TWI790846B - Piezoelectric stimulation method with a ultrasonic device - Google Patents

Abstract

The present invention provides a piezoelectric stimulation method with a ultrasonic device, comprising: providing a ultrasonic device included a lens and a plurality of ultrasonic actuators, wherein the lens has a first side and a second side opposite to each other, and the ultrasonic actuators are attached to the first side; and generating ultrasonic waves by using the ultrasonic actuators, wherein the ultrasonic waves propagate from the first side to the second side and generate transverse pressure difference and shear stress at the second side to provide shear stress stimulation to a piezoelectric material above the second side.

Description

Method for generating piezoelectric stimulation using an ultrasonic device

The present invention relates to a method for generating piezoelectric stimulation using an ultrasonic device, especially a method for greatly increasing phosphorylation of ERK (extracellular regulated protein kinase) in a living body by using an ultrasonic device for generating piezoelectric stimulation.

Ultrasound technology is widely used in the medical field, for example, for diagnosis, or as a treatment tool for fractures or soft tissue healing. Ultrasonic technology is one of the currently known methods to stimulate the piezoelectric effect of collagen in specific parts of the body. However, because collagen is a shear-type piezoelectric material, the efficiency of using pressure waves generated by ultrasonic technology to excite the piezoelectric effect is still too low, resulting in applications such as the treatment of spinal disc degeneration and degenerative arthritis. Still can't obtain expected and effective effect.

In order to solve the above problems, the main purpose of the present invention is to provide a method of applying an ultrasonic device to generate piezoelectric stimulation, including: providing an ultrasonic device comprising a lens and a plurality of ultrasonic sensors, wherein the lens has opposite first sides and the second side, and the plurality of ultrasonic sensors are attached on the first side; and using the plurality of ultrasonic sensors to generate shock waves, so that the shock waves are transmitted from the first side to the second side and generate lateral pressure difference and shear stress on the second side, so as to correspond to the second side The piezoelectric material on the upper side provides a shear stress stimulus.

In one embodiment, the piezoelectric material is hard bone, cartilage, endochondral cells/collagen or endochondral cells/collagen, and the shear stress stimulus is used to activate the hard bone, the cartilage, the endosteal cells/collagen protein or the endochondral cells/collagen.

In one embodiment, the shear stress stimulus is further used to activate G protein coupled receptors.

In one embodiment, the second side of the lens has a groove.

In one embodiment, the groove is a spherical groove.

In one embodiment, a plurality of oblique focusing portions are formed in the groove, and the plurality of oblique focusing portions are adjacent to each other and respectively correspond to the plurality of ultrasonic sensors.

In one embodiment, each of the plurality of oblique focusing portions is surrounded by an arc-shaped peripheral section, an arc-shaped diameter section, and a straight-line diameter section, and the intersection of the arc-shaped peripheral section and the arc-shaped diameter section is located at the center of the lens At the junction of the second side and the groove, the intersection point of the arc-shaped diameter section and the straight-line diameter section is located at the center of the lens, and the intersection point of the arc-shaped peripheral section and the straight-line diameter section is located at the periphery of the groove. There is a distance from the second side of the lens, and the distance between the intersection point of the arc-shaped diameter section and the straight diameter section and the second side of the lens is equal to or greater than the distance.

In one embodiment, the plurality of oblique focusing portions are adjacent to each other in such a manner that the arc-shaped diameter section of one of the plurality of oblique focusing portions is adjacent to the linear diameter section of the other of the plurality of oblique focusing portions.

In one embodiment, the ultrasonic device is used to generate a plurality of signals for respectively controlling the plurality of ultrasonic sensors, and the plurality of signals have equal phase differences, non-overlapping and equal duty cycles, or partially overlapping And the same amount of work cycle.

In one embodiment, the shock wave generated by the plurality of ultrasonic sensors is 1 to 15 MHz, and the shock wave is generated with an input voltage ranging from plus or minus 48V.

The present invention controls a plurality of ultrasonic transducers by generating complex signals with equal phase difference, non-overlapping and equal duty cycles or partially overlapping and equal duty cycles, or adopts a complex number of inclinations in its grooves The lens of the focusing part can further provide shear stress stimulation to the piezoelectric material behind the lens, so as to simultaneously use the pressure wave and the shear stress to jointly excite the piezoelectric effect. Compared with the situation of simply using ultrasound to excite the piezoelectric effect, the present invention can greatly improve the ERK phosphorylation reaction in the living body, which is beneficial to the treatment of, for example, spinal disc degeneration and degenerative arthritis.

