once per week. The shockwave is generated at a voltage of about 0.5kV (between about +0.4kV maximum and about-0.1 kV minimum) and a current of about 2300A (between about 1300A maximum and about-1000A minimum), which results in a total power of about 500kW per pulse and a transmitted energy of about 420mJ per pulse, and the shockwave is transmitted at a rate of about 30 Hz. In vivo swine experiments were similar except that a four minute shock wave was applied in each application. One week after six shock wave applications, biopsies were taken from each tattoo. All specimens were subjected to histopathological examination. The histopathologist reported that cell membrane disruption was observed and that tattoo particles of macrophages containing tattoo pigments dispersed into the treated tissue, such that the specimens subjected to the 4 minute treatment had a relatively large dispersion compared to the specimens subjected to the 2 minute treatment. No changes in adjacent tissues were observed-such as thermal damage, rupture of basal cells, or vacuole formation. These results are consistent with those observed for in vitro monkey experiments. Generally, these studies suggest increasing power and increasing the number of impacts (resulting in an increase in total delivered power-e.g., due to increased treatment duration).

Method

Diseases and/or conditions comprising particles agglomerated in a cellular structure include cancer, crystalline microparticles of the skeletal muscle system, or tattoo removal. These are merely non-limiting exemplary conditions that may be treated or addressed by rupturing or otherwise destroying cells containing particle agglomerates. In some embodiments, as discussed above, secondary non-thermal cell membrane degradation of particular cells may occur through non-linear processes accompanying the propagation of high frequency shock waves, resulting in the destruction of cells containing particle agglomeration.

Some general embodiments of the method include: a plurality of electro-hydraulically generated shock waves are transmitted (e.g., by one or more of the present devices) to at least one cellular structure comprising at least one region of heterogeneity until the at least one cellular structure is disrupted. In some embodiments, the shock wave is transmitted for no more than 30 minutes over a 24 hour period. In some embodiments, the shock wave is transmitted for no more than 20 minutes over a 24 hour period. In some embodiments, 200-5000 shockwaves are transmitted between 30 seconds and 20 minutes at each of a plurality of locations of the shockwave outlet.

A. Tattoo

Tattoos are essentially phagocytic cells such as fibroblasts and macrophages containing clumps of ink particles. Since the density of the captured ink particles is denser than the biological structure of the cells, there is a large difference in the elasticity of the tattoo or the cells containing the ink particles in their structure. When subjected to shock waves, cells containing ink particles are subjected to greater mechanical strain than other cells that do not contain dense particles. The shock wave can be configured to be transmitted at an optimal frequency and amplitude to sufficiently accelerate the ink particles to destroy specific cells while leaving fibroblasts without specific elastic differences. Details of tattoo and biological processes for release removal from cells are discussed further below.

The history of tattooing inks and dyes originates from substances found in nature, generally including isomeric suspensions of pigment particles and other impurities. One example is indian ink, which comprises carbon particles suspended in a liquid such as water. Tattoos are typically created by applying tattoo ink to the dermis, where the ink is generally substantially permanently retained. This technique introduces pigment suspension through the skin by alternating pressure suction caused by the elasticity of the skin accompanying the up and down movement of the tattoo needle. Water and other carriers of pigments introduced into the skin diffuse through the tissue and are absorbed. For most parts, 20% to 50% of the pigment is transmitted into the body. The remaining portion of the insoluble pigment particles is deposited in the dermis and remains there. In tattooed skin, pigment particles are generally phagocytosed by cells, causing pigment to agglomerate in the cytoplasm of the cells (i.e., in a membrane boundary structure called a secondary lysosome). The resulting pigment agglomerates ("particle agglomerates") may range up to several microns in diameter. Once the skin heals, pigment particles remain in the interstitial spaces of the skin tissue within the cells. Because of the relatively large amount of insoluble pigment particles within the cells, tattoo inks are generally not eliminated due to cell fixation. Tattoos fade over time but are generally retained during the life of the person tattooing.

