TRANSDUCER ARRAY HAVING A TEMPERATURE SENSOR ISOLATION LAYER BETWEEN A TEMPERATURE SENSOR AND EXTERNAL ENVIRONMENT

A transducer array, tumor treating field system, and method are herein disclosed. The transducer array comprises an electrode having a first side and a second side; a transfer layer covering the first side of the electrode and configured to transfer TTFields into a patient; a temperature sensor in contact with the second side of the at least one electrode; and an isolation layer covering the temperature sensor and at least a portion of the at least one electrode such that the temperature sensor is positioned between the isolation layer and the second side of the electrode, the isolation layer resisting at least one of heat flow and fluid flow through the isolation layer.

BACKGROUND

Tumor Treating Fields (TTFields or TTFs) are low intensity (e.g., 1-3 V/cm) alternating electric fields within the intermediate frequency range (e.g., 50 kHz to 1 MHz, such as 50-500 kHz) that target solid tumors by disrupting mitosis. This non-invasive treatment targets solid tumors and is described, for example, in U.S. Pat. Nos. 7,016,725; 7,089,054; 7,333,852; 7,565,205; 8,244,345; 8,715,203; 8,764,675; 10,188,851; and 10,441,776. TTFields are typically delivered through two pairs of transducer arrays that generate perpendicular fields within the treated tumor; the transducer arrays that make up each of these pairs are positioned on opposite sides of the body part that is being treated. More specifically, for the OPTUNE® system, one pair of electrodes of the transducer array is located to the left and right (LR) of the tumor, and the other pair of electrodes of the transducer array is located anterior and posterior (AP) to the tumor. TTFields are approved for the treatment of glioblastoma multiforme (GBM), and may be delivered, for example, via the OPTUNE® system (Novocure Limited, St. Helier, Jersey), which includes transducer arrays placed on the patient's shaved head. More recently, TTFields therapy has been approved as a combination therapy with chemotherapy for malignant pleural mesothelioma (MPM), and may find use in treating tumors in other parts of the body.

The device is intended to be continuously worn by the patient for 2-4 days before removal for hygienic care and re-shaving (if necessary), followed by reapplication with a new set of arrays. Because patients use the device and go about their daily activities, the device may be used for an extended period of time during which the transducer array may generate heat while activated. In order to ensure the patient is comfortable while wearing the transducer arrays, temperature sensors are placed within the arrays to monitor temperatures at the transducer array—skin interface.

SUMMARY OF THE DISCLOSURE

Traditionally, the temperature sensors are placed within a cavity of a transfer layer, i.e., dielectric layer, between an electrode of the transducer array and the patient's skin in order to measure a temperature close to the surface of the patient's skin. Advances in transducer array construction, however, have resulted in transfer layers that, while thinner and lighter, are resistant to forming the void in which to place the temperature sensor, and moving the temperature sensor further from the surface of the patient's skin may result in inaccuracies due to environmental temperature differences. Construction of these types of arrays requires that the temperature sensor is placed further from the transducer array—skin interface (e.g., wherein the electrode is disposed between the temperature sensor and the patient's skin) than is desirable thereby resulting in inaccuracies in temperature measurement by the temperature sensor due to interactions with the external environment.

Thus, new and improved systems that increase temperature measurement accuracy when the electrode element is disposed between the temperature sensor and the patient's skin are desired. It is to such systems and methods of producing and using the same, that the present disclosure is directed

The problem of temperature measurement inaccuracies due to environmental temperature differences is solved by a transducer array, tumor treating field system, and method for delivering TTFields to a body of a subject. In one embodiment, the transducer array comprises an electrode having a first side and a second side; a transfer layer covering the first side of the electrode and configured to transfer TTFields into a patient; a temperature sensor in contact with the second side of the at least one electrode; and an isolation layer covering the temperature sensor and at least a portion of the at least one electrode such that the temperature sensor is positioned between the isolation layer and the second side of the electrode, the isolation layer resisting at least one of a heat flow and fluid flow through the isolation layer.

In one embodiment, the tumor treating field system includes an electric field generator configured to generate an electrical signal having an alternating current waveform at a frequency in a range from 50 kHz to 1 MHz; a first conductive lead electrically coupled to the electric field generator, the first conductive lead configured to carry the electrical signal; a first transducer array coupled to the first conductive lead, a second conductive lead electrically coupled to the electric field generator; and a second transducer array coupled to the second conductive lead, the second transducer array receiving the electrical signal from the second conductive lead, and, in conjunction with the first transducer array, forming a tumor treating field. The first transducer array may include at least an electrode layer having a first surface, a second surface and an outer perimeter, a transfer layer in contact with the second surface of the electrode layer, a temperature sensor in contact with the first surface of the electrode layer, and an isolation layer disposed over the temperature sensor and at least a portion of the first surface of the electrode layer, the isolation layer resisting at least one of heat flow and a fluid flow through the isolation layer.

