FIELD

The invention relates to systems, apparatuses, and methods for testing and using tumor treating fields (TTFields). The disclosure includes descriptions of cage assemblies, treatment assemblies, and swivel systems for use with animal test subjects.

BACKGROUND

Tumor Treating Fields, or TTFields, are low intensity (e.g., 1-3 V/cm) alternating electric fields within the intermediate frequency range (100-300 kHz). This non-invasive treatment targets solid tumors and is described in U.S. Pat. No. 7,565,205, which is hereby incorporated herein by reference in its entirety. TTFields disrupt cell division through physical interactions with key molecules during mitosis. TTFields therapy is an approved mono-treatment for recurrent glioblastoma, and an approved combination therapy with chemotherapy for newly diagnosed patients. These electric fields are induced non-invasively by transducer arrays (i.e., arrays of electrodes) placed directly on the patient's scalp. TTFields also appear to be beneficial for treating tumors in other parts of the body. Laboratory research has begun to test intermediate frequency alternating electric fields (Tumor Treating Fields, or TTFields) to subcutaneous tumors and orthotropic tumors located in the torso of small animals (e.g., mice).

SUMMARY

Described herein, in various aspects, is a treatment assembly comprising an inner layer having an inner surface and an outer surface. Optionally, the treatment assembly can be positioned on animal test subjects, which can optionally be undergoing TTFields or control treatments. The inner layer can define a plurality of openings extending therethrough. The treatment assembly can further comprise a plurality of plates, each plate being at least partially received within a respective opening of the plurality of openings of the inner layer. The treatment assembly can further comprise treatment circuitry comprising a cable having a plurality of electrical leads and a plurality of lead ends, each electrical lead being electrically connected to a respective lead end of the plurality of lead ends. A cover layer can be attached to the outer surface of the inner layer and overlie the plurality of lead ends of the cable. The plurality of lead ends can be in contact with respective plates of the plurality of plates to define a plurality of electrodes, each electrode of the plurality of electrodes comprising a respective lead end and a respective plate.

At least one plate of the plurality of plates can comprise a ceramic plate.

At least one plate of the plurality of plates can comprise a glass plate.

At least one electrode of the plurality of electrodes can be configured to generate an electric field through a corresponding plate of the plurality of plates.

The plurality of electrodes of the treatment circuitry can have respective top surfaces. The cover layer can extend across the top surfaces of the electrodes of the cable.

Each plate of the plurality of plates can have a lower surface and an opposing upper surface. The treatment assembly can further comprise a layer of hydrogel on the lower surface of each plate of the plurality of plates.

The treatment circuitry can further comprise at least one temperature sensor.

The inner layer and the cover layer can cooperate to define a hole through the treatment assembly. The hole can be configured to receive a subcutaneous tumor therethrough.

The treatment assembly can further comprise a cap that extends across the hole and defines a receptacle therein that is configured to receive the subcutaneous tumor. The cap can be attached to the cover layer.

The plurality of plates can be are positioned radially outwardly of the hole defined through the treatment assembly.

The cap can comprise a peripheral rim. The treatment assembly can further comprise an adhesive ring that overlies the peripheral rim and secures the cap to the cover layer.

The treatment assembly can have a longitudinal dimension in a pre-use configuration. The cover layer can comprise a biocompatible non-woven adhesive. The non-woven adhesive can be elastic in the longitudinal dimension.

In a use configuration, the cable can extend perpendicularly or substantially perpendicularly relative to the longitudinal dimension.

The inner layer can comprise a biocompatible breathable polyurethane adhesive on the inner surface of the inner layer.

The cover layer can have an inner surface that comprises a biocompatible non-woven adhesive.

The plurality of electrodes can comprise a plurality of electric field-generating electrodes. The plurality of electric field-generating electrodes can be configured to transmit an electric field through corresponding plates of the plurality of plates.

The treatment circuitry can further comprise a plurality of thermistors.

A respective electrode of the plurality of electrodes and a respective thermistor of the plurality of thermistors can be in communication with each plate of the plurality of plates.

The treatment assembly can weigh less than 2.5 grams.

The treatment assembly can be sufficiently flexible to circumferentially conform to a portion of a torso of the animal subject.

The cable can comprise an end connector positioned on an end of the cable opposite the plurality of electrodes. The end connector can be configured to permit connection of the cable to an electrical signal generator.