Tattooing inks typically include aluminum (87% of pigment), oxygen (73% of pigment), titanium (67% of pigment), and carbon (67% of pigment). The relative distribution of elements to the tattoo ink composition is highly variable between different compounds. At least one study determined the particle size of three commercial tattoo inks shown in table 1:

table 1: tattoo pigment particle size

B. Tattoo removal

In conventional tattoos (decoration, makeup and reconstruction), as discussed above, once the pigment or dye is applied to the dermis to form the tattoo, the pigment or dye generally remains there permanently.

Although tattoos are generally permanent, it may be desirable for this reason to alter or eliminate the tattoo. For example, over time, a person may change mind (or change thoughts) and may want to remove or change the design of the decorative tattoo. As another example, a person wearing a cosmetic tattoo, such as an eye line, eyebrow, or lip coloring, may wish to change the color or area of the tattoo as fashion changes. Unfortunately, there is currently no simple and successful way to remove tattoos. Currently, methods of removing traditional tattoos (e.g., pigmented skin) may include salt abrasion, freezing, surgical excision, and CO₂And (4) laser. These methods may require invasive procedures associated with potential complications such as infection and often result in significant scarring. Recently, the use of Q-switched lasers to remove tattoos has gained widespread acceptance. By limiting the pulse duration, the ink particles typically reach very high temperatures, resulting in destruction of cells containing the tattoo ink pigments with relatively minimal damage to adjacent normal skin cells. This greatly reduces the scarring often obtained after non-selective tattoo removal methods such as abrasion or carbon dioxide laser treatment. The mechanism of Q-switched laser radiation to remove tattoos is still poorly understood. It is believed that the Q-switched laser more specifically removes tattoos through a selective photothermal and thermodynamically selective mechanism. Specifically, it is believed that pigments in cells can absorb laser light, causing heating of particles resulting in thermal destruction of cells containing the particles. The destruction of these cells results in the release of particles, which can then be removed from the tissue by the normal process of absorption.

While a Q-switched laser may be better for tattoo removal than some alternatives, it is not perfect. Some tattoos are resistant to all laser therapies, although the predicted high particle temperatures are achieved by selective photothermal action. Some reasons for tattoo removal failure include: absorption spectra of pigments, depth of pigments, and structural characteristics of certain inks. Adverse effects of laser tattoo treatment by Q-switched ruby lasers may include texture changes, scarring, and/or pigment changes. Transient hypopigmentation and texture changes have been reported to be as high as 50 and 12%, respectively, for patients treated with the Q-switched alexandrite laser. The pigmentation and texture changes are rare adverse effects of Q-switched Nd: YAG lasers, and the incidence of hypopigmentation changes is generally lower than with ruby lasers. The development of localized and generalized allergic reactions by Q-switched ruby and Nd: YAG lasers is also an unlikely, if not unusual, complication of tattoo removal. In addition, laser treatment can be painful, such as by local injection of lidocaine or the use of local anesthetic creams, often prior to laser treatment. Finally, laser ablation typically requires multiple treatment sessions (e.g., 5 to 20), and may require expensive equipment to provide maximum ablation. Typically, since many wavelengths are required to treat a multicolored tattoo, it is not possible to use only one laser system to remove all available inks and ink combinations. Even with multiple treatments, laser therapy can only eliminate 50-70% of tattoo pigment, resulting in residual stain.

Some embodiments of the method include: directing the electro-hydraulically generated shock waves (e.g., from embodiments of the present device) to cells of a patient; wherein the shock wave is configured to cause the particle to rupture one or more of the cells. Some embodiments include: embodiments of the present apparatus are provided; driving a device to form a shockwave configured to cause particles within a patient's body to rupture one or more cells of the patient; and directing the shock wave toward cells of the patient such that the shock wave causes the particles to rupture one or more of the cells (e.g., such as by degrading a cell wall or membrane). In some embodiments, the one or more shock waves are configured to have no persistent effect on cells in the absence of particles (e.g., are configured to not substantially cause permanent or persistent damage to cells that are not sufficiently close to particles to be damaged by the particles in the presence of the shock waves).

