Patent Publication Number: US-2017347952-A1

Title: Sensors for oral dosage forms

Description:
FIELD OF THE APPLICATION 
     The present invention relates generally to electronic sensors, and specifically to ingestible sensors for monitoring drug compliance. 
     BACKGROUND OF THE APPLICATION 
     Poor medication adherence is a common problem that leads to increased morbidity and death and is estimated to incur costs of approximately $100 billion per year (Osterberg L et al., “Adherence to medication,” N Engl J Med. 2005 Aug. 4; 353 ( 5) :487-97). Technological solutions to improve medication adherence have been proposed, including attaching radio frequency identification (RFID) tags and antennas to drug pills. 
     PCT Publication WO 2009/042812 to Hafezi et al. describes virtual dipole signal amplification for in-body devices, such as implantable and ingestible devices. Aspects of the in-body deployable antennas of the invention include antennas configured to go from a first configuration to a second configuration following placement in a living body, e.g., via ingestion or implantation. Embodiments of the in-body devices are configured to emit a detectable signal upon contact with a target physiological site. Also provided are methods of making and using the devices of the invention. 
     SUMMARY OF THE APPLICATION 
     In some embodiments of the present invention, a sensing apparatus is provided for use with an oral dosage form containing an oral drug. The sensing apparatus is configured emit a detectable signal upon contact with a target physiological liquid inside a body of a human subject, such as gastric acid, after the oral dosage form has been swallowed with the sensing apparatus attached thereto. The signal is detectable by a separate sensing unit, which is typically configured to be disposed external the subject&#39;s body. 
     The sensing apparatus is typically used to measure patient drug compliance, by definitely confirming that the patient has swallowed a particular oral dosage form as directed by a physician, as well as by creating a record of the precise times of drug administration. Accurate confirmation of patient drug compliance is important both for medical outcomes in individual patients, as well as for ensuring accurate results in multi-patient clinical drug trials (in which case some of the oral dosage forms may be placebos). For some applications, the emitted detectable signal is a generic signal that indicates that the oral dosage form has been swallowed (and reached a target site, such as the stomach or intestine). Alternatively, the signal may include a unique signature for a particular pill or batch of pills. 
     In some embodiments of the present invention, the sensing apparatus is shaped so as to define a surface that is attached to at least a portion of an external surface of the oral dosage form by friction. 
     In some embodiments of the present invention, the oral dosage form is a drug capsule containing the oral drug. The sensing apparatus comprises a housing, which is shaped so as to define exactly one hemispherical portion and exactly one cylindrical portion, which together define an internal surface for tight fitting to at least a portion of an external surface of the drug capsule. The sensing apparatus further comprises a sensor, which comprises: 
     first and second electrodes, which comprise first and second electrode surfaces, respectively; and 
     circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces. 
     The driving of the current between the first and the second electrode surfaces emits a detectable signal. 
     For some applications, the sensor (and the sensing apparatus) does not comprise a complete battery. Instead, the sensor derives energy from an acid (such as gastric acid) when the sensor comes in contact with the acid, such as when the sensing apparatus is disposed in the stomach upon being swallowed. Thus, contact with the acid (such as gastric acid) activates the circuitry. 
     In some embodiments of the present invention, the oral dosage form is a disk-shaped drug tablet that comprises the oral drug. The drug tablet has two major opposing surfaces connected by a cylindrical side wall. The sensing apparatus comprises a housing, which is shaped so as to define a ring for tight fitting around an external surface of the cylindrical side wall of the drug tablet. The sensing apparatus further comprises a sensor, as described above. 
     In some embodiments of the present invention, a sensing apparatus comprises a sensor, which is configured to assume compressed and expanded configurations. The sensor comprises (a) first and second electrodes, which comprise first and second electrode surfaces, respectively, and (b) circuitry, which is electrically coupled to the first and the second electrode surfaces. The sensor is: 
     configured such that when the sensor is in the compressed configuration, the first and the second electrode surfaces are disposed at a closest compressed-configuration distance from each other, 
     configured such that when the sensor is in the expanded configuration, first and second electrode surfaces are disposed at a closest expanded-configuration distance from each other, the closest expanded-configuration distance equal to between 2 and 8 times the closest compressed-configuration distance, and 
     configured to drive a current between the first and the second electrode surfaces when the sensor is in the expanded configuration. 
     The driving of the current between the first and the second electrode surfaces emits a detectable signal, such as described above. For some applications, the sensor comprises a hydrogel, which is configured to undergo expansion upon contact with a liquid (e.g., having a pH of 3 (such as gastric acid)), thereby transitioning the sensor from the compressed configuration to the expanded configuration, and increasing a closest distance between the first and the second electrode surfaces from the closest compressed-configuration distance to the closest expanded-configuration distance. For some applications, the first and the second electrodes further comprise first and second elongate support structures, respectively. 
     In some embodiments of the present invention, a method of assembling or manufacturing is provided, which comprises providing any of the sensing apparatus and oral dosage forms described herein, holding the oral dosage form (e.g., by an element of a manufacturing system, such as by a robot, or by a human hand), and attaching the sensing apparatus to the oral dosage form. 
