Various embodiments are directed to systems and methods of inducing hyperthermia in cells, such as cancer cells, within a body.
There are several related art methods of inducing hyperthermia in cancer cells within a body. For example, in some cases radio frequency (RF) energy is sourced outside the body, directed into the body, and focused on the cancer cells. The RF energy causes localized heating and eventually cell death. However, RF energy is indiscriminate—the RF energy induces hyperthermia in all cells at which the RF energy is focused, and to some extent cells through which the RF energy propagates to reach the focal point. That is, RF energy induces hyperthermia in all cells, whether cancer cells or normal, healthy cells. In other cases, the tumor sites are very localized and it is difficult to perform the conventional RF hyperthermia.
The various embodiments are directed to systems and methods of inducing hyperthermia in cancer cells. More particularly, various embodiments are directed to wireless methods of determining the presence of cancer cells proximate to a microchip device, and inducing hyperthermia in the cells.
Example embodiments implantable medical device for inducing hyperthermia in cancer cells, the medical device comprising a substrate of semiconductor material, an energy harvesting circuit defined on the substrate, and an energy delivery circuit defined on the substrate. The energy harvesting circuit configured to extract electrical energy from energy propagating proximate the medical device and to store electrical energy in a capacitor). The energy delivery circuit electrically coupled to the energy harvesting circuit, and the energy delivery circuit configured to induce hyperthermia in cells proximate to the substrate.
Implementations of the invention can include one or more of the following features:
The energy delivery circuit further includes a resistive element defined on the substrate and electrically coupled to the energy harvesting circuit, and the energy delivery circuit is configured to apply heat to the tissue by conduction to the tissue of heat created from the resistive element.
The resistive element may be any of the following, or combinations thereof: a resistor; a transistor biased into an active region; a bipolar junction transistor biased into an active region; and a complementary metal-oxide semiconductor transistor biased into an active region.
The energy delivery circuit can further include a first set of electrodes on the substrate and electrically exposed, the first set of electrodes configured to selectively couple to the energy harvesting circuit. And the energy delivery circuit configured to induce hyperthermia by electrical current flow through the cancer cells by way of the first set of electrodes. In some cases the first set of electrodes are separated by 1000 microns or less, and in other cases the first set of electrodes are separated by 10 microns or less.
The communication circuit can further include a communication antenna defined on the substrate, the communication antenna operates at a frequency above 1 Mega Hertz (MHz). The communication circuit configured to receive the command from an external device by way of the communication antenna.
The energy harvesting circuit can further include an energy harvesting antenna defined on the substrate, a rectifier defined on the substrate and electrically coupled between the energy harvesting antenna and the capacitor, and a power management unit defined on the substrate and electrically coupled to the capacitor. The energy harvesting antenna has an operating frequency above 1 Mega Hertz (MHz). The configured to rectify alternating current energy from the energy harvesting antenna to create rectified energy stored in the capacitor. The power management unit configured to produce a regulated direct current (DC) voltage from rectified energy stored on the capacitor.
The energy harvesting can further include a set of conductive pads electrically exposed on the substrate, a rectifier defined on the substrate and electrically coupled between the second set of conductive pads and the capacitor, and a power management unit defined on the substrate and electrically coupled to the capacitor. The rectifier circuit configured to rectify alternating current energy flowing through the set of conductive pads to create rectified energy stored on the capacitor. The power management unit configured to produce a regulated DC voltage from the rectified energy stored on the capacitor.
The substrate of the implantable medical device in some cases defines a length greater than a width, and the width is 500 microns or less, and in particular cases 200 microns or less.
The implantable medical device can further include an encapsulant that fully encapsulates the substrate and devices defined on the substrate, the encapsulant electrically non-conductive.
The implantable medical device can further include a communication circuit defined on the substrate. The communication circuit electrically coupled to the energy harvesting circuit and the energy delivery circuit, and the communication circuit configured to receive a command originated external to the implantable medical device. The energy delivery circuit is configured to induce hyperthermia responsive to the command received by the communication circuit.