The details of one or more implementations of the subject matter described in this specification are set forth in the accompanying drawings and the description below. Other aspects, features and advantages of the subject matter will become apparent from the description, the drawings, and the claims.

DETAILED DESCRIPTION

Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary language and results, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description. The inventive concept(s) is capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary—not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

Headings are provided for convenience only and are not to be construed to limit the disclosure in any manner. Embodiments illustrated under any heading or in any portion of the disclosure may be combined with embodiments illustrated under the same or any other heading or other portion of the disclosure. Any combination of the elements described herein in all possible variations thereof is encompassed by the disclosure unless otherwise indicated herein or otherwise clearly contradicted by context.

Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

All of the compositions, assemblies, systems, kits, and/or methods disclosed herein can be made and executed without undue experimentation in light of the present disclosure. Where a method claim does not specifically state in the claims or description that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of embodiments described in the specification.

The use of the term “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The term “plurality” refers to “two or more.”

In addition, the use of the term “at least one of X, Y, and Z” will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal number terminology (e.g., “first,” “second,” “third,” “fourth,” etc.) is solely for the purpose of differentiating between two or more items and is not meant to imply any sequence or order or importance to one item over another or any order of addition, for example.

The use of the term “or” in the claims is used to mean an inclusive “and/or” unless explicitly indicated to refer to alternatives only or unless the alternatives are mutually exclusive.

Circuitry, as used herein, may be analog and/or digital components, or one or more suitably programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. Also, “components” may perform one or more functions. The term “component,” may include hardware, such as a processor (e.g., microprocessor), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a combination of hardware and software, and/or the like. The term “processor” as used herein means a single processor or multiple processors working independently or together to collectively perform a task.

As used herein, all numerical values or ranges include fractions of the values and integers within such ranges and fractions of the integers within such ranges unless the context clearly indicates otherwise. The numerical ranges specified herein includes the endpoints, and all values, sub-ranges of values within the range, and fractions of the values and integers within said range. Thus, any two values within the range of 1 mm to 10 m, for example, can be used to set a lower and an upper boundaries of a range in accordance with the embodiments of the present disclosure.

As used herein, the term TTField (TTFields, or TTF(s)) refers to low intensity (e.g., 1-4 V/cm) alternating electric fields of medium frequencies (about 50 kHz-1 MHz, and more preferably from about 50 kHz-500 kHz) that when applied to a conductive medium, such as a human body, via electrodes may be used, for example, to treat tumors as described in U.S. Pat. Nos. 7,016,725, 7,089,054, 7,333,852, 7,565,205, 7,805,201, and 8,244,345 by Palti) and in a publication by Kirson (see Eilon D. Kirson, et al., Disruption of Cancer Cell Replication by Alternating Electric Fields, Cancer Res. 2004 64:3288-3295). TTFields have been shown to have the capability to specifically affect cancer cells and serve, among other uses, for treating cancer. TTFields therapy is an approved mono-treatment for recurrent glioblastoma (GBM), and an approved combination therapy with chemotherapy for newly diagnosed GBM patients.

As used herein, the term TTSignal is an electrical signal that, when received by electrodes applied to a conductive medium, such as a human body, causes the electrodes to generate the TTField described above. The TTSignal is often an AC electrical signal.

Referring now to the drawings and in particular toFIG.1, shown therein is an exemplary embodiment of a dividing cell10, under the influence of external TTFields, generally indicated as lines14, generated by a first electrode18ahaving a negative charge and a second electrode18bhaving a positive charge. Further shown are microtubules22that are known to have a very strong dipole moment. This strong polarization makes the microtubules22, as well as other polar macromolecules and especially those that have a specific orientation within the cell10or its surroundings, susceptible to electric fields. The microtubules22positive charges are located at two centrioles26while two sets of negative poles are at a center30of the dividing cell10and point of attachment34of the microtubules22to the cell membrane. The locations of the charges form sets of double dipoles and therefore are susceptible to electric fields of differing directions. In one embodiment, the cells go through electroporation, that is, DNA or chromosomes are introduced into the cells using a pulse of electricity to briefly open pores in the cell membranes.

Turning now toFIG.2, the TTFields described above that have been found to advantageously destroy tumor cells may be generated by an electronic apparatus50.FIG.2is a simple schematic diagram of the electronic apparatus50illustrating major components thereof. The electronic apparatus50includes an electric field generator54and a pair of conductive leads58, including first conductive lead58aand second conductive lead58b.The first conductive lead58aincludes a first end62aand a second end62b.The second conductive lead58bincludes a first end66aand a second end66b.The first end62aof the first conductive lead58ais conductively attached to the electric field generator54and the first end66aof the second conductive lead58bis conductively attached to the electric field generator54.

