PLATELET-RICH PLASMA ACTIVATION SYSTEM AND METHOD

A platelet-rich plasma (PRP) activation system for activating PRP contained in a container includes a housing, a power supply, a piezoelectric transducer array, a support structure, and a coupling medium. The power supply is located in the housing. The piezoelectric transducer array is operably connected to the power supply and is located in the housing. The piezoelectric transducer array is configured to generate a focused shock wave using power from the power supply. The support structure is operably connected to the housing and is configured (i) to receive the container, and (ii) to position the container at least partially within the housing, such that at least a portion of the PRP is located at a focal volume formed by the focused shock wave. The coupling medium is located in the housing and is positioned between the piezoelectric transducer array and the container.

FIELD

This disclosure relates to the field of platelet-rich plasma (PRP) therapy and, in particular, to activating the PRP before administration to a patient.

BACKGROUND

PRP therapy is a process in which PRP, also known as autologous conditioned plasma, is injected into a patient (human or animal) at an injury site to stimulate the healing process. PRP is a concentrate of platelet-rich plasma protein derived from whole blood that has been centrifuged to remove red blood cells and platelet-poor plasma. Typical injuries in which PRP therapy is utilized include injured tendons, ligaments, muscles, and joints. PRP therapy is also effective for treating osteoarthritis. Moreover, PRP therapy is used as a treatment option following oral surgery and plastic surgery. PRP therapy tends to reduce patients' need for anti-inflammatories and stronger medications like opioids. In addition, the side effects of PRP therapy are very limited because the PRP is typically extracted from the patient's blood. Allogeneic PRP therapy is also available for some treatments and injuries and also has very limited side effects.

During a PRP therapy session, the PRP is injected into the patient in an unactivated state or an activated state. Unactivated PRP includes growth factors useful for stimulating the healing process. Activating the PRP is a process in which the PRP is caused to release additional growth factors including vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and platelet-derived growth factor (PDGF). The additional quantity of growth factors released by the activated PRP tends to further stimulate the healing process.

There are several methods of activating PRP for PRP therapy. One method includes subjecting the PRP to a freeze-thaw cycle, which requires refrigeration equipment and, typically, multiple days between drawing the patient's blood and providing the patient with the PRP injection. Another method of activating PRP includes mixing the PRP with calcium chloride (CaCl2) and/or thrombin. This method of activation, however, is known to undesirably cause clotting of the PRP, which increases the difficulty in administering the activated PRP to the patient and may reduce the effectiveness of the PRP therapy. Thus, known methods for activating PRP are either time-consuming, increase the difficulty in administering the treatment, and/or reduce the effectiveness of the treatment.

Based on the above, further advancements are needed to improve the process for activating the PRP used in PRP therapy.

SUMMARY

According to an exemplary embodiment of the disclosure, a platelet-rich plasma (PRP) activation system for activating PRP contained in a container includes a housing, a power supply, a piezoelectric transducer array, a support structure, and a coupling medium. The power supply is located in the housing. The piezoelectric transducer array is operably connected to the power supply and is located in the housing. The piezoelectric transducer array is configured to generate a focused shock wave using power from the power supply. The support structure is operably connected to the housing and is configured (i) to receive the container, and (ii) to position the container at least partially within the housing, such that at least a portion of the PRP is located at a focal volume formed by the focused shock wave. The coupling medium is located in the housing and is positioned between the piezoelectric transducer array and the container. The coupling medium is configured to transmit the focused shock wave from the piezoelectric transducer array to the container.

According to another exemplary embodiment of the disclosure, a platelet-rich plasma (PRP) activation system for activating PRP contained in a container includes a housing, a power supply, a first piezoelectric transducer array, a second piezoelectric transducer array, and a support structure. The power supply is located in the housing. The first piezoelectric transducer array is operably connected to the power supply and is located in the housing. The first piezoelectric transducer array is configured to generate a first focused shock wave using power from the power supply. The second piezoelectric transducer array is operably connected to the power supply and is located in the housing. The second piezoelectric transducer array is configured to generate a second focused shock wave using the power from the power supply. The support structure is operably connected to the housing and is configured (i) to receive the container, and (ii) to position the container at least partially within the housing along a movement axis of the container, such that a first portion of the PRP is located at a first focal volume formed by the first focused shock wave and a second portion of the PRP is located at a second focal volume formed by the second focused shock wave. The first focal volume and the second focal volume are spaced apart from each other along the movement axis.

According to a further exemplary embodiment of the disclosure, a method of operating a platelet-rich plasma (PRP) activation system includes striking a first portion of PRP with a first focused shock wave generated by a first piezoelectric transducer array of the PRP activation system in order to activate the first portion of the PRP. The PRP is contained in a container received by the PRP activation system, and the container is located at a first position. The method further includes moving the container along a movement axis from the first position to a second position with a positioning device of the PRP activation system, and striking a second portion of the PRP with a second focused shock wave generated by the first piezoelectric transducer array in order to activate the second portion of the PRP. The container located at the second position.

