Low power battery and signaling systems

Abstract

Ingestible and / or implantable low power battery and signaling systems are generally provided. Advantageously, the systems and methods described herein may provide, in some embodiments, secure communication such that only authorized users and / or medical professionals can read sensor data and / or send valid commands to a system. Advantageously, the system and methods described herein may provide, in some embodiments, an energy-efficient security protocol to further improve the wireless communication (e.g., of an ingestible and / or implantable article). In some embodiments, the security protocol advantageously provides data encryption to protect sensor and command information and mutual authentication to prevent unauthorized access to both ingestible and external devices.

Description

[0001] LOW POWER BATTERY AND SIGNALING SYSTEMS

[0002] RELATED APPLICATIONS

[0003] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63 / 514,811, filed July 21, 2023, and entitled “IMPLANTABLE AND / OR INGESTIBLE ELECTRONIC ARTICLES FOR IMPROVED WIRELESS COMMUNICATION FIDELITY AND ASSOCIATED METHODS,” and to U.S. Provisional Patent Application No. 63 / 514,822, filed July 21, 2023, and entitled “LOW POWER BATTERY AND SIGNALING SYSTEMS,” both of which are incorporated herein by reference in its entirety for all purposes.

[0004] GOVERNMENT SPONSORSHIP

[0005] This invention was made with government support under FA8650-21-2-7120 awarded by the Air Force Office of Scientific Research. The government has certain rights in the invention.

[0006] TECHNICAL FIELD

[0007] The present invention generally relates to implantable and / or ingestible electronic articles for improved wireless communication fidelity and associated methods.

[0008] BACKGROUND

[0009] Ingestible devices have improved the quality of life of patients by providing medical services such as capsule endoscopy and enhanced therapeutic delivery inside the gastrointestinal (GI) tract. Moreover, their capability of residency inside the GI tract has enabled the long-term monitoring of pH, temperature, and bio signals directly from the GI tract. Long-term monitoring may inform our understanding of physiologic and pathophysiologic processes as well as support the development of new treatments. Designing such ingestible devices generally requires miniaturizing them to a swallowable size for safe transiting through the GI tract. Given the dimension constraints of an ingestible capsule there is limited space for the batteries. On the other hand, the data sent over a wireless medium is important as it generally comprises of the user’s private health information and the a command can invoke the operation of the ingestible device that directly affects the user’s health just as a therapeutic does. Therefore, secure communication is desirable so that only authorized users and medical professionals can read sensor data and send valid commands to such an ingestible device.

[0010] Accordingly, improved systems, articles and methods are needed.

[0011] SUMMARY

[0012] The present invention generally relates to implantable and / or ingestible electronic articles for improved wireless communication fidelity and associated methods. The subject matter of the present disclosure involves, in some cases, interrelated products, alternative solutions to a particular problem, and / or a plurality of different uses of one or more systems and / or articles.

[0013] Some aspects are related to articles. In some embodiments, the articles are implantable electronic articles for improved wireless communication fidelity. In some embodiments, the implantable electronic article for improved wireless communication fidelity comprises a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting, absorbing, and / or reflecting a signal from a location internal a subject to a receiver external to the subject.

[0014] In some embodiments, the ingestible electronic article for improved wireless communication fidelity comprises a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting, absorbing, and / or reflecting a signal from a location internal the subject to a receiver external to the subject.

[0015] Some aspects are related to methods. In some embodiments, the methods comprise a method of wirelessly communicating with an electronic article at a location internal to a subject. In some embodiments, the method of wirelessly communicating with an electronic article at a location internal to a subject comprises sending a signal to or from an electronic article at the location internal to the subject to an electromagnetic or acoustic receiver, transmitter, or transceiver external to the subject, wherein the electronic article comprises a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, and wherein the article tolerates signal strength degradation in excess of 15dBm with respect to performance in air, and electromagnetic receiver or transceiver has a sensitivity of at least -120dBm.

[0016] Some aspects are related to articles. In some embodiments, the articles comprise implantable electronic article for improved wireless communication fidelity. In some embodiments, the implantable electronic article for improved wireless communication fidelity comprises a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject.

[0017] In some embodiments, the implantable electronic article for improved wireless communication fidelity comprises a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting a radiofrequency signal from a location internal the subject to a receiver external to the subject.

[0018] Some aspects are related to methods. In some embodiments, the method comprises a method of wirelessly communicating with a medical device at a location internal to a subject. According to some embodiments, the method of wirelessly communicating with a medical device at a location internal to a subject comprises sending a wireless radiofrequency signal from an electronic article at the location internal to the subject, wherein the electronic article comprises: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, and receiving, with a receiver external to the subject, the wireless radiofrequency signal, wherein the radiofrequency signal has a carrier frequency of greater than or equal to 250 MHz and less than or equal to 6 GHz and a path loss of 20dBm and above as compared to air, and wherein the receiver has a sensitivity of at least -106dBm. Still other aspects are related to articles. In some embodiments, the article comprises ingestible and / or implantable electronic article. In some embodiments, the ingestible and / or implantable electronic article comprises a capsule suitable for administration to a location internal to a subject; a power source; a short-range wireless component in electrical communication with the power source; a microcontroller, wherein the microcontroller is configured to duty-cycle the short-range wireless component, wherein the ingestible electronic article is configured to send, via the short-range wireless component in electrical communication with the microcontroller, pre-shared authentication keys to a receiving device, if present, located external to the subject; and wherein operation of the microcontroller utilizes less than or equal to 1 microJoule of power for each authentication such that power source has a lifetime at the location internal to the subject of greater than or equal to 30 days.

[0019] Other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments of the disclosure when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control.

[0020] BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Non-limiting embodiments of the present disclosure will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale unless otherwise indicated. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the disclosure shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures:

[0022] FIG. 1 A is a schematic diagram of an implantable electronic article 100, according to one set of embodiments;

[0023] FIG. IB is a schematic diagram of an ingestible electronic article 200, according to one set of embodiments; FIG. 2 depicts a commercial chip antenna and an omnidirectional beam pattern of the commercial chip antenna, according to one set of embodiments;

[0024] FIG. 3A-FIG. 3C show (FIG. 3A) an in vitro setup to measure antenna resonant frequencies and measured resonant frequencies (FIG. 3B) over the air and (FIG. 3C) pH 2 SGF, according to one set of embodiments;

[0025] FIG. 4 is a schematic diagram depicting parameters for link budgeting, according to one set of embodiments;

[0026] FIG. 5A-FIG. 5B show (FIG. 5A) an in vitro setup and (FIG. 5B) measured received signal strengths, according to one set of embodiments;

[0027] FIG. 6 is a schematic diagram, including photographs, of an in vivo setup to measure the received signal strengths, according to one set of embodiments;

[0028] FIG. 7 is a plot of an in vivo measurement result on the received signal strength, according to one set of embodiments;

[0029] FIG. 8 is a schematic diagram illustrating a design of rigid-test PCB ver. 1 with a detachable antenna PCB, according to one set of embodiments;

[0030] FIG. 9 is a schematic diagram, including photographs, of an in vivo measurement setup with two rigid-test PCBs where d is the distance from skin to the external device, according to one set of embodiments;

[0031] FIG. 10A-FIG. 10C are plots of measured received signal strengths (RS Sis) (FIG. 10A) with communication channel distance varying from 5 cm to 50 cm upon time and (FIG. 10B) with fixed distances of 5 cm and (FIG. 10C) 10 cm, according to one set of embodiments;

[0032] FIG. 11 A-FIG. 1 IB depict (FIG. 11 A) Antenna PCB with and without encapsulation layer and (FIG. 1 IB) the measured resonance frequencies ( / r) of an antenna in each case, according to one set of embodiments;

[0033] FIG. 12 is a schematic diagram, including a photograph, depicting a measurement setup to evaluate the impact of the armor on the RS SI, according to one set of embodiments;

[0034] FIG. 13 is a set of plots depicting measurement results evaluating the impact of the armor on the RS SI, according to one set of embodiments;

[0035] FIG. 14 is a plot of measurement results evaluating the impact of the armor on the RS SI, according to one set of embodiments; FIG. 15A-FIG. 15B are plots of measured RSSI with and without armor at the communication distance of (FIG. 15 A) 26 cm and (FIG. 15B) 0 cm, according to one set of embodiments;

[0036] FIG. 16A-FIG. 16B are photographs of (FIG. 16 A) a fabricated rigid-test PCB as 915-MHz prototype and (FIG. 16B) a rigid-test PCB of BLE for comparison, according to one set of embodiments;

[0037] FIG. 17A-FIG. 17C show (FIG. 17A) a schematic diagram of a designed capsule prototype to implement an air gap around an antenna, (FIG. 17B) a photograph of a target chip antenna on a flexible PCB, and (FIG. 17C) a schematic diagram, including a photograph, of an in-vivo setup to measure the RSSI with an air gap in the 2.4GHz band, according to one set of embodiments;

[0038] FIG. 18A-FIG. 18B are plots of in-vivo RSSI measurement results in 2.4 GHz (FIG. 18A) when the air gap was 0.5 mm and (FIG. 18B) when 1.5 mm respectively, according to one set of embodiments;

[0039] FIG. 19 is a photograph of a 915-MHz rigid-test PCB and its capsule prototype, according to one set of embodiments;

[0040] FIG. 20 is an endoscopic image of a 915-MHz capsule device inside the stomach, according to one set of embodiments;

[0041] FIG. 21A-FIG. 21C are schematic diagrams of a design of MVP PCB ver. 1 (FIG. 21 A) when the PCB is unfolded and (FIG. 21B) folded and (FIG. 21C) MVP capsule prototype after assembled together with a single disassembly component and a single drug chamber that are replaceable, according to one set of embodiments;

[0042] FIG. 22 is a photograph of an assembled MVP PCB shown unfolded and inside capsule with quarter and batteries shown for scale, according to one set of embodiments;

[0043] FIG. 23 is a table detailing in-vivo experiments were performed with a system described herein, according to one set of embodiments;

[0044] FIG. 24 is photographs of device images associated with FIG. 23, according to one set of embodiments;

[0045] FIG. 25 A-FIG. 25B show endoscopic photos of a capsule inside the stomach when the capsule is (FIG. 25A) fully submerged in the gastric fluid and (FIG. 25B) out of fluid, showing dynamic GI environment, according to one set of embodiments; FIG. 26A-FIG. 26B show (FIG. 26A) a photo and (FIG. 26B) a 3D model of a 2.4-GHz chip-type monopole antenna, according to one set of embodiments;

[0046] FIG. 27A-FIG. 27B are plots showing return loss of a chip antenna (FIG. 27A) when the antenna was surrounded by air and (FIG. 27B) when submerged inside simulated gastric fluid (SGF), according to one set of embodiments;

[0047] FIG. 28A-FIG. 28C are (FIG. 28A) a schematic diagram of a 3D-printed case to evaluate an air-gap size to prevent antenna detuning, (FIG. 28B) a photograph of its in vitro test setup to evaluate the antenna resonant frequency, and (FIG. 28C) a schematic diagram of a capsule design to demonstrate the air-gap antenna performance in the ingestible device, according to one set of embodiments;

[0048] FIG. 29 is plots of antenna resonant frequency of a 2.4-GHz chip antenna surrounded by air gaps with various sizes when each capsule is over the air (top) and fully submerged inside the SGF (bottom), according to one set of embodiments; and

[0049] FIG. 30A-FIG. 3 OB are photographs of received signal strength (RSS) measurement setup in the (FIG. 30 A) in vitro and (FIG. 3 OB) in vivo tests, according to one set of embodiments.

[0050] FIG. 31 is a schematic diagram of an article, according to one set of embodiments.

[0051] FIG. 32 shows an exemplary implemented mutual authentication protocol, according to one set of embodiments.

[0052] FIG. 33 shows a comparison between wireless communication sources that are applicable to implantable electronics, according to one set of embodiments.

[0053] FIG. 34 shows a block diagram of an exemplary article, according to one set of embodiments.

[0054] FIG. 35 shows an exemplary BLE (Bluetooth Low Energy) timing diagram, according to one set of embodiments.

[0055] FIG. 36 shows an exemplary implemented mutual authentication process, according to one set of embodiments.

[0056] FIG. 37 shows an exemplary arrangement of batteries inside a 000 capsule and corresponding battery capacity for ingestible electronics, according to one set of embodiments. FIG. 38 shows an exemplary security-enhanced BLE communication using mobile BLE (mobile application) and capsule BLE (evaluation board), according to one set of embodiments.

[0057] FIG. 39 shows a flowchart of an exemplary Pseudo-Random Number Generator (PRNG), according to one set of embodiments.

[0058] FIG. 40 shows a BLE output measurement setup, according to one set of embodiments.

[0059] FIGs. 41 A-41B shows measured BLE TX output signals, according to one set of embodiments: (a) detailed view of a single channel output (channel #37) and (b) the outputs of the entire BLE channels (channels #0 ~ #39) from 2.402 GHz to 2.48 GHz.

[0060] FIG. 42. shows a plot of draining current from the simulated BLE that was used for the characterization of battery lifetime, according to one set of embodiments.

[0061] FIG. 43 shows an exemplary wake-up receiver-based ingestible BLE system, according to one set of embodiments.

[0062] FIGs. 44A-44C show, (a) Die photo of the FBAR provided by Broadcom, (b) lumped circuit model, and (c) measured and model-based simulated impedance of the FBAR, according to one set of embodiments.

[0063] FIG. 45 shows an exemplary timing diagram of the wake-up data transmission with its duty-cycling scheme, according to one set of embodiments.

[0064] FIG. 46 shows an exemplary overall architecture of a wake-up Rx, according to one set of embodiments.

[0065] FIG. 47 shows time-domain simulation results of the wake-up Rx, according to one set of embodiments.

[0066] FIG. 48 shows the power breakdown of the wake-up Rx, according to one set of embodiments.

[0067] FIGs. 49A-49C are photographs of exemplary articles comprising a capsule with electrical elements integrated into the capsule wall, for example an internal microphone and radio antenna, according to one set of embodiments.

[0068] FIG. 49D is a schematic illustration of an exemplary article (e.g., such as those shown in FIGs. 49A-49C) to be ingested and / or implanted, according to some embodiments. FIG. 50 shows the results from an in vivo system test of an article, according to some embodiments.

[0069] DETAILED DESCRIPTION

[0070] Overview

[0071] Implantable and / or ingestible electronic articles for improved wireless communication fidelity and associated methods are generally provided. In some embodiments, the electronic article comprises a capsule having a capsule wall, an antenna component at least partially disposed within the capsule, and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject. In some embodiments, the method is a method of wirelessly communicating with a medical device at a location internal to a subject. In some embodiments, the method comprises sending a wireless radiofrequency signal from an electronic article at the location internal to the subject, and receiving, with a receiver external to the subject, the wireless radiofrequency signal, wherein the radiofrequency signal has a carrier frequency of greater than or equal to 250 MHz and less than or equal to 6 GHz and a path loss of 20dBm and above as compared to air, and wherein the receiver has a sensitivity of at least -106dBm.

[0072] In certain embodiments, the inventors discovered that an interface (e.g., an air gap, an encapsulation layer) with a nonzero thickness between the antenna component and the capsule wall improved the operation of the antenna component by mitigating detuning of the antenna component. Such an interface was found by the inventors to stabilize the gain of the antenna component and improve received signal strength (RSS) (e.g., by 12 dB or more). In addition, in some cases, an interface with a nonzero thickness was surprisingly found to reduce power consumption of the electronic article.

[0073] In one aspect, articles are provided. In some embodiments, an implantable and / or ingestible electronic article is provided. These articles may be configured for improved wireless communication fidelity. The electronic article may be configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject. In some embodiments, the article is configured for gastric residence. In some embodiments, the article is configured to be transiently resident in the gastrointestinal tract.

[0074] In some embodiments, the article comprises a capsule. This capsule may have a capsule wall. The capsule may be sized and adapted for oral administration to a subject. The capsule may be configured as a suppository.

[0075] The capsule may have any suitable swallowable maximum dimension. For example, in some embodiments, the capsule has a swallowable maximum dimension of greater than or equal to 10 mm, greater than or equal to 15 mm, or greater than or equal to 20 mm. In some embodiments, the capsule has a swallowable maximum dimension of less than or equal to 30 mm or less than or equal to 25 mm. Combinations of the abovereferenced ranges are possible (e.g., greater than or equal to 10 mm and less than or equal to 30 mm, greater than or equal to 15 mm and less than or equal to 30 mm, greater than or equal to 20 mm and less than or equal to 25 mm). Other ranges are also possible. In certain embodiments, the capsule has a swallowable maximum dimension of 20 mm. The term swallowable refers to the ability of a subject to naturally swallow the capsule orally. In some embodiments, the dimensions of the capsule may be less than or equal to the dimensions corresponding to a 000 capsule size.