     There is therefore provided, in accordance with an application of the present invention, apparatus including: 
     an oral drug; 
     a drug capsule containing the oral drug; and 
     a sensing apparatus, which includes:
         a housing, which is shaped so as to define exactly one hemispherical portion and exactly one cylindrical portion, which together define an internal surface tightly fitted to at least a portion of an external surface of the drug capsule; and   a sensor, which includes:
           first and second electrodes, which include first and second electrode surfaces, respectively; and   circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces.   
               

     For some applications, the at least a portion is less than the entire external surface of the drug capsule. 
     For some applications, the drug capsule includes a capsule selected from, the group consisting of: a hard-shelled capsule and a soft-shelled capsule. 
     For some applications, the at least a portion is the entire external surface of the drug capsule. 
     For some applications, the housing is a first housing, and the sensing apparatus further includes a second housing, which is sized and shaped to engage the first housing. 
     For some applications, the circuitry is attached inside the housing. For some applications, the circuitry is attached outside the housing. 
     For some applications, a shortest path between the first and the second electrode surfaces that does not pass through any elements of the apparatus is at least 4 mm. For some applications, the shortest path is no more than 20 mm. 
     For some applications, the circuitry is attached to the hemispherical portion of the housing. 
     For some applications, the first electrode surface is attached to the hemispherical portion. 
     For some applications, the second electrode surface is attached to the housing within 3 mm of a far end of the cylindrical portion from the hemispherical portion. 
     For some applications, the first electrode surface is attached to the hemispherical portion. 
     For some applications, the first electrode surface is disposed inside the housing, and the second electrode surface is disposed outside the housing. 
     For some applications, the housing includes a material having an electrical resistance of at least 100 ohms. 
     For some applications, the housing includes gelatin. For some applications, the housing is non-biodegradable. 
     For some applications, the housing is configured, when 
     submerged in a liquid having a pH of 3, to remain attached to the circuitry for at least one minute. 
     For some applications, the drug capsule is configured, when submerged in a liquid having a pH of 3, to dissolve to release the oral drug in a first amount of time, and the housing is configured, when submerged in the liquid having the pH of 3, to remain attached to the circuitry for at least a second amount of time greater than the first amount of time. 
     There is further provided, in accordance with an application of the present invention, apparatus for use with a disk-shaped drug tablet (a) having two major opposing surfaces connected by a cylindrical side wall and (b) including an oral drug, the apparatus including: 
     a housing, which is shaped so as to define a ring for tight fitting around an external surface of the cylindrical side wall of the drug tablet; and 
     a sensor, which includes:
         first and second electrodes, which include first and second electrode surfaces, respectively; and   circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces.       

     For some applications, the first and the second electrode surfaces are disposed on the ring at least 160 degrees from each other around the ring. 
     For some applications, the first and the second electrode surfaces are disposed on the ring 180 degrees from each other around the ring. 
     For some applications, the first and the second electrode surfaces are disposed on the ring at a closest distance of at least 4 mm from each other. 
     For some applications, the ring includes a hydrogel that is configured to undergo expansion upon contact with a liquid, and to increase a closest distance between the first and the second electrode surfaces upon the expansion. 
     For some applications: 
     the ring is configured, when submerged in a liquid having a pH of 3, to dissolve first at a first circumferential location around the ring, 
     the first electrode surface is disposed on the ring at a second circumferential location less than 45 degrees clockwise from the first circumferential location, and 
     the second electrode surface is disposed on the ring at a third circumferential location less than 45 degrees counterclockwise from the first circumferential location, and 
     the ring is configured to open and become straighter upon dissolving at the first circumferential location. 
     For some applications, an inner perimeter of the ring is between 3 and 15 mm, and a thickness of less than 8 mm. 
     For some applications, the ring includes a hydrogel that is configured to undergo expansion upon contact with a liquid, and to increase a closest distance between the first and the second electrode surfaces upon expansion. 
     For some applications, the apparatus further includes the disk-shaped drug tablet, and the ring is tightly fitted around the external surface of the cylindrical side wall of the drug tablet. 
     There is still further provided, in accordance with an application of the present invention, apparatus for use with an oral dosage form, the apparatus including a sensor, which is configured to assume compressed and expanded configurations, and which includes: 
     first and second electrodes, which include first and second electrode surfaces, respectively; and 
     circuitry, which is electrically coupled to the first and the second electrode surfaces, 
     wherein the sensor is:
         (i) configured such that when the sensor is in the compressed configuration, the first and the second electrode surfaces are disposed at a closest compressed-configuration distance from each other, and   (ii) configured such that when the sensor is in the expanded configuration, the first and the second electrode surfaces are disposed at a closest expanded-configuration distance from each other, the closest expanded-configuration distance equal to at least 2 times the closest compressed-configuration distance, and   (iii) configured to drive a current between the first and the second electrode surfaces when the sensor is in the expanded configuration.       

     For some applications, the closest expanded-configuration distance equals at least 3 times the closest compressed-configuration distance. 