DETAILED DESCRIPTION

Aspects of the disclosure are disclosed in the accompanying description. Alternate embodiments of the disclosure and their equivalents may be devised without parting from the spirit or scope of the disclosure. It should be noted that any discussion herein regarding “one embodiment”, “an embodiment”, “an exemplary embodiment”, and the like indicate that the embodiment described may include a particular feature, structure, or characteristic, and that such particular feature, structure, or characteristic may not necessarily be included in every embodiment. In addition, references to the foregoing do not necessarily comprise a reference to the same embodiment. Finally, irrespective of whether it is explicitly described, one of ordinary skill in the art would readily appreciate that each of the particular features, structures, or characteristics of the given embodiments may be utilized in connection or combination with those of any other embodiment discussed herein.

The terms “comprising,” “including,” “having,” and the like, as used with respect to embodiments of the disclosure, are synonymous.

As shown inFIGS.1and2, a PRP activation system100is configured to activate PRP104(FIG.2) before a clinician injects the PRP104into a patient in the course of PRP therapy. The PRP activation system100uses focused acoustical shock waves106to activate the PRP104instead of the freeze-thaw cycle and instead of adding calcium chloride and/or thrombin to the PRP104. Activating the PRP104with the activation system100takes less than three minutes. Accordingly, the PRP activation system100overcomes the equipment difficulties (no refrigeration equipment is needed) and the time requirements of the freeze-thaw cycle activation approach. Moreover, shock waves, such as the focused shock waves106, have been found to result in a significant increase in growth factors in the PRP104without the clotting issues of calcium chloride and/or thrombin. As explained herein, the PRP activation system100is a portable and efficient system for activating PRP104, thereby increasing patient comfort and convenience, and decreasing the time required to prepare the PRP104for injection during PRP therapy.

With reference toFIG.1, the PRP activation system100is configured to receive a container108of PRP104(FIG.2). In the figures, the container108is shown as a syringe, but the container108may additionally or alternatively be provided as a vial or any other suitable vessel. The PRP activation system100includes a housing112, a shock wave generator assembly116, a container support structure120, and a coupling medium124. The exemplary container108includes a plunger130and a barrel134(FIG.2). In one embodiment, the housing112includes a base structure138, an intermediate structure142connected to the base structure138, and a cover or lid146connected to the intermediate structure142with fasteners150. The base structure138and the intermediate structure142define a housing space154(FIG.3) configured to receive operating electronics of the PRP activation system100. The intermediate structure142is configured to support the shock wave generator assembly116and the coupling medium124. The lid146is configured to close, at least partially, the housing space154. In an exemplary embodiment, the lid146is formed from a translucent material, such as acrylic. In other embodiments, the lid146is transparent or opaque and is formed from another suitable material. Moreover, in a further embodiment, the base structure138and the intermediate structure142are integrally formed as a single piece.

In some embodiments, as shown inFIG.1, the base structure138also supports a plurality of electrical connectors158, such as the illustrated subminiature version a (SMA) connectors, for electrically connecting the PRP activation system100to an external electrical device162. In other embodiments, the electrical connectors158are provided as any other suitable electrical connector format, such as a serial port and/or a universal serial bus (USB). In further embodiments, such as the PRP activation system700ofFIG.10, the PRP activation system100does not include the electrical connectors158and an interface190,708is used to control the system100.

As shown in the block diagram ofFIG.2, the operating electronics of the PRP activation system100include an interface190, a field programmable gate array (FPGA)194, and drive electronics198, each operably connected to a microcontroller202. The PRP activation system100also includes a power supply206within the housing112. Each of these elements is described herein.

The interface190, which is not shown inFIG.1, includes a display210and an input device214configured for operation by a user of the PRP activation system100. The display210is mounted on the housing112and is configured to display information and data pertaining to operation of the PRP activation system100, such as a number of the focused shock waves106to be administered to the PRP104, an energy level of the focused shock waves106, and a repetition frequency of the focused shock waves106. In one embodiment, the display210is a liquid crystal display (LCD).

The input device214is mounted on the housing112and is configured to generate input data when touched or pressed by the operator. For example, the input device112may be pressed to generate an electrical start signal for initiating a shock wave sequence for activating the PRP104within the container108. An exemplary input device214includes at least one push button.

In one embodiment, the input device214and the display210are combined as a touchscreen mounted on the housing112. In a further embodiment, the PRP activation system100does not include the interface190, and the operator interfaces with the PRP activation system100through the external electrical device162connected to electrical connectors158. The external electrical device162is configured as a laptop computer, a desktop computer, a signal generator, a tablet computer, a smartphone, and/or any other suitable computer device. In some embodiments, the external device162is wirelessly connected to the PRP activation system100via Bluetooth® or any other suitable wireless connection and data transfer protocol.

As shown inFIG.2, the FPGA194is configured to receive an activation signal from the microcontroller202, such as when the user operates the input device214, and causes the start signal for initiating the focused shock waves106to be generated. The activation signal causes the FPGA194to activate the drive electronics198for generating high-power electric signals that are supplied to the shock wave generator assembly116for generating the focused shock waves106.

The drive electronics198ofFIG.2are operably connected to the shock wave generator assembly116and are configured to generate high-voltage and high-current signals that are supplied to the shock wave generator assembly116through transducer channels224for causing the shock wave generator assembly116to generate the focused shock waves106. In one embodiment, the drive electronics198include a separate drive channel electronic unit (not shown) for each shock wave generating element228of the shock wave generator assembly116. Accordingly, the drive electronics198may include twenty drive channel electronic units for the twenty shock wave generating elements228.