[0076] The capsule may have a folded configuration prior to entry into a subject. Upon reaching the stomach of a subject, the capsule may unfold in the stomach. This unfolding may be due to gastric fluid dissolving a component of the article holding the capsule in a folded configuration. Accordingly, the capsule may have any suitable unfolded maximum dimension. For example, in some embodiments, the capsule has an unfolded maximum dimension of greater than or equal to 20 mm, greater than or equal to 25 mm, greater than or equal to 30 mm, greater than or equal to 35 mm, or greater than or equal to 40 mm. In some embodiments, the capsule has an unfolded maximum dimension of less than or equal to 500 mm, less than or equal to 400 mm, less than or equal to 300 mm, less than or equal to 200 mm, less than or equal to 100 mm, less than or equal to 80 mm, less than or equal to 60 mm, or less than or equal to 50 mm. Combinations of the above-referenced ranges are possible (e.g., greater than or equal to 20 mm and less than or equal to 500 mm, greater than or equal to 30 mm and less than or equal to 300 mm, greater than or equal to 40 mm and less than or equal to 80 mm). Other ranges are also possible. In certain embodiments, the capsule has an unfolded maximum dimension of 46 mm. In certain embodiments, the capsule has an unfolded maximum dimension of 60 mm.

[0077] In some embodiments, the article comprises an antenna component. The antenna component may be at least partially disposed within the capsule. In certain cases, the antenna component is fully disposed within the capsule. The antenna component may be entirely disposed on the capsule wall. In some embodiments wherein the antenna component is entirely disposed on the capsule wall, and interface between the antenna component and the capsule wall comprises air, a dielectric material, a ferromagnetic material, and / or a material with characterized electromagnetic material properties. In some embodiments wherein the antenna component is entirely disposed on the capsule wall, the main antenna element has been integrated into the design of the capsule chassis itself.

[0078] In some embodiments, the interface (e.g., air gap, encapsulation layer) is associated with the antenna component. In some embodiments, the interface is adjacent the antenna component. In some embodiments, the interface is directly adjacent the antenna component. The term “associated with” as used herein means generally held in close proximity. As used herein, when a component is referred to as being “adjacent” another component, it may be directly adjacent to (e.g., in contact with) the component, or one or more intervening components (e.g., an electronic component) may also be present. A interface that is “directly adjacent” an antenna component means that no intervening component(s) is present.

[0079] The antenna component may have any suitable passband. For example, in some embodiments, the antenna component has a passband within or equal to the range of greater than or equal to 250 MHz and less than or equal to 6 GHz, within or equal to the range of greater than or equal to 250 MHz and less than or equal to 3 GHz, within or equal to the range of greater than or equal to 500 MHz and less than or equal to 2 GHz, or within or equal to the range of greater than or equal to 750 MHz and less than or equal to 1 GHz. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 250 MHz and less than or equal to 2 GHz, greater than or equal to 500 MHz and less than or equal to 6 GHz). Other ranges are also possible. In certain embodiments, the passband of the antenna component facilitates wireless communication at 2.4 GHz. The antenna component may be in electrical communication with a PCB, point- to-point wired equipment, a battery, a molded interconnect device, and / or a three- dimensionally printed circuit. The antenna component may be in electrical communication with the PCB, the point-to-point wired equipment, the molded interconnect device, and / or the three-dimensionally printed circuit by electrical connection, the electrical connection comprising soldering components to wiring primitives, compression fits, conductive epoxies, conductive tapes, and / or conductive adhesives.

[0080] The antenna component may be a component of a PCB, point-to-point wired equipment, a battery, a molded interconnect device, or a three-dimensionally printed circuit.

[0081] In some embodiments, upon submersion of the capsule in a fluid, the antenna component is fluidically isolated from the fluid. In some such embodiments, the antenna is positioned entirely within the capsule chassis. The fluid in which the capsule is submerged may be a biological fluid, water, an acid, a base, an oil, an organic solvent, and / or an inorganic solvent.

[0082] The antenna component may exhibit a suitable path loss in simulated gastric fluid as compared to air. For example, in some embodiments, the antenna component may exhibit a path loss of greater than or equal to 20 dBm, greater than or equal to 30 dBm, greater than or equal to 40 dBm, or greater than or equal to 50 dBm in simulated gastric fluid as compared to air. In some embodiments, the antenna component may exhibit a path loss of less than or equal to 106 dBm, less than or equal to 100 dBm, less than or equal to 90 dBm, less than or equal to 80 dBm, less than or equal to 70 dBm, or less than or equal to 60 dBm in simulated gastric fluid as compared to air. Combinations of the above-referenced ranges are possible (e.g., greater than or equal to 20 dBm and less than or equal to 106 dBm, greater than or equal to 30 dBm and less than or equal to 100 dBm, greater than or equal to 40 dBm and less than or equal to 90 dBm). Other ranges are also possible. In certain embodiments, the antenna component may exhibit a path loss of 32dBm in simulated gastric fluid as compared to air.

[0083] The antenna component may be configured to omnidirectional signaling. In some embodiments, the antenna component may be configured for bidirectional signaling. Those of ordinary skill in the art would be capable of selecting other suitable antenna components based upon the teachings of this specification (e.g., having one or more of the parameters listed below such as gain, energy dissipation, link margin, etc.).

[0084] The antenna component may have any suitable gain. For example, in some embodiments, the antenna component has a gain of greater than or equal to 0.1 dBi, greater than or equal to 1 dBi, greater than or equal to 10 dBi, or greater than or equal to 25 dBi. In some embodiments, the antenna component has a gain of less than or equal to 90 dBi, less than or equal to 80 dBi, less than or equal to 75 dBi, less than or equal to 50 dBi, less than or equal to 40 dBi, or less than or equal to 30 dBi. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0.1 dBi and less than or equal to 90 dBi, greater than or equal to 0.1 dBi and less than or equal to 30 dBi, greater than or equal to 10 dBi and less than or equal to 80 dBi, or greater than or equal to 25 dBi and less than or equal to 50 dBi). Other ranges are also possible.

[0085] In the electronic article, the amount of energy dissipated in the antenna component and / or circuit elements may be expressed as return loss. In some embodiments, the electronic article operates with a return loss of less than or equal to 60 dBm, less than or equal to 52 dBm, less than or equal to 50 dBm, or less than or equal to 40 dBm. In some embodiments, the electronic article operates with a return loss of greater than or equal to 10 dBm, greater than or equal to 20 dBm, or greater than or equal to 30 dBm. Combinations of the above-referenced ranges are also possible (e.g., less than or equal to 60 dBm and greater than or equal to 10 dBm, less than or equal to 52 dBm and greater than or equal to 20 dBm, less than or equal to 50 dBm and greater than or equal to 30 dBm). Other ranges are also possible. In certain embodiments, the article operates with a return loss of less than or equal to 52 dBm.

[0086] The electronic article may have any suitable link margin. For example, in some embodiments, the electronic article has a link margin of less than or equal to 40 dBm, less than or equal to 35 dBm, or less than or equal to 30 dBm. In some embodiments, the electronic article has a link margin of greater than or equal to 10 dBm, greater than or equal to 15 dBm, or greater than or equal to 20 dBm. Combinations of the abovereferenced ranges are also possible (e.g., less than or equal to 40 dBm and greater than or equal to 10 dBm, less than or equal to 35 dBm and greater than or equal to 15 dBm, less than or equal to 30 dBm and greater than or equal to 20 dBm). Other ranges are also possible. In certain embodiments, the electronic article has a link margin of less than or equal to 30dBm.

[0087] In some embodiments, the article comprises an interface. This interface may be disposed between the antenna component and the capsule wall. In some cases, the interface comprises air, a dielectric material, a ferromagnetic material, and / or a material with characterized electromagnetic material properties. The dielectric material may comprise, e.g., silicone or ceramics. In some cases, the interface substantially encapsulates the antenna component. In other cases, the interface does not substantially encapsulate the antenna component. For example, at least a portion of the antenna may be positioned external to the capsule. In certain embodiments, the antenna component is fully separate from the capsule walls, with the interface in between the antenna component and the capsule walls.

[0088] The interface may have any suitable thickness, as measured between the surface of the antenna component and the capsule wall. For example, in some embodiments, the interface has a thickness of greater than or equal to 0 mm, greater than or equal to 0.5 mm, greater than or equal to 1 mm, greater than or equal to 1.5 mm, or greater than or equal to 2 mm. In certain embodiments wherein the thickness is 0 mm, the interface is not present between the antenna component and the capsule wall, and thus the antenna component is positioned at least partially exterior to the capsule. In some embodiments, the interface has a thickness of less than or equal to 5 mm, less than or equal to 4.5 mm, less than or equal to 4 mm, less than or equal to 3.5 mm, less than or equal to 3 mm, or less than or equal to 2.5 mm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0 mm and less than or equal to 5 mm, greater than or equal to 1 mm and less than or equal to 3 mm, greater than or equal to 1.5 mm and less than or equal to 2.5 mm). Other ranges are also possible. In certain embodiments, the interface has a thickness of 2 mm.

[0089] Another aspect of this disclosure is directed to methods of wirelessly communicating with a medical device at a location internal to a subject. In some embodiments, the method comprises sending a wireless radiofrequency signal from an electronic article at the location internal to the subject. In certain embodiments, the electronic article is an electronic article described herein. In some embodiments, the method further comprises receiving, with a receiver external to the subject, the wireless radiofrequency signal.

[0090] The radiofrequency signal may have any suitable carrier frequency. For example, in some embodiments, the radiofrequency signal has a carrier frequency of greater than or equal to 250 MHz, greater than or equal to 500 MHz, greater than or equal to 750 MHz, greater than or equal to 1 GHz, or greater than or equal to 2 GHz. In some embodiments, the radiofrequency signal has a carrier frequency of less than or equal to 6 GHz, less than or equal to 5 GHz, less than or equal to 4 GHz, or less than or equal to 3 GHz. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 250 MHz and less than or equal to 6 GHz, greater than or equal to 500 MHz and less than or equal to 5 GHz, greater than or equal to 1 GHz and less than or equal to 3 GHz). Other ranges are also possible. In certain embodiments, the radiofrequency signal has a carrier frequency of greater than or equal to 250 MHz and less than or equal to 6 GHz.

[0091] The radiofrequency signal may exhibit a suitable path loss at the location internal to the subject as compared to air. For example, in some embodiments, the radiofrequency signal may exhibit a path loss of greater than or equal to 20 dBm, greater than or equal to 30 dBm, greater than or equal to 40 dBm, or greater than or equal to 50 dBm at the location internal to the subject as compared to air. In some embodiments, the radiofrequency signal may exhibit a path loss of less than or equal to 106 dBm, less than or equal to 100 dBm, less than or equal to 90 dBm, less than or equal to 80 dBm, less than or equal to 70 dBm, or less than or equal to 60 dBm at the location internal to the subject as compared to air. Combinations of the above-referenced ranges are possible (e.g., greater than or equal to 20 dBm and less than or equal to 106 dBm, greater than or equal to 30 dBm and less than or equal to 100 dBm, greater than or equal to 40 dBm and less than or equal to 90 dBm). Other ranges are also possible. In certain embodiments, the radiofrequency signal may exhibit a path loss of 20 dBm and above at the location internal to the subject as compared to air.

[0092] The receiver may have a suitable sensitivity. For example, in some embodiments, a receiver has a sensitivity of greater than or equal to -150 dBm, greater than or equal to - 120 dBm, greater than or equal to -110 dBm, greater than or equal to -100 dBm, or greater than or equal to -90 dBm. In some embodiments, the receiver has a sensitivity of greater than or equal to -60 dBm, greater than or equal to -70 dBm, greater than or equal to -80 dBm. In some embodiments, the receiver may have a sensitivity less than or equal to any of the sensitivities listed above. Combinations of the above-referenced ranges are possible (e.g., less than or equal to -150 dBm and greater than or equal to -60 dBm, less than or equal to -100 dBm and greater than or equal to -70 dBm, less than or equal to -90 dBm and greater than or equal to -80 dBm). Other ranges are also possible. In certain embodiments, the receiver has a sensitivity of at least -106 dBm. In certain embodiments, the receiver has a sensitivity of -96 dBm.

[0093] FIG. 1 A is a schematic diagram of an implantable and / or ingestible electronic article 100, according to one set of embodiments. In some embodiments, implantable and / or ingestible electronic article 100 is provided for improved wireless communication fidelity. In some embodiments, electronic article 100 comprises a capsule 102 having a capsule wall 104; an antenna component 106 at least partially disposed within capsule 102; and an interface 108 disposed between antenna component 106 and capsule wall 104. In some embodiments, electronic article 100 is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject.

[0094] FIG. IB is a schematic diagram of an implantable and / or ingestible electronic article 200, according to one set of embodiments. In some embodiments, implantable and / or ingestible electronic article 200 is provided for improved wireless communication fidelity. In some embodiments, electronic article 200 comprises a capsule 202 having a capsule wall 204; an antenna component 206 at least partially disposed within capsule 202; and an interface 208 disposed between antenna component 206 and capsule wall 204. In some embodiments, electronic article 200 is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject.

[0095] FIG. 1C is a schematic diagram of an implantable and / or ingestible electronic article 300, according to one set of embodiments. In some embodiments, implantable and / or ingestible electronic article 300 is provided for improved wireless communication fidelity. In some embodiments, electronic article 300 comprises a capsule 302 having a capsule wall 304; an antenna component 306 at least partially disposed within capsule 302; and an interface 308 disposed between antenna component 306 and capsule wall 304. In some embodiments, electronic article 300 is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject.

[0096] The articles described herein may be useful, for example, as a general platform for delivery of a wide variety of pharmaceutical agents that otherwise are generally delivered via injection directly into tissue due to degradation in the GI tract. In some cases, the article may be configured to deliver therapeutic payloads at a desired location and / or at a desired time and / or over a desired duration to a subject.

[0097] Advantageously, in some embodiments, the articles described herein may be useful as a general platform for delivery of a wide variety of therapeutic payloads (e.g., bacteria, therapeutic agents) that are typically delivered via injection directly into tissue due to degradation in the GI tract. For example, the article may be capable of localizing itself to a specified location (e.g., allowing loaded drugs to avoid long passages through the GI tract fluid before diffusing into the blood stream). This article, in some cases, may serve as a platform to allow therapeutic payloads and / or drugs that are currently degraded by the enzymes in the GI tract to be absorbed with higher bioavailability.

[0098] Administration

[0099] In some embodiments, the article is administered to a subject (e.g., orally). In certain embodiments, the article may be administered surgically (e.g., implanted), orally, rectally, vaginally, nasally, or uretherally. In certain embodiments, the system is administered such that at least a portion of the system resides at a location internal to the subject (e.g., the gastrointestinal tract). In some embodiments, the location internally of the subject is the colon, the duodenum, the ileum, the jejunum, the stomach, or the esophagus.

[0100] Biocompatible

[0101] The article (or at least a portion of the article as described above and herein) is biocompatible. The term “biocompatible," as used in reference to an article, refers to an article that does not invoke a substantial adverse reaction (e.g., deleterious immune response) from an organism (e.g., a mammal), a tissue culture or a collection of cells, or invokes only a reaction that does not exceed an acceptable level. In some embodiments, the article (e.g., the capsule of the article) comprises polymers, networks of polymers, and / or multi-block combinations of polymer segments, that may comprise polymers or polymer segments that are for example: polyesters - such as including but not limited to, polycaprolactone, polypropylene fumarate), poly(glycerol sebacate), poly(lactide), poly(glycol acid), poly(lactic-glycolic acid), polybutyrate, and polyhydroxyalkanoate; polyethers -such as including but not limited to, poly(ethylene oxide) and polypropylene oxide); polysiloxanes - such as including but not limited to, poly(dimethylsiloxane); polyamides - such as including but not limited to, poly(caprolactam); polyolefins - such as including but not limited to, polyethylene; polycarbonates - such as including but not limited to polypropylene oxide); polyketals; polyvinyl alcohols; polyoxetanes; polyacrylates / methacrylates - such as including but not limited to, polypiethyl methacrylate) and polypthyl-vinyl acetate); polyanhydrides; and polyurethanes. In some embodiments, the polymer is cross-linked.

[0102] Physiological condition

[0103] The term physiological condition generally refers to a set of conditions of the external or internal milieu that occurs in an organism or cellular system (e.g., in contrast to laboratory conditions). For example, in some cases, a physiological condition ranges in temperature between about 20 °C and about 40 °C (e.g., between about 35 °C and about 38 °C) and / or atmospheric pressure of about 1 atm. In certain embodiments, the physiological conditions are that of an internal organ such as the stomach, intestines, bladder, lungs, and / or heart.

[0104] In some embodiments, the capsule is sized and adapted for implantation in and / or ingestion by a subject.

[0105] As will be apparent from the description throughout this disclosure, the invention(s) includes many variations of the above description, not limited to any particular type of electronic component (e.g., microcontroller, PCB, wireless component, etc.).

[0106] In some embodiments, the antenna operates at a frequency of greater than or equal to 100 kHz and less than or equal to 3 GHz. For example, in some embodiments, antenna operates at a frequency of greater than or equal to 100 kHz, greater than or equal to 500 kHz, greater than or equal to 1 MHz, greater than or equal to 5 MHz, greater than or equal to 10 MHz, greater than or equal to 50 MHz, greater than or equal to 100 MHz, greater than or equal to 500 MHz, greater than or equal to 1 GHz, greater than or equal to 2 GHz, or greater than or equal to 2.4 GHz. In some embodiments, the antenna operates at a frequency of less than or equal to 3 GHz, less than or equal to 2.4 GHz, less than or equal to 2 GHz, less than or equal to 1 GHz, less than or equal to 500 MHz, less than or equal to 100 MHz, less than or equal to 50 MHz, less than or equal to 10 MHz, less than or equal to 5 MHz, less than or equal to 1 MHz, or less than or equal to 500 kHz. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 100 kHz and less than or equal to 3 GHz). Other ranges are also possible.