1,5: lens

100: Ultrasonic device

11,54: first side

12,53: second side

13,51: Groove

2: Ultrasonic sensor

31,32,33,41,42,43: signal

52: Tilt focus unit

521: arc peripheral segment

522: arc diameter section

523: straight line diameter section

6:Fixer

7: screw

8: Housing

h: spacing

S1~S2: steps

FIG. 1 is a schematic flowchart of a method for generating piezoelectric stimulation using an ultrasonic device according to the present invention.

2A and 2B are three-dimensional schematic diagrams of different viewing angles of the lens and the ultrasonic sensor of the present invention.

FIG. 2C is an overall schematic diagram of the ultrasonic device used in the present invention.

FIG. 2D is an exploded schematic view of the ultrasonic device used in the present invention.

Fig. 3 is a schematic waveform diagram of the first embodiment of the present invention.

Fig. 4 is a schematic waveform diagram of the second embodiment of the present invention.

Fig. 5 is a perspective view of a lens used in the third embodiment of the present invention.

FIG. 6 is a schematic diagram comparing the output voltages of the present invention and the prior art.

Fig. 7 is a schematic diagram of the sound field distribution in the prior art.

Fig. 8 is a schematic diagram of the sound field distribution of the present invention.

Fig. 9 is a graph comparing the intensity of pERK reflected by the cells of the present invention and the prior art.

The implementation of the present invention will be described below by means of specific specific examples, and those who are familiar with this technology can easily understand other advantages and effects of the present invention from the content disclosed in this description, and can also use other different specific examples implement or apply.

Please refer to Fig. 1, Fig. 2A and Fig. 2B at the same time, which are the schematic diagrams of the method flow and the applied lens and ultrasonic sensor of the present invention using the ultrasonic device to generate piezoelectric stimulation. In step S1, the present invention applies the ultrasonic device The method for generating piezoelectric stimulation is to first provide an ultrasonic device 100 comprising a lens 1 and a plurality of ultrasonic sensors 2, wherein the lens 1 has opposite first sides 11 and second sides 12, and the plurality of ultrasonic sensors 2 are attached to 11 on the first side.

In step S2, a plurality of ultrasonic sensors 2 are used to generate shock waves, and the shock waves are transmitted from the first side 11 to the second side 12 and generate lateral pressure difference and shear stress on the second side 12 to counteract the pressure on the second side 12. The electrical material provides a shear stress stimulus. In one embodiment, the piezoelectric material can be hard bone, cartilage, endochondral cells/collagen or endochondral cells/collagen, and shear stress stimulation can activate hard bone, cartilage, endosteal cells/collagen, endochondral cells/ Collagen, cell activation can be detected by ERK phosphorylation reaction. In one embodiment, the shear stress stimulus is further used to activate G protein coupled receptors.

As shown in FIG. 2C and FIG. 2D , the ultrasonic device 100 may further include a fixing member 6 , a plurality of screws 7 and a casing 8 . The housing 8 can be in the shape of a cone, for example, the lens 1 can be accommodated in the housing 8, the fixing part 6 is attached with a plurality of ultrasonic sensors 2, and the plurality of screws 7 are passed through the fixing part 6 and locked to the lens 1, so as to prevent excessive The acoustic wave sensor 2 falls off the lens 1. In one embodiment, the ultrasonic device 100 may be a probe of an ultrasonic device, but it is not limited thereto.

The method of using an ultrasonic device to generate piezoelectric stimulation for providing shear stress stimulation in the present invention has various implementations, which will be described in detail below.

In the first embodiment, the method of using an ultrasonic device to generate piezoelectric stimulation of the present invention uses the lens 1 shown in FIG. 2A and FIG. 2B , and the second side 12 of the lens 1 has a groove 13 . In one embodiment, the groove 13 may be a spherical groove, but not limited thereto. As shown in FIG. 3 , the method of using the ultrasonic device to generate piezoelectric stimulation in the present invention is to use the ultrasonic device 100 to generate multiple signals 31 , 32 , and 33 that control multiple ultrasonic sensors 2 respectively. The complex signals 31, 32, 33 have an equal phase difference with each other. For example, when the number of ultrasonic sensors 2 is three, the phase difference between the signals 31, 32, and 33 is 120 degrees; if the number is four, the phase difference is 90 degrees, but the present invention does not rely on this limit.

