Patent Application
20240038419
This disclosure is directed to devices, systems and methods for implanting devices in the body of a patient. More particularly, the disclosure relates to devices, systems and methods for thermally severing a connector that couples a releasable device to an end portion of an elongated shaft through the use of a resistor device/heater that is adjacent to or in contact with the connector.
An aneurysm is a localized bulge in the wall of a blood vessel caused by a weakness in the blood vessel wall. As an aneurysm increases in size, the risk of rupture increases. Aneurysms can occur in any artery, with particularly detrimental examples including aneurysms in the brain and abdominal aortic aneurysms. Aneurysms can arise in the heart itself following a heart attack, including both ventricular and atrial septal aneurysms.
Aneurysms may be treated with a variety of methods, particularly depending on their size and location. Brain aneurysms are often treated using a variety of methods, or a combination of methods, depending on the type of aneurysm and the individual patient. These may include microsurgical clipping, endovascular coiling, endovascular stent coiling, artery occlusion and bypass, flow diversion with stents, and tubular retractor systems. Some of these methods involve the use of interventional devices that are delivered endovascularly.
Vascular interventional devices used for these procedures can have a wide variety of configurations, including detachable vasoocclusive balloons and embolus generating vasoocclusive devices. Embolus generating vasoocclusive devices are placed within an aneurysm stemming from the blood vessel to form an embolus within the aneurysm. The devices induce clotting (embolization) of the aneurysm and, in this way, prevent blood from further entering and enlarging the aneurysm. Typically, the device comprises a vasoocclusive coil, such as a helical wire coil having windings which may be dimensioned to engage the walls of the blood vessel. Other less stiff helically coiled devices have been described, as well as those involving woven braids.
The delivery of such vascular interventional devices has been accomplished by a variety of means, including via a catheter in which the device is pushed through an opening at the proximal end of the catheter by a pusher wire used to deploy the device. The device is radio-opaque, and the physician visualizes the position of the device as it is being introduced by using a fluoroscopic X-ray system. In some instances devices are produced in such a way that they will pass through the lumen of a catheter in a linear shape and then take on a complex shape as originally formed after being deployed into the area of interest, such as an aneurysm.
One conventional releasable endovascular therapeutic device used to embolize aneurysms has a polymer thread acting as a tether to attach a coil to a pusher wire. This permits the coil to be pushed and pulled via the pusher wire to position it in the aneurysm. This polymer thread runs adjacent to a miniature electrical heater element at the distal tip of the pusher wire such that when the heater is energized the polymer thread is melted and the coil is released. When the coil is thus detached from the pusher wire, it remains in position in the aneurysm while the pusher wire and heater assembly is withdrawn from the body.
A problem of prior art devices is that the heater element is formed from a coil of metal wire where the resulting resistance has a large tolerance due to variability in the manufacturing process. It is expensive to manufacture and the large tolerance in resistance value means that the amount of power dissipated in the heater also varies by a large amount from device to device. This adds further uncertainty to the resulting temperature of the heater element when energized.
In prior art devices, as shown in
Devices, systems and methods are provided for delivering a releasable device (e.g. releasable implantable device), where the system comprises an elongated shaft having a proximal end and a distal end, the distal end configured for advancement into the body. A coupling element (e.g. a polymeric thread) retains the releasable device near the distal end of the elongated shaft until sufficient thermal energy applied thereto alters the coupling element causing detachment of the releasable device. The coupling element may be any of a number of objects that are severable by the application of heat thereto. A heater (also referred to herein as a “resistor device”) disposed within or otherwise coupled to the elongated shaft is configured to apply thermal energy to the coupling element, wherein the thermal energy alters the coupling element in response to the actuation, releasing the implantable device. A controller is configured to deliver an electrical drive signal to alter the state of one or more switches between first and second states in order to respectively couple and decouple the heater from an electrical power source. That is, when the one or more switches are in the first state, electrical power is delivered to the heater and when the one or more switches are in the second state, electrical power is not delivered to the heater.
In some implementations, the heater comprises a coil of metal wire that will heat sufficiently to sever a thread (e.g. a polymeric thread), or other severable connector, when a sufficient amount of electrical current flows through the coil.