The implantable medical device can further include a sensing circuit defined on the substrate, the sensing circuit electrically coupled to the energy harvesting circuit and communicatively coupled to the communication circuit. The sensing circuit configured to sense a property of the cells proximate to or abutting the substrate. The property sensed by the sensing circuit can be any or all of: pH; resistivity; conductivity; impedance; transmittance; dielectric constant; and oxygen concentration or oxygen level.
Other example embodiments are methods of inducing hyperthermia in cancer cells within a body. The method may include charging a capacitor of a microchip device proximate to cells within the body (the charging by harvesting ambient energy by the microchip device), and when the energy on the capacitor reaches or exceeds a predetermined value inducing hyperthermia in the cells proximate to the microchip device using energy from the capacitor.
plementations of the method aspects of the invention can include one or more of the following features:
Charging the capacitor may further include harvesting electrical energy from electromagnetic waves sourced by a communication device external to the body.
Charging the capacitor may further include harvesting electrical energy from electrical current sourced by the communication device.
The methods of inducing hyperthermia can further include creating thermal energy by a resistive element defined on a substrate of the microchip device, and conducting the thermal energy from the microchip device to the cells proximate the microchip device.
The methods of inducing hyperthermia can further include flowing electrical current through the cells by way of set of electrodes defined on a substrate of the microchip device. Flowing the electrical may further include flowing electrical current between the set of electrodes spaced apart by 1000 microns or less. Flowing the electrical may further include flowing electrical current between the set of electrodes spaced apart by 10 microns or less.
The method of inducing hyperthermia can further include receiving a message by a communication circuit defined on the microchip device, and triggering the inducing hyperthermia responsive to the message.
The method of inducing hyperthermia can further include sensing, by the microchip device, whether the cells proximate to the microchip device are cancer cells. If the cells are cancer cells, the method may include triggering the inducing of hyperthermia.
The method of inducing hyperthermia can further include sensing a property of the cells. The property may be one or combinations of: pH; resistivity; conductivity; impedance; transmittance; dielectric constant; and oxygen level or oxygen concentration.
The method of inducing hyperthermia can further include sensing (by the first microchip device) a property of the cells proximate to the first microchip device, sending a value indicative of the property to a communication device external to the body, receiving (by a communication circuit defined on the microchip device) a message from the communication device external to the body, and triggering the inducing hyperthermia based on the message.
The method of inducing hyperthermia can further include, prior to charging the capacitor and inducing hyperthermia, implanting the microchip device to be proximate to the cells. The implanting may be by injecting the microchip device way of a needle.
Other example embodiments are medical devices for inducing hyperthermia in cancer cells. The example medical devices may include a substrate of semiconductor material, a means for harvesting energy defined on the substrate, a means for wireless communication with devices external to the substrate (the means for wireless communication defined on the substrate and electrically coupled to the means for harvesting energy), a means for sensing a property of a cells proximate to the substrate (the means for sensing electrically coupled to the means for harvesting and the means for wireless communication), and a means for inducing hyperthermia in cells proximate to the substrate (the means for inducing electrically coupled the means for harvesting and the means for wireless communication).
plementations of the medical device aspects of the invention can include one or more of the following features:
The means for harvesting may further include an energy harvesting antenna defined on the substrate (the energy harvesting antenna has an operating frequency above 1 Mega Hertz (MHz)). a rectifier defined on the substrate (the rectifier electrically coupled between the energy harvesting antenna and a capacitor) where the rectifier configured to rectify alternating current energy from the energy harvesting antenna to create rectified energy stored in the capacitor, and a power management unit defined on the substrate (the power management unit coupled to the capacitor) with the power management unit configured to produce a regulated direct current (DC) voltage from rectified energy stored on the capacitor.
The means for energy harvesting may further include a set of conductive pads electrically exposed on the substrate, a rectifier defined on the substrate and electrically coupled between the second set of conductive pads and the capacitor, a power management unit defined on the substrate and electrically coupled to the capacitor. The rectifier circuit configured to rectify alternating current energy flowing through the set of conductive pads to create rectified energy stored on the capacitor. And the power management unit configured to produce a regulated DC voltage from the rectified energy stored on the capacitor.
