Selective acoustic disruption of pathogens
Described herein are methods and devices for selectively diminishing viability of or killing bacterial, fungal, or viral pathogens using acoustic excitation below the thresholds for cavitation.
1 . A method for selectively killing or diminishing viability of a pathogen infecting a mammalian subject tissue, the method comprising:
contacting a mammalian subject tissue with one or more acoustic transducers; and
administering greater than ten thousand cycles of pressure variation below a threshold for cavitation of the mammalian subject tissue, whereby the greater than ten thousand cycles of pressure variation is sufficient to kill or diminish viability of a pathogen infecting the mammalian subject tissue without harming the mammalian subject tissue;
with the proviso that the only form of energy administered to kill or diminish the viability of the pathogen is acoustic energy.
2 . The method of claim 1 , wherein the pathogen is a cell having an internal static pressure of greater than 20 kPa above that of the mammalian subject tissue.
3 . The method of claim 1 , wherein the pathogen is a bacterium.
4 . The method of claim 1 , wherein the pathogen is a fungus.
5 . The method of claim 1 , wherein the pathogen is a virus.
6 . The method of claim 1 , wherein the shape, frequency, amplitude, and orientation of the one or more acoustic transducers is selected by finite element acoustic analysis of the mammalian subject tissue and of the pathogen.
7 . The method of claim 6 , wherein the finite element acoustic analysis permits application of pressure cycles at specific mammalian subject tissue sites without causing excessive heating.
8 . The method of claim 1 , wherein the one or more acoustic transducers are external to the mammalian subject tissue.
9 . The method of claim 1 , wherein the one or more acoustic transducers penetrate the mammalian subject tissue to make acoustic contact with a targeted tissue or an internal structure.
10 . The method of claim 1 , wherein the one or more acoustic transducers are shaped and excited to irradiate an extracorporeal fluid with greater than ten thousand cycles of pressure variation, wherein the amplitude, frequency, and number of the greater than ten thousand cycles of pressure variation diminish pathogen viability without causing excessive heating of the mammalian subject tissue.
11 . The method of claim 1 , wherein the greater than ten thousand cycles of pressure variation are selected to enable, accelerate, or potentiate the action of an antimicrobial pharmaceutical agent.
12 . The method of claim 1 , wherein the mammalian subject tissue geometry and composition are determined by biomedical imaging.
13 . The method of claim 12 , wherein the biomedical imaging is tomographic.
14 . The method of claim 1 , wherein the one or more acoustic transducers are arranged in a conformable piezoelectric transducer array, comprising:
a silicone elastomer substrate and a silicone elastomer superstrate;
a plurality of piezoelectric transducer elements disposed between the silicone elastomer substrate and the silicone elastomer superstrate;
a first electrical interconnect layer electrically interconnecting a first surface of the plurality of piezoelectric transducer elements adjacent to the silicone elastomer substrate; and
a second electrical interconnect layer electrically interconnecting a second surface of the plurality of piezoelectric transducer elements adjacent to the silicone elastomer superstrate.
15 . The method of claim 14 , wherein at least one of the plurality of piezoelectric transducer elements comprises a composite material.
16 . The method of claim 14 , wherein each of the plurality of piezoelectric transducer elements comprises a composite material.
17 . The method of claim 14 , wherein the first and second electrical interconnect layers have a patterned island and bridge structure that includes a plurality of islands electrically interconnected by bridges, each of the plurality of piezoelectric transducer elements being supported by one of the plurality of islands.
18 . A method for treating a mammalian subject infected by one or more pathogens using an acoustic transducer to selectively kill or diminish viability of the one or more pathogens, the method comprising:
contacting the acoustic transducer to an external surface of the mammalian subject such that the acoustic transducer conforms to the external surface, the acoustic transducer being a conformable piezoelectric transducer array, comprising:
a silicone elastomer substrate and a silicone elastomer superstrate;
a plurality of piezoelectric transducer elements disposed between the silicone elastomer substrate and silicone elastomer superstrate;
a first electrical interconnect layer electrically interconnecting a first surface of the plurality of piezoelectric transducer elements adjacent to the silicone elastomer substrate; and
a second electrical interconnect layer electrically interconnecting a second surface of the plurality of piezoelectric transducer elements adjacent to the silicone elastomer superstrate; and
administering greater than ten thousand cycles of pressure variation below a threshold for cavitation of the mammalian subject, whereby the greater than ten thousand cycles of pressure variation is sufficient to kill or diminish viability of the one or more pathogens infecting the mammalian subject without harming the mammalian subject;
with the proviso that the only form of energy administered to kill or diminish the viability of the one or more pathogens is acoustic energy.
19 . The method of claim 18 , further comprising, imaging the mammalian subject prior to and following the administering greater than ten thousand cycles of pressure variation, where the imaging comprises:
transmitting ultrasound waves into the mammalian subject using the confromable piezoelectric transducer array;
receiving ultrasound waves from the mammalian subject using the conformable piezoelectric transducer array; and
displaying an indication of the received ultrasound waves.
20 . The method of claim 18 , wherein the one or more pathogens is a cell having an internal static pressure of greater than 20 kPa above that of the mammalian subject.
21 . The method of claim 18 , wherein the one or more pathogens is a bacterium, fungus, virus, or combinations thereof.
22 . The method of claim 18 , wherein the greater than ten thousand cycles of pressure variation are below a threshold for excessive heating of a tissue of the mammalian subject.
23 . The method of claim 18 , wherein at least one of the plurality of piezoelectric transducer elements comprises a composite material.
24 . The method of claim 18 , wherein each of the plurality of piezoelectric transducer elements comprises a composite material.
25 . The method of claim 18 , wherein the first and second electrical interconnect layers have a patterned island and bridge structure that includes a plurality of islands electrically interconnected by bridges, each of the plurality of piezoelectric transducer elements being supported by one of the islands.