[0107] In some embodiments, one or more of the electronic components described herein comprises a (micro)controller and / or (micro)processor. In some embodiments, the controller is configured (e.g., programmed) to receive and transmit data commands to / from one or more components of the component and / or the smartphone (or other consumer electronic device). In some embodiments, the data includes one or more signals from one or more sensors. In some embodiments, the controller may be configured to adjust various parameters based on external metrics e.g., in response to a signal from a sensor in electrical communication with the controller.

[0108] The embodiments described herein can be implemented in any of numerous ways. For example, the embodiments may be implemented by any suitable type of analog and / or digital circuitry. In some embodiments, the embodiments may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on processing circuitry including any suitable processor (e.g., a microprocessor) or collection of processors, whether provided in a single computer or distributed among multiple computers (or other consumer electronic devices). It should be appreciated that any component or collection of components that perform the functions described above can be generically considered as one or more controllers that control the above-discussed functions. The one or more controllers can be implemented in numerous ways, such as with dedicated hardware or with one or more processors programmed using microcode or software to perform the functions recited above. The one or more embodiments can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0109] In some embodiments, the embodiments described herein comprise wireless capabilities for enabling suitable communication with other devices / sy stems (e.g., for controlling aspects of the electronic component(s), controlling a source of electromagnetic radiation, controlling a sensor or other component). Wireless devices are generally known in the art and may include, in some cases, LTE, WiFi and / or Bluetooth systems. In some embodiments, the systems and / or devices described herein comprise such a wireless device (e.g., a short-range wireless component).

[0110] In some embodiments, the embodiments described herein may be configured to adjust various parameters in response to an input from a user and / or a signal from a sensor and / or an externally located consumer electronic device.

[0111] In some embodiments, the system is associated with and / or comprises a power source. The power source may include any appropriate material(s), such as one or more batteries, photovoltaic cells, etc. Non-limiting examples of suitable batteries include Li- polymer (e.g., with between 100 and 1000 mAh of battery life), Li-ion, nickel cadmium, nickel metal hydride, silver oxide, or the like. In some cases, the battery may apply a voltage (e.g., to a degradable material as described herein) in response to a physiological and / or external metric and / or signal (e.g., by a user). For example, the voltage may be used to trigger the exit of the resident structure by e.g., applying a voltage to thermally sensitive degradable component as described herein. For example, the average magnitude of the voltage applied to the degradable component s) may be between 0.001 to 0.01 V, between 0.01 to 0.1 V, between 0.1 V and 10.0 V, between 1.0 V and 8.0 V, between 2.0 V and 5.0 V, between 0.1 V and 5.0 V, between 0.1 V and 1.5 V, between 0.1 V and 1.0 V, between 1.0 V and 3.0 V, between 3.0 V and 8.0 V, or any other appropriate range.

[0112] In some embodiments, the system is advantageously designed such that it may transmit and / or receive signals without the use of a power source. For example, in some embodiments, the antenna component is configured to operate using electromagnetic force and / or acoustic waves. Advantageously, the use of such antenna components may provide for battery-free systems. That is to say, in some embodiments, the article may be free of a power source (e.g., such as a battery). Any electronic component circuitry may be implemented by any suitable type of analog and / or digital circuitry. For example, the electronic component circuitry may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on any suitable processor (e.g., a microprocessor) or collection of processors. The one or more electronic components can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0113] In this respect, it should be appreciated that one implementation of the embodiments described herein comprises at least one computer-readable storage medium (e.g., RAM, ROM, EEPROM, flash memory or other memory technology, or other tangible, non-transitory computer-readable storage medium) encoded with a computer program (i.e., a plurality of executable instructions) that, when executed on one or more processors, performs the above-discussed functions of one or more embodiments. In addition, it should be appreciated that the reference to a computer program which, when executed, performs any of the above-discussed functions, is not limited to an application program running on a host computer. Rather, the terms computer program and software are used herein in a generic sense to reference any type of computer code (e.g., application software, firmware, microcode, or any other form of computer instruction) that can be employed to program one or more processors to implement aspects of the techniques discussed herein.

[0114] In some embodiments, the systems described herein are administered to a subject (e.g., surgically, endoscopically, orally). In certain embodiments, the system may be administered surgically (e.g., implanted), orally (e.g., swallowed, endoscopically), rectally, vaginally, nasally, or uretherally. In certain embodiments, the system is administered such that at least a portion of the system resides at a location internal to the subject (e.g., the gastrointestinal tract). In some embodiments, the location internal to the subject is the colon, the duodenum, the ileum, the jejunum, the stomach, or the esophagus. By way of example, and without wishing to be limited by such an exemplary set of embodiments, the system may be administered to a subject orally where it, in some cases, travels to the stomach of the subject, sinks to the bottom of the subject’s stomach. In some embodiments, the systems described herein are designed such that the system resides at a location internal to a subject (i.e. a residence time period) for at least 24 hours, at least 48 hours, at least 3 days, at 7 days, at least 1 month, at least 6 months, or at least 1 year. In certain embodiments, the residence time period is less than or equal to 2 years, less than or equal to 1 year, less than or equal to 6 months, less than or equal to 1 month, less than or equal to 7 days, less than or equal to 3 days, or less than or equal to 48 hours. Any and all closed ranges that have endpoints within any of the abovereferenced ranges are also possible (e.g., between 24 hours and 2 years, between 24 hours and 1 year, between 48 hours and 7 days, between 3 days and 1 month, between 7 days and 6 months, between 1 month and 1 year). Other ranges are also possible.

[0115] As described herein, in some embodiments, the structure is configured to adopt a shape and / or size compatible with oral administration to and / or ingestion by a subject. In some embodiments, the structure has a shape with a capacity for folding and / or packing into stable encapsulated forms. For example, in some embodiments the structure is designed to maximally pack and fill a capsule or other soluble container (e.g., a containing structure). In some embodiments, the structure has a shape that maximally fills and / or packs into a capsule or other soluble container.

[0116] In some embodiments, the article comprises the structure and a containing structure. In some embodiments, the structure comprises more than 60 vol% of the containing structure.

[0117] Based on the application, a capsule may be manufactured to particular specifications or a standard size, including, but not limited to, a 000, 00, 0, 1, 2, 3, 4, and 5, as well as larger veterinary capsules Su07, 7, 10, 12el, 11, 12, 13, 110ml, 90ml, and 36ml.

[0118] In some embodiments, the structure may be provided in capsules, coated or not. The capsule material may be either hard or soft, and as will be appreciated by those skilled in the art, typically comprises a tasteless, easily administered and water soluble compound such as gelatin, starch or a cellulosic material.

[0119] In other embodiments, the structure is retained in a packed shape by a soluble retaining element, such as a band or surgical thread. In some embodiments, the structure comprises optimal combinations of materials with high and low elastic moduli, giving the structure the capacity to alter its shape and / or size once the soluble container and / or soluble retaining element is removed. In some such embodiments, the structure is a capsule retained in a packed shape by a soluble retaining element.

[0120] Any terms as used herein related to shape, orientation, alignment, and / or geometric relationship of or between, for example, one or more articles, compositions, structures, materials and / or subcomponents thereof and / or combinations thereof and / or any other tangible or intangible elements not listed above amenable to characterization by such terms, unless otherwise defined or indicated, shall be understood to not require absolute conformance to a mathematical definition of such term, but, rather, shall be understood to indicate conformance to the mathematical definition of such term to the extent possible for the subject matter so characterized as would be understood by one skilled in the art most closely related to such subject matter. Examples of such terms related to shape, orientation, and / or geometric relationship include, but are not limited to terms descriptive of: shape - such as, round, square, circular / circle, rectangular / rectangle, triangular / triangle, cylindrical / cylinder, elipitical / elipse, (n)polygonal / (n)polygon, etc.; angular orientation - such as perpendicular, orthogonal, parallel, vertical, horizontal, collinear, etc.; contour and / or trajectory - such as, plane / planar, coplanar, hemispherical, semi-hemispherical, line / linear, hyperbolic, parabolic, flat, curved, straight, arcuate, sinusoidal, tangent / tangential, etc.; surface and / or bulk material properties and / or spatial / temporal resolution and / or distribution - such as, smooth, reflective, transparent, clear, opaque, rigid, impermeable, uniform(ly), inert, non-wettable, insoluble, steady, invariant, constant, homogeneous, etc.; as well as many others that would be apparent to those skilled in the relevant arts. As one example, a fabricated article that would described herein as being “ square" would not require such article to have faces or sides that are perfectly planar or linear and that intersect at angles of exactly 90 degrees (indeed, such an article can only exist as a mathematical abstraction), but rather, the shape of such article should be interpreted as approximating a “ square," as defined mathematically, to an extent typically achievable and achieved for the recited fabrication technique as would be understood by those skilled in the art or as specifically described.

[0121] A “subject” refers to any animal such as a mammal (e.g., a human). Non-limiting examples of subjects include a human, a non-human primate, a cow, a horse, a pig, a sheep, a goat, a dog, a cat or a rodent such as a mouse, a rat, a hamster, a bird, a fish, or a guinea pig. Generally, the invention is directed toward use with humans. In some embodiments, a subject may demonstrate health benefits, e.g., upon administration of the systems described herein.

[0122] Ingestible and / or implantable low power battery and signaling systems are generally provided. As would be understood by those of ordinary skill in the art, data sent over a wireless medium are generally important as, in some embodiments, the data comprises a user’s (and / or patient’s) private health information. In some cases, a command can invoke the operation of the ingestible device that directly affects the user’s health just as a therapeutic does. Advantageously, the systems and methods described herein may provide, in some embodiments, secure communication such that only authorized users and / or medical professionals can read sensor data and / or send valid commands to a system. Advantageously, the system and methods described herein may provide, in some embodiments, an energy-efficient security protocol to further improve the wireless communication (e.g., of an ingestible and / or implantable article). In some embodiments, the security protocol advantageously provides data encryption to protect sensor and command information and mutual authentication to prevent unauthorized access to both ingestible and external devices. In some embodiments, the security protocol uses low energy by, at least in part, adopting Speck, a lightweight block cipher that is optimized for software implementation, and symmetric challenge-response protocol as a base protocol.

[0123] In some embodiments, an ingestible and / or implantable electronic article is provided. In some embodiments, the article comprises a capsule suitable for administration to a location internal to a subject.

[0124] In some embodiments, the article comprises a power source.

[0125] In some embodiments, the article comprises a short-range wireless component (e.g., electrical communication with the power source).

[0126] For example, as shown illustratively in FIG. 31, article 400 comprises capsule 410, power source 420, and a short-range wireless component 430.

[0127] In some embodiments, the article comprises a microcontroller. In some embodiments, the microcontroller is configured to duty-cycle the short-range wireless component. In some embodiments, the duty-cycle is greater than or equal to 1 second, greater than or equal to 2 seconds, greater than or equal to 5 seconds, greater than or equal to 10 seconds, greater than or equal to 30 seconds, greater than or equal to 60 seconds, or greater than or equal to 90 seconds. In some embodiments, the duty-cycle is less than or equal to 180 seconds, less than or equal to 90 seconds, less than or equal to 60 seconds, less than or equal to 30 seconds, less than or equal to 10 seconds, or less than or equal to 5 seconds. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 1 second and less than or equal to 180 seconds). Other ranges are also possible.

[0128] In some embodiments, the microcontroller is configured for Bluetooth communication. In some embodiments, the microcontroller comprises a wake-up receiver configured as a wireless switch for a Bluetooth transceiver. Other wireless protocols are also possible, as described below.

[0129] In some embodiments, the microcontroller is configured for a periodic wireless connection. In some embodiments, the microcontroller is configured for periodic advertising for a wireless connection.

[0130] In some embodiments, the microcontroller comprises a mutual authentication protocol. In some embodiments, the mutual authentication protocol comprises a symmetric challenge-response protocol. In some embodiments, the mutual authentication protocol comprises a random number generator.

[0131] In some embodiments, the article is configured to send pre-shared authentication keys e.g., to a receiving device, if present, located external to the subject. In some embodiments, the article sends the pre-shared authentication keys the short-range wireless component in electrical communication with the microcontroller. The receiving device may comprise, in some embodiments, a consumer electronic device such as cellular phones (e.g., smartphones, iPhones, Android phones), digital cameras, tablets (e.g., iPads), laptop computers, home automation devices, watches (e.g., smartwatches), and / or desktop computers. However, the articles and methods are not limited to use with consumer-level electronics and may be used with other systems and devices as well.

[0132] In some embodiments, the articles described herein use relatively low energy consumption. For example, in some embodiments, the energy consumption for a 10 day, 30 day, 60 day, or 90 day or greater operation of the article is less than or equal to 500 J (e.g., less than or equal to 400 J, less than or equal to 300 J, less than or equal to 200 J, or less than or equal to 100). For example, in some embodiments, the article described herein may operate for greater than or equal to 90 days and have a total energy consumption of less than or equal to 500 J. Those of ordinary skill in the art would understand that operation of the article generally refers to regular use (e.g., sending / receiving signals, sharing authentication keys, operating a wireless component) of the article (e.g., in accordance with the embodiments described herein).

[0133] In some embodiments, operation of the microcontroller utilizes less than or equal to 1 microJoule, less than or equal to 0.5 microJoule, less than or equal to 0.3 microJoule, less than or equal to 0.2 microJoule, or less than or equal to 0.1 microJoule of power for each authentication (e.g., such that power source has a lifetime at the location internal to the subject of greater than or equal to 10 days, greater than or equal to 30 days, greater than or equal to 60 days, or greater than or equal to 90 days). In some embodiments, operation of the microcontroller utilizes greater than or equal to 0.01 microJoule, greater than or equal to 0.1 microJoule, greater than or equal to 0.2 microJoule, greater than or equal to 0.3 microJoule, or greater than or equal to 0.5 microJoule of power for each authentication (e.g., such that power source has a lifetime at the location internal to the subject of greater than or equal to 10 days, greater than or equal to 30 days, greater than or equal to 60 days, or greater than or equal to 90 days). Combinations of the above-references ranges are also possible (e.g., less than or equal to 1 micro Joule and greater than or equal to 0.01 micro Joule).

[0134] In some embodiments, the article comprises various components described herein (e.g., microcontroller, power source, etc.) such that the power source has a lifetime (e.g., power sufficient to operate the device) at the location internal to the subject of greater than or equal to 1 days, greater than or equal to 5 days, greater than or equal to 10 days, greater than or equal to 30 days, greater than or equal to 60 days, greater than or equal to 90 days, or greater than or equal to 180 days. In some embodiments, the power source has a lifetime (e.g., power sufficient to operate the device) at the location internal to the subject of less than or equal to 360 days, less than or equal to 180 days, less than or equal to 90 days, less than or equal to 60 days, less than or equal to 30 days, less than or equal to 10 days, or less than or equal to 5 days. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 1 day and less than or equal to 360 days). Other ranges are also possible.

[0135] In some embodiments, the ingestible electronic article is configured for gastric residence for greater than or equal to 24 hours. In some embodiments, the short-range wireless component operates at a frequency of greater than or equal to 100 kHz and less than or equal to 3 GHz. For example, in some embodiments, the short-range wireless component operates at a frequency of greater than or equal to 100 kHz, greater than or equal to 500 kHz, greater than or equal to 1 MHz, greater than or equal to 5 MHz, greater than or equal to 10 MHz, greater than or equal to 50 MHz, greater than or equal to 100 MHz, greater than or equal to 500 MHz, greater than or equal to 1 GHz, greater than or equal to 2 GHz, or greater than or equal to 2.4 GHz. In some embodiments, the short-range wireless component operates at a frequency of less than or equal to 3 GHz, less than or equal to 2.4 GHz, less than or equal to 2 GHz, less than or equal to 1 GHz, less than or equal to 500 MHz, less than or equal to 100 MHz, less than or equal to 50 MHz, less than or equal to 10 MHz, less than or equal to 5 MHz, less than or equal to 1 MHz, or less than or equal to 500 kHz. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 100 kHz and less than or equal to 3 GHz). Other ranges are also possible.

[0136] As described herein, in some embodiments, the structure is configured to adopt a shape and / or size compatible with oral administration to and / or ingestion by a subject. In some embodiments, the structure has a shape with a capacity for folding and / or packing into stable encapsulated forms. For example, in some embodiments the structure is designed to maximally pack and fill a capsule or other soluble container (e.g., a containing structure). In some embodiments, the structure has a shape that maximally fills and / or packs into a capsule or other soluble container.

[0137] In some embodiments, the system comprises the structure and a containing structure. Based on the application, a capsule may be manufactured to particular specifications or a standard size, including, but not limited to, a 000, 00, 0, 1, 2, 3, 4, and 5, as well as larger veterinary capsules Su07, 7, 10, 12el, 11, 12, 13, 110ml, 90ml, and 36ml. In some embodiments, the structure may be provided in capsules, coated or not. The capsule material may be either hard or soft, and as will be appreciated by those skilled in the art, typically comprises a tasteless, easily administered and water soluble compound such as gelatin, starch or a cellulosic material.