The electric field generator54is configured to supply power and generate desirable electric signals (TTSignals) in the shape of waveforms or trains of pulses as an output. The second end62bof the first conductive lead58ais connected to a transducer array70aand the second end66bof the second conductive lead58bis connected to a transducer array70b.Both of the transducer array70aand the transducer array70bare supplied with the electric signals (e.g., TTSignals, wave forms). The transducer array70aand the transducer array70b,being supplied with the electric signals, causes an electrical current to flow between the transducer array70aand the transducer array70b.The electrical current generates an electric field (i.e., TTField), having a frequency and an amplitude, to be generated between the transducer array70aand the transducer array70b.

While the electronic apparatus50shown inFIG.2comprises only two transducer arrays70(i.e., the transducer array70aand the transducer array70b), in some embodiments, the electronic apparatus50may comprise more than two transducer arrays70.

The electric field generator54generates an alternating voltage wave form (i.e., TTSignal) at frequencies in the range from about 50 kHz to about 1 MHz (preferably from about 100 kHz to about 500 kHz). The required voltages are such that an electric field intensity in tissue within the treatment area is in the range of about 0.1 V/cm to about 10 V/cm. To achieve this electric field intensity, the potential difference between the two conductors18(e.g., the electrode element78inFIG.3) in each of the transducer array70aor the transducer array70bis determined by the relative impedances of the system components, e.g., a fraction of the electric field on each component is given by that component's impedance divided by a total circuit impedance.

In certain particular (but non-limiting) embodiments, the transducer array70aand the transducer array70bgenerate an alternating electric current and field within a target region of a patient. The target region typically comprises at least one tumor, and the generation of the alternating electric current and field selectively destroys and/or inhibits growth of the tumor. The alternating electric current and field may be generated at any frequency that selectively destroys or inhibits growth of the tumor, such as at any frequency of a TTField.

In certain particular (but non-limiting) embodiments, the alternating electric current and field may be imposed at two or more different frequencies. When two or more frequencies are present, each frequency is selected from any of the above-referenced values, or a range formed from any of the above-referenced values, or a range that combines two integers that fall between two of the above-referenced values.

In order to optimize the electric field (i.e., TTField) distribution, the transducer array70aand the transducer array70b(pair of transducer arrays70) may be configured differently depending upon the application in which the pair of transducer arrays70are to be used. The pair of transducer arrays70, as described herein, are externally applied to a patient, that is, are generally applied to the patient's skin, in order to apply the electric current, and electric field (TTField) thereby generating current within the patient's tissue. Generally, the pair of transducer arrays70are placed on the patient's skin by a user such that the electric field is generated across patient tissue within a treatment area. TTFields that are applied externally can be of a local type or widely distributed type, for example, the treatment of skin tumors and treatment of lesions close to the skin surface.

In one embodiment, the user may be a medical professional, such as a doctor, nurse, therapist, or other person acting under the instruction of a doctor, nurse, or therapist. In another embodiment, the user may be the patient, that is, the patient (and/or a helper) may place the transducer array70aand the transducer array70bon the patient's treatment area.

According to another exemplary embodiment, the electronic apparatus50includes a controller74. In one embodiment, the controller74comprises circuitry configured to control the output of the electric field generator54, for example, to set the output at the maximal value that does not cause excessive heating of the treatment area. The controller74may issue a warning, or the like, when a temperature of the treatment area (as sensed by one or more of a plurality of temperature sensors104, discussed in more detail below) exceeds a preset limit. The temperature sensors may be mechanically connected to and/or otherwise associated with the transducer array70aand/or the transducer array70bso as to sense the temperature of the treatment area at either one or both of the transducer array70aor the transducer array70bas described below in more detail.

In one embodiment, the controller74may turn off, or decrease power of the TTSignal generated by the electric field generator54, if a temperature sensed by the temperature sensor104meets or exceeds a comfortability threshold. In one embodiment, the comfortability threshold is the temperature at which a patient would be made uncomfortable while using the transducer array70aand the transducer array70b.For example, the comfortability threshold may be a temperature at or about 40 degrees Celsius. In one embodiment, the comfortability threshold is a temperature of between about 39 degrees Celsius and 42 degrees Celsius, or a specific selected temperature between about 39 degrees Celsius and 42 degrees Celsius.

The conductive leads58are isolated conductors with a flexible metal shield, preferably grounded thereby preventing spread of any electric field generated by the conductive leads58. The transducer array70aand the transducer array70bmay have specific shapes and positioning so as to generate the TTField of a desired configuration, direction, and intensity at the treatment area and only at that treatment area so as to focus the treatment.

The specifications of the electronic apparatus50as a whole and its individual components are largely influenced by the fact that at the frequency of the TTFields, living systems behave according to their “Ohmic”, rather than their dielectric properties.