In the second embodiment, the method of the present invention using an ultrasonic device to generate piezoelectric stimulation is to use the same lens 1 as in the first embodiment, and use the ultrasonic device 100 to generate and control multiple ultrasonic sensors 2 separately. the complex signal. As shown in Figure 4, different from the first embodiment, the complex signals 41, 42, 43 in the second embodiment have non-overlapping and equal duty cycles, such as the number of ultrasonic sensors 2 When there are three, in a complete duty cycle (100%), the respective duty cycles of the signals 41 , 42 , and 43 are about 33% (100% in total). In other embodiments, the heads and tails of the signals 41, 42, and 43 can also partially overlap, for example, the respective duty cycles of the signals 41, 42, and 43 are 50% (total 100% after partial overlap), but the signals 41, 42, and 43 The respective duty cycles must be less than 100% (ie not completely overlapping). Non-overlapping duty cycles save more energy than overlapping duty cycles.

In the third embodiment, the method of using an ultrasonic device to generate piezoelectric stimulation in the present invention is to use different lenses and signals from the first and second embodiments. As shown in FIG. 5, the first side 54 of the lens 5 A plurality of ultrasonic sensors 2 are attached on the top, and a groove 51 is provided on the second side 53, and a plurality of oblique focusing parts 52 are formed in the groove 51, and the plurality of oblique focusing parts 52 are adjacent to each other and correspond to the plurality of ultrasonic sensors respectively. 2. The inclined focusing portion 52 is surrounded by an arc-shaped peripheral section 521, an arc-shaped diameter section 522 and a straight line diameter section 523. The intersection of the arc-shaped peripheral section 521 and the arc-shaped diameter section 522 is located at the second side 53 of the lens 5 and the concave At the junction of the groove 51, the intersection point of the arc-shaped diameter section 522 and the straight-line diameter section 523 is located at the center of the lens 5, and the intersection point of the arc-shaped peripheral section 521 and the straight-line diameter section 523 is located at the periphery of the groove 51 and is connected to the second edge of the lens 5. There is a distance h between the two sides 53, and the distance between the intersection point of the arc-shaped diameter section 522 and the straight diameter section 523 and the second side 53 of the lens 5 is equal to or greater than the distance h (that is, the center of the lens 5 starts from the second side 53). side 53 is recessed by a distance equal to or greater than the pitch h). In addition, the plurality of oblique focusing portions 52 are adjacent to each other, which is achieved in such a way that the arc-shaped diameter segment 522 of one of the plurality of oblique focusing portions 52 is adjacent to the linear diameter segment 523 of the other of the plurality of oblique focusing portions 52, that is, the complex oblique The focusing portion 52 may jointly fill up the bottom surface of the groove 51 . Through the design of the lens 5 with a plurality of tilted focusing parts 52, it is not necessary for the ultrasonic device 100 to generate the complex signals 31, 32, 33, 41, 42, 43 in the aforementioned first and second embodiments, and only the general signals are required. , can also provide a shear stress stimulus to the piezoelectric material on the second side 53 .

In the aforementioned first, second, and third embodiments, the shock waves generated by the plurality of ultrasonic sensors 2 are 1 to 15 MHz, and the shock waves are generated with an input voltage ranging from plus or minus 48V. In one embodiment, the optimal shock wave generated by the ultrasonic sensor 2 is 1 MHz, but the present invention is not limited thereto.

In addition, the method of using an ultrasonic device to generate piezoelectric stimulation in the present invention can be realized by using one of the first, second, and third embodiments, or by any combination of the first, second, and third embodiments. For example, the lens 5 in the third embodiment is used to replace the lens 2 in the first and second embodiments, and the present invention is not limited thereto.

Please refer to Fig. 6, under the same input voltage, the ultrasonic wave (pressure wave) and the output voltage of the shear stress produced by the method of applying the ultrasonic device to generate piezoelectric stimulation of the present invention are obviously lower than those in the prior art that only produce ultrasonic waves output voltage, there will be a gap between the two because of the generated Shear stress, i.e. the fraction of the input voltage that has been converted into shear stress. Similarly, at the center of the lens 1 shown in Figure 7 and Figure 8, Figure 7 uses the lens 1 and the general signal shown in Figure 2A to generate ultrasonic waves, and Figure 8 uses the lens 1 shown in Figure 2A and Figure 3 with etc. The complex signals 31, 32, 33 of the phase difference of the quantity produce lateral pressure difference, ultrasonic wave (pressure wave) and shear stress, and the ultrasonic schematic diagram shown in Fig. 8 is obviously more concentrated than the ultrasonic schematic diagram shown in Fig. 7, This also proves the generation of lateral pressure difference and shear stress.