[0138] In some embodiments, the capsule is sized and adapted for implantation in and / or ingestion by a subject.

[0139] As will be apparent from the description throughout this disclosure, the invention(s) includes many variations of the above description, not limited to any particular type of electronic component (e.g., microcontroller, PCB, wireless component, etc.).

[0140] In some embodiments, one or more of the electronic components described herein comprises a (micro)controller and / or (micro)processor. In some embodiments, the controller is configured (e.g., programmed) to receive and transmit data commands to / from one or more components of the component and / or the smartphone (or other consumer electronic device). In some embodiments, the data includes one or more signals from one or more sensors. In some embodiments, the controller may be configured to adjust various parameters based on external metrics e.g., in response to a signal from a sensor in electrical communication with the controller.

[0141] The embodiments described herein can be implemented in any of numerous ways. For example, the embodiments may be implemented by any suitable type of analog and / or digital circuitry. In some embodiments, the embodiments may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on processing circuitry including any suitable processor (e.g., a microprocessor) or collection of processors, whether provided in a single computer or distributed among multiple computers (or other consumer electronic devices). It should be appreciated that any component or collection of components that perform the functions described above can be generically considered as one or more controllers that control the above-discussed functions. The one or more controllers can be implemented in numerous ways, such as with dedicated hardware or with one or more processors programmed using microcode or software to perform the functions recited above. The one or more embodiments can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0142] In some embodiments, the embodiments described herein comprise wireless capabilities for enabling suitable communication with other devices / sy stems (e.g., for controlling aspects of the electronic component(s), controlling a source of electromagnetic radiation, controlling a sensor or other component). Wireless devices are generally known in the art and may include, in some cases, LTE, WiFi and / or Bluetooth systems. In some embodiments, the systems and / or devices described herein comprise such a wireless device (e.g., a short-range wireless component).

[0143] In some embodiments, the embodiments described herein may be configured to adjust various parameters in response to an input from a user and / or a signal from a sensor and / or an externally located consumer electronic device.

[0144] In some embodiments, the system is associated with and / or comprises a power source. The power source may include any appropriate material(s), such as one or more batteries, photovoltaic cells, etc. Non-limiting examples of suitable batteries include Li- polymer (e.g., with between 100 and 1000 mAh of battery life), Li-ion, nickel cadmium, nickel metal hydride, silver oxide, or the like. In some cases, the battery may apply a voltage (e.g., to a degradable material as described herein) in response to a physiological and / or external metric and / or signal (e.g., by a user). For example, the voltage may be used to trigger the exit of the resident structure by e.g., applying a voltage to thermally sensitive degradable component as described herein. For example, the average magnitude of the voltage applied to the degradable component s) may be between 0.001 to 0.01 V, between 0.01 to 0.1 V, between 0.1 V and 10.0 V, between 1.0 V and 8.0 V, between 2.0 V and 5.0 V, between 0.1 V and 5.0 V, between 0.1 V and 1.5 V, between 0.1 V and 1.0 V, between 1.0 V and 3.0 V, between 3.0 V and 8.0 V, or any other appropriate range.

[0145] Any electronic component circuitry may be implemented by any suitable type of analog and / or digital circuitry. For example, the electronic component circuitry may be implemented using hardware or a combination of hardware and software. When implemented using software, suitable software code can be executed on any suitable processor (e.g., a microprocessor) or collection of processors. The one or more electronic components can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above.

[0146] In this respect, it should be appreciated that one implementation of the embodiments described herein comprises at least one computer-readable storage medium (e.g., RAM, ROM, EEPROM, flash memory or other memory technology, or other tangible, non-transitory computer-readable storage medium) encoded with a computer program (i.e., a plurality of executable instructions) that, when executed on one or more processors, performs the above-discussed functions of one or more embodiments. In addition, it should be appreciated that the reference to a computer program which, when executed, performs any of the above-discussed functions, is not limited to an application program running on a host computer. Rather, the terms computer program and software are used herein in a generic sense to reference any type of computer code (e.g., application software, firmware, microcode, or any other form of computer instruction) that can be employed to program one or more processors to implement aspects of the techniques discussed herein.

[0147] In some embodiments, the systems described herein are administered to a subject (e.g., surgically, endoscopically, orally). In certain embodiments, the system may be administered surgically (e.g., implanted), orally (e.g., swallowed, endoscopically), rectally, vaginally, nasally, or uretherally. In certain embodiments, the system is administered such that at least a portion of the system resides at a location internal to the subject (e.g., the gastrointestinal tract). In some embodiments, the location internal to the subject is the colon, the duodenum, the ileum, the jejunum, the stomach, or the esophagus. By way of example, and without wishing to be limited by such an exemplary set of embodiments, the system may be administered to a subject orally where it, in some cases, travels to the stomach of the subject, sinks to the bottom of the subject’s stomach.

[0148] In some embodiments, the systems described herein are designed such that the system resides at a location internal to a subject (i.e. a residence time period) for at least 24 hours, at least 48 hours, at least 3 days, at 7 days, at least 1 month, at least 6 months, or at least 1 year. In certain embodiments, the residence time period is less than or equal to 2 years, less than or equal to 1 year, less than or equal to 6 months, less than or equal to 1 month, less than or equal to 7 days, less than or equal to 3 days, or less than or equal to 48 hours. Any and all closed ranges that have endpoints within any of the abovereferenced ranges are also possible (e.g., between 24 hours and 2 years, between 24 hours and 1 year, between 48 hours and 7 days, between 3 days and 1 month, between 7 days and 6 months, between 1 month and 1 year). Other ranges are also possible.

[0149] The following examples are intended to illustrate certain embodiments of the present invention, but do not exemplify the full scope of the invention.

[0150] EXAMPLE 1

[0151] Antenna specifications There were two important requirements for the selection of an antenna design. Firstly, the antenna was designed to have an omni-directional beam pattern. This is because the antenna on the capsule will rotate inside the stomach, and exact alignment with the external antenna would be unreliable. Secondly, the antenna was designed to have a small form factor so that it could be integrated into capsule design with the target form factor of 000 capsules. Therefore, the chip-type antenna was chosen for the first trial. One of the commercial chip antennas (Fusca from Antenova M2M) chosen is shown in FIG. 2. It has an omnidirectional beam pattern and has a form factor of 4x3 x 1.1 mm3. This antenna had a peak gain of 0.8 dBi, which is close to the ideal gain of the omnidirectional antenna.

[0152] Bench tests over the air and in vitro measurements with simulated gastric fluids (SGF)

[0153] (a) The issue of antenna resonant frequency shifting

[0154] To characterize the chip antenna, first were measured the resonance frequency of the antenna over the air and SGF by using a network analyzer (Key sight E8362B), as shown in FIG. 3 A. The resonant frequency can be found at the frequency showing the lowest return loss, meaning the highest conversion of energy into radiated power. When the antenna was over the air, it showed the resonance frequency at 2.4 GHz as it was designed, as shown in FIG. 3B. However, when the antenna was inside the SGF, the resonance frequency shifted to 0.4 GHz, as shown in FIG. 3C. This is because the resonant frequency of an antenna depends on the dielectric permittivity of the material in the immediate vicinity of the antenna. This resonance frequency shifting decreased the radiation efficiency as well as the antenna gain at the target frequencies, 2.402 GHz and 2.48 GHz in this case.

[0155] (b) Characterization of received signal strength (RSS)

[0156] Bench tests were conducted to measure the received signal strength using two target chip antennas. By considering the general distance between the user and the mobile device held in hand, the channel distance over the air was set as 30 cm. When both antennas were over the air without any obstacles between them (i.e., clear line of sight), the test showed the received signal strengths to be between -32 dBm and -40 dBm. These values are comparable to the theoretical received signal of -28 dBm, which is explained in the next paragraph. The following can be factors that make the difference between the actual measured received signal strengths (-32 dBm ~ -40 dBm) and the theoretical one (-28 dBm): (1) the impedance mismatches between antenna, cable, and connector; (2) the misalignment between the two antennas.

[0157] The link budgeting equation to calculate the theoretical received signal strength is shown in the equation below, and each description can be found in FIG. 4 and Table 1. Here the antenna gains were set as 0.8 dB by considering the peak gain of the target chip antenna. The path loss of -29.6 dB was calculated by considering the 30-cm channel over the air.

[0158] Received signal strength over the 30-cm air channel with line of sight:

[0159] PRx,Air30cm=TX + GTX+ Lpath, Air, 30cm + GRX(Equation 1)

[0160] = 0 dBm + 0.8 dB — 29.6 dB + 0.8 dB

[0161] = —28 dBm

[0162] Table 1. Parameters used in the link budgeting equation

[0163] Symbol PRXPTXGTXLpath GRX

[0164] Received

[0165] TX antenna RX antenna

[0166] Parameter signal TX output power Path loss gain gain strength

[0167] In the same manner, in vitro measurements were conducted with SGF. If one antenna was inside SGF with pH 2, representing a capsule antenna inside a stomach, as shown in FIG. 5A, the measured received signals were -70 dBm ~ -90 dBm, which is shown in FIG. 5B and Table 2. The received signal strengths may have decreased for at least one of two reasons. First, the SGF hay have increased the path loss by converting more RF energy into heat. Secondly, the SGF may have decreased the gain of the antenna (either GTXor GRX) by shifting its resonant frequency. It is important to note that all the measured received signal strengths were higher than the RX sensitivity of the target BLE chip (nRF52832), or -96 dBm. This means that the BLE devices could communicate with each other without significant errors.

[0168] Table 2. Measured received signal strength over the air and in SGF

[0169] Condition Air (measured) SGF (measured)

[0170] Measured received signal strength -32 ~ -40 dBm -70 ~ -90 dBm

[0171] Preliminary result on in vivo measurement

[0172] To acquire more representable results on the received signal strength, a preliminary in-vivo test was conducted. Commercial BLE boards (Adafruit Feather nRF52 Bluefruit LE) were used with the form factor of 51 mm x 23 mm, which was small enough to be used in the animal-terminal test. As shown in FIG. 6, one of the BLE boards had been encapsulated using the polyethylene pouch to protect it against any fluids and placed inside the stomach of the Swine full of gastric fluids (GF). Since the antenna was matched for the communication over the air, it was not matched inside the GF, which caused a loss of antenna efficiency. In this setup, -78 ~ -80 dBm was measured, as shown in FIG. 7, when another BLE board was placed on the skin of the Swine (FIG. 6). However, the received signal strengths are highly affected by the PCB design and antenna design, and further in-vivo tests are warranted.

[0173] Design of rigid test PCB

[0174] As described in the last section, a custom capsule PCB may be important for more accurate evaluations on the received signal strength. However, it was found that 3 weeks were utilized to fabricate each capsule PCB, which was too long to have multiple design iterations. The lead time for capsule PCB became longer than the general case because it included special processes, such as flexible PCB substrate, fine pitch, and narrow PCB traces to fabricate the miniaturized capsule PCB. Therefore, rigid test PCBs were fabricated as an intermediate stage. The rigid test PCB had the same hardware design but was implemented on a larger PCB enabling a general PCB process with a shorter lead time to be used.

[0175] A rigid test PCB was designed, whose design is shown in FIG. 8. At the left side of the PCB, there was a BLE module with a u.FL-type RF connector, which could be connected to any antenna PCB via a cable as shown in FIG. 8. Four silver oxide batteries could be mounted on the bottom side of this PCB for its wireless operation, and the same batteries may be used for the capsule PCB. Additionally, there were circuits to trigger drug release and capsule disassembly, such as 2.5-V output LDOs and 1 :8 demultiplexers. The control pins of these circuits were connected to the BLE-MCU GPIO pins so that the BLE-MCU could control triggering. The total size of the rigid test PCB was 60 mm x 13 mm. This small form factor (especially the narrow PCB width) facilitates it to be used in survival tests without harming tissues.

[0176] Two major factors affect the received signal strength, which affects wireless communication fidelity. Firstly, an antenna may comprise a keep-out region, which is an area around the antenna trace where any additional copper traces, planes, or metallic components should not be located to ensure the ideal radiation of the antenna. However, it is challenging to secure a keep-out region within a confined 000 capsule volume. A design that does not follow this guidance may result in reduced antenna gain. Secondly, animal tissues and gastric fluids have a high impact on the received signal strength by making the antenna resonance frequency change depending on the antenna’s location relative to air and gastric fluids, thus reducing the antenna gain.

[0177] Evaluating and developing communication fidelity

[0178] 1) Evaluation of the received signal strength in animal model

[0179] We conducted in vivo tests to characterize the received signal strength (RSS) in an animal model. As shown in FIG. 9, two rigid-test printed circuit boards (PCBs) were fabricated and used. For the BLE radio operation, each rigid-test PCB was connected to an antenna PCB with a chip antenna (ANT3216LL00R2400A from Yageo) mounted on top of it. One set of the PCBs was placed approximately 5-50 cm from the skin of the swine as an external device. Then another set was vacuum-packaged using a polyethylene pouch to protect it against any fluids and placed inside the stomach mimicking the ingestible electronics. A matching network was designed for the communication over the air for both sets of the PCBs. However, as the stomach was full of gastric fluid (GF), the resonance frequency ( / r) of an antenna inside the stomach was shifted, which caused a loss in the antenna efficiency and gain.

[0180] FIG. 10A-FIG. 10C shows the measured RSSIs when the external PCB set was separated by various distances from the skin of the swine (d). The distance was gradually increased (d) from 5 cm to 50 cm, and the measured RSSIs decreased from -75 dBm to - 95 dBm as the path loss over the air increased (FIG. 10 A). To further investigate the RS SI, another in-vivo test was conducted with the fixed distances (d) of 5 cm and 10 cm, results shown in FIG. 10B and FIG. 10C, respectively. The RS SI decreased from -70 dBm ~ -90 dBm to -80 dBm ~ -90 dBm as the distance increased from 5 cm to 10 cm. In summary, all the RSSIs were higher than the sensitivity level of the BLE receiver (-96 dBm for target BLE part, the nRF52832 from Nordic Semiconductor). These results indicate that the BLE devices could communicate with each other with the bit-error rate (BER) less than 10'3, validating the communication fidelity of these BLE electronics even without proper antenna matching for the ingestible BLE in gastric fluid.

[0181] 2) Preliminary evaluation of antenna isolation to improve communication fidelity

[0182] The antenna resonance frequency (fr) shifting becomes an issue as it can reduce antenna efficiency, gain, and overall RSSI of the link. Therefore, isolating the antenna to mitigate antenna resonance frequency (fr) shifting and further improving communication fidelity was explored.

[0183] The frof an antenna is dependent on the dielectric permittivity (er) of its nearfield region as shown in Equation 2. (Equation 2)

[0184] However, this exemplary capsule resided inside the stomach, so it was expected to be exposed to varying environments such as gastric fluid (GF), tissues, and air with different permittivities (er). These varying environments can be included in the near- fi eld region of the antenna in this capsule design, and hence the frcan be shifted according to the environment.

[0185] Therefore, isolating the antenna by encapsulation to mitigate the frshifting was considered. To prove this concept, a prototype was made by encapsulating an antenna PCB with silicone rubber, as shown in FIG. 11 A. The encapsulated PCB has a total thickness of 4 mm, which is ~2.5 times shorter than the diameter of 000 capsules (9.9 mm). We also prepared another PCB without encapsulation for comparison and measured the frof an antenna on each PCB.

[0186] As shown in FIG. 1 IB, the frof an antenna without encapsulation shifted by 4.31 times as its environment changed from air to water with increased dielectric permittivity. However, for the case of an antenna with encapsulation, its frshifted by 1.19 times in the same condition. This indicates that the amount of frshifting decreased by applying the encapsulation.

[0187] From the measurement results, it was estimated the bandwidth required to keep the antenna resonating at 2.4-GHz ISM band that BLE is working even after frshifting. Table 3 shows the estimated bandwidths for the antennae with and without the encapsulation layer. For instance, the inventors predicted that if the fris 3.77 GHz over the air without encapsulation, the frwill be shifted to 2.4 GHz when applying the encapsulation and putting it inside the water. Therefore, the inventors estimated the bandwidth required for the encapsulated antenna as 3.17 GHz ~ 3.77 GHz+.

[0188] Table 3. Expected antenna bandwidth required for resonating at 2.4 GHz inside the water and air.

[0189] Required fr air Required fr, water Required bandwidth

[0190] Antenna without GHz+ 2.4 GHz - 10.3 GHz+ encapsulation (2.4 GHz X2,5 GHz) (>8 GHz)

[0191] 1 v0.58 GHz7

[0192] Antenna with 3.17 GHz 3.77 GHz 3.17 GHz - 3.77 GHz+ encapsulation (2.4 GHz X (> 0.6 GHz)

[0193] 1 v

[0194] As a required bandwidth was from 3.17 GHz to 3.77 GHz, an antenna with the bandwidth including such frequencies may have been needed. However, it is challenging to find an off-the-shelf antenna specialized for these frequencies or to find a wide-band antenna with a small form factor due to the tradeoff between the size and the bandwidth in antenna design. Other encapsulation materials with different permittivity can be considered to shift the frto those of other off-the-shelf. However, some encapsulation material has the potential of further reducing signal strength. In the case of enclosing the antenna with an air gap, however, the frof the antenna may not be shifted, and one can directly use one of the off-the-shelf antennas designed for BLE. Therefore, the inventors determined to test the air gap as a promising methodology to isolate an antenna and mitigate frshifting.