The means for wireless communication can further include a communication antenna defined on the substrate (the communication antenna operates at a frequency above 1 Mega Hertz (MHz)), and the means for wireless communication receives commands from an external device by way of the communication antenna.
The means for inducing hyperthermia may further include a means for creating thermal energy on the substrate, the means for creating electrically coupled to the means for harvesting, and the thermal energy created on the substrate induces hyperthermia by conduction from the substrate to the cells. In some cases the means for creating thermal energy is a resistor.
The medical device may further include a means for encapsulating and electrically isolating the substrate.
The means for inducing hyperthermia may further include a first set of electrodes on the substrate and that are electrically exposed, the first set of electrodes configured to selectively couple to the means for harvesting energy. The means for inducing may induce hyperthermia by electrical current flow through the cells by way of the first set of electrodes. The first set of electrodes may be separated by 1000 microns or less. The first set of electrodes may be separated by 10 microns or less.
The means for sensing may sense one or a combination of: pH; resistivity; conductivity; impedance; transmittance; dielectric constant; and oxygen level.
The substrate defines a length greater than a width, and the width is 500 microns or less. In some cases, the width is 200 microns or less.
For a detailed description of example embodiments, reference will now be made to the accompanying drawings (not necessarily to scale) in which:
Various terms are used to refer to particular system components. Different companies may refer to a component by different names—this document does not intend to distinguish between components that differ in name but not function. In the following discussion and in the claims, the terms “including” and “comprising” are used in an open-ended fashion, and thus should be interpreted to mean “including, but not limited to . . . .” Also, the term “couple” or “couples” is intended to mean either an indirect or direct connection. Thus, if a first device couples to a second device, that connection may be through a direct connection or through an indirect connection via other devices and connections.
“Electromagnetic waves” shall mean alternating electric and magnetic fields propagating through a medium.
“Hyperthermia” shall mean heating of cells causing cellular death.
“Proximate,” as it relates to proximity of a microchip device and cancer cells, shall mean that the cancer cells are within one centimeter of the microchip device.
The following discussion is directed to various embodiments of the invention.
Although one or more of these embodiments may be preferred, the embodiments disclosed should not be interpreted, or otherwise used, as limiting the scope of the disclosure, including the claims. In addition, one skilled in the art will understand that the following description has broad application, and the discussion of any embodiment is meant only to be exemplary of that embodiment, and not intended to intimate that the scope of the disclosure, including the claims, is limited to that embodiment.
Various embodiments are directed to systems and related methods to induce hyperthermia in cells, such as cancer cells, within a body. More particularly, various example embodiments are directed to a microchip device that is implanted or injected into the body (e.g., by way of a needle and syringe) to be proximate to cells within the body. The microchip device harvests ambient energy and stores the energy on a capacitor formed on a substrate of the microchip device. In example cases, and after implantation, the microchip device reads electrical properties of cells proximate to the microchip device, and if the cells are determined to be cancer cells the microchip device induces hyperthermia in the cancer cells. In some cases, inducing hyperthermia involves creating heat on the substrate of the microchip device (e.g., heat created by electrical current flowing through a resistive element), and the heat then transfers by conduction to the cells proximate to the substrate. In other cases, the microchip device induces hyperthermia by flowing electrical current through the cells proximate to the microchip device. Because the hyperthermia is induced based on harvesting ambient energy, the application is periodic or pulsed. The specification now turns to an example environment in which the microchip devices may be used.
In accordance with example systems the microchip device 106 (regardless of placement) does not have batteries; rather, the microchip devices in accordance with various embodiments have energy harvesting circuits that extract electrical energy from energy propagating proximate to each microchip device (hereafter “ambient energy”). The ambient energy could take many forms. For example, the communication device 108 (or other devices and systems) may send electromagnetic waves through the body that intersect the location of the microchip device 106. In other cases, the communication device 108 (or other devices and systems) may induce electrical current flow through the body that flows proximate to the microchip device 106. In yet still other cases, the communication device 108 (or other devices and systems) may launch acoustic energy toward the microchip device 106. Charging time varies based on the ambient energy available, and could be from a few minutes to an hour or more. The charging energy is sufficiently low (and the frequency selected) so as not to damage other bodily cells, tissue, and functions. Various example structures for harvesting ambient energy are discussed more below.