Referring now toFIG.3, shown therein is a diagram of an exemplary embodiment of the transducer array70constructed in accordance with the present disclosure. The transducer array70includes one or more electrode element78. As shown inFIG.3, each transducer array70is configured as a set of one or more electrode elements78. In the example shown, the transducer array70includes 9 electrode elements78. Transducer arrays70may utilize electrode elements78that are capacitively coupled. In the example shown inFIG.3, the transducer array70is configured as multiple electrode elements78(for example, about 2 cm in diameter) that are interconnected via flex wires90(and connected to the electric field generator54via the conductive lead58). Each electrode element78is discussed in more detail below and shown inFIG.4. In one embodiment, the transducer array70includes an outer peripheral edge84.

Referring now toFIG.4, shown therein is a cross-sectional diagram of an exemplary embodiment of one of the electrode elements78ofFIG.3constructed in accordance with the present disclosure. The electrode element78generally comprises an electrode100, a temperature sensor104, an isolation layer108, and a transfer layer112. In some embodiments, the electrode element78further comprises a patient interface member116and/or a top-coat layer120.

The electrode100comprises and/or consists of at least one conducting element and/or compound, including, by way of example only, elemental silver. In some embodiments, the electrode100further includes a conductive support layer electrically coupled to the electrode100. The electrode100may be selected from any conductive material having desirable properties such as, but not limited to, high conductivity, strong biocompatibility, and low reactivity with other layers or components of the transducer array70. When present, the conductive support layer may be formed of a conductive carbon film, or conductive fabric, configured to support the electrode100. In one embodiment, the conductive support layer may be electroplated or otherwise bonded to the electrode100.

In one embodiment, the electrode100is electrically conductive and comprises, at least in part, a material selected from one or more of the following: silver, tin, aluminum, titanium, platinum, an alloy thereof, and/or some combination thereof.

The electrode100further includes a first surface124and a second surface128. The temperature sensor104may be in contact with and supported by the second surface128of the electrode100such that the temperature sensor104may detect and/or correspond to a temperature experienced by the patient where the electrode100is placed. In some embodiments, the first surface124of the electrode100is in contact with the transfer layer112when the transfer layer112is present.

In one embodiment, the temperature sensor104may comprise an outer surface132, wherein any environment, or atmosphere, in contact with the outer surface132of the temperature sensor104affects a temperature of the temperature sensor104. The outer surface132of the temperature sensor104may be considered to have at least two surface portions: a contact portion136, e.g., a surface portion of the outer surface132in contact with the second surface128of the electrode100, and an exposed portion140, e.g., a surface of the outer surface132that is not in contact with the second surface128of the electrode100.

In some embodiments, the temperature sensor104comprises a thermistor wherein a temperature of the thermistor may be determined by routing a known current through the thermistor and measuring a voltage that appears across the thermistor. In one embodiment, the temperature sensor104is mechanically connected to and/or otherwise associated with a particular one of the electrode element(s)78of the transducer array70so as to infer a temperature of the treatment area at the particular one or more electrode element78location.

In one embodiment, the isolation layer108has a first surface144and a second surface148and comprises a thermal insulator operable to resist a transfer of heat through the thermal insulator and/or a water-resistant material operable to resist a transfer of fluid, e.g., gas or liquid through the water-resistant material. For example, the isolation layer108resists heat transfer from the temperature sensor to the environment more than that of a standard bandage. In one embodiment, the isolation layer108resists heat flow and fluid flow and comprises a thermally insulating matrix material, such as, for example, a thermally insulating foam material or an epoxy material. The thermally insulation matrix material may also be a hydrophobic and thermally insulating matrix material, epoxy material, or a liquid resistant matrix material. The fluid flow can be a liquid flow and/or a gas flow. An example of a gas flow is a flow of air containing water vapor. In some embodiments, the isolation layer108may be constructed of a non-epoxy material having insulating properties such as the foam materials described herein as well as water proof sealants (e.g., silicone water proof sealant, liquid rubber, and the like), waterproof fabric such as a synthetic rubber that may be produced by polymerization of chloroprene (e.g., neoprene) or the like.

An exemplary thermally insulating and hydrophobic foam material includes a closed cell foam, such as a closed cell polyethylene foam, which may be coated with a pressure sensitive adhesive so as to bond the isolation layer108to the electrode100. In some embodiments, the isolation layer108has a thickness of 0.9 mm. In some embodiments, the isolation layer108can be constructed of a medical foam tape identified by model no. 1773 obtainable from the 3M Company of Saint Paul Minnesota in the United States.