[0195] To estimate the required air-gap size, first was calculated the size of near-field region of the target chip antenna (2450AT18A100E from Johanson Technology, monopole antenna). For the calculation, Equation 3 was used, where D indicates the maximum linear dimension of the antenna or its PCB (3.2 mm ~ 20 mm; dependent on ground plane design) and is the wavelength of the 2.4-GHz signal over the air (125 mm).

[0196] 2D2

[0197] Radiative near-field region: — — (Equation 3)

[0198] A

[0199] As its near-field region is expected to be 0.16 mm ~ 6.4 mm from the center of the chip antenna, the target air gap sizes were set as 0.5 mm, 1.0 mm, and 1.5 mm. Enclosures were fabricated to implement each air gap surrounding an antenna by using a 3-D printer. Then was measured the frof the antenna when it was placed inside each enclosure to check the impact of each air gap, as shown in FIG. 12.

[0200] The measurement results are shown in FIG. 13. With a 0.5-mm air gap, the frwas shifted to outside of 2.4-GHz band when the enclosure was submerged in the water. However, by increasing the air-gap size to 1 mm or 1.5 mm, the amount of frshifting decreased and the frwas maintained inside the 2.4-GHz band even inside the water. This is promising when considering the fact that the frwas shifted to 0.58 GHz without air gap as shown in FIG. 1 IB.

[0201] By mitigating the frshifting, the antenna gain can be increased, which was decreased due to the frshifting and the RS SI can be increased as shown in Equation 4 with all parameters in dB scale. RS SI T = TX output power + TX (or RX) antenna gain + Path loss + RX (or TX) antenna gain T (Equation 4)

[0202] Therefore, RS SI measurements were conducted to characterize the RS SI increase by having the air gap. As shown in FIG. 14, the RSSI was around -45 dBm ~ -46 dBm with or without the air gap. However, the RSSI with the 1-mm air gap was about 12 dB higher than that without any air gap when submerged. This indicates that the RSSI can be increased by ~12 dB by including 1-mm air gap. Or one can choose to decrease the TX output power (PTX) by ~12 dB and have the same level of RSSI by applying the air gap. By decreasing PTX, one can reduce the level of stress applied to the battery, which helps to prevent degradation on the battery life due to high discharging current. Also, one can reduce the energy consumed by the power amplifier of the BLE transmitter, and the total energy of the ingestible BLE the inventors expected to be decreased by ~7% when they decrease PTXfrom +4 dBm to -8 dBm. (Exact number of the saved energy can be different upon the BLE setup).

[0203] In summary, the inventors expected to increase the RSSI or secure additional energy margin by applying the proper air gap surrounding the antenna.

[0204] 3) Impact of armor on the received signal strength

[0205] The inventors analyzed loss due to body armor a warfighter might be wearing. This represents an extreme case where the warfighter is unable to remove their body armor, position their phone at positions with no armor, or slide their phone between themselves and the armor. By using a real-time spectrum analyzer (Tektronix RSA306B) and candidate chip antenna (Antenova A10192-U1) it was found the armor adds at most 20 dB of loss, as shown in FIG. 15A-FIG 15B. This is dependent on the position as the inventors believe the signals may have been moving around the armor thus there is a tradeoff between absolute signal strength (the farther away from the receiver, the lower the signal strength) and loss introduced by the armor (the closer the transmitter is to the surface, the harder it is for signals to pass around the armor).

[0206] 4) Design and fabrication of 915-MHz rigid-test PCB In parallel with the development of the BLE rigid-test PCB for fast testing, while the capsule PCB was fabricated, the inventors also designed, had fabricated, and assembled an alternate solution using a different frequency for wireless communication. FIG. 16A shows a second rigid-test PCB utilizing the 915MHz communication frequency. This PCB had the same features as a BLE rigid-test PCB (shown in FIG. 16B), facilitating the same test strategies; evaluation of multiple candidate antennas using the u.FL connector, the small form factor for endoscopic placement in vivo tests, and validation of disassembly circuitry. The inventors have successfully brought up the board.

[0207] Summary

[0208] The inventors used an air gap to increase the in-vivo average received signal strength indicator (RSSI) with a capsule form-factor device in the 2.4GHz band. To further de-risk 2.4GHz communication, they also showed successful in-vivo communication using the 915MHz band. To begin work on clinical translation of the project they designed, fabricated, and assembled a mass-manufacturable minimum viable product (MVP) printed circuit board (PCB). They also developed a mobile app that works with an energy-efficient communication protocol to maintain low power communication and enable 60-day residency.

[0209] In-vivo RSSI tests in the 2.4 GHz band

[0210] The inventors determined that the antenna's resonant frequency is dependent on the dielectric constant of the surrounding environment. This is not a problem for communication through free space, in which the selected chip antennas are designed to operate, but does require a workaround in-vivo. This issue can be mitigated by separating the antenna from nonstandard media with an appropriate air gap. Theory of action for this strategy will be explained later in this example. A 1.5-mm air gap was found to be sufficient through in-vivo experiments, and can be fabricated within the volume constraints of the MVP capsule. FIG. 17A-FIG. 17C show the in-vivo antenna test setup. The asymmetric design of the mock capsule seen in FIG. 17A is to simulate placement of the antenna within a final capsule design, where proximity to the capsule edge is the most important factor for antenna resonant frequency. FIG. 17B shows the layout of the Antenna PCB, and was fabricated using flexible printed circuit (FPC) technology to be the same as the final capsule design.

[0211] FIG. 17C shows the in-vivo measurement setup. The antenna PCB was placed inside the capsule, connected to a 2.4GHz rigid test PCB through a u.FL. cable and then placed inside the stomach of the large swine laparoscopically. The 2.4-GHz Bluetooth Low Energy (BLE) transmitter was set to output +4-dBm power. An external rigid PCB used as the receiver was placed with varied distance (labelled “d”) between 5 cm and 1 m from the skin of the animal.

[0212] FIG. 18A-FIG. 18B shows the measured RSSI with 0.5-mm and 1.5-mm air gaps. For both tests, communication distance was extended until device signal was lost. This occurred at about -96 dBm, the BLE receiver sensitivity. The 0.5-mm air gap was only able to communicate at 5 cm from the animal, but the 1.5-mm test was able to be extended to 1 m from the animal. This is a factor of 20 improvement. Additionally, measurement results with a mobile device are detailed in Table 4. This is a simulation of expected final device operation which will make use of a warfighter’s personal mobile device to serve as the external control interface for the device. To summarize these results: the average RSSI of the 1.5-mm air gap test was approximately -60 dBm with a distance of 5 cm and was approximately 10 dB to 20 dB greater than the RSSI of a 0.5- mm air gap with the same distance. These results validate the resonant frequency shifting mitigation strategy.

[0213] Table 4. RSSI data measured using a researcher’s personal mobile device. Distance is fixed at 5cm across all trials.

[0214] The theory of air gap influence has been researched, and may be explained in the following manner, without wishing to be bound by any particular theory. This will be an overview of two means of energy loss, and therefore lower RSSI, resulting from antennas being placed in non-standard environments. Relative permittivity (parametrized as “k”) is a dimensionless quantity comparing the permittivity of a material to that of a perfect vacuum, which has k defined as 1. Air may be measured to have k=1.0006, but water may be temperature dependent with k between 70 and 80 at body temperature. The “near field” region of the antenna may contain primarily decoupled electrical and magnetic fields, with the “far field” containing primarily coupled fields which propagate as radiation and carry energy away from the antenna. These decoupled fields may be responsible for the resonant behavior of the antenna. From the electric fields can be abstracted a natural capacitance of the antenna, and from the magnetic field an inductance. It is the relationship between the capacitance and inductance which may determine resonant frequency, since together they form a second order underdamped electrical oscillator. When excited with a signal close to the resonant frequency, no losses may occur in a perfect oscillator. In the real world, natural resistance of the antenna may dissipate energy and form a means of energy loss within the antenna. This may be negligible for signals close to resonance, but losses from damping may increase with excitations more distant from the resonant frequency. If the near field region contains material with k greater than that of air, which all consumer grade antennas are designed to operate within, this may change the antenna resonant behavior because the capacitance may be modified and the inductance remains the same. This is the type of change observed in biological environments since magnetic permeability (parametrized as “p”), a similar concept to electric permittivity for the magnetic field, remains about the same in air(p =1) and water (p =0.999992). This may happen to some degree to any antenna placed in a medium in which it was not designed to operate, and can be accounted for through the removal of the offending material from the near field region.

[0215] In addition to this, a second more common form of loss may be amplified through the placement of the RF transceiver circuit in the body. The ratio of these capacitive and inductive values can be measured as a common figure of merit for high frequency electrical systems: the characteristic impedance. In the body, the characteristic impedance of the antenna differs from the nominal value of 50ohms in air. An impedance mismatch between the antenna and the RF front end of the BLE transceiver designed to operate with 50ohms may be formed, losing energy to reflections from the antenna and reducing the amount of energy available to radiate. This can be mitigated by the inclusion of impedance matching circuitry between the front end of the transceiver and the antenna, which is a common step in the design of radio communication systems. This step alone will not fundamentally change the resonant frequency of the antenna, so energy losses within the antenna may still occur.

[0216] In-vivo RSSI tests in the 915 MHz band for de-risking

[0217] For the purpose of de-risking the 2.4GHz BLE solution, the inventors evaluated communication fidelity in the 915MHz band by conducting an in-vivo RSSI test on the identical animal with a 915MHz rigid PCB. As shown in FIG. 19, the rigid PCB that was fabricated during the last reporting period was enclosed inside a 3D-printed capsule prototype. The air gap around the antenna was about 1 mm. This capsule prototype was designed to have a small form factor of 9.5 x 22 x 13 mm3, so that the device could be placed inside the stomach by means of endoscopy. FIG. 20 shows an endoscopic image of the 915MHz capsule device.

[0218] The measured RSSI is shown in FIG. 20. While the 915MHz transmitter was set to +14 dBm, the RSSI was -72.4 dBm on average with a 3.0-dBm deviation. It shows successful communication between ingestible and external devices.

[0219] Designed and fabricated MVP PCB ver. 1

[0220] The inventors designed, fabricated, and assembled a capsule PCB prototype with the main goal of handing off a manufacturable design to Triple Ring (CDMO) to help support the externally manufactured prototypes for eventual human administration. This device differed from prior capsule prototype designs in several key ways: (1) expanded manufacturing tolerances, (2) drug chamber and disassembly electrode coupling strategies, and (3) antenna placement informed by airgap studies. The net effect of these differences was a device that matched gastric retention constraints and supported both active disassembly and drug chamber integration. The design of the MVP PCB is shown in FIG. 21 A-FIG. 21C and the photo of the fabricated / assembled device is shown in FIG.

[0221] 22.

[0222] (1) Manufacturing tolerances and strategy:

[0223] The PCB made use of flexible Printed Circuit (FPC) technology like other prototype designs. The team relaxed tolerances for the MVP device from 2.4-mil trace and spacing to 4-mil, which allowed for the use of external manufacturing services at the cost of a reduction in the number of drug chambers. Companion PCBs for gold dissolution integration were also included. The PCBs were then fitted into 3D-printed capsule enclosures and sealed with superglue.

[0224] (2) Electrode coupling strategy:

[0225] The MVP device supported electromechanical connection to gold dissolution electrodes. This was accomplished through the use of small form factor mezzanine connectors, which is a notably different strategy to that of prior designs which relied on direct integration of the electrodes with the capsule PCB. This facilitated the reuse of the main capsule PCB, at a cost to the volume budget of the electrical subsystem. This was acceptable as the overall solution was still within the bounds of FDA-approved ingestibles as well as retention structure dimensions.

[0226] (3) Antenna placement

[0227] The antenna was placed between the batteries and the drug chambers. This volume of free space, originally allocated for a 5th button cell battery, would have been otherwise unused and was a natural solution to airgap positioning within the device. It should be noted that there was close proximity (about 2 mm) to electrically grounded objects in this location which was suboptimal.

[0228] Electronics integrated with retention mechanisms

[0229] In the prior section was presented the realized iRES (formerly named MVP) PCB with a 3D printed case for electrical testing without retention. Since then, the inventors have brought the iRES PCB to maturity and successfully showed communication with the device through thoracic tissue. Ten in-vivo experiments were performed with this system and are detailed in FIG. 23. FIG. 23 includes in-vivo communication signal strength data. Tx and Rx power measurement units are [dBm], that is decibels relative to 1 milliwatt. FIG. 24 is photographs of device images associated with FIG. 23. All iRES device experiments resulted in acceptable communication performance. These tests were performed with the device placed endoscopically through the esophagus without an incision to the stomach. This creates the most realistic test scenario for this device: without a direct path through air to the receiver as is the case through a laparoscopic placement. The worst possible conditions using the iRES design had a 14dB signal strength margin before the -97dBm sensitivity of this device. Precursor device experiments are included in the table for completeness and ease of comparison.

[0230] To compare these communication results against the inventors’ past experiments where the devices were too large to be placed endoscopically, the inventors tested laparoscopic placement as in the inventors’ previous experiments with the same devices. This showed negligible change in communication fidelity (shown in FIG. 23), and the inventors conclude that laparoscopic and endoscopic placement are equivalent from an experimental design perspective.

[0231] Following validation that the inventors could communicate with the iRES PCB device in-vivo, they then integrated it with retention mechanisms. An air gap of 0.5mm was included in the design to ensure good communication, which was shown to work best. An initial long term retention study was started with this prototype iRES device, but communication was lost shortly after placement. After an analysis of the device postretrieval, the inventors found it had completely drained the batteries. This was diagnosed a firmware fault causing the device to draw high current when in a default implementation of an error-handler state, which has since been resolved. The device now automatically resets preventing this continuous high current draw. This event does provide insight as to when one should consider these batteries dead, and the inventors have selected 1.8V to be their operating limit (1.5x the dead voltage observed).

[0232] EXAMPLE 2

[0233] In this example, the inventors propose an air-gap-based antenna solution to stabilize the wireless communication of an ingestible system. By surrounding an antenna with a small air gap, the antenna may be isolated from the dynamic GI environment (e.g., FIG. 25), helping the antenna resonate at the target frequency regardless of the GI environment. The air gap may stabilize the antenna gain to its own value, therefore, compensate for the high path loss that comes from the high carrier frequency, facilitating stable wireless communication at 2.4 GHz of which short wavelength allows to miniaturize the antenna form factor.

[0234] AIR-GAP-BASED ANTENNA SOLUTION

[0235] A. Air Gap to Mitigate Antenna Detuning

[0236] For an ingestible device, omnidirectional antennas may be used because it randomly rotates inside the GI tract. FIG. 26Ashows one of omnidirectional antennas, 2450AT18A100E from Johanson Technology Inc., which is a chip-type monopole antenna and has a miniaturized form factor of 3.2* 1.6* 1.3 mm3. As shown in FIG. 26B, monopole antennas are designed to have its conductor net length (Lantenna) be approximately one quarter of the wavelength at the target carrier frequency as described in Equation 5, so that the antenna can resonate at the target carrier frequency ( / c) over the air.

[0237] ^antenna ~ ^-c / (Equation 5)

[0238] However, as described in Equation 6 and Table 5, this wavelength (Ac) shortens as the dielectric permittivity of the environment becomes higher (er>1) than the air (er=1). In this situation, the antenna no longer resonates at the carrier frequency, which results in lower antenna gain than it is designed for. (Equation 6)

[0239] Table 5. Parameters in Equation 6

[0240] To evaluate how the antenna detunes with the ingestible device, the inventors performed an in vitro test with pH 2 simulated gastric fluid (SGF) by using a vector network analyzer (VNA, Keysight E8362B). The resonant frequency (fr) could be found at the frequency showing the return loss (Sn) less than -10 dB, which means high energy conversion ratio into radiated power. Fig. 4(a) shows that the antenna resonated at 2.4 GHz over the air. However, in FIG. 27B, submerged into the SGF of which dielectric permittivity is 70-80 times higher than that of the air, the peak resonant frequency shifted from 2.4 GHz to 0.4 GHz.

[0241] One solution to mitigate this antenna detuning is adopting a wideband antenna that resonates between 0.4 GHz - 2.4 GHz. However, within a small ingestible form factor, it has many challenges to design such antenna without compromising other performance such as gain or directivity.

[0242] In this example, the inventors propose the encapsulation of an antenna with thin layers of air. In this structure, by having these consistent air gaps around the antenna, the dynamic influence of the GI environment that changes over time and place can be reduced, and the characteristic of the antenna designed to resonate at 2.4 GHz over the air can be preserved. In addition, since the antenna resonated at only 2.4 GHz and didn’t need to cover lower frequency ranges, which may have required relatively larger physical structures to resonate with longer wavelengths, the proposed solution has merits in the miniaturization of the antenna form factor.

[0243] To evaluate this solution, 3D-printed cases (liquid photopolymer, er=3.16 at 1 MHz) were designed to enclose an antenna and the PCB with thin layers of air above and below equally (FIG. 28A). The width of the fabricated cases was 11 mm with 0.5-mm thickness, and three different thicknesses of the air gaps, 0.5 mm, 1.0 mm, and 1.5 mm, were evaluated to explore their effectiveness.