The microcontroller202is provided as any desired processor, microprocessor, controller, and/or microcontroller. In a specific embodiment, the microcontroller202is a 32F413 microprocessor by STMicroelectronics.

The power supply206, in the exemplary embodiment ofFIG.2, is a power source for generating the focused shock waves106and for powering all electronics of the PRP activation system100. In one embodiment, the power supply206includes at least one rechargeable battery located within the housing112. For example, the power supply206includes a rechargeable lithium-ion battery or any other suitable battery technology having a high power density. In such an embodiment, no connection to a wall outlet supply of electricity (i.e., mains power) is required to generate the focused shock waves106. That is, in some embodiments, the power supply206, as a rechargeable battery, is the only power source for generating the focused shock waves106. As such, the PRP activation system100is portable and can be operated anywhere. In another embodiment, the power supply206is a switching power supply and/or a linear power supply configured for connection to the wall outlet supply of electricity. The power supply206is located in the housing112.

As shown inFIG.2, the shock wave generator assembly116includes four concentrically-arranged transducer arrays236, each operably connected to the power supply206. Each transducer array236is configured to generate a corresponding focused shock wave106using power from the power supply206. Each transducer array236is located in the housing112and includes a corresponding support frame240and five of the shock wave generating elements228. The support frames240are each mounted to the intermediate structure142(FIG.1) and are positioned around the coupling medium124. The support frames240define an arc-shaped surface242facing the coupling medium124. The coupling medium124and the transducer arrays236are concentrically arranged about a center point244. When the container108is supported by the support structure120, the center point.244is located within a volume of the container108that contains the PRP104. In other embodiments, the shock wave generator assembly116includes from one to forty of the transducer arrays236.

With reference again toFIG.1, each support frame240defines a plurality of cavities248for receiving a corresponding one of the shock wave generating elements228. In the illustrated example, each support frame240defines five of the cavities248. The cavities248extend completely through the support frames240and form openings in the arc-shaped surface242. The cavities248extend from the arc-shaped surface242into the support frame240. In other embodiments, each support frame240may define from one to twenty of the cavities248at least some of which are configured to receive a corresponding shock wave generating element228.

The support frames240, as shown inFIG.1, are formed from a rigid thermoplastic or another suitably rigid and generally non-electrically conductive material. Moreover, in one embodiment, each support frame240is positioned within a corresponding positioning jig252(FIG.1) of the intermediate structure142and is attached to the intermediate structure142by fasteners254. The positioning jigs252“aim” the transducer arrays236(FIG.2) so that the resulting focused shock waves106are aimed and/or focused at the center point244and form a focal volume258within the container108. The positioning jigs252also simplify assembly of the PRP activation system100.

As shown inFIG.2, the shock wave generating elements228of the transducer arrays236are configured to generate individual acoustical shock waves250for activating the PRP104within the container108. The individual shock waves250generated by the elements228are sound waves. In particular, the individual shock waves250are short duration, acoustic pulses having a very high positive pressure amplitude and a steep pressure increase compared to the ambient pressure. Shock waves are similar to ultrasound but have a different wave profile. Typically, ultrasound waves have a periodic oscillation between positive and negative pressure along with a narrow bandwidth. Whereas, shock waves typically exhibit a single positive pressure pulse containing a broad bandwidth. Shock waves are different than radial pressure pulses due to their higher pressure, faster rise time, shorter duration, and ability to be focused. Radial pressure waves are not shock waves and cannot be focused.

In an exemplary embodiment, the shock wave generating elements228are piezoelectric elements and the transducer arrays236are configured as piezoelectric transducer arrays236. The piezoelectric elements are each configured to generate the individual shock waves250in response to receiving the high voltage and high current signal from the drive electronics198. In a specific embodiment, the shock wave generating elements228are “dice-and-fill” composite piezoelectric material and epoxy having vertical columns of piezoceramic material. These elements228have higher efficiency (coupling coefficients) and a lower acoustic impedance that is easier to match to water or tissue. Additionally, the shock wave generating elements228are constructed using a “soft” piezoceramic material having a high dielectric constant and high coupling. In other embodiments, the shock wave generating elements228are formed from any other suitable material or materials.

The shock wave generating elements228are arranged at least partially in the cavities248in the support frames240along the arc-shaped surface242. Each individual shock wave250is emitted from a corresponding face272(FIG.2) of one of the shock wave generating elements228. Accordingly, due to the shape of the arc-shaped surface242the individual shock waves250converge, constructively combine, and/or are mechanically focused at the center point224, at the focal volume258, and/or at another predetermined point within the container108as the focused shock waves106. Each transducer array236of the PRP activation system100is configured to generate a corresponding one of the focused shock waves106.

As shown inFIG.2, the focal volume258is a three-dimensional space in which the focused shock waves106are delivered with an energy level that is suitable for activating the PRP104. In one embodiment, the focal volume258is formed by a constructive combination of the focused shock waves106. In the example ofFIG.2, the focal volume258is formed by the constructive combination of two of the focused shock waves106, of three of the focused shock waves106, or of four of the focused shock waves106.