     For some applications, the sensor is constrained when in the compressed configuration, and unconstrained when in the expanded configuration. 
     For some applications, the first and the second electrode surfaces surface have shape memories, which are configured to transition the sensor from the compressed configuration to the expanded configuration. 
     For some applications, the sensor includes a hydrogel, which is configured to undergo expansion upon contact with a liquid, thereby transitioning the sensor from the compressed configuration to the expanded configuration, and increasing a closest distance between the first and the second electrode surfaces from, the closest compressed-configuration distance to the closest expanded-configuration distance. 
     For some applications: 
     the first electrode further includes a first elongate support structure, which is coupled to the circuitry at a first-structure coupling site along the first elongate support structure, 
     the first electrode surface is (A) electrically coupled to the circuitry via the first elongate support structure, and (B) disposed at a first electrode site along the first elongate support structure, wherein, when the sensor is in the expanded configuration, the first electrode site is disposed (x) within 2 mm of an end of the first elongate support structure, measured along the first elongate support structure, and (y) at least 3 mm from the first-structure coupling site, measured along the first elongate support structure, 
     the second electrode further includes a second elongate support structure, which is coupled to the circuitry at a second-structure coupling site along the second elongate support structure, and 
     the second electrode surface is (A) electrically coupled to the circuitry via the second elongate support structure, and (B) disposed at a second electrode site along the second elongate support structure, wherein, when the sensor is in the expanded configuration, the second electrode site is disposed (x) within 2 mm of an end of the second elongate support structure, measured along the second elongate support structure, and (y) at least 3 mm from the second-structure coupling site, measured along the second elongate support structure. 
     For some applications: 
     the sensor includes a hydrogel, which is configured to undergo expansion upon contact with a liquid, thereby transitioning the sensor from the compressed configuration to the expanded configuration, and 
     the first and the second elongate support structures are arranged such that the expansion of the hydrogel increases a closest distance between the first and the second electrode surfaces from the closest compressed-configuration distance to the closest expanded-configuration distance. 
     For some applications, the first and the second elongate support structures and the circuitry are embedded in the hydrogel. For some applications, an expanded volume of the hydrogel equals at least 1.5 times a compressed volume of the hydrogel. For some applications, the hydrogel is generally spherical when the sensor is in both the compressed configuration and the expanded configuration. For some applications, the apparatus further includes the oral dosage form, which includes a drug capsule, in which the sensor is disposed. 
     For some applications, the apparatus further includes the oral dosage form. 
     There is additionally provided, in accordance with an application of the present invention, apparatus including: 
     an oral dosage form; and 
     a sensing apparatus, which includes:
         a housing, which is shaped so as to define a surface that is attached to at least a portion of an external surface of the oral dosage form by friction;   a sensor, which includes:
           first and second electrodes, which include first and second electrode surfaces, respectively; and   circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces.   
               

     There is yet additionally provided, in accordance with an application of the present invention, a method including: 
     receiving, by a human subject, (a) a drug capsule containing an oral drug and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define exactly one hemispherical portion and exactly one cylindrical portion, which together define an internal surface tightly fitted to at least a portion of an external surface of the drug capsule, and (ii) a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first, and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; and 
     swallowing, by the human subject, (a) the drug capsule and (b) the sensing apparatus while the internal surface is tightly fitted to the at least a portion of the external surface of the drug capsule. 
     For some applications, the at least a portion is less than the entire external surface of the drug capsule. For other applications, the at least a portion is the entire external surface of the drug capsule. 
     For some applications, the housing is a first housing, and the sensing apparatus further includes a second housing, which is sized and shaped to engage the first housing. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the circuitry is attached inside the housing. For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the circuitry is attached outside the housing. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while a shortest path between the first and the second electrode surfaces that does not pass through any elements of the method is at least 4 mm. 
     For some applications, the shortest path is no more than 20 mm. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the circuitry is attached to the hemispherical portion of the housing. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the first electrode surface is attached to the hemispherical portion. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the second electrode surface is attached to the housing within 3 mm of a far end of the cylindrical portion from the hemispherical portion. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the first electrode surface is attached to the hemispherical portion. 
     For some applications, receiving the drug capsule and the sensing apparatus includes receiving the drug capsule and the sensing apparatus while the first electrode surface is disposed inside the housing, and the second electrode surface is disposed outside the housing. 
     For some applications, the housing includes a material having an electrical resistance of at least 100 ohms. 
     For some applications, the housing includes gelatin. For some applications, the housing is non-biodegradable. 
     For some applications, the housing is configured, when submerged in a liquid having a pH of 3, to remain attached to the circuitry for at least one minute. 
     For some applications, the drug capsule is configured, when submerged in a liquid having a pH of 3, to dissolve to release the oral drug in a first amount of time, and the housing is configured, when submerged in the liquid having the pH of 3, to remain attached to the circuitry for at least a second amount of time greater than the first amount of time. 