An exemplary epoxy material may include a two-part epoxy resin. The epoxy material may be an epoxy, a polyester resin, and/or an epoxy acrylate. Prior to polymerization/polymer crosslinking, one or more component of the epoxy may be combined with a thermal insulation component to impart desirable thermal insulation properties into the polymerized epoxy and/or a water-resistant component to impart desirable hydrophobic properties into the epoxy.

In one embodiment, the isolation layer108is air-impermeable to prevent, limit, and/or minimize exposure of the temperature sensor104to the environment, or atmosphere. That is, the isolation layer108prevents, limits, and/or minimizes air from moving between the second surface148of the isolation layer108and the first surface144of the isolation layer108.

In one embodiment, the isolation layer108, when placed on the temperature sensor104such that the first surface144substantially covers the exposed portion140of the outer surface132, resists heat flow and liquid flow between the temperature sensor104and an environment, or atmosphere, on the second surface148of the isolation layer108.

In one embodiment, the first surface144of the isolation layer108substantially surrounds and is in contact with the exposed portion140of the outer surface132, e.g., the outer surface132of the temperature sensor104excepting the contact portion136of the outer surface132that is in contact with the electrode100. By substantially surrounding and being in contact with the exposed portion140, the isolation layer108thermally isolates the temperature sensor104from the environment, or atmosphere, in contact with the second surface148of the isolation layer108.

In one embodiment, the isolation layer108is constructed of more than one insulating material. For example, the isolation layer108may be comprised of a first insulating material in contact with the temperature sensor104, and a second insulating material disposed against the first insulating material and exposed to the environment, or atmosphere. In some embodiments, the first insulating material and the second insulating material are composed of the same insulating material but have differing insulating characteristics, the first insulating material and the second insulating material are composed of differing insulating materials but have similar insulating characteristics, or some combination thereof. For example, the first insulating material may be an insulating foam material having a first insulating value while the second insulating material may be an insulating epoxy material having a second insulating value the same as the first insulating value. Conversely, the first insulating material may be an insulating epoxy material having a first insulating value and the second insulating material may be an insulating epoxy material having a second insulating value different from the first insulating value.

In one embodiment, the isolation layer108may be constructed of more than one material having different properties. For example, the isolation layer108may be comprised of a first isolating material having a thermal insulation property (resisting thermal transfer through the isolation layer108) and a second isolating material having a water-repellant and/or hydrophobic property (resisting liquid/fluid transfer through the isolation layer108). The first isolation material and the second isolation material may be disposed in layers over the temperature sensor104and, in some embodiments, below the top-coat layer120.

In one embodiment, the isolation layer108covers the temperature sensor and only a portion of the second side of the electrode100, e.g., the isolation layer108does not extend across the entirety of the second surface128of the electrode100. In some embodiments, a first surface area of the first surface144of the isolation layer108is less than twice a second surface area of the exposed portion140of the outer surface132of the temperature sensor104. In other embodiments, the first surface area of the first surface144of the isolation layer108is less than 20% of a surface area of the second surface128of the electrode100. In yet other embodiments, the first surface area of the first surface144of the isolation layer108is less than 50% of the surface area of the second surface128of the electrode100.

In one embodiment, the isolation layer108has a thickness152of between 0.9 mm-1 cm and generally between 0.9 mm-5 mm. In one embodiment, the top coat layer120may have a thickness of 0.3 mm-0.4 mm. In one embodiment, the isolation layer108has a thickness at least twice as thick as the top-coat layer120. In other embodiments, the isolation layer108has a thickness between 2 times the thickness of the top-coat layer and 6 times the thickness of the top-coat layer120. In yet other embodiments, the isolation layer108has a thickness of 4-6 times the thickness of the top-coat layer120. In some embodiments, the top coat layer120may be a non-conductive top-coat layer.

In one embodiment, to limit and/or prevent shorting out the isolation layer108and/or the electrode100, the isolation layer108is not electrically conductive, e.g., is non-conducting. The isolation layer108, being non-conductive, may increase safety of the electrode element78by preventing the patient, or other user, from coming into contact with the thermistor during operation of the transducer array70and electronic apparatus50.

In one embodiment, the isolation layer108is hydrophobic, i.e., resists a flow of fluid, e.g., liquid and/or gas through the isolation layer108. The isolation layer108may be constructed of a water impermeable material, a hydrophobic material, a water-resistant material, and/or a water-repellant material. In one embodiment, the isolation layer108restricts moisture of the environment from contacting the temperature sensor104. In some embodiments, the isolation layer108does not include any perforation, channel, or other opening through which a liquid might travel.

In one embodiment, the isolation layer108is air-impermeable, that is, the isolation layer108restricts air transfer through the isolation layer108such that air from the environment is restricted from contact with the temperature sensor108. In some embodiments, the isolation layer108does not include any perforation, channel, or other opening through which air might travel.