In order to further mechanically focus the individual shock waves250, the microcontroller202configures the drive electronics198to activate each shock wave generating element228with a predetermined time delay and/or a predetermined time advance. The set of time delays and/or time advances for each of the elements228is referred to herein as a timing sequence and/or a timing program. When the shock wave generating elements228are activated according to the timing sequence, the individual shock waves250generated by the elements228arrive at the focal volume258simultaneously or substantially simultaneously as the focused shock wave106. The timing sequence may cause each element228to be activated at a different time in order to form the focused shock wave106. In an example, the timing sequence causes a first element228to be activated at a first time and causes a second element228to be activated at a second time that is different from the first time. The individual shock waves250generated by the two elements228arrive at the focal volume258substantially simultaneously. The first and second elements228may be located in the same transducer array236or in different transducer arrays236.

As used herein, the focused shock wave106includes any constructive combination of two or more shock waves250. Thus, as used herein, focusing refers to constructively combining shock waves250at the focal volume258. The focused shock wave106can be formed by mechanical focusing in which the elements228are pointed at the same spot (i.e., the focal volume258). The focused shock wave106can also be formed by using acoustic lenses and/or reflectors to focus the shock waves250at the focal volume258. In some embodiments, the focused shock wave106is generated without using the time delays and/or time advances of the timing sequence. The timing sequence is not required to generate the focused shock wave106. Focusing the shock waves250concentrates the pressure of the shock waves250at the focal volume258.

In one embodiment, the predetermined time delays are based on a reference time delay. For example, the reference time delay is arbitrarily chosen as 500 ns. The time delays either lead, lag, or are equal to the reference time delay. The elements228generating individual shock waves250that lead the reference time delay, receive time delays less than the reference time delay, whereas the elements228generating individual shock waves250that lag the reference time delay receive time delays that are greater than the reference time delay. In an example, about150ns span between the first element228to be activated and the last element228to be activated during the generation of the focused shock wave106.

The timing sequence(s) are stored in the FPGA194, for example, or in a separate non-transitory electronic memory (not shown) of the PRP activation system100. As used herein, “substantially simultaneously” means that the individual shock waves250each arrive at the focal volume258within plus or minus 20 nanoseconds to form a corresponding one of the focused shock waves106.

As shown inFIG.2, the shock wave generating elements228are arranged concentrically and are each approximately the same distance from the center point244. Nevertheless, due to slight positioning and alignment differences (i.e., tolerances), when the shock wave generating elements228are each activated at the same time, at least some of the individual shock waves250arrive at the focal volume258at different times. The timing sequences account for the tolerances in the construction of the transducer arrays236and the structural differences in the shock wave generating elements228, so that the individual shock waves250arrive at the focal volume258substantially simultaneously.

In one embodiment, the location of the focal volume258of the focused shock waves250is “tunable” (i.e., movable or positionable) to any location within the container108that is in a plane262(FIG.3) of the shock wave generating elements228. The location of the focal volume258is moved and/or tuned by changing and/or adjusting the timing delays applied to the shock wave generating elements228by the drive electronics198. For example, with reference toFIG.2, the focal volume258is moved closer to the left transducer array236by activating the elements228of the left transducer array236prior to activating the elements228of the right transducer array236.

As shown inFIG.2, the concentrically arranged transducer arrays236each emit the corresponding focused shock wave106toward the center point244. Specifically, with reference toFIG.2, the left transducer array236emits the focused shock wave106in a first direction256toward the center point244, the top transducer array236emits the focused shock wave106in a different second direction260toward the center point244, the right transducer array236emits the focused shock wave106in a different third direction264toward the center point244, and the bottom transducer array236emits the focused shock wave106in a different fourth direction268toward the center point244. The support structure120enables movement of the container108in directions along the movement axis288which are different from and perpendicular to the directions256,260,264,268.

The shock wave generator assembly116, as illustrated in the figures, includes four of the transducer arrays236that each include five of the elements228. The segmentation of the transducer array236into four separate segments provides benefits including providing a mechanical support for the cover146. The segmented transducer array236also simplifies application of an impedance matching layer266(FIG.2) to the elements228. Moreover, having a segmented transducer array236enables repairs to the PRP activation system100by removing only the defective transducer array236instead of removing all of the transducer arrays236as is required with a unitary (non-segmented) transducer array236structure.

In other embodiments, the shock wave generator assembly116includes from one to twenty-four of the transducer arrays236, and the transducer arrays236each include from one to ten of the elements228. The transducer array236is referred to as an “array” even when it includes only one of the elements228. In yet other embodiments, the shock wave generator assembly116includes a single transducer array236that extends from 90° to 360° around the center point244.

The number of elements228included in the transducer array(s)236is based on a predetermined pressure level and/or predetermined energy level to be achieved at the focal volume258by the focused shock wave106. Including more elements228in the generation of the focused shock wave106results in a greater pressure level at the focal volume258, and including fewer elements228in the generation of the focused shock wave106results in less pressure at the focal volume258.

For an element228having a shock wave generating area of 0.25 to 1.0 cm2it was found that twenty of the elements228generates a focused shock wave106at the focal volume258with a predetermined pressure level and/or predetermined energy level suitable for activating the PRP104.