[0244] B. In Vitro and In Vivo Evaluation Results

[0245] FIG. 28B shows the in vitro measurement setup in which each antenna PCB in the 3D- printed case was placed over the air or inside the SGF, and then the antenna fr was measured using the VNA. As shown in the top of FIG. 29, the fr of all samples over the air remained around 2.4 GHz. When the air-gap antenna was submerged inside the SGF, however, the fr of the sample with a 0.5-mm air gap shifted to 2.02 GHz - 2.16 GHz, and its Sn at 2.4 GHz increased to about -1.5 dB, which is much higher than -10 dB and not desirable to be used in 2.4-GHz RF communication. When testing 1-mm and 1.5-mm air gaps fr slightly shifted to around 2.35 GHz, but still resonated at 2.4 GHz with the Sn of - 11.2 dB and -10.1 dB respectively. To summarize, a l~2-mm air gap is sufficient to mitigate the antenna detuning and preferable due to its small size for this antenna PCB. FIG. 28C shows the 3D-printed capsule we designed to demonstrate the air-gap antenna performance in the ingestible device. The capsule had a 10-mm diameter and a 16.5-mm height, and the antenna PCB was placed inside the capsule with a 2-mm air gap created on top of the chip antenna. After sealing, the capsule was deployed in the stomach of a 98-kg anesthetized Yorkshire pig. Then, the antenna fr was measured when the capsule was placed out of fluid, fully submerged inside the gastric fluid (GF), and near the GI tissues by deflating the stomach. The antenna that was tuned to 2.45 GHz ~ 2.6 GHz over the air outside the stomach kept resonated at the same frequencies without antenna detuning regardless of the location of the capsule inside the stomach. On the other hand, the fr of another antenna PCB that was tuned to 2.37 GHz - 2.52 GHz without an air gap was detuned to 1.78 GHz - 1.9 GHz inside the GF and around 2 GHz near the tissues. It indicates that the 2-mm air gap helped the antenna resonate at the same frequencies and stabilized the antenna gain.

[0246] Received signal strengths (RSSs) were measured with the capsule antennas to analyze how the air-gap antenna contributed to the stable wireless communication of an ingestible device. Two BLE transceivers (Nordic Semiconductor, nRF52832) were used in the in vitro and in vivo tests (FIG. 30A-FIG. 30B) to evaluate the RSSs at 2.48 GHz that both capsule antennas with and without the air gap resonated over the air. While an external BLE transmitted +4-dBm output power through a 12-dBi gain antenna (TE Connectivity Laird, MD23-12) as a TX, another BLE was connected to the capsule antenna and recorded the RSSs as an RX from the ingestible device side. The TX and RX antennas were in the line of sight with a 30-cm distance in the in vitro test (FIG. 30A ). In the in vivo test, the RX antenna (the capsule antenna) was deployed in a location of the stomach and the TX antenna was right on top of the swine (FIG. 3 OB). Since the location of the antenna inside the stomach can be hardly controlled, the line of site between TX and RX antennas could not be guaranteed, therefore highest RSS was recorded while moving the external antenna around the swine.

[0247] Table 6 shows the RSSs of the capsule antennas. In the in vitro test over the air, both capsule antennas resulted in similar RSSs of -18 dBm and -20 dBm without and with air gap respectively, which indicates that the air gap and the enclosure have negligible impacts on the antenna gain. When the capsule antenna without an air gap was submerged in the SGF, the RSS severely decreased to -63 dBm due to antenna detuning and gain degradation. However, with the 2-mm air-gap antenna, the RSS decreased only to -51 dBm. The proposed 2-mm air gap antenna solution achieved 12 dB higher RSS than the antenna without any air gap. Likewise, in the in vivo test, both capsule antennas that were out of fluids showed similar RSSs of -95 ~ -96 dBm. When the capsule was inside the GF and near the tissues of the stomach, the RSSs were below -100 dBm without an air gap, however, by applying the air gap RSSs improved to -84 ~ -81 dBm. To summarize, the air-gap solution helped to stabilize the antenna gain and improve the RSSs by 12 dB or more.

[0248] Table 6. Received Signal Strengths (RSSs) in the In Vitro and In Vivo Tests

[0249] While satisfying miniaturized implementation within the capsule form factor, the airgap solution facilitated the TX output power to decrease by 12 dB, for example from +4 dBm to -8 dBm, and in the case of nRF52832 it reduced the BLE TX power consumption by 41.3%. This reduced power consumption helps to increase the device lifetime inside the GI tract and to make the ingestible system safer by decreasing the energy absorbed by tissues. Instead of lowering the output power, the gain of the proposed air-gap solution can be used to compensate for the high path loss at 2.4 GHz. It facilitates stable wireless communication at 2.4 GHz, and users to easily access their ingestible devices using mobile devices with BLE.

[0250] EXAMPLE 3

[0251] Energy-Efficient Lightweight Security Protocol In typical wireless communication, the transmitted / received information may be vulnerable to being eavesdropped on by nearby devices other than the intended recipient. Under a more adverse scenario, another device can inject its data into the shared messages, making the two devices think they are communicating securely with one another (man-in-the-middle attack). In wireless communications, in some cases, interception of data may be inevitable. Hence, mutual authentication is generally desirable between an external device and an ingestible device to prevent over-the-air messages from being understood or controlled by unknown devices.

[0252] An energy-efficient mutual authentication protocol was implemented based on a symmetric challenge-response protocol to protect our ingestible system from wireless security attacks. In one example, protocol was implemented on the ARM Cortex-M4 microcontroller of the Bluetooth Low Energy (BLE) chip (Nordic Semiconductor, nRF52832). The protocol is elaborated in FIG. 32. Here the ingestible device and the external device have already agreed upon a common pre-shared key, and the mutual authentication is done by proofing its possession.

[0253] In more detail, FIG. 32 shows (i) The authentication is initiated by the ingestible device sending a cryptographically secure 64-bit random number RA to the external device as a challenge. Generally, the RA may be non-repeatable, (ii) On the externaldevice end, the device generates another independent cryptographically secure 62-bit random number RB. Upon receiving RA, the external device concatenates RA, RB, and the 2 -bit user’s command (cmd). The concatenation of RA, RB, and cmd, in this specific order, is denoted by RA||RB||cmd and is 128 bits in length (64 + 62 + 2 bits). Finally, the external device encrypts this concatenated value with the pre-shared key to generate a 128-bit Ci and shares it back to the ingestible device.

[0254] (iii) The ingestible device, upon receiving Ci, decrypts it and verifies its correctness by comparing the most significant 64 bits of the decrypted data with RA. If Ci was corrupted during transmission, the above matching would fail with extremely high probability; hence, any data corruption would be detected. In the case of mismatch of RA, the authentication fails, and the ingestible device closes BLE connection to reduce unnecessary energy consumption. In this example, only the party possessing the key can successfully perform the correct encryption / decry ption. Hence, receiving the correct encrypted value indicates that the other party communicating possesses the same key. (iv) Conversely, if RA is verified, the ingestible device authenticates the external device and performs the received command, such as therapeutic release. Then, the ingestible device re-sends a message C2 made by encrypting RB, RA, and its response (ack) (in this order). Again, the external device decrypts this message and checks its validity by verifying whether RB is received correctly.

[0255] The principal idea of the protocol is that every execution involves random numbers (RA and RB) generated by each party. So, no two sets of messages exchanged between both parties are the same (thus, preventing any replay attack).

[0256] To summarize, only three times of data transmission is necessary for mutual authentication and data exchange of command (cmd) and corresponding response (ack), thus making it practical for low-power implementation.

[0257] A. Energy-Efficient Cryptographic Implementation

[0258] The implementation described generally uses Advanced Encryption Standard (AES). AES is a symmetric encryption algorithm that was selected in 2001 by the National Institute of Standards and Technology (NIST). However, in recent years, lightweight ciphers have grown in popularity because of their low area / power / latency requirements. Hence, a Speck cipher was used in this Example. Speck is generally a family of lightweight block ciphers publicly released by the National Security Agency (NSA). The rationale for choosing Speck is that it is optimized for performance in software implementations. Based on the embedded implementation on the ARM Cortex- M4 microcontroller (Table I), Speck required more than 6* less energy for encryption and 18x less energy for decryption as compared to AES with the same 128-bit security level.

[0259] Table I. Performance Comparison between Embedded Implementations of AES and Speck

[0260] B. Generation of Cryptographically Secure Random Numbers

[0261] In order to effectively generate cryptographically secure-random numbers, the existing implementation of the Speck cipher was used as a Pseudo-Random Number Generator (PRNG). It generates pseudo-random numbers by encrypting a counting variable (counter). The value of the counter increases by one whenever the BLE radio is newly connected and requires a new random number.

[0262] In conclusion, the energy-efficient security protocol prevents eavesdropping from unauthorized devices. To prolong the lifetime of the ingestible device, the protocol is implemented in low energy by applying a lightweight cipher, Speck, and a base protocol of symmetric challenge-response without compromising the security level. The security protocol enables stable and secure wireless communication at 2.4 GHz that allows authorized users to access their own ingestible devices by using their mobile devices with BLE.

[0263] EXAMPLE 4

[0264] This example demonstrates the (1) choice of wireless communication method; 2) implementation of a duty-cycling-based low-power communication system and its energy estimation; 3) analysis of the energy budget by considering capsule form factor and battery solutions.

[0265] Wireless communication methods. To be applied to ingestible electronics, wireless communication should generally be possible through across 10 cm of tissue by considering the distance between the ingestible device and the external transceiver while minimizing the power consumption. Its transceiver and devices may be small enough to be implemented in a 000 capsule with the form factor of ~9.9 mm X 26 mm (or form factor consistent with FDA-approved ingestible electronics like a video capsule endoscope). It may be tolerant to misalignment in consideration of the free movement of the capsule inside the stomach. It is important to minimize the number of external devices for user convenience.

[0266] By considering these requirements, wireless communication sources were evaluated that have been used for implantable systems and have device dimensions smaller than a 000 capsule to guide our solution for the ingestible electronic device. First, magnetic fields and infrared sources may present some field challenges for this application since they generally require strict alignments of fields or a narrow beam. Importantly, large 1 xl x0.5 inch rare earth magnets are often carried by service men / women. Therefore, this may represent a potential alternative for actuation / triggering. Ultrasound may overcome the alignment requirements through animal tests in pigs, but it generally requires the user to carry external devices including a transducer. As such, efforts focused on radio-frequency (RF) communication. And within RF communication it is important to note that 433-MHz carrier frequency (a commonly used frequency for device communication), the user would potentially need to carry an external transceiver operating at 433 MHz (if they don’t carry one already) in addition to a mobile phone as standard mobile phones generally do not provide 433-MHz band communication. On the other hand, Bluetooth Low Energy (BLE) uses a 2.4 GHz ISM band, and it can directly communicate with a mobile phone system that users already carry. Also, BLE systems have a smaller antenna than 433-MHz antennas given their shorter wavelength. Therefore, BLE was chosen for our ingestible electronics system.

[0267] FIG. 33 shows a comparison between wireless communication sources that are applicable to implantable electronics.

[0268] Implementation of duty-cycled BLE system. As described above, RF communication using BLE reduces the burden of carrying external devices by enabling direct communication between the mobile phone and ingestible electronics and alleviates the requirements on strict alignment between devices, maximizing user convenience. Its antenna size is generlaly smaller than those of sub-GHz transceivers thanks to shorter wavelength and chip-type commercial antennas can be as small as 3.2 mm x 1.6 mm. The use of a small antenna makes it possible to implement BLE transceiver inside a 000 capsule.

[0269] Its high carrier frequency of 2.4 GHz requires the circuit speed to be higher, which leads to high power consumption. For instance, an exemplary BLE device named nRF52832 from Nordic Semiconductor consumes a 5.3 mA peak current in TX mode with 0 dBm output power and 5.4 mA peak current in RX mode. To be more specific, the current consumption during advertising mode with 20-msecond interval already reaches 359 uA on average, which leads to 1.11 mW by considering 3.1 V supply voltage (e.g., from two silver oxide batteries in series connection). In this case, the energy consumption for 60 days is estimated to be about 5769 J, and this is over 9 times higher than the capsule energy budget (625 J).

[0270] To reduce the energy consumption, two different strategies were implemented: (1) wake-up approach and (2) duty-cycling approach. For the wake-up approach, the wake-up receiver works as a wireless switch that turns on the BLE transceiver. This approach reduced the overall power consumption since a power-hungry circuit of commercial BLE can be almost always turned off while the low-power wake-up receiver is on to receive communication request. Since the wake-up receiver is mostly turned on, it is generally important to reduce its power consumption. To implement a low-power wake-up receiver with off-the-shelf solutions, other communication sources with lower carrier frequency and higher channel gain compared to RF signal such as ultrasound may be used. The duty-cycling approach was added to the BLE system to make it meet the low-energy requirement for ingestible electronics. Here the capsule BLE is duty-cycled and advertises itself periodically for the possible scanning event from mobiles to enable the BLE connection. Mobile’s scanning may last long enough to be aligned with the capsules advertisements, and this increases the latency involved in establishing a communication link. With a lower duty ratio, the overall energy of the ingestible electronics generally decreases as a function of longer latency, without wishing to be bound by such theory.

[0271] FIG. 34 shows the overall block diagram of an exemplary system, including the mobile and ingestible electronics. The BLE component has an internal module called the Real-Time Counter (RTC), and this module can use the system clock to generate timing events every 60s while only consuming 2 uA. These low-frequency timing events were used to control the BLE radio activity and briefly enable advertising once per RTC period, which is known as “duty cycling.”

[0272] In exemplary BLE design, the capsule BLE works as a server that stores data internally, and mobile BLE works as a client that can access data inside a capsule remotely. At the same time, the mobile BLE works as a central device (called initiator after BLE connection) which scans for Bluetooth devices to connect. The capsule BLE works as a peripheral device (called responder after BLE connection) which can be scanned by the mobile BLE.

[0273] As shown in FIG. 35, the capsule BLE advertises itself by sending 5 continuous advertising packets over 1 second as a peripheral and repeats advertisement every 60 second. Mobile BLE performs on-demand scanning according to the user input to mobile application as a Central. Once two events of advertising and scanning are aligned together, two BLE devices can be connected and perform data communication to receive a command from the mobile and to receive a corresponding response from the capsule.

[0274] As described above, by increasing the duty cycling period (Tadv -event), the on- average power of radio operation decreases, and the system power consumption is further reduced. 60 seconds was chosen as Tadv_event for the design, but other duty cycles are also possible.

[0275] Security enhancement in BLE communication using mutual authentication.

[0276] In BLE communication, information is generally shared over the air, and it can be seen by nearby devices other than the intended recipient (passive eavesdropping). Furthermore, an attacking device can inject its own data before passing the message along, making the two devices think they are communicating securely with each other (man-in-the-middle attack or active eavesdropping). In wireless communications, interception of data may be inevitable. Hence, mutual authentication is useful between the mobile and the capsules BLEs to prevent over-the-air messages from being understood or controlled by unknown devices.

[0277] To protect the system from eavesdropping, an energy-efficient mutual authentication protocol based on a symmetric challenge-response protocol. The protocol was implemented on the ARM Cortex-M4 microcontroller of the BLE chip. Her,e capsule and mobile have the pre-shared key and authentication is done by proofing the possession of this secret key. To be specific, unilateral authentication was used as follows:

[0278] Capsule -> Mobile : rA(challenge)

[0279] Capsule <- Mobile : EK(rA) (response)

[0280] Capsule-. DK(EK(rA)) (proofing)

[0281] The capsule sends a random number (r^) to the mobile as a challenge. Then, mobile encrypts rAusing the pre-shared key and encryption algorithm. It then sends the key back to the capsule as a response. If the mobile used the pre-shared key and the same encryption algorithm that the capsule is using, then the capsule will get rAas a result of decryption that is paired with the encryption algorithm. In other words, if the decryption result matches rA, it means the mobile is the authenticated device that has a pre-shared key, and the capsule allows the mobile to request commands. (Only the party possessing the key can successfully perform the correct encryption / decryption. Hence, receiving the correct encrypted value indicates that the other party communicating possesses the same key.)

[0282] This authentication process generally prevents replay attacks. Since the capsule uses a new rAwhenever there is a new BLE connection, its response for authentication also changes. Therefore, even if an attacker captures the previous response and replays it next time, it does not authenticate the attacker. In some cases, a 128-bit secret key was used, which leads to 128-bit secret level, and it will take the order of 2128trials to break the system with a brute-force attack based on trial-and-error to guess the pre-shared key (without wishing to be bound by theory). As such, the capsule BLE with 60-second duty cycling allows only 86,400 (< 217) times of trials for 60 days of operation time, and this is a relatively short-term period to be broken by brute-force attack. The exemplary system implemented mutual authentication for both capsule and the mobile, and authentication works right after two devices are connected. As shown in FIG. 36, the capsule starts the BLE communication by sending a rAto mobile. Mobile encrypts rAbut including its self-generated random number rBfor the capsule’s authentication and user command with the pre-shared key and sends it back to the capsule. Then the capsule decrypts the message and proofs if rAis correct. In the case of incorrect rA, capsule unauthorizes mobile and finishes BLE connection to reduce unnecessary energy consumption. On the other hand, if rAis correct, the capsule authenticates mobile and performs the received command such as drug release. The capsule re-sends a message made by encrypting rB, rA, and its response (ack). Again, mobile decrypts this message and check if the authorized capsule got the command by proofing if rBis correct and check ack. The principal idea of the protocol is that every execution of the protocol involves random numbers generated by each party. So, no two sets of messages exchanged between both parties are the same (thus, preventing replayattack). To sum up, only three times of data sending or receiving is necessary for mutual authentication as well as data exchange of command (cmd) and corresponding response (ack) and it is helpful for low-power implementation.