In one embodiment, when the isolation layer108is applied to the transducer array70having a plurality of electrode elements78each having an electrode100, the isolation layer108comprises a plurality of isolation sections with at least some of the isolation sections disposed over each the temperature sensor104and second surface128of each electrode100of the plurality of electrode elements78to separately isolation each of the temperature sensors104. In some embodiments, when one or more particular electrode100of the plurality of electrode elements78is not in contact with the temperature sensor104, the isolation layer108may either be excluded from that particular electrode100or may be placed on the second surface128of the electrode100without the temperature sensor104disposed therein.

In one embodiment, the transfer layer112covers the first surface124of the electrode100and is configured to transfer TTFields into the patient. In some embodiments, the transfer layer112is non-electrically conductive. For example, the transfer layer112may include a dielectric layer such as a ceramic disk and/or a high-dielectric, or non-conductive, thin-film polymer layer.

Alternative constructions for the transfer layer112may be used, including, for example, ceramic elements that are disc-shaped, ceramic elements that are not disc-shaped, and non-ceramic dielectric materials disposed adjacent the first surface124of the electrode100. In some embodiments, the transfer layer112extends beyond the electrode100to the outer peripheral edge84of the transducer array70. Exemplary non-ceramic dielectric materials positioned over a plurality of electrode100include: polymer films, such as a non-conductive, thin-film high-dielectric polymer.

In some embodiments, the transducer array70includes one or more electrode element78that is not capacitively coupled to the patient. In this situation, each electrode element78of the transducer array70may be implemented using the transfer layer112comprising a conductive material that is configured for placement against a person's body, with no insulating dielectric layer disposed between the electrode elements78and the transfer layer112. Examples of the conductive material include a conductive film, conductive foam and/or a conductive fabric. Other alternative constructions for implementing the transducer array70may also be used, as long as they are capable of delivering TTFields to the patient's body.

In one embodiment, the patient interface member116is optional, that is, some embodiments of the transducer array70do not include the patient interface member116. When present, the patient interface member116may be disposed between the transfer layer112and the patient's body in any of the embodiments described herein.

In one embodiment, the patient interface member116is electrically conductive and biocompatible when used for an extended period of time. In one embodiment, the patient interface member116is a gel layer, or a hydrogel layer, constructed in accordance with the gel/hydrogel layers described in U.S. Patent Publication No. 2021/0346693 A1, published Nov. 11, 2021 and entitled “CONDUCTIVE PAD GENERATING TUMOR TREATING FIELD AND METHODS OF PRODUCTION AND USE THEREOF” and U.S. Pat. No. 11,458,298, issued on Oct. 4, 2022, and entitled “ASSEMBLIES CONTAINING TWO CONDUCTIVE GEL COMPOSITIONS AND METHODS OF PRODUCTION AND USE THEREOF”.

In one embodiment, the patient interface member116comprises one or more layer of material configured to be one or more of electrically conductive, biocompatible when in contact with the patient's skin for an extended period of time, e.g., from 3 hours to a week at a time, flexible so as to not impede movement of the patient while the transducer array70is in place, and resistant to movement on the patient's skin as the patient goes about their daily routine.

In one embodiment, the patient interface member116is constructed of one or more layers of conductive carbon adhesive and graphite/anisotropic materials. Exemplary patient interface members116may be constructed in accordance with U.S. patent application Ser. No. 17/899,220, filed Aug. 30, 2022 and entitled “ELECTRODE ASSEMBLY WITH A SKIN CONTACT LAYER COMPRISING A CONDUCTIVE ADHESIVE COMPOSITE, AND SYSTEMS AND METHODS OF APPLYING TUMOR TREATING FIELDS USING SAME”.

In some embodiments, the patient interface member116extends as far as the electrode100whereas in other embodiments, the patient interface member116extends at least to the outer peripheral edge84of the transducer array70or beyond.

In one embodiment, the top-coat layer120may increase safety of the transducer array70and/or electrode element78by preventing or limiting contact with the electrode100to guard against accidental electrocution when the electrode element78is activated. The top-coat layer120may be constructed of a durable, non-conductive material, such as a non-conductive fabric. In some embodiments, the non-conductive fabric may have a plurality of perforations. In one embodiment, the top-coat layer has a thickness of less than 1 mm and generally has a thickness of about 0.5 mm.

In one embodiment, the top-coat layer120may extend within the outer peripheral edge84of the transducer array70or beyond and may have an extent similar to that of the patient interface member116. In some embodiments, the top-coat layer120extends to cover the second surface128of the electrode100. In one embodiment, the top-coat layer120may extend beyond any other component of the transducer array70and, having an adhesive on a surface of the top-coat layer120, adhere to the patient's skin to prevent the transducer array70and/or electrode element78from moving relative to the patient's skin once placed on the patient.

In one embodiment, the top-coat layer120has an insulation value that is lesser than the insulation value of the isolation layer108. The insulation value of the top-coat layer120may be in a range from ½ to ¼ of the insulation value of the isolation layer108.