The shock wave generating elements228are positioned against an impedance matching layer266(FIG.2) of the transducer arrays236. In one embodiment, the matching layer266is applied to the arc-shaped surface242and the shock wave generating elements228. The material(s) of the matching layer266is selected to transmit the individual shock waves250from the shock wave generating elements228to the coupling medium124with minimal reflection and with minimal attenuation. That is, the matching layer266steps the acoustical impedance down from the material(s) of the shock wave generating elements228to that of the coupling medium124to aid in energy transfer of the individual shock waves250and to avoid reflections of the individual shock waves250at the interface of the elements228and the coupling medium124. The matching layer266includes composite epoxy and cerium oxide powder having specific mix ratios, in one embodiment. In other embodiments, the matching layer266is formed from any other suitable material. Moreover, in other embodiments, the transducer arrays236include multiple matching layers266of different materials.

As shown inFIG.2, the coupling medium124is located in the housing112between the transducer arrays236and the container108in the plane262(FIG.3). Moreover, the coupling medium124is “sandwiched” between the lid146and the intermediate housing142. Specifically, the coupling medium124extends from the matching layer266to the container108. In one embodiment, the coupling medium124is positioned against and is in direct contact with the matching layer226and the container108. The individual shock waves250generated by the transducer arrays236travel through the matching layer266, through the coupling medium124, and through the container108before arriving at the focal volume258inside of the container108as the focused shock waves106.

In one embodiment, the coupling medium124is substantially cylindrical with a centrally located hole or opening270(FIG.2) to receive the container108. Thus, the coupling medium124is doughnut-shaped or shaped as a toroid. The material of the coupling medium124is selected to transmit the shock waves106,250with minimal attenuation. In one embodiment, the coupling medium124is formed from hydrogel and/or another suitable hydrophilic polymer. Accordingly, the coupling medium124is disposable and is replaced periodically to achieve high levels of transmission of the shock waves106,250to the PRP104. In another embodiment, the coupling medium124is formed from a polymer-gel and tends not to require periodic replacement. For example, a more permanent coupling medium124is formed from styrene-ethylene-butylene-styrene (SEBS). It is noted that hydrogel tends to attenuate shock waves less than SEBS and results in a higher energy-flux density in the PRP104but, as mentioned, the coupling medium124formed from hydrogel typically requires periodic replacement.

As shown inFIG.3, the support structure120, which is also referred to herein as a container support, a collar support, and/or a mounting structure, includes a collar278and a set screw280. The collar278is mounted on the lid146of the housing112and defines an opening284through which the container108extends. The support structure120receives the container108through the opening284so that the container108is positioned through the lid146and at least partially within the housing112(i.e., at least partially within the housing space154). The set screw280is threadingly received by the collar278and is adjustable against the container108to hold the container108in a selected location along the movement axis288. Accordingly, the container108is adjustable in position along the movement axis288, relative to the transducer arrays236, so that a predetermined portion of the PRP104can be positioned in the focal volume258to receive the focused shock waves106. In one embodiment, a flange292of the container108prevents the container108from extending any further into the housing space154along the movement axis288.

FIG.3also illustrates a support sleeve296and a base member300of the housing112. The support sleeve296is received by the intermediate structure142and is configured to guide the container108into the PRP activation system100. An opening274of the support sleeve296is centered at the center point244. The base member300is an elastomer that safely contacts the container108and limits the depth to which the container108is inserted into the PRP activation system100.

The portion of the container108containing the PRP104(i.e., the barrel134of the syringe) is formed from a material that minimizes reflection of the shock waves106,250and promotes passage of the shock waves106,250therethrough. For example, in one embodiment, the container108is formed from TPX (polymethylpentene (PMP)). The container108is typically not formed from glass or polypropylene because these materials tend to reflect rather than transmit shock waves. Whereas, the container108formed from TPX minimizes and/or tends to reduce reflection of shock waves because TPX has an acoustic impedance similar to the material of the coupling medium124and the PRP104. Moreover, TPX has a low attenuation to ultrasound. Accordingly, the shock waves106,250pass through the walls of the container108and are imparted upon the PRP104at the focal volume258with minimal reflection and attenuation. In one embodiment, the container108includes a 12 ml barrel134. The PRP activation system100is configured to accommodate any size and volume of container108provided as vials, test tubes, syringes, and the like.

In operation, the PRP activation system100is incorporated in a PRP therapy session. An exemplary usage of the PRP activation system100is described by the method400illustrated inFIG.4. The method400begins at block404by drawing a quantity of blood of a patient. The patient may be a human or animal patient that has suffered a soft tissue injury and/or a joint injury, for example. Exemplary animals that are known to benefit from PRP therapy include horses, dogs, cats, and other mammals. Typically, about 30-60 ml of blood is drawn, but this amount may vary depending on the size and weight of the person or animal.

Next, at block408the collected blood is placed in a centrifuge device (not shown) to separate the blood into a red blood cell portion, a PRP portion, and a platelet-poor plasma portion. The centrifuge process typically takes less than fifteen minutes to separate the blood into the above-identified constituents. Any suitable centrifuge device may be used at block408. Portable centrifuges are available so that the method400can be performed at any location.