Some methods of the present methods include focusing one or more shock waves on a particular region of tissue containing cells. In some embodiments, the region of tissue where the one or more shock waves are focused is a region at a depth below the patient's skin. The shockwave may be focused by any of a variety of mechanisms. For example, a surface of the present device (e.g., a surface of the exit component 70 a) configured to contact the patient during use may be shaped (e.g., convex) to focus or shaped (e.g., convex) to disperse the shockwave, such as, for example, to narrow or expand the shock wave-guiding region. The focused shockwave can result in higher pressures on the target cell, such as, for example, pressures of 10MPa, 15-25 MPa, or greater. In some embodiments, the convex profile is configured to tension a portion of the patient's skin when the outlet component is pressed against the skin.

Some embodiments of the method further comprise: target cells of the patient to be disrupted are identified (e.g., prior to directing one or more shock waves to the target cells). In various embodiments, the target cell may comprise any of a variety of target cells, such as, for example, target cells comprising conditions or diseases involving clumping of cell particles. For example, the target cells may include: tattoos, musculoskeletal cells including crystalline microparticles, keratin-containing hair follicles, dental bubbles including enamel, and/or cancer cells, and the like. As another example, the target cell may comprise one or more skin diseases selected from the group consisting of comedones, papules, pustules, cysts, and whiteheads.

In some embodiments, the particles may comprise non-natural particles. One example of non-natural particles includes tattoo pigment particles, such as are often disposed in human dermis to create a tattoo. In some embodiments, the pigment may comprise an element having an anatomical number less than 82. In certain embodiments, the particles may comprise any one or combination of gold, titanium dioxide, iron oxide, carbon, and/or gold. In some embodiments, the particles have an average diameter of less than 1000nm (e.g., less than 500nm and/or less than 100 nm).

FIG. 10 illustrates one embodiment of a method 700 of using the device 10 to direct a shockwave toward a target tissue. In the illustrated embodiment, the method 700 includes a step 704 of identifying target cells 708 of a tissue 712 of a patient for treatment. For example, tissue 712 may comprise skin tissue and/or target cells 708 may comprise tattoo pigment-containing cells within or near the skin tissue. In the illustrated embodiment, method 700 further includes a step 716 of positioning probe 38 proximate tissue 712 and/or target cell 708 such that a shockwave from probe 38 can be directed to target cell 708. In the illustrated embodiment, the method 700 further includes a step 720 of coupling the pulse generation system 26 with the probe 38. In the illustrated embodiment, as shown, method 700 further includes a step 724 of activating pulse generation system 26 to generate a spark across an electrode within probe 38 to generate a shockwave in probe 38 for transmission to target cell 708. In the illustrated embodiment, method 700 further includes an optional step 728 of decoupling pulse generation system 26 from probe 38 and removing or moving probe 38 relative to tissue 712. In the illustrated embodiment, the target cells 708 are omitted from step 728, representing that they are destroyed. Other embodiments of the method may include some or all of the steps shown in fig. 10.