Referring now toFIG.5, shown therein is an exemplary embodiment of a process200of using the electronic apparatus50and the transducer array70to apply a TTField to a patient in accordance with the present disclosure. The process200generally comprises the steps of: applying the transducer array70aand the transducer array70bto the Patient (step204) and generating an alternating electric field having a frequency in a range of from about 50 kHz to about 1 MHz for a period of time (step208).

The step of applying the transducer array70aand the transducer array70bto the Patient (step204) may be performed by the user. In one embodiment, before applying the transducer array70ato the patient's skin, the patient's skin may need to be cleaned (e.g., such as but not limited to, cleansing of the skin of foreign matter or biological matter and shaving of the skin, if necessary) to enable the transducer array70ato adhere to the patient's skin.

The step of generating an alternating electric field (TTField) (step208) may be performed by the electric field generator54and may be instantiated by an operation performed by the user or controller74. In one embodiment, step208may be performed more than one time and the period of time for which the step208is performed a first time may be the same as or different from the period of time for which the step208is performed a second time (or other period(s) of time beyond the second time). In some embodiments, step208is only performed once before the process200is repeated. There may be a time period between each time the process200is repeated. Each time the process200is repeated, the time period may be the same as or different from the previous time period. Each time the process200is repeated, the first conductive pad100aand the second conductive pad100bmay be placed in the same or a different position on the patient's skin.

The step of generating an alternating electric field (TTField) (step208) may be performed by generating the alternating electric current and field at two or more different frequencies within the range of 50 kHz to 1 MHz. When two or more frequencies are present, each frequency is selected from any of the above-referenced values, or a range formed from any of the above-referenced values, or a range that combines two integers that fall within the range of the above-referenced values.

In one embodiment, the step of generating an alternating electric field (TTField) (step208) may be performed by supplying a first alternating electric current and field to a first pair of transducer arrays70for a first period of time and supplying a second alternating electric current and field to a second pair of transducer arrays70for a second period of time. In one embodiment, the first period of time may be of a similar duration to the second period of time whereas in other embodiments, the first period of time may be of a different duration to the second period of time. Additionally, the first period of time may or may not overlap with the second period of time.