At block412, the PRP104is extracted from the centrifuged blood. Typically, the PRP104is located between the red blood cells (not shown) and the platelet-poor plasma (not shown). The PRP104is removed using the container108and a corresponding needle (not shown), for example. Any desired process may be used to extract the PRP104at block412of the method400. When 30-60 ml of blood is drawn, typically about 3-6 ml of PRP104will be extracted therefrom.

Then, at block416of the method400, the extracted PRP104is activated using the PRP activation system100. To activate the PRP104using the PRP activation system100, the container108containing the extracted PRP104is placed through the opening284of the collar278and into the housing space154of the housing112. Then, the set screw280is gently tightened to secure the position of the container108along the movement axis288.

After container108is positioned in the housing112, the PRP activation system100is caused to generate the shock waves106,250. The PRP activation system100is operated using either the interface190or the external device162. The focused shock waves106,250are generated by the elements228and pass through the matching layer266, the coupling medium124, and the wall of the container108. Due to the material of the container108(i.e., TPX), the focused shock waves106pass through the container108and are imparted on and/or strike the PRP104at the focal volume258. When the focused shock waves106are imparted on the PRP104and/or strike the PRP104, the PRP104is “activated.” As used herein, “activating” the PRP104causes the PRP104to generate and/or to release additional growth factors as compared to unactivated PRP. The growth factors are beneficial to the healing process and improve the efficacy of the PRP therapy.

At block416, the PRP104is activated with a predetermined number of pulses of the focused shock waves106. For example, the PRP104may be activated with from five to one hundred thousand pulses of the focused shock waves106. In one embodiment, all of the shock wave elements228of each shock wave generator assembly116are activated during one “pulse” of the focused shock waves106.

In an exemplary embodiment, the PRP104is activated by striking the PRP104with approximately 1,000 of the focused shock waves106generated at a frequency of 10 Hz and with an energy level of 0.15 mJ/mm2per focused shock wave106. In other embodiments, the PRP104is activated by striking the PRP104with from approximately five to 100,000 of the focused shock waves106generated at a frequency of from approximately 1 Hz to 1 kHz, and with an energy level of from approximately 0.05 to 0.50 mJ/mm2per focused shock wave106.

In the illustrated embodiment ofFIG.3, the length of the focal volume258along the movement axis288is approximately the same as the height of the PRP104within the container108. Thus, substantially all of the PRP104is struck with the focused shock waves106without moving the barrel134along the movement axis288. As used in this context, “substantially” includes at least 90% of the PRP104.

In other embodiments, the height of the PRP104within the container108is greater than the length of the focal volume258along the movement axis288. In such a situation, the barrel134is moved to a predetermined number of locations or positions during the shock wave activation process of block416. For example, the container108may be moved to three different locations along the movement axis288so that three different areas or portions of the PRP104are dosed with the focused shock waves106. The container108may be moved from zero to ten different positions along the movement axis288during the shock wave process of block416depending on the configuration of the container108and the amount of the PRP104therein. The method800of the flowchart ofFIG.8further describes such a process.

Next, at block420the activated PRP104is administered to the patient by injecting the activated PRP104into the patient at the site of the injury or treatment area. Injecting the activated PRP104into the patient typically completes the PRP therapy session.

The shock wave process of activating the PRP104at block416requires approximately two to five minutes from start to finish. Accordingly, the PRP activation system100offers huge advantages over known PRP activation devices and methods. First, there is no cumbersome and expensive refrigeration equipment needed to perform a freeze-thaw cycle to activate the PRP104. Second, there is no need to wait for the freeze-thaw cycle to conclude. A typical freeze-thaw cycle may take hours or days and significantly delays administration of the activated PRP104. Third, nothing is added to the unactivated PRP104, such as calcium chloride (CaCl2) and/or thrombin, which can cause clotting of the activated PRP104, thereby potentially reducing the effectiveness of the PRP therapy.

Instead, the PRP activation system100disclosed herein enables the PRP therapy session to be completed from start (drawing blood, block404) to finish (injecting the activated PRP104, block420) at the side of the patient and within only a few minutes to about 0.5 hour. Moreover, the PRP104can be activated anywhere since no connection to an external power source is required. The PRP activation system100offers a better quality PRP therapy, in less time, and with nothing added to the patient's blood.

FIGS.5A,5B, and5Cillustrate graphs showing test results of the PRP activation system100. To conduct the tests, a fiber optic hydrophone probe (Onda HFO-609) is placed in the center of a 10 ml container108full of water. In this example, a first focused shock wave106from a first array236is aimed at the center of the container108. Then, a second focused shock wave106from a different second array236is aimed at the center of the container108without activating the first array236. Next, both the first and the second array236are activated simultaneously to generate the combined signal shown in the figures.FIG.5Ais a graph of a time response of the focused shock waves106. As shown inFIG.5A, the focused shock waves106from the first and second arrays236are additive and constructively combine to generate the combined signal that has a pressure greater than 2.0 MPa within the container108at the focal volume258.FIG.5Bis a graph of a power spectral density of the focused shock waves106and the combined signal.FIG.5Cis a graph of a frequency response of the focused shock waves106and the combined signal. Each graph illustrates the additive effect of the focused shock waves106.