According to other implementations, the heater comprises a surface-mount device resistor (also known as a “chip resistor”). A chip resistor is a passive electronic component that is designed to limit the flow of current. The traditional use of a chip resistor is to lower the voltage or maintain the current constant inside an electronic circuit. Chip resistors are widely used in applications such as automotive and transportation, consumer electronics, industrial and IT and telecommunications. The resistive elements of chip resistors may comprise, for example, thin film resistors, thick film resistors and foil resistors. The present invention uses the chip resistor in a non-traditional way by utilizing its resistive element to convert electrical energy into thermal energy so that the chip resistor functions as a heater.
Thick film and thin film chip resistors used in the electronics industry come in a variety of package/case sizes, such as 0201(inch size)/0510 (metric) or package/case size of 0.01005(inch)/0402 (metric) or package/case size of 009005(inch)/0301 (metric) or smaller. One advantage of using these commercially available resistors as heaters is that they are available with a narrow resistance tolerance, typically +/−1% tolerance or better, so that the total heater resistance tolerance can be more tightly controlled.
When detaching an implantable device using a thermal detachment method, it is advantageous to control the heater to a specific temperature in situ, rather than relying on a certain amount of energy delivery (a certain power for a specific time, or a certain voltage or current for a specific time) to raise the temperature of the heater to an approximate temperature to sever the thermally severable connector that tethers the implantable device to its delivery platform. This method is susceptible to variation in the surrounding thermal milieu, causing the temperature of the heater to vary from case to case despite the electrical energy delivered being the same. If a constant voltage or constant current is supplied to the heater the resulting temperature is also susceptible to variation in the electrical resistance of the heater, which is a manufacturing variable that is not perfectly controlled, particularly when the resistive element of the heater is a coiled metal wire.
Prior art designs using coiled metal resistive elements require tuning the heater power and duration: too high a power or too long and the plastic delivery system (e.g. the surrounding microcatheter/delivery catheter) can be thermally damaged so the introducer has difficulty being pulled out, and too little power or too short duration means it will not always detach. For these reasons, according to one aspect the heater is controlled to a specific temperature or a specific temperature range to ensure the releasable implantable device detaches reliably and does not result in damage to the delivery system.
Ways to heat to a specific temperature include measuring a temperature of the heater in a feedback scheme to control the power going to the heater to drive it to a specific temperature. A feedback scheme is possible to measure the temperature of the heater and then control the power to the heater in order to control its temperature to a setpoint/target temperature. The target temperature may be a temperature range, such as 200 degrees C. ±20 degrees C.
According to one aspect of the invention, first and second electrically conductive elements (also referred to herein as “electrical conductors”) made of dissimilar metals (those having different Seebeck coefficients) are respectively coupled to first and second electrical terminals of the heater. According to some implementations, disposed between the first and second electrically conductive terminals is a resistive element made of an electrically conductive material that heats up when a current passes through it. As explained above, the resistive element may be a coiled metal wire or may be in the form of a thin film, thick film or foil resistor associated with a chip resistor.
In accordance with the present invention, the first and second electrically conductive elements serve two functions. A first function is to deliver electrical power to the heater device. A second function is to form a part of a divided junction thermocouple that monitors a temperature of the heater. A temperature of the heater is controlled by alternately coupling the first and second electrically conductive elements to a power source and to a temperature sensing electronic circuit. When the electrically conductive elements are coupled to the temperature sensing circuit, a controller associated with the temperature sensing circuit uses the sensed temperature to determine when the first and second electrically conductive elements are to be coupled to the power source. According to some implementations, the temperature sensing circuit comprises a voltage detector to which ends of the first and second electrically conductive elements are electrically couplable. Correlation methods well known in the art may be implemented by the controller to determine the temperature of the heater based on a voltage difference detected by the voltage detector and the temperature of the electronic circuit.
According to some implementations the systems and methods disclosed herein are for the purpose of delivering a therapeutic releasable device (e.g. an embolic coil) to a treatment site inside a patient (e.g. the site of an aneurysm). A pushwire and delivery catheter, in conjunction with other tools, are typically used in the delivery process with the pushwire being configured to carry the releasable device to the treatment site through a lumen of the delivery catheter.