The example system thus further comprises communication device 108. Communication device 108 may be communicatively coupled to the microchip device 106. In particular, the communication device 108 in example embodiments is wirelessly coupled to the microchip device 106, as illustrated by double-headed arrow 110. Various mechanisms for wireless communication between the communication device 108 and the microchip device 106 are discussed more below. Suffice it to say at this stage that the communication device 108 may communicate individually to the microchip device 106 (and other microchip devices not specifically shown). The communication device 108 may take many forms. In some cases the communication device 108 resides outside the body containing the example pituitary gland 104, and is physically placed abutting or proximate to the patient's skin. In other cases, the communication device 108 may be implanted under the patient's skin, such as subcutaneous placement. In yet still other cases, the functionality of the communication device 108 may be divided between a subcutaneously placed portion and an external portion, with the two portions communicatively coupled.
In some example systems, after insertion into the body the microchip device 106 operates autonomously, sensing or detecting the presence of cancer cells, and inducing hyperthermia in the cancer cells proximate to the microchip device 106—limited only by an amount of time needed to scavenge or harvest energy for application of the next hyperthermia inducing event. Thus, in the autonomous versions, the microchip devices may omit a communication circuit, discussed more below. In other cases, the microchip device 106 operates autonomously, detecting cancer cells and inducing hyperthermia in the cancer cells proximate to the microchip device 106, but reports findings and hyperthermia inducing events to the communication device 108. In yet still other example systems, the communication device 108 controls the microchip device 106 by commanding the microchip device 106 at each step of the process. Consider, for example, the case of a microchip device 106 first commanded to sense a property of cells proximate to the microchip device 106 (sensing properties, discussed more below). The microchip device 106 may then communicate the results to the communication device 108, which makes the determination regarding the presence or absence of cancer cells proximate to the microchip device 106. If cancer cells are present, the communication device 108 may command the microchip device 106 to induce hyperthermia in the cancer cells (either immediately, or after sufficient energy has been harvested). Once the hyperthermia inducement has concluded the process may begin again.
In some example situations one or more microchip devices may be injected or otherwise implanted into a location where cancer cells are known to be present. The microchip devices may then harvest energy and induce hyperthermia in the cancer cells. Periodically, or perhaps before each hyperthermia inducing event, each microchip device could sense electrical properties of cells proximate to the microchip device, and make a determination as to whether cells proximate to the microchip device are still cancer cells (the determination made either internally or with the help of an external communication device 108), with hyperthermia inducing events ceased if no cancer cells are present. In yet still other cases, one or more microchip devices may be injected or implanted in such a way as to detect whether cancer has begun to regrow in a particular area. For example, after a surgical procedure to remove a cancerous mass, one or more microchip devices may be placed in the surrounding tissue at a location where the cancer has yet to spread. The microchip devices may periodically sense electrical properties of cells proximate to the microchip devices, and each make a determination as to whether cells proximate to the microchip device have become cancer cells (the determination made either internally or with the help of an external communication device 108). If new cancer growth is thus detected, the one or more microchip devices may inform the communication device by way of wireless communication, and also induce hyperthermia in the cells to reduce or eliminate the further cancer growth. The specification now turns to a description of an example microchip device 106.
The energy harvesting circuit 202 is defined on the substrate and is electrically coupled to a capacitor (not shown in
The microchip device 106 of
The example microchip device 106 of
Consider first the energy harvesting circuit 202. In the various embodiments the microchip device 106 harvests ambient energy to provide operational power to the other devices and components on the substrate. In some cases, the microchip device 106 harvests ambient energy in the form of electromagnetic waves propagating near, around, and/or past the microchip device 106. To that end, some example energy harvesting circuits 202 implement an energy harvesting antenna 300 illustratively shown as a dipole antenna. In example cases, the energy harvesting antenna 300 has an operating frequency of 1 Mega-Hertz (MHz) or above, in some cases having an operating frequency of between 1 MHz and 10 GigaHertz (GHz) inclusive, and in specific cases between 100 MHz and 1 GHz inclusive. The energy harvesting antenna 300 may be monolithically created on the substrate 200 by deposition of metallic material and selective etching to create metallic conductors. Other monolithically created antenna types may be equivalently used, such as bow tie antennas and patch antennas.
