Flexible transducer arrays with a polymer insulating layer for applying tumor treating fields (TTFields)
Described herein are devices for applying an alternating electric field to a living subject or an in vitro medium at a frequency between 100 kHz and 500 kHz. Also described herein are methods of using the described devices for applying an AC electric field to a target region comprising rapidly dividing cells, e.g., cells associated with a variety of disorders or conditions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
1 . An apparatus for applying an alternating electric field to a living subject, the apparatus comprising:
a layer of conductive material having a skin-facing front face, the front face having an area;
a flexible polymer layer disposed forward of the layer of conductive material and positioned against the skin-facing front face of the layer of conductive material so as to cover at least a portion of the area of the front face of the layer of conductive material, the polymer layer having a skin-facing front face; and
an electrical lead positioned in electrical contact with the layer of conductive material,
wherein the polymer layer comprises at least one polymer selected from Poly(VDF-TrFE-CTFE), Poly(VDF-TrFE-CFE), and Poly(VDF-TrFE-CFE-CTFE),
wherein the apparatus is configured to apply the alternating electric field at a frequency between 100 kHz and 500 kHz and at a field intensity ranging from 0.1 V/cm to 10 V/cm to selectively destroy or inhibit the growth of rapidly dividing cells located within a target region of the subject.
2 . The apparatus of claim 1 , further comprising a flexible third layer positioned rearward of the layer of conductive material, the flexible third layer having a skin-facing front face,
wherein at least a portion of the front face of the third layer is coated with an adhesive,
wherein a first region of the adhesive of the third layer is positioned directly rearward of the layer of conductive material and supports the layer of conductive material, and
wherein a second region of the adhesive is positioned outwardly with respect to the first region and is configured to (a) when pressed against a region of skin, adhere to the skin and hold the polymer layer adjacent to the skin, and (b) be removable from the skin.
3 . The apparatus of claim 2 , further comprising a layer of conductive hydrogel disposed on the front face of the polymer layer, wherein the layer of conductive hydrogel is positioned to make contact with the skin when the polymer layer is being held adjacent to the skin by the second region of the adhesive.
4 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 20 μm or less.
5 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 10 μm or less.
6 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 5 μm or less.
7 . The apparatus of claim 1 , wherein the polymer comprises 30 mol % to 80 mol % VDF and 5 mol % to 60 mol % TrFE, with CFE and/or CTFE constituting the balance of the mol %.
8 . The apparatus of claim 1 , wherein the polymer layer comprises ceramic nanoparticles mixed into at least one of Poly(VDF-TrFE-CTFE), Poly(VDF-TrFE-CFE), and Poly(VDF-TrFE-CFE-CTFE).
9 . The apparatus of claim 8 , wherein the ceramic nanoparticles comprise at least one of barium titanate and barium strontium titanate.
10 . The apparatus of claim 1 , wherein the polymer layer comprises a plurality of flexible polymer regions.
11 . The apparatus of claim 10 , wherein the layer of conductive material comprises a plurality of conductive pads, and wherein the plurality of polymer regions is printed, sprayed, or cast directly onto the plurality of conductive pads.
12 . The apparatus of claim 10 , wherein each of the polymer regions independently has a thickness of 10 μm or less.
13 . The apparatus of claim 10 , wherein the layer of conductive material comprises a plurality of conductive pads, and wherein the areas of the plurality of conductive pads collectively add up to at least 25 cm 2 .
14 . The apparatus of claim 1 , wherein the polymer comprises 30 mol % to 80 mol % VDF and 5 mol % to 60 mol % TrFE, with CFE and/or CTFE constituting the balance of the mol %, and wherein the polymer layer has a thickness of 10 μm or less.
15 . The apparatus of claim 1 , wherein the polymer layer comprises ceramic nanoparticles mixed into at least one of Poly(VDF-TrFE-CTFE), Poly(VDF-TrFE-CFE), and Poly(VDF-TrFE-CFE-CTFE), wherein the ceramic nanoparticles comprise at least one of barium titanate and barium strontium titanate.
16 . A method of selectively destroying or inhibiting the growth of rapidly dividing cells located within a target region of a subject, comprising:
a) positioning a first apparatus of claim 1 at a first location near the target region;
b) positioning a second apparatus of claim 1 at a second location near the target region, wherein the second location opposes the first location; and
c) applying an AC voltage between the first apparatus and the second apparatus, thereby imposing an AC electric field in the target region, wherein the frequency of the AC electric field ranges from 100 kHz to 500 kHz, wherein the AC electric field has a field intensity ranging from 0.1 V/cm to 10 V/cm, and wherein when the AC electric field is imposed in the target region for a duration of time, the AC electric field destroys or inhibits the growth of rapidly dividing cells within the target region.
17 . The method of claim 16 , wherein the rapidly dividing cells are present in a tumor.
18 . The method of claim 16 , wherein the rapidly dividing cells are cancer cells.
19 . The apparatus of claim 1 , wherein the layer of conductive material comprises metal foil.
20 . The method of claim 16 , wherein each of the first apparatus and the second apparatus has:
a flexible third layer positioned rearward of the layer of conductive material, the flexible third layer having a skin-facing front face,
wherein at least a portion of the front face of the third layer is coated with an adhesive,
wherein a first region of the adhesive of the third layer is positioned directly rearward of the layer of conductive material and supports the layer of conductive material, and
wherein a second region of the adhesive is positioned outwardly with respect to the first region,
wherein the second region of the adhesive is pressed against a region of skin of the subject to adhere to the skin and hold the polymer layer adjacent to the skin, and
wherein the second region of the adhesive is removable from the skin.
21 . The apparatus of claim 1 , wherein the polymer layer has a dielectric constant of at least 20 measured when the alternating electric field is provided at a frequency of 200 kHz and within a temperature range of 30° C. to 42° C.
22 . The method of claim 16 , wherein the polymer layer of the first apparatus has a dielectric constant of at least 20 measured when the alternating electric field is provided at a frequency of 200 kHz and within a temperature range of 30° C. to 42° C.
23 . The apparatus of claim 21 , wherein a thickness of the polymer layer multiplied by a dielectric strength of the polymer layer is at least 400 V.