One design includes first and second electrical conductors extending from the proximal end of the pushwire (the power supply end) to the distal end where the releasable implant and heater are located. As noted above, according to some implementations the heater includes a resistive element disposed between first and second electrical terminals to which the first and second electrical conductors are respectively electrically coupled. As also noted above, these electrical conductors are made of dissimilar metals and may comprise, for example, a nickel conductor and a stainless steel conductor. According to some implementations, a portion of the pushwire itself, which may be made of stainless steel, is used for at least a portion of one of the first and second electrical conductors. This advantageously makes it possible to use only one additional electrically conductive wire for connecting the heater to the power source and the thermocouple to the voltage detector that forms a part of the temperature sensing circuit. According to this example configuration, there will be a dissimilar junction at one side of the heater to the stainless steel conductive element and another dissimilar junction at the other side of the heater to the nickel conductive element. At the proximal end of the pushwire assembly this combination, which acts like a thermocouple, can be measured by well-known circuitry that includes a voltage detector as discussed above. The temperature reported will be in the middle of the temperatures at the electrical terminals of the heater where the dissimilar junctions occur. It does not matter what the material of the heater is as long as it is electrically conductive. For example, it can be platinum or another metal or a thick film resistor material.
In instances when the elongated shaft comprises a pushwire, the pushwire may be configured in a variety of ways. According to one implementation, the pushwire comprises a hypotube along substantially its entire length with a distal end electrically coupled to one of the electrical terminals of the heater. According to such an implementation, a length of the one additional electrically conductive wire may pass through an inner lumen of the hypotube or may alternatively run entirely external to the hypotube. According to another implementation, the pushwire comprises a solid core wire having a distal end electrically coupled to one of the electrical terminals of the heater, and the one additional electrically conductive wire runs external to the core wire. According to yet another implementation, the pushwire comprises a hypotube having a distal end to which a solid core wire is mechanically and electrically coupled. According to one such implementation, a distal end portion of the core wire is tapered with a distal end of the core wire being electrically coupled to one of the electrical terminals of the heater. It should be pointed out that pushwires used to delivery an embolic coil to the site of an aneurysm are relatively long (180 cm in some instances) and have a very small diametric profiles (e.g. 0.25 millimeters).
It is noted that adding multiple additional wires beyond what is needed to supply heater power complicates the design and adds cost to the delivery system and may not even be possible as they must fit in the very small diameter lumens involved.
An advantage in applications involving the implantation of therapeutic devices inside the human body is that the starting temperature of the resistor device/heater and electrically conductive elements prior to energizing the heater is always at body temperature at about 37 degrees C. Many errors can be eliminated in determining a temperature of the resistor device/heater because the starting temperature can be assumed to be within three degrees of 37 degrees C. For example, the output of the temperature sensing circuit can be measured prior to application of power to the heater, and this represents an initial value at approximately 37 degrees C. Then a setpoint can be determined as a delta from this initial value. This delta represents a specific temperature difference of the heater from the approximately 37 degrees. When the heater is subsequently powered to reach and be maintained at the setpoint it will thus be maintained at a specific absolute temperature which is a delta from the approximately 37 degrees.
According to one implementation a system is provided that includes an elongated shaft having a distal end portion to which a releasable device is coupled by a thermally severable connector. The system further includes a resistor device/heater that includes a first terminal, a second terminal and a resistive element disposed between and electrically coupled to the first and second terminals. The thermally severable connector is located adjacent to or in contact with at least a portion of the resistive element. First and second electrically conductive elements, that each have a first end and a second end, are used in connecting the resistor device/heater to a power source and alternatively to a voltage detector that forms a part of a temperature sensing circuit. The first ends of the first and second electrically conductive elements are electrically couplable to the power source, and the second ends of the first and second electrically conductive elements are respectively coupled to the first and second terminals of the resistor device/heater. The first electrically conductive element is made of a first metal and the second electrically conductive element is made of a second metal that is different than the first metal. The first and second electrically conductive elements are configured such that when there is a temperature difference between their respective first and second ends, a voltage is induced between the first and second electrically conductive elements that is proportional to the temperature difference.