     There is also provided, in accordance with an application of the present invention, a method of assembly including: 
     providing (a) a drug capsule containing an oral drug and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define exactly one hemispherical portion and exactly one cylindrical portion, which together define an internal surface for tight fitting to at least a portion of an external surface of the drug capsule, and (ii) a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; 
     holding the drug capsule; and 
     attaching the sensing apparatus to the drug capsule by tightly fitting the internal surface to the at least a portion of the external surface of the drug capsule. 
     For some applications, providing the drug capsule containing the oral drug includes filling the drug capsule with the oral drug. 
     There is further provided, in accordance with an application of the present invention, a method including: 
     receiving, by a human subject, (a) a disk-shaped drug tablet (i) having two major opposing surfaces connected by a cylindrical side wall and (ii) including an oral drug, and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define a ring tightly fitted around an external surface of the cylindrical side wall of the drug tablet, and (ii) a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; and 
     swallowing, by the human subject, (a) the disk-shaped drug tablet and (b) the sensing apparatus while the ring is tightly fitted around the external surface of the cylindrical side wall of the drug tablet. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped drug tablet and the sensing apparatus while the first and the second electrode surfaces are disposed on the ring at least 160 degrees from, each other around the ring. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped drug tablet and the sensing apparatus while the first and the second electrode surfaces are disposed on the ring 180 degrees from each other around the ring. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped drug tablet and the sensing apparatus while the first and the second electrode surfaces are disposed on the ring at a closest distance of at least 4 mm from, each other. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped, drug tablet and the sensing apparatus while the ring includes a hydrogel that is configured to undergo expansion upon contact with a liquid, and to increase a closest distance between the first and the second electrode surfaces upon the expansion. 
     For some applications: 
     the ring is configured, when submerged in a liquid having a pH of 3, to dissolve first at a first circumferential location around the ring, 
     receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped, drug tablet and the sensing apparatus while (a) the first electrode surface is disposed on the ring at a second circumferential location less than 45 degrees clockwise from the first circumferential location, and (b) the second electrode surface is disposed on the ring at a third circumferential location less than 45 degrees counterclockwise from, the first circumferential location, and 
     the ring is configured to open and become straighter upon dissolving at the first circumferential location. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped drug tablet and the sensing apparatus while an inner perimeter of the ring is between 3 and 15 mm, and a thickness of less than 8 mm. 
     For some applications, receiving the disk-shaped drug tablet and the sensing apparatus includes receiving the disk-shaped drug tablet and the sensing apparatus while the ring includes a hydrogel that is configured to undergo expansion upon contact with a liquid, and to increase a closest distance between the first and the second electrode surfaces upon expansion. 
     There is still further provided, in accordance with an application of the present invention, a method of assembly including: 
     providing (a) a disk-shaped drug tablet (i) having two major opposing surfaces connected by a cylindrical side wall and (ii) including an oral drug, and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define a ring for tight fitting around an external surface of the cylindrical side wall of the drug tablet, and (ii) a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; 
     holding the drug tablet; and 
     attaching the sensing apparatus to the disk-shaped drug tablet by tightly fitting the ring around the external surface of the cylindrical side wall of the drug tablet. 
     There is additionally provided, in accordance with an application of the present invention, a method including: 
     receiving, by a human subject, (a) an oral dosage form and (b) a sensor, which is in a compressed configuration, and which includes (i) first and second electrodes, which include first and second electrode surfaces, respectively, and (ii) circuitry, which is electrically coupled to the first and the second electrode surfaces, wherein when the sensor is in the compressed configuration, the first and the second electrode surfaces are disposed at a closest compressed-configuration distance from each other; and 
     swallowing, by the human subject, (a) the oral dosage form and (b) the sensor while the sensor is coupled to the oral dosage form, such that the sensor, upon contact with gastric acid in a stomach of the human subject, transitions from the compressed configuration to an expanded configuration, in which (i) the first and the second electrode surfaces are disposed at a closest expanded-configuration distance from each other, the closest expanded-configuration distance equal to at least 2 times the closest compressed-configuration distance, and (ii) the sensor is configured to drive a current between the first and the second electrode surfaces. 
     For some applications, the closest expanded-configuration distance equals at least 3 times the closest compressed-configuration distance. 
     For some applications: 
     receiving the oral dosage form and the sensor includes receiving the oral dosage form and the sensor while the sensor is constrained in the compressed configuration, and 
     swallowing the oral dosage form and the sensor includes swallowing the receiving the oral dosage form and the sensor such that that the sensor becomes unconstrained in the expanded configuration. 
     For some applications, the first and the second electrode surfaces surface have shape memories, which are configured to transition the sensor from the compressed configuration to the expanded configuration. 
     For some applications, the sensor includes a hydrogel, which is configured to undergo expansion upon contact with the gastric acid, thereby transitioning the sensor from the compressed configuration to the expanded configuration, and increasing a closest distance between the first and the second electrode surfaces from the closest compressed-configuration distance to the closest expanded-configuration distance. 