The treatment assembly can further comprise a release layer that contacts the biocompatible breathable polyurethane adhesive on the inner surface of the inner layer.

The release layer can have a shape that is complementary to a shape of the cover layer.

The cover layer can define at least one tab portion that extends beyond the inner layer.

The at least one tab portion can comprise two opposing tab portions that are complementary to one another when the cover layer defines a circumferential loop.

The plurality of openings can comprise a plurality of longitudinally spaced openings.

The treatment circuitry and the cable can be unitarily constructed as a flexible printed circuit board.

A method of making a treatment assembly can comprise positioning the plurality of plates within respective openings in the inner layer of the treatment assembly, positioning each electrode of the plurality of electrodes of the treatment circuitry in contact with a plate of the plurality of plates, and attaching the cover layer to the outer surface of the inner layer. The cover layer can overlie the plurality of electrodes of the treatment circuitry.

The method can further comprise applying a layer of hydrogel to lower surfaces of each plate of the plurality of plates.

The lower surfaces of at least two plates of the plurality of plates can share a layer of hydrogel.

A method can comprise electrically coupling at least a portion of the electrodes of the treatment assembly to an electrical signal generator and attaching the treatment assembly to an animal subject having a tumor. The plates of the treatment assembly can surround at least a portion of the tumor. The electrical signal generator can be used to generate an electrical signal (e.g., an electric potential). The at least a portion of the electrodes of the treatment assembly can be used to deliver the electrical signal through corresponding plates of the plurality of plates, thereby generating an electric field.

The tumor can be an organ tumor. In a pre-use configuration, the plurality of openings and the plurality of plates can be longitudinally spaced along a longitudinal axis of the treatment assembly. In a use configuration, the plurality openings and the plurality of plates can be circumferentially spaced about a torso of the animal subject to surround the organ tumor.

The tumor can be a subcutaneous tumor. The plurality of openings can be radially spaced from a hole extending through the treatment assembly. The hole can receive at least a portion of the subcutaneous tumor.

The method can further comprise positioning a cap over the subcutaneous tumor and securing the cap to the cover layer of the treatment assembly.

Using the electrical signal generator to generate the electrical signals can comprise sequentially generating first and second electrical signals. Using said at least a portion of the electrodes of the treatment assembly to generate, from the electrical signal, the electric field can comprise using first and second electrodes to generate, from the first electrical signal, a first electric field across the tumor and using third and fourth electrodes to generate, from the second electrical signal, a second electric field across the tumor.

The first and second electric fields can have respective axes of propagation, and the axis of propagation of the first electric field can intersect the axis of propagation of the second electric field.

Using the electrical signal generator to generate an electrical signals can comprise generating the electrical signals at a frequency of between 50 and 500 kHz. The electrical signals can correspond to an alternating current provided at a frequency of between 50 and 500 kHz (or 150 kHz to 300 kHz or at or about 200 kHz) that is configured to produce a TTField as further disclosed herein.

The animal subject can be a member of an experimental group. The method can further comprise electrically coupling at least a portion of the electrodes of a control heating device to an electrical signal generator. The control heating device can be attached to a second animal subject having a tumor. The second animal subject can be a member of a control group. The heaters of the second treatment assembly can surround at least a portion of the tumor. The electrical signal generator can be used to generate heat through heaters of the control heating device. The at least a portion of the electrodes of the second treatment assembly can deliver the heat through corresponding plates of the plurality of plates. The heat generated by the control heating device can simulate heat generated by the first treatment assembly during delivery of the electric field.

A control heating device can comprise circuitry comprising a plurality of zones that are positioned in a spaced configuration that matches a configuration of the plurality of electrodes of the treatment assembly, at least one heater positioned in each zone of the plurality of zones, at least one temperature sensor, and a cable in communication with the at least one heater and the at least one temperature sensor of the circuitry.

The at least one temperature sensor can comprise a plurality of temperature sensors, wherein each temperature sensor of the plurality of temperature sensors is positioned at each zone of the plurality of zones.

The circuitry and the cable can be unitarily constructed as a flexible printed circuit board.

The control heating device can further comprise an inner layer having an upper surface and comprising a plurality of openings and a cover layer extending across the upper surface of the inner layer. Each of the zones can be disposed within an opening of the plurality of openings.

Additional advantages of the invention will be set forth in part in the description that follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