The system used to collect the data shown in the graphs ofFIGS.5A,5B, and5Ctends to under report high-frequency content in the curves because the propagation direction of the focused shock wave106is perpendicular to the axis of the measurement probe, i.e. oblique incidence. Nevertheless, the data shown in the graphs ofFIGS.5A,5B, and5Cconfirms that: 1.) it is possible to transmit shock wave energy from the arrays236to the center point244of the container108at the focal volume258, and 2.) the energy contributions of multiple arrays236(i.e., shock wave generating elements228) is additive and/or constructively combines. Thus, the data ofFIGS.5A,5B, and5Cillustrates that the individual shock waves250constructively combine to form the focused shock wave106that activates the PRP104located at the focal volume258.

As shown inFIG.6, another embodiment of a PRP activation system500includes a stacked configuration of the transducer arrays536. In the illustrated embodiment, the PRP activation system500includes sixteen of the transducer arrays536stacked along the movement axis288in four layers504. The layers504are also referred to herein as circumferential belts. Due to the cross sectional view, only twelve of the transducer arrays536are shown. Each of the layers504includes four of the concentrically-arranged transducer arrays536. In other embodiments, the PRP activation system500includes from two to ten of the layers504and may include from two to forty of the transducer arrays536. Some of the layers504may include more or fewer than four transducer arrays536. For example, some of the layers504may include only two of the transducer arrays536while other layers504of the same PRP activation system500may include six, eight, or ten of the transducer arrays536depending on the circumferential extent of each of the transducer arrays536, among other factors. The PRP activation system500is otherwise the same as the PRP activation system500.

The transducer arrays536of each layer504may be activated to generate the focused shock waves106all at once, or the transducer arrays536may be activated to generate the focused shock waves106one layer504at a time. Each layer504of activated transducer arrays536has a corresponding focal volume258within the container108. That is, the focused shock waves106of each layer504constructively combine with each other at a corresponding one of the focal volumes258. The focal volumes258are spaced apart from each other along the movement axis288. The support structure520positions the container108so that different and spaced apart portions of the PRP104are located at each of the focal volumes558.

The PRP activation system500having the multiple focal volumes558is configured to activate a greater quantity of the PRP104at once than the PRP activation system100having only the single focal volume258. Accordingly, the PRP activation system500may prevent the operator from having to move the container108to the predetermined number of locations along the movement axis288during the shock wave activation process of block416, because substantially all of the PRP104can be activated with the container108in a single location.

As shown inFIG.7, another embodiment of a PRP activation system600includes a housing602and four transducer arrays604(three are shown inFIG.7) concentrically arranged in one layer606, a microcontroller608, a power supply610, and a positioning device612configured to move the container108when the container108is positioned in an opening616defined by a support structure620. The PRP activation system600is otherwise the same as the PRP activation system100, and includes corresponding drive electronics, an FPGA, and an interface, which are not shown inFIG.7.

The microcontroller608is the same as the microcontroller202and may be provided as any desired processor, microprocessor, controller, and/or microcontroller. In a specific embodiment, the microcontroller608is a 32F413 microprocessor by STMicroelectronics.

The positioning device612, in one embodiment, is operably connected to the microcontroller608and the power supply610, and includes an electric motor624, a shaft628, and a lift plate632. The positioning device612is further operably connected to the container108for moving the container108along the movement axis288relative to the support structure620. In one embodiment, the electric motor624is a stepper motor, but in other embodiments the electric motor624is any desired type of electric motor including brushed and brushless motor types.

The shaft628is a threaded shaft that extends from the electric motor624and is rotated by the electric motor624either directly or through a gear arrangement (not shown).

The lift plate632is operably connected to the shaft628and defines an opening636configured to threadingly receive the shaft628. In one embodiment, the lift plate632extends through a corresponding slot638in the support sleeve642. Accordingly, the lift plate632is prevented from rotating relative to the housing112, but is movable in both directions along the movement axis288in the slot638. In some embodiments, a spacer block640is positioned between the container108and the lift plate632.

In response, to activation of the electric motor624, the electric motor624is configured to rotate the shaft628. The rotation of the shaft628causes the lift plate632to move along movement axis288to a selected position and/or to a predetermined position. The container108rests upon the lift plate632and/or the support block640. Accordingly, the movement of the lift plate632moves the container108along the movement axis288. In particular, the movement of the lift plate632positions the container108so that a predetermined portion of the PRP104is in the focal zone258of the transducer arrays604. The predetermined portion of the PRP104is struck with the focused shock waves106.

As shown inFIG.8, a method800of operating the PRP activation system600automatically moves the container108during activation of the PRP104using the positioning device612. At block804, the PRP activation system600receives the container108by placing the container108into the opening616in the support structure620. A set screw644of the support structure620is not tightened so that the container108is movable along the movement axis288relative to the housing602and the support structure620.

Next at block808, the microcontroller608activates the positioning device612to move the lifting plate632to the position shown inFIG.7, which is referred to as a lower position or a first position. At the lower position, the transducer arrays604are positioned to strike a first portion of the PRP104with the focused shock waves106.