     For some applications: 
     the first electrode further includes a first elongate support structure, which is coupled to the circuitry at a first-structure coupling site along the first elongate support structure, 
     the first electrode surface is (A) electrically coupled to the circuitry via the first elongate support structure, and (B) disposed at a first electrode site along the first elongate support structure, wherein, when the sensor is in the expanded configuration, the first electrode site is disposed (x) within 2 mm of an end of the first elongate support structure, measured along the first elongate support structure, and (y) at least 3 mm from the first-structure coupling site, measured along the first, elongate support, structure, 
     the second electrode further includes a second elongate support structure, which is coupled to the circuitry at a second-structure coupling site along the second elongate support structure, and 
     the second electrode surface is (A) electrically coupled to the circuitry via the second elongate support structure, and (B) disposed at a second electrode site along the second elongate support structure, wherein, when the sensor is in the expanded configuration, the second electrode site is disposed (x) within 2 mm of an end of the second elongate support structure, measured along the second elongate support structure, and (y) at least 3 mm from the second-structure coupling site, measured along the second elongate support structure. 
     For some applications: 
     the sensor includes a hydrogel, which is configured to undergo expansion upon contact with the gastric acid, thereby transitioning the sensor from the compressed configuration to the expanded configuration, and 
     the first and the second elongate support structures are arranged such that the expansion of the hydrogel increases a closest distance between the first and the second electrode surfaces from the closest compressed-configuration distance to the closest expanded-configuration distance. 
     For some applications, the first and the second elongate support structures and the circuitry are embedded in the hydrogel. 
     For some applications, an expanded volume of the hydrogel equals at least 1.5 times a compressed volume of the hydrogel. 
     For some applications, the hydrogel is generally spherical when the sensor is in both the compressed configuration and the expanded configuration. 
     There is yet additionally provided, in accordance with an application of the present invention, a method of assembly including: 
     providing (a) an oral dosage form and (b) a sensor, which is in a compressed configuration, and which includes (i) first and second electrodes, which include first and second electrode surfaces, respectively, and (ii) circuitry, which is electrically coupled to the first and the second electrode surfaces, wherein when the sensor is in the compressed configuration, the first and the second electrode surfaces are disposed at a closest compressed-configuration distance from each other, wherein the sensor is configured, upon contact with gastric acid in a stomach of a human subject, to transition from the compressed configuration to an expanded configuration, in which (i) the first and the second electrode surfaces are disposed at a closest expanded-configuration distance from each other, the closest expanded-configuration distance equal to at least 2 times the closest compressed-configuration distance, and (ii) the sensor is configured to drive a current between the first and the second electrode surfaces; 
     holding the oral dosage form; and 
     coupling the sensor to the oral dosage form. 
     There is also provided, in accordance with an application of the present invention, a method including: 
     receiving, by a human subject, (a) an oral dosage form, and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define a surface that is attached to an external surface of the oral dosage form by friction, (ii) and a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; and 
     swallowing, by the human subject, (a) the oral dosage form and (b) the sensing apparatus while the surface is attached to the at least a portion of the external surface of the oral dosage form. 
     There is further provided, in accordance with an application of the present invention, a method of assembly including: 
     providing (a) an oral dosage form, and (b) a sensing apparatus, which includes (i) a housing, which is shaped so as to define a surface that is attachable to at least a portion of an external surface of the oral dosage form by friction, and (ii) a sensor, which includes (A) first and second electrodes, which include first and second electrode surfaces, respectively, and (B) circuitry, which (a) is attached to the housing, (b) is electrically coupled to the first and the second electrode surfaces, and (c) is configured to drive a current between the first and the second electrode surfaces; 
     holding the oral dosage form; and 
     attaching the sensing apparatus to the oral dosage form by friction. 
     The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A-B  are schematic illustrations of sensing apparatus and a drug capsule containing an oral drug, in accordance with an application of the present invention; 
         FIG. 2  is a bottom-view of the sensing apparatus of  FIGS. 1A-B  before attachment to the drug capsule of  FIGS. 1A-B , in accordance with an application of the present invention; 
         FIGS. 3A-B  are schematic illustrations of an alternative configuration of the sensing apparatus of  FIG. 1A-B , in accordance with an application of the present invention; 
         FIG. 4A  is a schematic illustration of another configuration of the sensing apparatus of  FIGS. 1A-B  and  2 , in accordance with an application of the present invention; 
         FIG. 4B  is a schematic illustration of yet another configuration of the sensing apparatus of  FIGS. 1A-B  and  2 , in accordance with an application of the present invention; 
         FIG. 5  is a schematic illustration of the sensing apparatus of  FIGS. 1A-B  and  2  after having been swallowed by a human subject, in accordance with an application of the present invention; 
         FIGS. 6A-B  are schematic illustrations of sensing apparatus for use with a disk-shaped drug tablet, in accordance with an application of the present invention; 
         FIG. 7  is a schematic illustration of another configuration of the sensing apparatus of  FIGS. 6A-B , in accordance with an application of the present invention; 
         FIGS. 8A-B  are schematic illustrations of yet another configuration of the sensing apparatus of  FIGS. 6A-B , in accordance with an application of the present invention; 
         FIGS. 9A-B  are schematic illustrations of still another configuration of the sensing apparatus of  FIGS. 6A-B , in accordance with an application of the present invention; and 
         FIGS. 10A-B  are schematic illustrations of another sensing apparatus for use with an oral dosage form, in accordance with an application of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF APPLICATIONS 
       FIGS. 1A-B ,  2 , and  3 A-B are schematic illustrations of sensing apparatus  20  and a drug capsule  22  containing an oral drug, in accordance with respective applications of the present invention.  FIGS. 1A and 1B  show sensing apparatus  20  before and after attachment to drug capsule  22 , respectively.  FIG. 2  is a bottom-view of sensing apparatus  20  before attachment to drug capsule  22 .  FIGS. 3A and 3B  show an alternative configuration of sensing apparatus  20  before and after attachment to drug capsule  22 , respectively. Alternatively, drug capsule  22  contains a placebo. For some applications, sensing apparatus  20  is provided (e.g., sold or distributed) with drug capsule  22 , while for other applications, sensing apparatus  20  is provided (e.g., sold or distributed) without drug capsule  22 , i.e., an apparatus may be provided that comprises sensing apparatus  20  and not drug capsule  22 . Although drug capsule  22  is illustrated as a hard-shelled capsule comprising two pieces fitted together (a cap  42  and a body  44  (i.e., the lower-diameter half)), drug capsule  22  may alternatively comprise a soft-shelled capsule (also known as a gel capsule), which typically comprises a single piece that contains the oral drug therein. Alternatively, for some applications, sensing apparatus  20  is used with an oblong drug tablet, which may be shaped like a capsule. 