The energy harvesting antenna 300 electrically couples to an impedance matching network 302 (shown in block diagram form and labeled “Z”). As the name implies, the impedance matching network 302 matches impedance between the energy harvesting antenna 300 and the downstream devices to ensure low reflected energy and thus efficient energy transfer to the downstream devices. The impedance matching network 302, in turn, electrically couples to the rectifier 304. The rectifier 304 rectifies the alternating current energy from the energy harvesting antenna 300, and applies the energy to capacitor 306. The block diagram form showing the rectifier 304 illustratively shows a single diode; however, the rectifier may take any suitable form, including the half-wave rectification by way of a single diode, full-wave rectification by way of a diode bridge, and rectification by switches operated as diodes (to reduce energy loss in the form of diode voltage drop). In some cases, the rectifier 304 directly applies the rectified energy to the capacitor 306, but in other cases the rectifier 304 may further include circuitry to increase the voltage, such as a Dickson Charge Pump. In either event the rectified energy (with or without voltage step-up) is applied to the capacitor 306. The voltage on the capacitor 306 is referred to herein as the unregulated voltage (VUNREG), and in some cases may be on the order of 1.6 Volts when fully charged.
The example energy harvesting circuit 202 further comprises a power management unit (PMU) 308 defined on the substrate 200. The power management unit 308 is electrically coupled to the capacitor 306, and thus is electrically coupled to the unregulated voltage. In example systems, the power management unit 308 comprises one or more circuits that selectively produce a regulated voltage (VREG) from the unregulated voltage. In some cases the regulated voltage may be about 1.0 Volt. The example power management unit 308 also produces an enable signal 310 coupled to various other of the circuits. In accordance with example embodiments, the power management unit 308 de-asserts the enable signal 310 during periods of time when the energy stored on the capacitor 306 is below a predetermined threshold. With the remaining circuits disabled and thus not consuming power or consuming significantly reduced power, the energy harvesting circuit 202 can more quickly charge the capacitor 306 from ambient energy. Once the energy stored reaches or exceeds the predetermined threshold (again, e.g., 1.6 V), the power management unit 308 asserts the enable signal 310 thus enabling the remaining circuits to operate, such as sensing electrical properties by the sensing circuit 208, inducing hyperthermia by the energy delivery circuit 206, and sending and/or receiving communications by way of the communication circuit 204.
Still referring to
In operation, the communication device 108 (
To send and receive messages, the radio 316 is electrically coupled to communication antenna 318, illustratively shown as a dipole antenna. In example cases, the communication antenna 318 has an operating frequency above 1 MHz, in some cases having an operating frequency of between 1 MHz and 1 Giga-Hertz (GHz) inclusive, and in specific cases between 100 MHz and 1 GHz inclusive. The communication antenna 318 may be monolithically created on the substrate 200 by deposition of metallic material and selective etching to create metallic conductors. Other monolithically created antenna types may be equivalently used, such as bow tie antennas and patch antennas.
Still referring to
The sensor interface circuit 324 may sense electrical properties of the cells by way of the conductive pads 326. For example, the sensor interface circuit 324 may sense localized pH (as voltage across the conductive pads 326 where one conductive pad is glass covered and sensitive to hydrogen-ion concentration, and the second conductive pad is a reference electrode). In other cases the electrical properties sensed are responsive to applying voltage and/or current to the cells by way of the conductive pads 326. For example, the sensor interface circuit 324 may apply a voltage (e.g., direct current (DC), alternating current (AC), or a voltage pulse or impulse) and then sense the electrical current response to determine electrical properties such as resistance, complex impedance, conductivity, and dielectric constant. Example circuits implemented by the sensor interface circuit 324 are discussed more below.