C. Method for removing tissue markers

Some embodiments of the present method of eliminating tissue marks (e.g., tattoos) caused by pigment in dermal tissue include the use of one of the present devices. In this method, a high frequency shock wave is delivered into the skin of the patient such that, when the shock wave generated from the device of the present disclosure reaches the dermal cells and vibrates or accelerates the intradermal particles, the particles undergo movement relative to the cell membrane which can result in fatigue degradation and rupture of the cells, thereby releasing the pigment particles. The released particles can then be removed from the surrounding tissue by the normal suction process of the patient's body. In some embodiments, one of the devices may be placed in proximity and/or the shock waves from the device directed to a tattooed tissue site, other tissue markers, or other cellular structures containing particle agglomerates. To cause the particles to change (e.g., cell degradation sufficient to release the particles for absorption), a shock wave may be transmitted to a particular region for a sufficient time to rupture cells containing and/or near the pigment particles such that the pigment particles are released. In some embodiments, the present device has a focusing or active area that may be smaller than the tattoo, such that the device may periodically and sequentially focus and direct different areas of the tattoo to cause a reduction in the perceptible pigment over the entire area of the tattoo. For example, parameters of embodiments of the apparatus disclosed herein may be modified to achieve a desired number of impacts delivered to a particular location in a desired time. For example, in one embodiment, shock waves are generated from acoustic waves at a frequency of at least 1MHz and exposed to a particular treatment site for a suitable time in accordance with aspects of the present disclosure to transmit at least about 100, 200, 300, 400, 500, or 1000 shock waves to the treatment site. The shockwaves may be transmitted all at once or at intervals (e.g., strings) of shockwaves, such as 5, 10, 15, 20, 25, 30, 40, 50 shockwaves at a time, etc. The appropriate intervals and the time between intervals may be modified and/or determined to achieve a desired effect on the treatment site, e.g., disruption of the target cellular structure. It should be appreciated that if acoustic waves having higher frequencies, such as 2MHz, 3MHz, 4MHz, or 5MHz, are used, the treatment time may be adjusted, possibly a shorter exposure time, to achieve the desired amount of shock waves delivered to the treatment area.

It will be appreciated by the person skilled in the art that in embodiments of the present method for removing a tattoo, the particles influenced by the shock wave may comprise, for example, tattoo pigments (particles) which may be arranged, for example, at least partially, between and/or within skin cells of the patient. Such pigment particles may, for example, comprise at least one of titanium, aluminum, silicon oxide, copper, chromium, iron, carbon, or oxygen, or any combination thereof.

The use of high frequency shock waves to remove or reduce skin marks has many advantages over the use of lasers. For example, laser treatment for tattoo removal can be very painful. Conversely, high frequency shock waves (e.g., ultrasonic shock waves) may be configured and/or applied, particularly, for example, where the shock waves are targeted or otherwise configured to only degrade cells containing tattoo pigment, such that tattoos or other skin markers may be removed or eliminated with little, if any, pain to the patient. As another example, it has been found that laser light directed at tissue causes damage or destruction of surrounding tissue; while high frequency shock waves may be applied to cause little damage or destruction to surrounding tissue (e.g., due to non-tattooed surrounding tissue typically lacking tattooing pigments or other particles that would otherwise interact with adjacent cells to cause cell deterioration). Finally, laser tattoo removal often requires multiple treatment sessions (e.g., 5-20 sessions) for maximum tattoo removal and/or often requires the use of expensive equipment. In addition, since lasers may require many wavelengths to remove a multi-colored tattoo, multiple laser systems may be required to remove various available inks and/or combinations of available inks. As a result, the total cost of laser tattoo removal may be prohibitively high. Even with multiple treatments, laser therapy may be limited to eliminating only 50-70% of the tattoo pigment and leaving residual "smudges". In contrast, the high frequency shock waves are independent of the color of the tattoo pigment, such that therapeutic application of the high frequency shock waves does not require a different device for different color pigments, and such that the high frequency shock waves can be applied to a relatively large area (e.g., the entire area of the tattoo), thereby reducing the number of sessions required to achieve a patient-acceptable level of tattoo removal or reduction (e.g., a reduction of 30%, 40%, 50%, 60%, 70, 80%, 90%, 95% or greater percentage of the perceptible pigment in the patient's skin).

In some embodiments, the method includes applying a high frequency shock wave (e.g., by one or more of the present devices) and applying a laser. For example, some embodiments of the method further comprise directing the beam from the Q-switched laser to a target cell (e.g., tattooed skin). In some embodiments, the directing of the one or more shock waves and the directing of the light beam are performed in an alternating order.

In some embodiments, before, after, and/or while directing one or more shock waves at the target cell, the method includes delivering one or more chemical or biological agents (e.g., configured to aid in removing a tissue marker such as a tattoo) to a location on or near the target cell. For example, some embodiments of the present methods further comprise applying a chemical or biological agent to the skin (e.g., before, after, and/or while directing one or more shock waves and/or laser beams to the skin). Examples of chemical or biological agents include: chelating agents (e.g., ethylenediaminetetraacetic acid (EDTA)); immunomodulators (e.g., Imiquimod [5 ]); combinations thereof; and/or other suitable chemical or biological agents. In various embodiments, the chemical or biological agent is delivered (e.g., injected) transdermally and/or systemically to the target cells (e.g., can be applied topically to tattooed skin).