     Sensing apparatus  20  is configured emit a detectable signal upon contact with a target physiological liquid inside a body of a human subject, such as gastric acid, after drug capsule  22  has been swallowed with sensing apparatus  20  attached thereto. The signal is detectable by a separate sensing unit, which is typically configured to be disposed external the subject&#39;s body, such as described hereinbelow with reference to  FIG. 5 . 
     Sensing apparatus  20  comprises a housing  30 , which is shaped so as to define exactly one hemispherical portion  34  and exactly one cylindrical portion  32 , which together define an internal surface  36  for tight fitting to at least a portion  38  of an external surface  40  of drug capsule  22 . Optionally, internal surface  36  of housing  30  is attached to the at least a portion  38  by friction. 
     For some applications, such as shown in  FIGS. 1A-B  and  5 , the at least a portion  38  of external surface  40  of drug capsule  22  is less than the entire external surface  40  of drug capsule  22 . For some applications, the at least a portion  38  of external surface  40  of drug capsule  22  comprises a cap  42  of drug capsule  22 , such as shown (and may optionally include a portion of body  44  of drug capsule  22 ). For other applications, the at least a portion  38  of external surface  40  of drug capsule  22  comprises body  44  of drug capsule  22  (and may optionally include a portion of cap  42  of drug capsule  22 ) (configuration not shown). For still other applications, cap housing  30  itself is shaped as (a) the cap of drug capsule  22 , in which case the at least a portion  38  of external surface  40  of drug capsule  22  is the portion of body  44  of drug capsule  22  that overlaps housing  30 , or (b) the body of drug capsule  22 , in which case the at least a portion  38  of external surface  40  of drag capsule  22  is the portion of cap  42  of drug capsule  22  that overlaps housing  30 . 
     For other applications, such as shown in  FIGS. 3A-B , the at least a portion  38  of external surface  40  of drug capsule  22  is the entire external surface  40  of drug capsule  22 . For some of these applications, housing  30  is a first housing  30  that comprises one piece of a two-piece capsule (either a cap (as shown) or a body (i.e., the lower-diameter half) (configuration not shown)), and sensing apparatus  20  further comprises a second housing  46 , which is sized and shaped to engage first housing  30 . For some applications, second housing  46  is shaped so as to define exactly one hemispherical portion and exactly one cylindrical portion, as shown. For some applications, first and second housings  30  and  46  together surround and contain drug capsule  22 , as shown in  FIG. 3B . 
     Sensing apparatus  20  further comprises a sensor  50 , which comprises: 
     first and second electrodes  51  and  53 , which comprise first and second electrode surfaces  52  and  54 , respectively; and 
     circuitry  56 , which (a) is attached to housing  30 , (b) is electrically coupled to first and second electrode surfaces  52  and  54 , and (c) is configured to drive a current between first and second electrode surfaces  52  and  54 . 
     First and second electrode surfaces  52  and  54  are the interface portions of first and second electrodes  51  and  53  through which current can flow from the electrodes to the environment surrounding the electrodes. 
     The driving of the current between first and second electrode surfaces  52  and  54  emits a detectable signal. For some applications, circuitry  56  is configured to generate the detectable signal as a series of pulses. For some applications, circuitry  56  is configured to intermittently short the electrodes. (Typically, first and second electrodes  51  and  53  do not function as an antenna.) 
     As used in the specification, including in the claims “electrically coupled” means electrically coupled over one or more conductive elements of the sensing apparatus, such as wires, and does not include wirelessly coupled. For some applications, sensor  50  comprises a plurality of sets of first and second electrodes  51  and  53 , and, optionally, separate circuitry  56  for each set. 