At block812of the method800, the microcontroller608activates the transducer arrays604to generate the focused shock waves106(i.e., a first focused shock wave), which strike a first portion of the PRP104at the focal volume258. As shown inFIG.7, there is an additional quantity of the PRP104located below the focal volume258that is not struck by the focused shock waves106. Instead of having the user manually move the container108along the movement axis108, and then generate additional focused shock waves106to strike the remaining portions of the PRP104, the PRP activation system600is configured to move the container108automatically, thereby simplifying this process for the user.

To this end, at block816and with reference toFIG.9, the microcontroller608activates the electric motor624of the positioning device612to move the lift plate632to an upper position or a second position along the movement axis288. In the second position, a different second portion of the PRP104is positioned in the focal volume258of the transducer arrays604. The positioning device612is configurable to position the container108and the PRP104so that any desired portion of the PRP104is positioned in the focal volume258.

At block820, the microcontroller608activates the transducer arrays604to generate the focused shock waves106(i.e., a second focused shock wave), which strike the second portion of the PRP104at the focal volume258. The process of moving the container108along the movement axis288and striking the PRP104is repeated until the entire amount of the PRP104is exposed to the focused shock waves. Accordingly, in other embodiments, the positioning device612is used to move the container108to a third position, which causes a third portion of the PRP104to be struck by the focused shock waves106at the focal volume258. The microcontroller608and the positioning device612automate the positioning and repositioning of the container108so that all of the PRP104within the container108is exposed to the focused shock waves258in a fast and convenient manner.

In another embodiment, the positioning device612is used to slowly and continuously move the container108during generation of the focused shock waves106. For example, the positioning device612is configured to move the container108from the lower position to the upper position during a predetermined time period of from thirty seconds to two minutes. During the predetermined time period (i.e., during the continuous movement of the container108) the transducer arrays604generate the focused shock waves106at a predetermined frequency ranging from 1 to 100 Hz.

As shown inFIG.10, another embodiment of a PRP activation system700includes a housing704having an interface708including a display712and an input device716. The interface708is mounted on an exterior of the housing704.

The display712is configured to display information and data pertaining to operation of the PRP activation system700, such as a number of the focused shock waves106(FIG.2) to be administered to the PRP104, an energy level of the focused shock waves106, and a repetition frequency of the focused shock waves106. In one embodiment, the display712is a liquid crystal display (LCD). The display712is substantially the same or the same as the display210.

The input device716is configured to generate input data when touched or pressed by the operator. For example, the input device716may be pressed to generate an electrical start signal for initiating a shock wave sequence for activating the PRP104within the container108. The input device716includes at least one push button. The input device716is substantially the same or the same as the input device214.

A lid720of the PRP activation system700is operably connected to the housing704at a hinge724. The lid720includes a ridge728forming a convenient spot for grasping the lid720and for opening the lid720to access the interior of the housing704. The lid720is opened, for example, to monitor and/or to replace the coupling medium124(FIG.2). With the lid720opened, the coupling medium124can be removed from the interior of the housing704and replaced with a fresh, new, and/or different coupling medium124.

The PRP activation system700is otherwise the same as the PRP activation system100, and includes corresponding drive electronics, an FPGA, a power supply, and a shock wave generator assembly, which are not shown inFIG.10. The PRP activation system700includes a support structure732configured to receive the container108and to position the container108within the housing704so that the PRP104is positionable in a corresponding focal volume258to receive the focused shock waves106generated by the shock wave generator assembly for activating the PRP104. In some embodiments, the PRP activation system700also includes the positioning device612.

In another embodiment of the PRP activation system100the elements228are activated simultaneously without the timing sequence that focuses the individual shock waves250. In this embodiment, the individual shock waves250strike the PRP104at different times and with a time dispersion that is greater than 20 nanoseconds. Stated differently, the unfocused individual shock waves250arrive at the center point244over a time period that is greater than 20 nanoseconds. Since, the individual shock waves250are not focused, the shock waves250strike the PRP104with a lower total energy level and with less intensity than the focused shock wave106, but still with enough energy to activate the PRP104. In an example, the unfocused shock waves250strike the PRP104at an energy level that is 50% of the energy level resulting from the focused shock wave106. As a consequence of the simultaneous activation of the elements228, the power supply206is subject to a greater instantaneous power demand. Thus, the simultaneous activation of the elements228tends to use more energy from the power supply206and tends to deliver less energy to the PRP104. Whereas, activating the elements228at different times using the timing sequence subjects the power supply206to a lower instantaneous power demand, such that activating the elements228according to the timing sequence tends to use less energy from the power supply206and tends to deliver more energy to PRP104. Accordingly, the PRP activation system100using the timing sequence is well-suited for low energy consumption, high portability, and sufficiently activated PRP104using fewer shockwaves106.

In another embodiment, the PRP activation system100includes a different type of shock wave generator assembly116. For example, instead of a shock wave generator assembly116including the piezoelectric elements228, the shock wave generator assembly116includes an electromagnetic shock wave generator (not shown) that is configured to generate the focused shock wave106at the focal volume258. Alternatively, the shock wave generator assembly116includes an electro hydraulic transducer (not shown) that is configured to generate the focused shock wave106at the focal volume258.