Some embodiments of the present methods of tattoo removal include applying the shock wave to the tattoo skin tissue multiple times (e.g., at least 1 second (e.g., 10 seconds or more), once per week, for 6 weeks or more).

D. Methods of treating additional diseases and conditions

In addition to tattoo removal, embodiments of the present methods may include applying high frequency shock waves to treat various diseases under conditions caused by or including symptoms of cellular particle masses and/or particles disposed in the intracellular and/or interstitial spaces. For example, such diseases and/or conditions may include: crystalline joint, ligament, tendon and muscle diseases and/or skin diseases including particle agglomeration including acne, pigmented spots, etc. Additionally, embodiments of the method may include applying a high frequency shockwave after delivery of the nanoparticles to the region of the patient containing the target cells. For example, in some embodiments, nanoparticles (e.g., gold nanoparticles) are delivered intravenously to a patient's bloodstream and allowed to travel to a region of the patient containing target cells (e.g., such as a tumor, etc.), such that high frequency shock waves can be directed to the target region to cause the nanoparticles to interact with the target cells and destroy them.

Also, embodiments of the present apparatus (e.g., apparatus 10) may be used for wrinkle reduction. For example, some embodiments of the present method of generating therapeutic shock waves include: providing any one of the present devices (e.g., device 10); and a drive device to generate one or more shock waves. Some embodiments further comprise: the device (e.g., the outlet end 34 of the housing 18) is positioned adjacent to the tissue of the patient such that the at least one shock wave enters the tissue. In some embodiments, the tissue comprises skin tissue on the face of the patient.

In embodiments of the present methods that include directing particles (e.g., microparticles and/or nanoparticles) to a location on or near a target cell (prior to directing a shockwave to the cell), the particles may include: silk, silk fibrin, carbon nanotubes, liposomes, and/or gold nanoshells. For example, in some embodiments, directing the particles may include injecting a fluid suspension containing the particles into the patient. The suspension may for example comprise physiological saline and/or hyaluronic acid.

The deposition of crystals and other miscellaneous crystals in joints and specific tissues may lead to several disease states. For example, sodium urate monohydrate (MSUM) deposits in joints can lead to gout. As another example, dehydrated calcium pyrophosphate (CPPD) in articular tissues and fluids can cause a number of diseases such as, for example, cartilage calcification (i.e., the presence of calcium-containing crystals in articular cartilage that are detected as radiodensity). As another example, Hydroxyapatite (HA) crystal deposition can lead to calcified tendonitis and scapulohumeral periarthritis. In some embodiments in the present methods, the particles may comprise natural particles (e.g., particles that occur naturally within the body), such as, for example, crystalline microparticles such as may be from and/or become disposed in the musculoskeletal system of a patient. Other examples of natural particles that may be processed and/or dispensed in the present methods include: urate crystals, calcium containing crystals and/or hydroxyapatite crystals.

In embodiments of the present methods for treating acne or other skin-based conditions, the particles may comprise dirt and/or debris distributed in one or more pores in the skin of the patient, and/or may comprise keratin distributed in the skin of the patient. In embodiments of the present method of treating conditions associated with (e.g., pathological) bone and musculoskeletal environments and soft tissues by the application of shock waves, local trauma and apoptosis (including microdisruption) may be induced, or osteoblastic responses such as cell recruitment may be induced, stimulating molecular bone, cartilage, tendon, fascial formation and soft tissue morphogenesis and growth factors, and/or neovascularization may be induced.

Some embodiments of the present methods of treating tumors or other conditions include applying a shockwave to a target tissue (e.g., a tumor, an area of skin having acne or other conditions, etc.) multiple times, such as, for example, for at least 1 second (e.g., 10 seconds or more), once per week, for 6 weeks or more.