     For some applications, sensor  50  (and sensing apparatus  20 ) does not comprise a complete battery when initially coupled to drug capsule  22 , prior to being swallowed. Instead, sensor  50  derives energy from an acid (such as gastric acid) when sensor  50  comes in contact with the acid, e.g., is submerged in the acid, such as when sensing apparatus  20  is disposed in the stomach upon being swallowed. Thus, contact with the acid (such as gastric acid) activates circuitry  56 . 
     For some applications, first and second electrodes  51  and  53  are configured to function as a cathode and an anode, respectively, or vice versa, and the gastric acid functions as an electrolyte, such that the cathode, anode, and electrolyte together operate as a complete battery that generates a voltage between the electrodes, when first and second electrode surfaces  52  and  54  come in contact with the gastric acid in the stomach. First and second electrodes  51  and  53  comprise two dissimilar electrochemical materials. For example, the anode may comprise Mg+ or Ca++, and the cathode may comprise AgCl, or other suitable combinations of biocompatible, non-toxic materials as is known in the battery art. 
     For some applications, first and second electrode surfaces  52  and  54  (or the other electrode surfaces described hereinbelow in other configurations) are coated with a biocompatible coating, which is configured to dissolve when submerged in a liquid having a pH of 3 (such as gastric acid). Dissolving of the coating exposes first and second electrode surfaces  52  and  54  to the acid, which functions as an electrolyte and generates a voltage, as described above. In addition, in some configurations, such as those shown in  FIGS. 4A and 4B , the coating prevents the visible exposure of metal on an external surface of housing  30 , which may lead to corrosion of the metal and/or be unappealing to patients. 
     For some applications, housing  30  comprises gelatin. For some applications, housing  30  is non-biodegradable. For some applications, housing  30  is configured, when submerged in a liquid having a pH of 3 (such as gastric acid), to remain attached to circuitry  56  for at least one minute, and/or sufficient time for the electrodes to begin generating a voltage and sensing apparatus  20  to generate the signal, as discussed above. For some applications, drug capsule  22  is configured, when submerged in a liquid having a pH of 3, to dissolve to release the oral drug in a first amount of time, and wherein housing  30  is configured, when submerged in the liquid having the pH of 3, to remain attached to circuitry  56  (and, typically, electrically-insulating) for at least a second amount of time greater than the first amount of time, such as at least 50% greater and/or 30 seconds, e.g., one minute, longer. This greater amount of time allows for the establishment and maintenance of the shortest path between the first and the second electrode surfaces, as described hereinbelow. 
     Reference is still made to  FIGS. 1A-B ,  2 , and  3 A-B, and is additionally made to  FIG. 4A , which is a schematic illustration of another configuration of sensing apparatus  20 , in accordance with an application of the present invention. For some applications, such as shown in  1 A-B,  2 , and  3 A-B, circuitry  56  is attached inside housing  30 , while for other applications, such as shown in  FIG. 4A , circuitry  56  is attached outside housing  30 . Alternatively or additionally, for some applications, such as shown in  FIGS. 1A-B ,  2 ,  3 A-B, and  4 A, circuitry  56  is attached to hemispherical portion  34  of housing  30 . 
     For some applications, such as shown in  FIGS. 1A-B ,  2 ,  3 A-B, and  4 A, second electrode surface  54  is attached to housing  30  within 3 mm of (e.g., with 2 mm of, or within 1 mm of, such as at) a far end  58  of cylindrical portion  32  from hemispherical portion  34 . Alternatively or additionally, for some applications, such as shown in  FIGS. 1A-B ,  2 ,  3 A-B, and  4 A-B, first electrode surface  52  is attached to hemispherical portion  34 . 
     Reference is made to  FIG. 4B , which is a schematic illustration of yet another configuration of sensing apparatus  20 , in accordance with an application of the present invention. For some applications, first electrode surface  52  is disposed inside housing  30 , and second electrode surface  54  is disposed outside housing  30 . Typically, both first and second electrode surfaces  52  and  54  are attached to hemispherical portion  34  of housing  30 , such as shown. Alternatively, one or more of first and second electrode surfaces  52  and  54  are attached to cylindrical portion  32 , For some applications, housing  30  comprises a material having an electrical resistance of at least 100 ohms. 
     For some applications, a shortest path P between first and second electrode surfaces  52  and  54  that does not pass through any elements of sensing apparatus  20  is at least 4 mm (such as at least 6 mm), no more than 20 mm (such as no more than 10 mm), and/or between 4 and 20 mm (such as between 6 and 10 mm). Disposition of first and second electrode surfaces  52  and  54  at these effective distances from, each other increases the distance from which the signal generated by the circuitry  56  can be readily detected, such as by sensing unit  60 , described hereinbelow with reference to  FIG. 5 . Typically, housing  30  comprises an electrically-insulating material, which lengths shortest path P, thereby increasing the effective distance between the electrode surfaces. (For clarity of illustration, a portion of shortest path P is shown in  FIG. 4B  as not quite touching the external surface of housing  30 , although in reality this portion of shortest path P is measured on the external surface of housing  30 .) 