[0283] Analysis on energy consumption of ingestible electronics.

[0284] As described above, the capsule BLE is currently designed to advertise itself every 60 seconds. BLE communication can also be requested from during this advertising time. To characterize the system’s energy consumption, it was assumed that the capsule BLE will communicate every 60 seconds (although other time periods are also possible). It represents the worst-case scenario when there is a continuous adversarial attack for energy-draining, which leads to 86,400 times of communication for 60 days even though authorized mobile will ask connection for tens of times just to request for drug release, status assessment and capsule disassembly at last. BLE output power was also maximized to +4 dBm to evaluate the highest energy consumption. 3.1 V was supplied to the ingestible electronics from two silver oxide batteries in series, for energy measurement. The evaluation board named nRF52-DK includes nRF52832, the target BLE IC, and it was used to prototype the capsule BLE and to characterize energy consumption. Table II. shows the energy measurement results and the estimated energy level of capsule BLE for 60-day operation. According to our measurements, the capsule BLE consumed 3 uA during standby mode, 150 uA during each advertisement period, and 300 uA for 1 cycle of BLE connection, communication, data processing, and authentication. The estimated energy levels for a 60-day operation can be calculated by using the equation below. The current capsule BLE is expected to consume 209 J in total as shown in Table II.

[0285] E60d=lavg x 3.1

[0286] Current Duration On-average Energy for

[0287] Mode ( ) (TON) current (Iavg) 60 days

[0288] Standby 3 uA Steady 3 uA 48 J

[0289] Radio

[0290] 150 uA 1 sec / 60 sec 2.5 uA 40 J

[0291] (advertising)

[0292] Radio

[0293] (connection,

[0294] 300 uA 1.5 sec / 60 sec 7.5 uA* 121 J communication, processing)

[0295] Total - 209 J

[0296] Table II. Energy consumption of current capsule BLE. (* The power for random number generation has not been calculated.)

[0297] To achieve this energy level, the following low-power solutions were used. First, a switching DC / DC converter that is designed inside the BLE chip instead of using LDO to increase power conversion efficiency. Second, a preliminary mobile app was designed that allows the user to enter commands in advance before BLE connection and this mobile app can automatically respond to the capsule BLE after connection. This reduces radio operation time and corresponding energy consumption for both BLE devices. Third, SPECK was used which is a lightweight block cypher for energy-efficient implementation.

[0298] The required clock cycles for encryption and decryption for both cyphers were measured then converted each clock-cycle number into energy consumption by using the following equation, where the term “3.1 V x 51.6 uA / MHz x faock” presents the processing power of the core processor while reading from RAM.

[0299] Energy = 3.1 V X 51.6

[0300] = 160 pj / cycle X Nclock Cycle

[0301] As shown in Table IV, we could see that SPECK required more than 6 times less energy for encryption and 18 times less energy for decryption when compared to AES with the same security level of 128 bit. Therefore, we selected SPECK for our energyefficient mutual authentication protocol.

[0302] Clock Cycle Number Energy Consumption [J]

[0303] Cypher AES-128 SPECK-128 AES-128 SPECK-128

[0304] Encryption 8866 1334 1.418u 0.213u

[0305] Decryption 29745 1574 4.758u 0.252u

[0306] Table IV. Clock cycle and energy consumption comparison between two block cyphers, AES and SPECK with 128-bit security level.

[0307] Analysis on capsule energy budget.

[0308] To secure more battery capacity, coin-type batteries inside a 000 capsule may be stacked, such that the diameter of batteries is shorter than the diameter of a 000 capsule, or 9.9 mm.

[0309] Various batteries of which size is comparable to a 000 capsule to find the battery solution as shown in Table V. Lithium battery provides high energy density, but it is less suitable to be used for the capsule design since the diameter of the lithium battery with the shortest diameter (10 mm) is longer than that of the capsule (9.9 mm). Second, the diameter of an alkaline battery (7.9 mm) can be shorter than that of the size of a 000 capsule (9.9 mm), but it has lower energy density. On the other hand, silver oxide batteries providing shorter diameter of 6.8 mm is appropriate for capsule design and provides high energy density of 1.66 J / mm3. Also, these are recognized as safer from a toxicity perspective as compared across four different batteries in Table V. Therefore, silver oxide batteries were used.

[0310] However, silver oxide batteries may have a low dischargeable current which is limited to 40 uA to guarantee its full battery capacity. When connecting two silver oxide batteries in parallel, the maximum dischargeable current increases to 80 uA. In this case, the use of lithium-ion batteries together with silver oxide batteries may provide higher current and the current limit of lithium-ion battery is 6 times higher than that of silver oxide battery.

[0311] Battery Supply Supply Current Battery Energy

[0312] Form Factor

[0313] Type Voltage Limit Capacity Density

[0314] ~ 10 mm* 324 J

[0315] Lithium 3 V - 1.65 J / mm3

[0316] X 2.5 mm (30 mAh)

[0317] ~ 7.9 mm* 243 J

[0318] Alkaline 1.5 V - 1.38 J / mm3

[0319] X 3.6 mm (45 mAh)

[0320] Silver ~ 6.8 mm 156 J

[0321] 1.55 V 40 uA 1.66 J / mm3oxide X 2.6 mm (28 mAh)

[0322] Lithium- ~ 6.8 mm 250 uA 59.4 J

[0323] 3 V 0.78 J / mm3ion x 2.1 mm (50 % capacity) (5.5 mAh)

[0324] Table V. Comparison between various batteries of which sizes are comparable to

[0325] 000 capsule form factor (~9.9 mm X 26 mm). (*considering lithium battery and alkaline battery with minimum lengths)

[0326] As shown in FIG. 37, 2 pairs of silver oxide batteries may be used in parallel to generate 3.1 V for electronics supplies with 625 J of energy. Alongside this, in case the drug release circuitry or the capsule decomposition circuitry requires a high current over 80 uA, which is a dischargeable current from a silver oxide battery without degrading the battery lifetime, a separate 3-V lithium-ion battery may be used together with silver oxide batteries. In this orientation, it can provide 655 J of energy for the entire 60-day operation. As previously described in Table IV, the capsule electronics design is expected to consume 333 J, within the energy budget of 625-655 J. Secure user interface

[0327] By using the preliminary mobile app, the user can request a BLE connection and send a command to an ingestible electronics (capsule BLE) via security-enhanced BLE communication described above.

[0328] Two BLEs are working as follows: once the user pushes one of the LED buttons in the mobile application, the mobile BLE starts scanning the capsule’s advertising events. After two BLEs are connected, the capsule BLE starts data communication by sending a random number to the mobile BLE as a challenge for the mobile’s authentication. Then the mobile sends back the encrypted response, including the command based on the LED button the user pressed before the BLE connection. If the mobile is proven to be an authenticated device by the capsule BLE, then the capsule BLE turns on one of the LEDs upon the user command. As shown in FIG. 38, it was demonstrated that a mobile device with the correct key successfully controlled the capsule BLE by making it turn on the LED1, while the mobile with the incorrect key failed to control capsule BLE. Random number generators have not been implemented yet from both the mobile and the capsule side. But we successfully showed that our preliminary mobile application controlled the capsule system through security-enhanced BLE communication.

[0329] Implementation of a random number generator for the authentication protocol

[0330] As described above, a capsule was designed with an energy-efficient mutual authentication protocol based on symmetric challenge-response protocol. Both the capsule and mobile devices have the pre-shared key (k), and authentication is done by proofing the possession of this secret key.

[0331] Capsule -> Mobile : rA(challenge)

[0332] Capsule <- Mobile : EK(rA) (response) (proofing) On the assumption that rAis chosen by a random process only the device with the pre-shared key can generate a correct response for each challenge to be authenticated. However, if rAis not a random number, an adversary can intercept the correct response from the mobile, re-transmit it to the capsule device, and it can be authenticated when the capsule is transmitting the same rAagain, which is called a replay attack. Therefore, it is important for the capsule device to have rAas a random number to mitigate this type of attack, and a random number generator was implemented.

[0333] Two different random number generators were considered: 1) a true random number generator (TRNG) and 2) a pseudo-random number generator (PRNG). The first generator is supported by the BLE-MCU (nRF52832) and produces true random numbers using internal thermal noise. It consumes approximately ~ 1.488 nJ to generate an 8-byte (64-bit) random number as shown in the equation below.

[0334] ETRNG = VsuppiylrRNG tTRNG = 3.1 V x 0.5 mA x 120 nsec / byte X 8 bytes

[0335] = 1.488 nJ

[0336] Over the course of 60 days and attempting to authenticate at every opportunity when the capsule BLE is on once every minute, this results in the total energy consumption of ~0.129 J (Please refer to Table 1.3.1). Alternatively, PRNG can be another solution to generate random numbers, one based on the encryption algorithm. PRNG generates pseudo-random numbers by encrypting a counting variable (N). The value of this counting variable (N) increases by one whenever the BLE radio is newly connected and requires a new random number as a challenge, as shown in FIG. 39.

[0337] When implementing a PRNG, a large enough size of the counting variable may be used to prevent its overflow so the PRNG will not generate the same sequence of pseudo-random numbers that have already been used. As with TRNG, the user can attempt to be authenticated once every minute over the 60-day operation time, which corresponds to 86,400 authentication attempts. Therefore, the PRNG could generate up to 86,400 random numbers in the worst-case scenario. In this design, the variable (N) has a size of 64 bits and can increase up to 264, which is higher than 86,400. Therefore, the counting variable (N) will not overflow. The same sequence of counting numbers and pseudo-random number sequences will not be generated, making the wireless communication system secure against replay attacks. It is important to note that, in some embodiments, only the device with a pre-shared key and the same encryption algorithm can generate the correct response against the challenge generated from this PRNG for the authentication.

[0338] Using PRNG the overhead of resources such as memory may also be minimized by re-using the Speck encryption algorithm implemented for the authentication protocol. PRNG consumes —0.213 / ij to generate each random number (64 bit) and a total of 0.018 J total over 60 days. This energy level is lower than the energy consumed by the TRNG as shown in Table VI. Therefore, we implemented a mutual authentication protocol that works with the PRNG to generate rAfor mobile authentication.

[0339] Table VI. Energy comparison between the two random number generators

[0340] Random number Energy for single generation Energy for 60 days generator (ERNG, single) (ERNG,60CI=86,400 X ERNG:Singie)

[0341] TRNG -1.488 mJ -0.129 J

[0342] PRNG -0.213 mJ -0.018 J

[0343] Overall energy consumption of the capsule BLE remains the same, even including the PRNG energy consumption, as shown in Table VII. The random number generator may work in a mobile device to generate a random number rBfor capsule authentication. Independently, a time-out function that the capsule BLE can automatically end the BLE connection after a given period may be used. This function may advantageously save energy in case of no response or long response delay from the mobile BLE.

[0344] Table VII. Energy consumption of the capsule BLE, including the PRNG

[0345] Current Duration On-average Energy for

[0346] Mode

[0347] (ION) (TON) current ( / ) 60 days (E60d)

[0348] Standby 3 uA Steady 3 uA 48 J Radio

[0349] 150 uA 1 sec / 60 sec 2.5 uA 40 J

[0350] (advertising)

[0351] Radio

[0352] (connection, 300 uA 1.5 sec / 60 sec 7.5 uA 121 J communication, processing)

[0353] Total - 209 J

[0354] Characterization of received signal strength

[0355] The received signal strength was also characterized. Before doing so, the output power of the BLE transmitter was measured, the antenna spec was designed, and the initial target antenna was chosen, which is used for the link analysis. The resonant frequencies of the antenna was measured and the received signal strengths were characterized by performing in-vitro and in-vivo experiments.

[0356] 1) BLE output power and signal characteristics

[0357] To measure the BLE output signal, a spectrum analyzer (Key sight N9020A) was directly connected to the evaluation board of the target BLE chip (Nordic Semiconductor nRF52-DK), as shown in FIG. 40. FIG. 41 A shows the output spectrum of a single BLE channel (channel 37 in this case). As defined in the BLE specification, the output was measured to be GFSK-modulated and showed two peaks in two different frequencies with a 500-kHz difference to transmit binary data information. As shown in FIG. 4 IB, the entire 40 channels of BLE from 2.402 GHz to 2.48 GHz were observed. Specifically, BLE is using 3 of these channels (channel #37 at 2.402 GHz, channel #38 at 2.426 GHz, and channel #39 at 2.48 GHz) for general advertisement, and another 37 channels (channel #0 ~ #36) are available for use during connected communication. One of the 37 channels is chosen by adaptive frequency hopping to avoid any collisions with other BLE or WiFi devices using the same 2.4-GHz ISM band. Therefore, the antenna and the received signal strengths were characterized over the overall channel bandwidth from 2.402 GHz to 2.48 GHz, which will be described in the next section. Characterization of battery lifetime

[0358] As described above, the lifetime of a silver-oxide battery generally degrades when draining currents higher than its specified dischargeable current limit of ~50 uA. However, the BLE drains high peak current over 1 mA during its radio operation, so it can shorten the battery lifetime. Therefore, the battery lifetime was measured when draining the batteries from simulated BLE current loads. The same battery configuration of the ingestible system was used with four silver oxide batteries with 56-mAh capacity. As shown in FIG. 42, the standby current was increased by 3.3 times and radio-mode current by 2 times, respectively, compared to the ingestible BLE. This increased the stress level applied to the batteries, which helped consider worse conditions than our actual BLE. Also, it shortened the testing time from 6 months to 2 months, enabling battery characterization as shown in Table VIII.

[0359] Table VIII. Comparison of the supply current and battery lifetime between actual BLE and simulated BLE.

[0360] Actual BLE Simulated BLE Multiplication Factor

[0361] Mode

[0362] Ideal lifetime of the

[0363] 4308 hours 1292 hours

[0364] 56-mAh batteries 3.3

[0365] (179.5 days) (53.8 days)

[0366] (56 mAh / Iavg

[0367] Table IX shows the battery characterization results. As the on-average current of the simulated BLE was 43.3 uA, the 56-mAh batteries were expected to survive for 53.8 days without any degradation. However, the test was terminated due to an unexpected malfunction of the recorder on the 46thday of testing, at which point the batteries were still charged and operating normally. If we assume that the batteries ran out on the 46thdate, the battery degradation factor is 16.4% ( 1 —x100%). Table IX. Test results of the battery lifetime.

[0368] Measured lifetime

[0369] Ideal lifetime of Degradation Factor of

[0370] 56-mAh batteries . (C1“Tmeasbatt / Tldeaibatt) x

[0371] 56-mAh batteries

[0372] (Tideal batt) 100%) meas_batt)

[0373] 53.8 days 45 days

[0374] 16.4%

[0375] (1292 hours) (1080 hours)

[0376] As shown in Table X, the same degradation factor was applied to the energy budget of the ingestible system (625 J), and the estimated energy budget was 522 J. As stated in the previous report, our ingestible system is expected to consume 333 J for the 60-day operation of all Tasks 3, 4, and 5, and this is 63.8% of the estimated energy budget. This result validates that the ingestible system has enough energy for at least a 60-day operation even with the high peak current from the BLE operation.

[0377] Table X. Comparison between the estimated energy budget and the energy consumption of the ingestible system for 60 days.

[0378] Ideal energy Estimated energy budget Energy consumption of budget (Eest-batt= Eideal-batt:x (1 - the ingestible system fiideal_batt) 16.4%)

[0379] 625 J 522 J 333 J (63.8%

[0380] EXAMPLE 5

[0381] Custom wake-up receiver.

[0382] A custom wake-up receiver(Rx) ASIC was designed. The TSMC 65-nm CMOS process was used with the options of mixed-signal / RF and low-power (TSMC-65 MS / RF LP). The capsule BLE system with this wake-up Rx is shown in FIG. 43. When the user wants to trigger a drug release or read status from the capsule, the user can send a wake-up pattern (RWUP) by using an external BLE device through its advertising packet. If the sent RWUP has a high correlation with the pattern that the wake-up Rx already has, the wake-up Rx generates a wake-up signal (WU) and enables the commercial BLE-MCU, waking it from sleep-mode. Subsequently, the commercial BLE-MCU has direct access to the BLE physical layer and conducts BLE protocol operations normally. In this system, the commercial BLE stays in sleep mode until the custom Rx captures an advertisement packet, which keeps average theoretical system power draw below luA DC.

[0383] It is important to note that the RWUP may be updated by the external device during the connection session as shown in FIG. 43. This advantageously prevents user device impersonation and hardens system security against wake-up signal replay attacks. It should be noted that MCU code handles authentication, so if a successful wake up command is received but authentication fails, RWUP will not change. This means the final step for securing against wake-up circuit power drain attacks is to rate-limit the wake-up interface. The MCU may control this aspect with built-in hardware timer peripherals, in some cases.