The above specification and examples provide a description of the structure and use of exemplary embodiments. Although certain embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the scope of this invention. Thus, the various illustrative embodiments of the present device are not intended to be limited to the particular forms disclosed. Rather, they encompass all modifications and alternatives falling within the scope of the claims, and embodiments other than the illustrated embodiments may include some or all of the features of the illustrated embodiments. For example, the components may be combined into a unified structure. Also, where appropriate, aspects of any of the examples described above may be combined with aspects of any of the other examples described to form other examples having equivalent or different performance and addressing the same or different problems. Similarly, it is to be understood that the benefits and advantages described above may relate to one embodiment or may relate to several embodiments.

The claims are not intended to be inclusive and should not be construed to include means + or step + functional limitations unless such limitations are expressly set forth in a given claim by the use of the phrases "means for …" or "step for …," respectively.

Reference to the literature

[1]Burov,V.A.,Nonlinear ultrasound:breakdown of microscopic biological structures and nonthermal impact on malignant tumor. Doklady Biochemistry and Biophysics Vol.383,pp.101-104(2002).

[2]Delius,M.,Jordan,M.,&et al.(1988).Biological effects of shock waves:Kidney Haemorrhage by shock waves in dogs--administration rate dependence.Ultrasound in Med.&Biol.,14(8),689-694.

[3]Fernandez,P.(15May 2006).A master relation defines the nonlinear viscoelasticity of single fibroblasts.Biophysical journal,Vol.90,Issue 10,3796-3805.

[4]Freund,J.B.,Colonius,T.,&Evan,A.P.(2007).A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy. Ultrasound in Med&Biol,33(9),1495–1503.

[5]Gillitzer,R.,&et al.(2009).Low-frequency extracorporeal shock wave lithotripsy improves renal pelvic stone disintegration in a pig model. BJU Int,176,1284-1288.

[6]Kasza,K.E.(2007).The cell as a material.Current Opinion in Cell Biology 2007,19:101-107.

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Claims (10)

1. An apparatus for generating therapeutic shock waves, the apparatus comprising:

a module having a first end configured to be removably coupled to a probe handle and a second end defining a shockwave outlet through which shockwaves are transmitted, the module defining a chamber between the first end and the second end in which a plurality of electrodes are disposed and configured to be filled with a liquid, the module comprising:

a body;

the plurality of electrodes disposed within the chamber cavity and defining one or more spark gaps; and

a plurality of electrical connectors electrically connected with the plurality of electrodes and configured to releasably connect the electrodes to a pulse generation system to generate a spark across the one or more spark gaps;

wherein the module comprising the body, the plurality of electrical connectors, and the plurality of electrodes is removable from the probe handle.

2. The apparatus of claim 1, wherein the module is a spark head.

3. The apparatus of claim 1, wherein the module further comprises a hinge coupled to a first electrode of the plurality of electrodes, the hinge configured to enable a change in a physical position of the first electrode relative to a second electrode of the plurality of electrodes.

4. The apparatus of claim 3, wherein the first electrode is coupled to an electrical connector among the plurality of electrical connectors via the hinge.

5. The device of claim 1, wherein the module further comprises one or more fluid connectors coupled to the body.

6. The apparatus of claim 5, wherein the one or more liquid connectors are configured to enable liquid to be supplied to the chamber cavity.

7. The device of claim 5, wherein the body comprises a channel extending between the one or more fluid connectors and the chamber cavity.

8. The apparatus of claim 1, further comprising:

a handle of the probe is arranged on the probe,

wherein, the probe handle contains:

a first end coupled to a first end of the module; and

a second terminal having a voltage connector configured to be coupled to a pulse generation system.

9. The device of claim 1, further comprising a cap member coupled to the body.

10. The apparatus of claim 1, wherein the plurality of electrodes are configured to: receiving voltage pulses from a pulse generating system at a rate between 10Hz and 5MHz, and when the chamber cavity is filled with a liquid and the plurality of electrical connectors are coupled to the pulse generating system, a spark generated from the spark gap produces a shockwave that propagates through the liquid and the opening.