The system may further comprise a control circuit that is configured to control a temperature of the resistor device/heater to a target temperature by alternately electrically coupling the first ends of the first and second electrically conductive elements to the power source and to a voltage detector with the first ends being repeatedly electrically coupled to the voltage detector. The control circuit is configured such that when the voltage detected by the voltage detector is above or at a target voltage that corresponds to the target temperature of the resistor device/heater, the first ends of the first and second electrically conductive elements are maintained electrically coupled to the voltage detector until the voltage detected by the voltage detector is below the target voltage, at which time the first ends are electrically decoupled from the voltage detector and electrically coupled to the power source. The target temperature of the resistor device/heater is selected to be sufficient to cause the thermally severable connector to sever.
When the first and second electrically conductive elements have been electrically coupled to the power source for the purpose of increasing the temperature of the heater, thereafter the control circuit momentarily and repeatedly couples the first ends of the first and second electrically conductive elements to the voltage detector to measure the heater temperature. The repeated and momentary connection of the first ends to the voltage detector continues until the target temperature of the heater is achieved, wherein thereafter, the first ends remain connected to the voltage detector until the detected temperature of the heater again falls below the target temperature.
Some metal conductors that are used in traditional thermocouple applications are not suitable for use in some of the devices and systems disclosed herein. In applications of the current invention, the first and second electrically conductive elements that form a part of the divided junction thermocouple are not only used to carry currents on the order of microamperes when measuring temperature, but must also carry much higher currents (e.g. 10-200 milliamperes) for the purpose of powering the heater. Moreover, when an electrically conductive element is in the form of a wire, the gauge of the wire used is very small (typically 43 AWG or smaller). Metal conductors that have high electrical resistivity (e.g. 0.5 micro-ohm-meter), such as constantan, are not suitable for conducting the higher heater currents found in thermal embolic coil delivery systems where the length of the wires are long and their diameters are very small. One concern with using, for example, one copper wire and one constantan wire is that the electrical resistivity of constantan is approximately thirty times that of copper. This means that for the constantan wire to have the same electrical resistance of its copper neighbor, to carry the current needed for the heater, it needs to be about five times the diameter of the copper wire. Very fine, high gauge number copper wires (e.g. 43 ga.) are already being used to power such heaters in order to fit into the small catheter lumen, and the resistance of the existing art copper wire, one half of the two wire circuit, is typically 12 ohms. So having a much larger diameter constantan wire would be a problem getting it to fit. For this reason, according to some implementations, the electrically conductive elements that provide power to the heater are made of other lower resistivity metals, such as nickel which has a resistivity that is around four times that of copper.
Although wound-wire heaters and chip resistors are suitable for applying thermal energy to a thread to cause it to sever, chip resistors have a number of advantages over wound-wire heaters. First, because the coil of a coiled wire heater is typically made of a platinum alloy, the material cost is significant and the fabrication cost in winding it is also significant. Chip resistors are much less expensive and typically cost pennies. Another advantage is that chip resistors are available in a huge number of resistance values that facilitate optimization when designing systems that incorporate such devices. Chip resistors can also be significantly shorter than wound platinum alloy heaters. Wound-wire heaters on the market today have lengths between to 1.1 millimeters. Chip resistors, on the other hand, can have lengths of 0.3 to 0.4 millimeters (including its terminals). Moreover, larger resistance is possible with chip resistors which means less power is wasted in the resistance of the connected wires and more power is delivered to the heater itself. This is highly beneficial when the power source is a battery.
These and other advantages and features will become apparent in view of the figures and of the detailed description.
The description that follows is directed primarily to thermally severing a connector that couples an embolic coil to an end portion of a pushwire with the use of a resistor device that is adjacent to or in thermal contact with the connector. It is appreciated that the scope of the invention is not limited to embolic coil delivery systems, but is applicable to any system in which it is desirable to release a device from an end of an elongated shaft.
It is important to note that the drawings are not intended to depict the system components in precise detail, but are instead intended to show a general arrangement of the components for the purpose conveying how the components collectively function in the quest of thermally severing a connector that holds a releasable device to an end of an elongated shaft. It is also to be noted that the components depicted in the drawings are not to scale.