ILLUSTRATIVE EMBODIMENTS

The following is a number list of non-limiting illustrative embodiments of the inventive concept disclosed herein:1. A transducer array, comprising:an electrode having a first side and a second side;a transfer layer covering the first side of the electrode and configured to transfer TTFields into a patient;a temperature sensor in contact with the second side of the electrode; andan isolation layer covering the temperature sensor and at least a portion of the electrode such that the temperature sensor is positioned between the isolation layer and the second side of the electrode, the isolation layer resisting at least one of a heat flow and fluid flow through the isolation layer.2. The transducer array of illustrative embodiment 1, further comprising a top-coat layer disposed over the isolation layer and an exposed portion of the second side of the electrode not in contact with the temperature sensor and the isolation layer, the top-coat layer having a first thickness lesser than a second thickness of the isolation layer.3. The transducer array of illustrative embodiment 2, wherein the isolation layer has the second thickness in a range of 2-6 times thicker than the first thickness of the top-coat layer.4. The transducer array of any of illustrative embodiments 1-3, wherein the isolation layer is a thermal insulator.5. The transducer array of illustrative embodiment 2, wherein the isolation layer comprises a thermally insulating matrix material, the thermally insulating matrix material configured to resist a heat flow from the temperature sensor to an atmosphere outside of the isolation layer more than that of a the top-coat layer.6. The transducer array of any of illustrative embodiments 1-5, wherein the isolation layer comprises a liquid resistant matrix material, the liquid resistant matrix material configured to resist a liquid flow through the isolation layer.7. The transducer array of illustrative embodiment 6, wherein the isolation layer is hydrophobic.8. The transducer array of any of illustrative embodiments 1-7, wherein the isolation layer covers the temperature sensor and only a portion of the second side of the electrode.9. The transducer array of illustrative embodiment 8, wherein the isolation layer covers the temperature sensor and is in contact with less than 20% of the second side of the electrode.10. The transducer array of any of illustrative embodiments 1-9, wherein the isolation layer comprises at least one of an epoxy material, a thermally insulating foam material, and a hydrophobic material.11. The transducer array of any of illustrative embodiments 1-19, wherein the isolation layer is non-conducting.12. The transducer array of any of illustrative embodiments 1-12, wherein the transfer layer is a non-conductive, thin-film polymer layer.13. The transducer array of any of illustrative embodiments 1-12, wherein the temperature sensor is a thermistor.14. The transducer array of any of illustrative embodiments 1-13, wherein the isolation layer has a first insulation value, and wherein the electrode has an outer perimeter, and further comprising a non-conductive top-coat layer disposed on the isolation layer, the non-conductive top-coat layer extending within the outer perimeter and beyond the outer perimeter of the electrode, the non-conductive top-coat layer having a second insulation value less than the first insulation value.15. The transducer array of any of illustrative embodiments 1-14, further comprising a patient interface member covering the transfer layer such that the transfer layer is positioned between the patient interface member and the first side of the electrode, the patient interface member being configured for placement between the transfer layer and a patient's skin.16. A tumor treating field system, comprising:an electric field generator configured to generate an electrical signal having an alternating current waveform at a frequency in a range from 50 kHz to 1 MHz;a first conductive lead electrically coupled to the electric field generator, the first conductive lead configured to carry the electrical signal;a first transducer array coupled to the first conductive lead, the first transducer array comprising at least an electrode layer having a first surface, a second surface and an outer perimeter, a transfer layer in contact with the first surface of the electrode layer, a temperature sensor in contact with the second surface of the electrode layer, and an isolation layer disposed over the temperature sensor and at least a portion of the second surface of the electrode layer, the isolation layer resisting at least one of a heat flow and a fluid flow through the isolation layer;a second conductive lead electrically coupled to the electric field generator; anda second transducer array coupled to the second conductive lead, the second transducer array receiving the electrical signal from the second conductive lead, and, in conjunction with the first transducer array, forming a tumor treating field.17. The tumor treating field system of illustrative embodiment 16, wherein the first transducer array further comprising a top-coat layer disposed over the isolation layer and an exposed portion of the second surface of the electrode layer not in contact with the temperature sensor and the isolation layer, the top-coat layer having a first thickness lesser than a second thickness of the isolation layer.18. The tumor treating field system of any of illustrative embodiments 16-17, wherein the isolation layer has a first insulation value, and wherein the first transducer array further comprises a non-conductive top-coat layer disposed on the isolation layer, the non-conductive top-coat layer extending within the outer perimeter and beyond the outer perimeter of the electrode layer, the non-conductive top-coat layer having a second insulation value less than the first insulation value.19. The tumor treating field system of any of illustrative embodiments 16-18, wherein the transfer layer is a non-conductive, thin-film polymer layer.20. The tumor treating field system of any of illustrative embodiments 16-19, wherein the electrode layer of the first transducer array comprises a plurality of electrodes, each electrode comprising a first surface and a second surface and having a temperature sensor in contact with the first surface, and wherein the isolation layer includes a plurality of isolation sections with at least some of the isolation sections disposed over the temperature sensors and at least a portion of the first surface of each electrode.21. The tumor treating field system of any of illustrative embodiments 16-20, wherein the isolation layer comprises a thermally insulating matrix material, the thermally insulating matrix material configured to resist a heat flow from the temperature sensor to an atmosphere outside of the isolation layer more than that of a the top-coat layer.22. The tumor treating field system of any of illustrative embodiments 16-21, wherein the isolation layer comprises a liquid resistant matrix material, the liquid resistant matrix material configured to resist a liquid flow through the isolation layer.23. The tumor treating field system of any of illustrative embodiments 16-22, wherein the isolation layer is non-conducting.24. The tumor treating field system of any of illustrative embodiments 16-23, wherein the transfer layer includes a high-dielectric polymer film.25. The tumor treating field system of any of illustrative embodiments 16-24, wherein the temperature sensor is a thermistor.

From the above description, it is clear that the inventive concepts disclosed and claimed herein are well adapted to carry out the objects and to attain the advantages mentioned herein, as well as those inherent in the disclosure. While exemplary embodiments of the inventive concepts have been described for purposes of this disclosure, it will be understood that numerous changes may be made which will readily suggest themselves to those skilled in the art and which are accomplished within the spirit of the inventive concepts disclosed and claimed herein.

The foregoing description provides illustration and description, but is not intended to be exhaustive or to limit the inventive concepts to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practice of the methodologies set forth in the present disclosure.

Even though particular combinations of features and steps are recited in the claims and/or disclosed in the specification, these combinations are not intended to limit the disclosure. In fact, many of these features and steps may be combined in ways not specifically recited in the claims and/or disclosed in the specification. Although each dependent claim listed below may directly depend on only one other claim, the disclosure includes each dependent claim in combination with every other claim in the claim set.

Similarly, although each illustrative embodiment listed above may directly depend on only one other illustrative embodiment, the disclosure includes each illustrative embodiment in combination with every other illustrative embodiment in the set of illustrative embodiments for each mode of the inventive concepts disclosed herein.

No element, act, or instruction used in the present application should be construed as critical or essential to the disclosure unless explicitly described as such outside of the preferred embodiment. Further, the phrase “based on” is intended to mean “based, at least in part, on” unless explicitly stated otherwise.