Inducing hyperthermia in cells is both a time- and temperature-based operation. The shorter the time of application of increased temperature, the greater the temperature needed to induce cellular death. Conversely, the longer the time of exposure to increased temperature, the lower the increased temperature needed to induce cellular death. For example, it may be possible to induce hyperthermia in cells by application of an increase over ambient body temperature of 20 degrees Fahrenheit (e.g., about 118 degrees Fahrenheit) for as short as one millisecond. Thus, in some cases creating the heat for inducing hyperthermia may involve directly coupling the resistive element 330 to the regulated voltage VREG and/or the unregulated voltage VUNREG until the energy stored on the capacitor 306 is depleted—creating a high temperature increase for a short period of time. Likewise, it may be possible to induce hyperthermia by application of a lower temperature increase (e.g., 10 degrees Fahrenheit) for an extended period of time, such as 10 milliseconds. Thus, in yet still other cases the power driver circuit 328 may regulate energy delivery to the resistive element 330 (e.g., pulse width modulating the applied voltage, or controlling the resistance across the resistive element in the form of a transistor by controlling the bias current and/or voltage at the gate or base)—creating a lower temperature increase but for a longer period of time.
In addition to, or in place of, creating heat by way of resistive element 330 on the substrate, the energy delivery circuit 206 may create heat in the cells proximate to the microchip device 106 by causing electrical current flow through the cells. Thus, in yet still further embodiments the energy delivery circuit 206 may comprise electrodes 332. It follows that, when present, the electrodes 332 are electrically exposed to the cells and tissue surrounding the microchip device 106 (such as exposed through windows in the biocompatible material 210 (
In some cases, the power driver circuit 328 applies the voltage from the capacitor to the electrodes 332 in a DC sense—resulting in the electrical current from the capacitor flowing from one electrode to the other without change of direction. In other cases, the power driver circuit 328 may implement a switch bridge such that the voltage is applied in an AC sense—resulting in electrical current flow first in one direction, and then the other direction, and so on. Stated slightly differently, during periods of time when electrical current flows through the tissue and cells, the power driver circuit may operate switches to alternate the polarity of the voltage that induces the electrical current flow.
The electrical current flow through the tissue and cells between the electrodes 332 is dictated, at least in part, by the voltage applied and the impedance of the underlying tissue. However, for an assumed voltage level, energy dissipated (and thus heat created) by the electrical current flow in the cells and tissue increases with decreasing impedance. Thus, in some embodiments the electrodes 332 are constructed to be relatively close together to limit the presented impedance. Stated slightly differently, assuming an impedance per unit distance of the cells proximate to the electrodes 332, closer spacing of the electrodes 332 results in lower impedance between the electrodes (and thus higher delivered power for a constant voltage). Thus, in some cases the spacing S between the closest points of the electrodes 332 may be 1000 microns or less, and in some cases 10 microns or less, and in a particular case the spacing S may be 2 microns or less (but greater than zero).
Finally with respect to
Measuring the property may take many forms. For example, in some embodiments the processor 314 may apply a DC voltage, as shown by graph 410. Thus, in these embodiments processor 314 drives the digital-to-analog converter 400 to create a constant voltage over time. The amplifier 402, deriving amplifying energy from either the regulated voltage VREG and/or the unregulated voltage VUNREG (e.g., having its power rails coupled to the regulated voltage VREG and/or the unregulated voltage VUNREG as shown), generates a DC voltage that is applied to the tissue and cells 408 by way of the conductive pads 326. Using the example analog-to-digital converter 404 and inline resistor 406, the processor 314 may thus determine the voltage applied across the conductive pads 326 (using one leg of the connection to the converter 404) and the responsive electrical current flow (as a differential voltage reading). Thus, the processor 314 may be able to calculate the electrical property of resistance (or its inverse, conductance) of the tissue and cells 408—where resistance may be indicative of whether the cells of the tissue are cancer cells.