In the description that follows several types of heaters are disclosed for use in thermally severing a connector (e.g. a polymeric thread/wire) that tethers a releasable device (e.g. embolic coil) to an end portion of an elongated shaft (e.g. a pushwire). According to some implementations, the heater is a wound-wire heater 30, as shown in
According to one implementation, each of the hypotube 103 and core wire 104 of the pushwire 102 comprises stainless steel and the additional electrically conductive element 105 comprises nickel. The embolic coil 120 is mechanically coupled to a distal end portion of the core wire 104 by a thermally severable connector 110 (e.g. a polymeric thread) that extends through a retention ring 111 associated with the embolic coil. In
A salient feature of the systems and methods disclosed herein is that the electrically conductive elements that provide power to the heater are made of dissimilar metals. This allows the electrical conductors to serve two functions. A first function is to deliver electrical power to the heater terminals. A second function is to form a part of a divided junction thermocouple that is used to monitor a temperature of the heater. This allows the temperature of the heater to be controlled by a control circuit 700 like that depicted in
With particular reference to
The control circuit 700 is configured to repeatedly electrically couple the pushwire 102 and wire 105 to the voltage detector 710 in order that the temperature of the heater 30 may be monitored to determine if it is operating above or below the target temperature. The control circuit 700 is configured such that when the voltage detected by the voltage detector 710 is above or at a target voltage that corresponds to the target temperature, switches 704 and 705 assume their second state to connect the pushwire 102 and wire 105 to the voltage detector 710. The switches 704 and 705 remain in their second state until the voltage detected by the voltage detector is below the target voltage at which time the switches transition to their first state to electrically couple the pushwire 102 and wire 105 to the power source 720.
When the switches 704 and 705 have assumed their first state, the control circuit 700 is configured to momentarily and repeatedly transition the switches to their second state for the purpose of monitoring the heater 30 temperature as the temperature is ramped up. The repeated and momentary transitioning of the switches 704 and 705 to their second state continues until the target temperature of the heater is achieved, wherein thereafter, the switches 704 and 705 remain in their second state until the detected temperature of the heater falls below the target temperature.
In the implementation of
According to some implementations the controller 702 includes a processor 702a and a memory 702b that stores instructions to be executed by the processor. The processor 702a, through the use of data and/or instructions stored in memory 702b, processes signals 750/751 to determine the type of control signal 752/753 to be outputted by the controller. According to some implementations, the controller 702 also includes a clock 702c that is useable by the controller to switch the switches 704 and 705 between their first and second states at a fixed rate (e.g. 200 Hz rate) with a duty cycle such that the power source is coupled to the pushwire 102 and wire 105 for 4.5 milliseconds of every duty cycle and such that the thermocouple (formed by pushwire 102 and wire 105) is coupled to the voltage detector for 0.5 millisecond of every duty cycle. Other duty cycles and intervals are also contemplated.
The system of
The system of
According to another implementation, as shown in
In the forgoing examples, the pushwire 102 is electrically conductive with a distal end being coupled to one of the electrically conductive terminals of heater 30 (
It should be recognized that the scope of the invention is not limited to the particular implementations disclosed herein, and that various modifications can be made without departing from the spirit and scope of the invention. For example, the invention is not limited to the electrically conductive materials disclosed herein, nor is it limited to the arrangements depicted in the drawings. Additionally, the invention encompasses heater types other than wound-wire types and chip resistor types. Moreover, it is appreciated that controllers other than the type disclosed herein may be used to implement the control schemes disclosed herein.
The clauses that follow disclose additional implementations.
Clause 1. A system comprising:
Clause 2. The system according to clause 1, further comprising a control circuit that is configured to control a temperature of the resistor device to a target temperature by alternately electrically coupling the first ends of the first and second electrically conductive elements to the power source and to a voltage detector, the first ends being repeatedly electrically coupled to the voltage detector (“repeatedly electrically coupled” meaning that the first ends are coupled and decoupled from the voltage detector at time intervals, which may be predetermined time intervals), the control circuit being configured such that when the voltage detected by the voltage detector is above or at a target voltage that corresponds to the target temperature, the first ends of the first and second electrically conductive elements are maintained electrically coupled to the voltage detector until the voltage detected by the voltage detector is below the target voltage at which time the first ends are electrically decoupled from the voltage detector and electrically coupled to the power source, the target temperature of the resistor device being sufficient to cause the thermally severable connector to sever.