[0384] (1) Strategies for low-power implementation

[0385] Only the wake-up Rx is active until RWUP is captured. Therefore, the sleep energy of the capsule electronics mostly that of the wake-up Rx. To design a highly performant system, the following four strategies were applied. First, the wake-up Rx is designed with a supply voltage of 0.7 V which is lower than the nominal supply voltage of the fabrication process (1.2 V) to reduce power consumption. Second, a low-power local oscillator was implimented by using a Flim Bulk Acoustic-Wave Resonator (FBAR). FBARs have a high quality factor (Q-factor), which enables generation of a stable carrier frequency of 2.48 GHz without the need of phase-locked loops (PLL). The FBAR die is provided by Broadcom and has the advantage of a small surface area of around 0.6 X 0.8 mm2, and can be stacked on top of the wake-up Rx die while not requiring additional area on the miniaturized capsule PCB. The FBAR die was measured using an on-die probe and a vector network analyzer, made a lumped-circuit model and showed the FBAR impedance based on the circuit model well matches the measured FBAR impedance. This lumped-circuit model for our low-power FBAR oscillator circuit design (FIGs. 14A-14C).

[0386] Third, the symbol rate of the wake-up data transmission was decreased for both low power and high sensitivity implementation. The mobile BLE device has a nominal BLE data rate of 1 Mbps. By making the BLE repeat the same bit we can effectively decrease the symbol rate. In this design the mobile BLE device will transmit the same bit 8 times consecutively, which decreases the symbol rate from 1 Mbps to 125 kbps. This generally relaxes the speed requirements on the RF interface circuitry, reducing power consumption. Also, the Rx circuit has a narrow bandwidth, so signal to noise ratio improves dramatically without the cost of additional power.

[0387] Fourth, the energy consumption may be further reduced by duty-cycling the wake-up Rx. For example, the mobile device sends advertisements periodically with intervals of 30 msec as shown in FIG. 45. Consequently, the wake-up Rx is enabled for TRX to catch the signal. TRX can be elongated to provide resiliency to packet loss. In the case of duty cycling the wake-up Rx with a 30-sec period (Tduty), can reduce its power consumption by 1000 times compared to always-on performance. This is the selected duty cycle for the sake of RF communication performance but can be further slowed for the sake of security. The system is also capable of falling back to the validated MCU- controlled wake-up strategy if a power drain attack is detected (in the form of receiving a wake-up signal followed by an unsuccessful authentication). Wake-up control can be returned to the low power Rx as appropriate.

[0388] (2) Implementation of the wake-up Rx.

[0389] The overall architecture of the designed wake-up Rx is shown in FIG. 46. The low-noise amplifier (LNA) amplifies the 2.48-GHz RF signal received by the capsule antenna. The output of the LNA is mixed to transform the RF signal into an intermediate frequency (IF) signal around 9.73 MHz. Next, the IF amplifier (IF Amp) amplifies the IF signal so that the Frequency Shift Keying (FSK) demodulator can produce a message in the baseband. The following comparator that consists of a baseband amplifier (BB Amp) and a Schmitt Trigger feeds 10 banks of correlators with an oversampling ratio of 10 to search for the device RWUP. Schmitt triggers are binary buffers with hysteresis, so they act as a final safeguard against noise propagating through the multistage amplifier circuit. If the decoded input data matches the device RWUP, the authentication correlator subsystem exceeds its threshold and produces a wake-up signal (Wu). The 10-x oversampling accounts for baseband synchronization with the external BLE transmitter. Here it is worth noting that the required clock signals are generated from the FBAR oscillator.

[0390] FIG. 47 shows the time-domain simulation results. As shown in the last waveform (LO_+), the FBAR oscillator started to oscillate with its start-up time of 3 us. As described above, the RF signal passes through LNA, mixer, IF amplifier, FSK demodulator, and is then transformed into digital bits as shown in the output waveform of the Schmitt Trigger, or Schmitt Out tran of FIG. 47.

[0391] The wake-up Rx is designed under the following specifications. First, the target Rx sensitivity is set to be -90 dBm. According to our previous animal tests, it was found that the received signal strengths are around -70 dBm and -90 dBm between the external BLE device and the capsule BLE. In order to receive the weakest signal, the sensitivity level was targeted at -90 dBm. To achieve this low sensitivity level, the low-noise- amplifier-first architecture was chosen. The LNA in the first stage of the signal chain increases the signal level against the noise power and improves the sensitivity at the cost of higher power consumed by the LNA. From simulations, the wake-up Rx achieved the sensitivity level (PSensitivity) of -93 dBm and its sensitivity level can be calculated as below.

[0392] ^sensitivity -174 dBm + 10 log10(Bie / / ) + NFeff+ SNRrequired

[0393] • NFeff = 10 dB (simulated)

[0394] • BWeff = 0.5 MHz (simulated)

[0395] • SNRrequired = 14 dB (for BER<10“3GFSK)

[0396] Second, it was determined that the symbol rate of the wake-up pattern to be 125 kbps by considering the false alarm rate and the security level. In this system, the wakeup pattern (RWUP) is transmitted through an advertising packet of the external BLE, where the user has full control over 31 bytes (or 248 bits) of data with 1-Mbps data rate. Since it was chosen to send the wake-up pattern at 125 kbps, the external BLE will repeat the same bit 8 times, leading the maximum wake-up pattern length (LWUP) to 31 bits. It indicates 31 bits of security level which is enough for the wake-up Rx when considering the main security function of the mutual authentication during the BLE communication. On the other hand, these 31 bits of LWUP also determine the false alarm rate as 0.156 per month. It indicates that there will be unlikely a false alarm during the 2- month operation. It can be calculated that the false alarm rate can be calculated as below. Assuming that the bits are independent and random, each bit has a 50% probability of being ‘ 1 ’ or ‘O’.

[0397] 1

[0398] = (-)31x (30.25 msec X 125 kbps — 31 + 1) x 31 / 30 sec

[0399] = 0.000001805

[0400] = 0.156 alarms I month

[0401] Third, the active power of the wake-up Rx is ~1 mW. The power breakdown of the individual components is shown in FIG. 48. By applying a duty cycle with a period of 30 sec, an average power consumption of 1 uW can be achieved. Compared to the commercial BLE system it can be expected to save 74.6% of total sleep energy expended. Here it was assumed that the user may wake the system 10 times over 60-day operation time, resulting in the energy consumptions of 4.65 mJ and 13.95 mJ in BLE advertising mode and communication.

[0402] Table XI. Energy comparison between two ingestible BLE systems: (1) a system based on commercial BLE part and (2) another system including a wake-up Rx.

[0403] Commercial BLE Only With Wake-Up Rx

[0404] On-average Energy for On-average Energy for

[0405] Mode power (Pavg) 60 days (E60d) power (Pavg) 60 days (E60d)

[0406] Duty-cycling

[0407] 9.3 uW 48 J 9.3 uW 48 J clock

[0408] Radio l uW 5.1 J

[0409] (wake-up listen)

[0410] Radio 7.75 uW 40 J - 4.65 mJ* (advertising)

[0411] Radio

[0412] (connection,

[0413] 23.25 uW 121 J - 13.95 mJ* communication, processing)

[0414] Total 209 J 53.1 J

[0415] EXAMPLE 6

[0416] This example describes a demonstration of in vivo electronics, according to some embodiments.

[0417] FIGs. 49A-49C are photographs of exemplary articles to be ingested and / or implanted. Element 500 of the article is an external electrical element. FIG. 49D is a CAD drawing of the types of articles shown in FIGs. 49A-49C. FIG. 50 shows the results from an in vivo system test, showing a frequency shift in vivo, e.g., due to gastric shielding. In FIGs. 49A-49D, the article comprises a capsule with electrical elements integrated into the capsule wall (bottom side, highlighted red in CAD rendering shown in FIG. 49D), having an internal microphone and radio antenna.

[0418] While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present invention is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, and / or methods, if such features, systems, articles, materials, and / or methods are not mutually inconsistent, is included within the scope of the present invention.

[0419] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.”

[0420] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B,” when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0421] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0422] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0423] As used herein, “wt%” is an abbreviation of weight percentage. As used herein, “at%” is an abbreviation of atomic percentage.

[0424] Some embodiments may be embodied as a method, of which various examples have been described. The acts performed as part of the methods may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include different (e.g., more or less) acts than those that are described, and / or that may involve performing some acts simultaneously, even though the acts are shown as being performed sequentially in the embodiments specifically described above.

[0425] Use of ordinal terms such as “first,” “second,” “third,” etc., in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements.

[0426] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

CLAIMSWhat is claimed is:

1. An implantable electronic article for improved wireless communication fidelity, the electronic article comprising: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting, absorbing, and / or reflecting a signal from a location internal a subject to a receiver external to the subject.

2. An ingestible electronic article for improved wireless communication fidelity, the electronic article comprising: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting, absorbing, and / or reflecting a signal from a location internal the subject to a receiver external to the subject.

3. An electronic article as in any preceding claim, wherein the antenna component is configured to operate using electromagnetic force and / or acoustic waves.

4. An electronic article as in claims 1 or 2, wherein the antenna component is entirely disposed on the capsule wall.

5. An electronic article as in claims 1 or 2, wherein the capsule is sized and adapted for oral administration to a subject.

6. A method of wirelessly communicating with an electronic article at a location internal to a subject, the method comprising: sending a signal to or from an electronic article at the location internal to the subject to an electromagnetic or acoustic receiver, transmitter, or transceiver external to the subject, wherein the electronic article comprises:a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, and wherein the article tolerates signal strength degradation in excess of 15dBm with respect to performance in air, and electromagnetic receiver or transceiver has a sensitivity of at least -120dBm.

7. A method as in any preceding claim, wherein the antenna component has a lowpass cutoff frequency less than or equal to 6 GHz.

8. An article or method as in any preceding claim, wherein the wireless communication system exhibits a total received signal strength degradation in excess of 20dBm in simulated gastric fluid as compared to air.

9. An article or method as in any preceding claim, wherein the antenna component has a gain of greater than or equal to 0.1 dBi and less than or equal to 30 dBi.

10. An implantable electronic article for improved wireless communication fidelity, the electronic article comprising: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting a radiofrequency signal from a location internal a subject to a receiver external to the subject.

11. An ingestible electronic article for improved wireless communication fidelity, the electronic article comprising: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, wherein the electronic article is configured for transmitting a radiofrequency signal from a location internal the subject to a receiver external to the subject.

12. An implantable electronic article as in claim 10, wherein the interface comprises air, a dielectric material, a ferromagnetic material, and / or a material with characterized electromagnetic material properties.

13. An ingestible electronic article as in claim 11, wherein the interface comprises air, a dielectric material, a ferromagnetic material, and / or a material with characterized electromagnetic material properties.

14. An ingestible electronic article as in claim 11, wherein the article is configured to be transiently resident in the gastrointestinal tract.

15. An implantable electronic article as in claim 10, wherein the antenna component is entirely disposed on the capsule wall.

16. An ingestible electronic article as in claim 11, wherein the antenna component is entirely disposed on the capsule wall.

17. An ingestible electronic article as in claim 11, wherein the capsule is sized and adapted for oral administration to a subject.

18. A method of wirelessly communicating with a medical device at a location internal to a subject, the method comprising; sending a wireless radiofrequency signal from an electronic article at the location internal to the subject, wherein the electronic article comprises: a capsule having a capsule wall; an antenna component at least partially disposed within the capsule; and an interface disposed between the antenna component and the capsule wall, and receiving, with a receiver external to the subject, the wireless radiofrequency signal, wherein the radiofrequency signal has a carrier frequency of greater than or equal-n- to 250 MHz and less than or equal to 6 GHz and a path loss of 20dBm and above as compared to air, and wherein the receiver has a sensitivity of at least -106dBm.

19. A method as in claim 18, wherein the interface comprises air, a dielectric material, a ferromagnetic material, and / or a material with characterized electromagnetic material properties.

20. An article or method as in claim 12, 13, or 19, wherein the dielectric material comprises silicone or ceramics.

21. An article or method as in any preceding claim, wherein the interface does not substantially encapsulate the antenna component.

22. An article or method as in any preceding claim, wherein the antenna component has a passband within the range of greater than or equal to 250 MHz and less than or equal to 6 GHz.

23. An article or method as in any preceding claim, wherein the interface has an average thickness of greater than or equal to 0 mm and less than or equal to 5 mm, as measured between the surface of the antenna component and the capsule wall.

24. An article or method as in any preceding claim, wherein the antenna component is in electrical communication with a PCB, point-to-point wired equipment, a battery, a molded interconnect device, or a three-dimensionally printed circuit.

25. An article or method as in claim 24, wherein the antenna component is in electrical communication with the PCB, the point-to-point wired equipment, the molded interconnect device, or the three-dimensionally printed circuit by electrical connection, the electrical connection comprising soldering components to wiring primitives, compression fits, conductive epoxies, conductive tapes, and / or conductive adhesives.

26. An article or method as in any preceding claim, wherein the antenna component is a component of a PCB, point-to-point wired equipment, a battery, a molded interconnect device, or a three-dimensionally printed circuit.

27. An article or method as in any preceding claim, wherein, upon submersion of the capsule in a fluid, the antenna component is fluidically isolated from the fluid.

28. An article or method as in claim 27, wherein the fluid is a biological fluid, water, an acid, a base, an oil, an organic solvent, and / or an inorganic solvent.

29. An article or method as in any preceding claim, wherein the capsule is suitable for oral administration or is configured as a suppository.

30. An article or method as in any preceding claim, wherein the electronic article is configured for gastric residence.

31. An article or method as in any preceding claim, wherein the article is configured to be transiently resident in the gastrointestinal tract.

32. An article or method as in any preceding claim, wherein the antenna component exhibits a path loss of 20dBm and above in simulated gastric fluid as compared to air.

33. An article or method as in any preceding claim, wherein the capsule has a maximum swallowable dimension of less than or equal to 60 mm and greater than or equal to 20 mm.

34. An article or method as in any preceding claim, wherein the antenna component exhibits a path loss of 20dBm and above in simulated gastric fluid as compared to air.

35. An article or method as in any preceding claim, wherein the antenna component is configured to omnidirectional signaling.

36. An article or method as in any preceding claim, wherein the antenna component has a gain of greater than or equal to 0.1 dBi and less than or equal to 90 dBi.

37. An article or method as in claim 36, wherein the antenna component has a gain of greater than or equal to 0.1 dBi and less than or equal to 30 dBi.

38. An article or method as in any preceding claim, wherein the article operates with a return loss of less than or equal to 52 dBm.

39. An article or method as in any preceding claim, wherein a link margin is less than or equal to 30dBm.

40. An ingestible and / or implantable electronic article, comprising: a capsule suitable for administration to a location internal to a subject; a power source; a short-range wireless component in electrical communication with the power source; a microcontroller, wherein the microcontroller is configured to duty-cycle the short-range wireless component, wherein the ingestible electronic article is configured to send, via the short-range wireless component in electrical communication with the microcontroller, pre-shared authentication keys to a receiving device, if present, located external to the subject; and wherein operation of the microcontroller utilizes less than or equal to 1 microJoule of power for each authentication such that power source has a lifetime at the location internal to the subject of greater than or equal to 30 days.

41. An ingestible and / or implantable electronic article as claim 40, wherein the ingestible electronic article is configured for gastric residence for >24 hours.

42. An ingestible and / or implantable electronic article as in any preceding claim, wherein the short-range wireless component operates at a frequency of greater than or equal to 100 kHz and less than or equal to 3 GHz.

43. An ingestible and / or implantable electronic article as in any preceding claim, wherein the capsule is an 000 or smaller sized capsule.

44. An ingestible and / or implantable electronic article as in any preceding claim, wherein the capsule is sized and adapted for implantation in and / or ingestion by a subject.

45. An ingestible and / or implantable electronic article as in any preceding claim, wherein microcontroller is configured for Bluetooth communication.

46. An ingestible and / or implantable electronic article as in any preceding claim, wherein the microcontroller comprises a wake-up receiver configured as a wireless switch for a Bluetooth transceiver.

47. An ingestible and / or implantable electronic article as in any preceding claim, wherein the microcontroller is configured for periodic advertising for a wireless connection.

48. An ingestible and / or implantable electronic article as in any preceding claim, wherein the duty cycle is greater than or equal to 1 second and less than or equal to 180 seconds.

49. An ingestible and / or implantable electronic article as in any preceding claim, wherein the microcontroller comprises a mutual authentication protocol.

50. An ingestible and / or implantable electronic article as in any preceding claim, wherein the mutual authentication protocol comprises a symmetric challenge-response protocol.

51. An ingestible and / or implantable electronic article as in any preceding claim, wherein the mutual authentication protocol comprises a random number generator.

52. An ingestible and / or implantable electronic article as in any preceding claim, wherein the power source provides less than or equal to 5 V and greater than or equal to 1 V of voltage to the microcontroller.

53. An ingestible and / or implantable electronic article as in any preceding claim, wherein the energy consumption for a 10 day, 30 day, 60 day, or 90 day or greater operation of the article is less than or equal to 500 J.

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