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US-20260124445-A1 - Flexible Transducer Arrays With A Polymer Insulating Layer For Applying Tumor Treating Fields (TTFields)

US20260124445A1US 20260124445 A1US20260124445 A1US 20260124445A1US-20260124445-A1

Abstract

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.

Inventors

  • Yoram Wasserman
  • Stas Obuchovsky
  • Nataliya Kuplennik

Assignees

  • NOVOCURE GMBH

Dates

Publication Date
20260507
Application Date
20251218

Claims (20)

  1. 1 . An apparatus for applying an alternating electric field to a living subject or an in vitro medium at a frequency between 100 kHz and 500 kHz, the apparatus comprising: a layer of conductive material having a front face, the front face having an area; a flexible polymer layer positioned against the front face of the conductive material so as to cover at least a portion of the area, the polymer layer having a 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).
  2. 2 . The apparatus of claim 1 , further comprising a flexible third layer positioned behind the layer of conductive material, the flexible third layer having a 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 is positioned directly behind 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 easily removable from the skin.
  3. 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. 4 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 20 μm or less.
  5. 5 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 10 μm or less.
  6. 6 . The apparatus of claim 1 , wherein the polymer layer has a thickness of 5 μm or less.
  7. 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. 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. 9 . The apparatus of claim 8 , wherein the ceramic nanoparticles comprise at least one of barium titanate and barium strontium titanate.
  10. 10 . The apparatus of claim 1 , wherein the polymer layer comprises a plurality of flexible polymer regions.
  11. 11 . The apparatus of claim 10 , wherein the plurality of polymer regions is printed, sprayed, or cast directly onto the plurality of conductive pads.
  12. 12 . The apparatus of claim 10 , wherein each of the polymer regions independently has a thickness of 10 μm or less.
  13. 13 . The apparatus of claim 10 , wherein the areas of the plurality of conductive pads collectively add up to at least 25 cm 2 .
  14. 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. 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. 16 . A method of selectively destroying or inhibiting the growth of rapidly dividing cells located within a target region, 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, and wherein when the AC electric field is imposed in the target region for an effective duration of time, the AC electric field selectively destroys or inhibits the growth of rapidly dividing cells within the target region of the subject.
  17. 17 . The method of claim 16 , wherein the rapidly dividing cells located within a target region of a subject.
  18. 18 . The method of claim 16 , wherein the rapidly dividing cells are present in a tumor.
  19. 19 . The method of claim 16 , wherein the rapidly dividing cells are cancer cells.
  20. 20 . The method of claim 16 , wherein the rapidly dividing cells are present in an in vitro medium.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser. No. 17/362,966, filed Jun. 29, 2021; which claims the benefit of U.S. Application No. 63/046,337, filed on Jun. 30, 2020; U.S. Application No. 63/083,557, filed on Sep. 25, 2020; and U.S. Application No. 63/146,516, filed on Feb. 5, 2021, the contents of which are hereby incorporated by reference in their entirety. BACKGROUND Tumor Treating Fields (TTFields) therapy is a proven approach for treating tumors, and the Optune® system is an apparatus that is used to deliver TTFields. Optune® uses four transducer arrays that are placed on the patient's skin in close proximity to a tumor (e.g., front, back, right, and left with respect to the tumor) to deliver an alternating electric field to the tumor. These transducer arrays are driven by an AC signal generator that operates at, e.g., 100-500 kHz. U.S. Pat. No. 8,715,203 depicts a design for these transducer arrays that uses a plurality of ceramic discs. One side of each ceramic disc is positioned against the patient's skin, and the other side of each disc has a conductive backing. Electrical signals are applied to this conductive backing, and these signals are capacitively coupled into the patient's body through the ceramic discs. In some embodiments, the capacitance of each of these discs is at least 2 nF. In some embodiments the capacitance of each of these discs is at least 20 nF. SUMMARY Although the transducer arrays described in U.S. Pat. No. 8,715,203 are effective, those transducer arrays are relatively stiff because they are made using solid ceramic discs with diameters on the order of 2 cm and a thickness on the order of 1 mm. This stiffness can make it harder to position the transducer arrays in the desired location and/or can cause a mild degree of discomfort to the patient. Until now, using ceramic-based transducer arrays (with extremely high dielectric constants) was the only way to obtain a sufficiently high level of capacitance, which is necessary to effectively capacitively couple AC signals into the patient's body. More specifically, transducer arrays could heretofore not be built using a polymer insulating layer to capacitively couple an AC signal into the person's body, because all polymers'dielectric constants were much too low to provide a sufficient degree of capacitive coupling. The embodiments described herein rely on polymer compositions that have significantly higher dielectric constants than conventional polymers. More specifically, for the first time, the dielectric constant of these recently discovered polymer compositions is high enough to build a transducer array (or a simple electrode) that can effectively capacitively couple an AC signal into a person's body through a polymer insulating layer. One aspect of the invention is directed to a first apparatus for applying an alternating electric field to a living subject or an in vitro medium at a frequency between 100 kHz and 500 kHz. The first apparatus comprises a layer of conductive material having a front face with an area; a flexible polymer layer positioned against the front face of the conductive material so as to cover at least a portion of the area (including for example, the entire area), the polymer layer having a front face; and an electrical lead positioned in electrical contact with the layer of conductive material. The polymer layer comprises at least one of Poly(VDF- TrFE-CTFE), Poly(VDF-TrFE-CFE), and Poly(VDF-TrFE-CFE-CTFE). Some embodiments of the first apparatus further comprise a flexible third layer positioned behind the layer of conductive material, the flexible third layer having a front face. At least a portion of the front face of the third layer is coated with an adhesive. A first region of the adhesive is positioned directly behind the layer of conductive material and supports the layer of conductive material. 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 easily removable from the skin. Optionally, these embodiments may further comprise a layer of conductive hydrogel disposed on the front face of the polymer layer. 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. In some embodiments of the first apparatus, the polymer layer has a thickness of 20 μm or less, e.g., from 1 μm to 20 μm. In some embodiments of the first apparatus, the polymer layer has a thickness of 10 μm or less, e.g., from 1 μm to 10 μm. In further embodiments of the first apparatus, the polymer layer has a thickness of 5 μm or less, e.g., from 1 μm to 5 μm. In still further embodiments of the first apparatus, the polymer layer has a thickness of 3 μm or less, e.g., from 1 μm to 3 μm, or