Clause 3. The system according to clause 2, wherein upon the first and second electrically conductive elements being electrically coupled to the power source for the purpose of increasing the temperature of the heater, the control circuit is configured to momentarily and repeatedly couple the first ends of the first and second electrically conductive elements to the voltage detector to measure the heater temperature, the repeated and momentary connection of the first ends of the first and second electrically conductive elements to the voltage detector continues until the target temperature of the heater is achieved, wherein thereafter, the first ends of the first ends of the first and second electrically conductive elements remain connected to the voltage detector until the detected temperature of the heater falls below the target temperature.
Clause 4. The system according to any of the preceding clauses, wherein the resistive element is a coiled metal wire.
Clause 5. The system according to any of the preceding clauses, wherein the resistor device is a surface-mount device resistor.
Clause 6. The system according to any of the preceding clauses, wherein the first electrically conductive element comprises stainless steel and the second electrically conductive element comprises nickel.
Clause 7. The system according to any of clauses 2, wherein the control circuit includes a controller that is configured to control a state of the first and second electrically actuated switches, each of the first and second electrically actuated switches being transitional between a first state and a second state, when in their first state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the power source, when in their second state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the voltage detector.
Clause 8. The system according to clause 7, wherein the controller is configured to cause the first and second electrically actuated switches to assume their first state at times when the voltage detected by the voltage detector is below the target voltage.
Clause 9. The system according to clause 7, wherein the controller is configured to cause the first and second electrically actuated switches to maintain their second state when the voltage detected by the voltage detector is at or above the target voltage.
Clause 10. The system according to clause 8, wherein the controller is configured to cause the first and second electrically actuated switches to maintain their second state when the voltage detected by the voltage detector is at or above the target voltage.
Clause 11. The system according to any of the preceding clauses, wherein the elongated shaft is at least a part of one of the first and second electrically conductive elements.
Clause 12. The system according to any of the preceding clauses, wherein the elongated shaft is a push wire of an embolic coil delivery device, and the releasable device is an embolic coil.
Clause 13. A method for thermally severing a connector that couples a releasable device to an end portion of an elongated shaft through the use of a resistor device that is adjacent to or in thermal contact with the connector, the resistor device including a first terminal, a second terminal and a resistive element disposed between and electrically coupled to the first and second terminals, electrically coupled to the first and second terminals are second ends of respective first and second electrically conductive elements, the first ends of the first and second electrically conductive elements are electrically couplable to a power source, the first electrically conductive element being made of a first metal, the second electrically conductive element being made of a second metal that is different than the first metal, the first and second electrically conductive elements being configured such that when there is a temperature difference between their respective first and second ends, a voltage is induced between the first and second electrically conductive elements that is proportional to the temperature difference, the method comprising:
Clause 14. The method according to clause 13, wherein the resistive element is a coiled metal wire.
Clause 15. The system according to clause 13, wherein the resistor device is a surface-mount device resistor.
Clause 16. The method according to any of the preceding clauses, wherein the first electrically conductive element comprises stainless steel and the second electrically conductive element comprises nickel.
Clause 17. The method according to clause 13, wherein the control circuit includes first and second electrically actuated switches, each of the first and second electrically actuated switches being transitional between a first state and a second state, when in their first state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the power source, when in their second state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the voltage detector, the method comprising the first and second electrically actuated switches assuming their first state at times when the voltage detected by the voltage detector is below the target voltage.
Clause 18. The method according to clause 13, wherein the control circuit includes first and second electrically actuated switches, each of the first and second electrically actuated switches being transitional between a first state and a second state, when in their first state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the power source, when in their second state the first and second electrically actuated switches electrically couple the first ends of the first and second electrically conductive elements to the voltage detector, the method comprising the first and second electrically actuated switches assuming their second state when the voltage detected by the voltage detector is at or above the target voltage.
Clause 19. The method according to clause 17, further comprising the first and second electrically actuated switches assuming their second state when the voltage detected by the voltage detector is at or above the target voltage.
Clause 20. The method according to any of the preceding clauses, wherein the elongated shaft is a push wire of an embolic coil delivery device, and the releasable device is an embolic coil.
This application relates to and claims the benefit and priority to Provisional Patent Application No. 63/369,499, filed on Jul. 26, 2022 which is incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63369499 | Jul 2022 | US |