In yet still other cases, the processor 314 may apply an AC voltage, as shown by graph 412. Thus, in these embodiments the processor 314 drives the digital-to-analog converter 400 to create a time varying voltage with a particular frequency, which frequency may be from a few kilo-Hertz (kHz) into the Mega-Hertz (MHz) range. In some cases the amplifier 402 generates a higher amplitude AC signal that is applied to the tissue and cells 408 by way of the conductive pads 326. In other cases the amplifier 402 is a voltage follower, but amplifies or increases available power to suppled the downstream devices. Using the example analog-to-digital converter 404 and inline resistance 406, the processor 314 may thus determine the voltage applied across the conductive pads 326 and the responsive electrical current flow. Thus, the processor 314 may be able to calculate the electrical property impedance (or its inverse admittance) of the tissue and cells 408—where impedance may be indicative of whether the cells of the tissue are cancer cells. Moreover, by varying the frequency of the applied voltage, the processor 314 may be able to calculate the relationship of impedance to frequency—where the relationship of impedance to frequency may be indicative of whether the cells of the tissue are cancer cells.
In yet still other cases, the processor 314 may apply voltage pulse, as shown by graph 414. Thus, in these embodiments the processor 314 drives the digital-to-analog converter 400 to create a voltage pulse. The amplifier 402 generates the signal that is applied to the tissue and cells 408 by way of the conductive pads 326. Using the example analog-to-digital converter 404 and inline resistor 406, the processor 314 may thus determine the voltage applied across the conductive pads 326 and the responsive electrical current flow during application of the voltage pulse. Moreover, the processor 314 may continue to monitor voltage across the tissue and cells 408 after the voltage pulse has ceased. Thus, the processor 314 may be able to calculate the electrical property resistance (during the pulse) as well as other electrical properties, such as dielectric strength (e.g., based on a capacitance determination and accounting for parasitic capacitance of the circuits of the microchip device). Here again, the relationship of response to the voltage pulse by the tissue and cells 408 may be indicative of whether the cells of the tissue are cancer cells.
In other cases, the property sensed may be property of the cells that is sensed electrically. As discussed above, for example, the sensing circuit 208 may be designed and constructed to sense pH. In other cases, the sensing circuit may be designed and constructed to sense oxygen level or oxygen concentration proximate to the microchip device. For example, the sensing circuit 208 of the microchip device 106 may include a Clark-type electrode, or may be designed and constructed to measure oxygen saturation using photodiodes similar to a transmission or reflectance pulse oximetry measurement. In other cases, the microchip device may implement a titanium oxide-based oxygen sensor, where the resistance of the sensor changes as a function of oxygen concentration of the tissue and cells to which the sensor is exposed. Titanium oxide-based sensors are suited to the microchip device environment because such sensors to do not require access to reference air to make the oxygen concentration measurement.
In yet still other cases, the microchip devices may be placed directly. For example, in the situation where microchip devices are placed during a surgical procedure to remove cancerous tissue, the microchip devices may be physically placed by the surgeon at various locations to monitor for re-growth of the cancer cells (and possibly inducing hyperthermia when such cells are detected) without the use of the syringe system 500 noted above. Any physical system and method that places the microchip devices to abut tissue may be used.
The above discussion regarding energy harvesting and inducing hyperthermia is meant to be illustrative of the principles and various embodiments. Numerous variations and modifications will become apparent to those skilled in the art once the above disclosure is fully appreciated. For example, the specification refers to conductive pads with respect to energy harvesting, sensing, and communications, but refers to electrodes with respect to inducing hyperthermia; however, the distinction is merely grammatical, and metallic material electrically coupled to the tissue and cells within the body may be of similar construction—such as platinum, iridium, titanium, gold, or any metallic material suitable for extended use within the body. It is intended that the following claims be interpreted to embrace all such variations and modifications.
This application claims priority to U.S. Patent Application Ser. No. 62/396,590 filed Sep. 19, 2016 titled “Pulsed Hyperthermia Based on Microchip Integrated Circuits.” The provisional application is hereby incorporated by reference in its entirety for all purposes.
Filing Document | Filing Date | Country | Kind |
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PCT/US17/52163 | 9/19/2017 | WO | 00 |
Number | Date | Country | |
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62396590 | Sep 2016 | US |