As shown in Figure 9, the ultrasonic wave (pressure wave) and shear stress generated by the method of applying the ultrasonic device to generate piezoelectric stimulation in the present invention can produce about 1.6 times the ERK phosphorylation reaction in the nucleus pulposus cells compared to the control group , while those who only produce ultrasonic waves in the prior art only produce about 1.2-1.3 times the ERK phosphorylation reaction, so it can be seen that the present invention has indeed broken through the stimulation limit of the prior art to the phosphorylation reaction of cellular ERK.

To sum up, the method of the present invention using an ultrasonic device to generate piezoelectric stimulation can use ultrasonic waves (pressure waves) and shear stress to guide the generation of piezoelectric effects in living organisms, compared with the method of simply using ultrasonic waves to stimulate piezoelectric effects In some cases, the present invention can greatly improve the phosphorylation reaction of ERK in the living body, which is beneficial for the treatment of degeneration of intervertebral disc and degenerative arthritis.

The above-mentioned embodiments are only illustrative of the technical principles, features and effects of the present invention, and are not intended to limit the scope of the present invention. Any person familiar with this technology can use the The above embodiments are modified and changed. However, any equivalent modifications and changes accomplished by using the teachings of the present invention should still be covered by the scope of the following patent applications. The scope of protection of the rights of the present invention should be listed in the scope of patent application as follows.

S1~S2: steps

Claims (10)

A method for generating piezoelectric stimulation using an ultrasonic device, comprising: An ultrasonic device comprising a lens and a plurality of ultrasonic sensors is provided, wherein the lens has opposite first and second sides, and the plurality of ultrasonic sensors are attached to the first side; and Using the plurality of ultrasonic sensors to generate shock waves, the shock waves are transmitted from the first side to the second side and generate lateral pressure difference and shear stress on the second side, so as to provide the piezoelectric material located above the second side Shear stress stimulus. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 1, wherein the piezoelectric material is hard bone, cartilage, endochondral cells/collagen or endochondral cells/collagen, and the shear stress stimulus is used To activate the bone, the cartilage, the cells/collagen in the bone or the cells/collagen in the cartilage. The method for generating piezoelectric stimulation using an ultrasonic device as described in claim 2, wherein the shear stress stimulation is further used to activate G protein-coupled receptors. The method for generating piezoelectric stimulation using an ultrasonic device as claimed in claim 3, wherein the second side of the lens has a groove. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 4, wherein the groove is a spherical groove. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 4, wherein a plurality of oblique focusing portions are formed in the groove, and the plurality of oblique focusing portions are adjacent to each other and respectively correspond to the plurality of ultrasonic sensors. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 6, wherein each of the plurality of tilted focusing parts is composed of an arc-shaped peripheral section, an arc-shaped diameter section, and a straight-line diameter section Surrounded by the boundary, the intersection of the arc-shaped peripheral section and the arc-shaped diameter section is located at the junction of the second side of the lens and the groove, and the intersection of the arc-shaped diameter section and the straight-line diameter section is located in the center of the lens , the intersection point of the arc-shaped peripheral section and the straight-line diameter section is located at the periphery of the groove and has a distance from the second side of the lens, and the intersection point of the arc-shaped diameter section and the straight-line diameter section and The distance between the second sides of the lens is equal to or greater than the pitch. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 7, wherein the arc-shaped diameter section of one of the plurality of inclined focusing parts is adjacent to the linear diameter section of the other of the plurality of inclined focusing parts , so that the plurality of oblique focus portions are adjacent to each other. The method for generating piezoelectric stimulation using an ultrasonic device as described in Claim 3, wherein the ultrasonic device is used to generate a plurality of signals for respectively controlling the plurality of ultrasonic sensors, and the plurality of signals have an equal phase with each other Poor, non-overlapping and equal duty cycles, or partially overlapping and equal duty cycles. The method for generating piezoelectric stimulation using an ultrasonic device as described in claim 3, wherein the shock wave generated by the plurality of ultrasonic sensors is 1 to 15 MHz, and the shock wave is generated with an input voltage ranging from plus or minus 48V.

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