     Reference is now made to  FIG. 5 , which is a schematic illustration of sensing apparatus  20  after having been swallowed by a human subject while sensing apparatus  20  while internal surface  36  is tightly fitted to the at least a portion  38  of external surface  40  of drug capsule  22 , in accordance with an application of the present invention. In this application, a sensing unit  60  is provided, which comprises circuitry configured to sense the signal emitted by sensing apparatus  20 . Typically, sensing unit  60  is configured to be disposed external to the subject&#39;s body. For example, sensing unit  60  may be integrated into an article of clothing, such as a wristwatch, or provided on an adhesive patch, which may be placed on the subject&#39;s skin, e.g., on the front or back of the subject&#39;s torso, or on the subject&#39;s wrist or arm. For some applications, sensing unit  60  comprises electrodes, such as surface electrodes, e.g., EMG electrodes, as are known in the EMG art. For some applications, sensing unit  60  is configured to be coupled, either wirelessly or over wires, with a data processing unit, such as a smartphone or a wireless or wired network. 
     Reference is now made to  FIGS. 6A-B , which are schematic illustrations of sensing apparatus  120  for use with a disk-shaped drug tablet  122 , in accordance with an application of the present invention.  FIGS. 6A and 6B  show sensing apparatus  120  before and after attachment to drug tablet  122 , respectively. Drug tablet  122  has two major opposing surfaces  102 A and  102 B connected by a cylindrical side wall  104 , and comprises an oral drug. Alternatively, disk-shaped drug tablet  122  comprises a placebo. 
     Sensing apparatus  120  comprises a housing  130 , which is shaped so as to define a ring  132  for tight fitting around an external surface  134  of cylindrical side wall  104  of drug tablet  122 , The shape of ring  132  will depend on the shape of external surface  134 ; for example, ring  132  may be circular, as shown, or may have another shape, such as a regular polygon, e.g., a hexagon. For some applications, an inner perimeter of ring  132  is at least 3 mm, no more than 12 mm, and/or between 3 mm to 15 mm, such as at least 5 mm, no more than 10 mm, and/or between 5 and 10 mm, and a thickness of at least 1 mm, no more than 8 mm, and/or between 1 and 8 mm, such as at least 2 mm, no more than 5 mm, and/or between 2 and 5 mm. Optionally, ring  132  is attached to external surface  134  by friction. 
     Sensing apparatus  120  further comprises a sensor  150 , which comprises: 
     first and second electrodes  151  and  153 , which comprise first and second electrode surfaces  152  and  154 , respectively; and 
     circuitry  156 , which (a) is attached to housing  130 , (b) is electrically coupled to first and second electrode surfaces  152  and  154 , and (c) is configured to drive a current between first and second electrode surfaces  152  and  154 , as described hereinabove regarding sensing apparatus  20  with reference to  FIGS. 1A-B ,  2 , and  3 A-B. 
     The driving of the current between first and second electrode surfaces  152  and  154  emits a detectable signal, such as described hereinabove with reference to  FIGS. 1A-B ,  2 , and  3 A-B. Circuitry  156  and/or electrodes  151  and  153  may be configured as described hereinabove with reference to  FIGS. 1A-B ,  2 , and  3 A-B regarding circuitry  56  and/or electrodes  51  and  53 , mutatis mutandis. For some applications, sensor  150  comprises a plurality of sets of first and second electrodes  151  and  153 , and, optionally, separate circuitry  156  for each set. 
     Reference is made to  FIG. 7 , which is a schematic illustration of another configuration of sensing apparatus  120 , in accordance with an application of the present invention. In this configuration, first and second electrode surfaces  152  and  154  are disposed on ring  132  at angle α (alpha) of at least 160 degrees from each other around ring  132 , such as 180 degrees (as shown). For some applications, first and second electrode surfaces  152  and  154  are disposed on ring  132  at a closest distance D of at least 4 mm (e.g., at least 6 mm, such as at least 8 mm) from each other (i.e., measured across a portion of the space surrounded by ring  132 ). As described hereinabove with reference to  FIGS. 1A-5 , disposition of first and second electrode surfaces  152  and  154  at a greater distance from each other increases the distance from which the signal generated by the circuitry can be readily detected, such as by sensing unit  60 , described hereinabove with reference to  FIG. 5 . 
     Reference is now made to  FIGS. 8A-B , which are schematic illustrations of yet another configuration of sensing apparatus  120 , in accordance with an application of the present invention.  FIG. 8A  shows ring  132  in its initial configuration, in which it is attached to drug tablet  122  (for clarity of illustration, drug tablet  122  is not shown).  FIG. 8B  shows ring  132  after it has opened in the stomach, as described below. 
     In this configuration, ring  132  is configured, when submerged in a liquid having a pH of 3 (such as gastric acid), to dissolve first at a first circumferential location  170  around ring  132  (labeled in  FIGS. 8A-B , as well as in  FIG. 6A ). First electrode surface  152  is disposed on ring  132  at a second circumferential location less than 45 degrees (e.g., less than 30 degrees, such as less than 15 degrees) counterclockwise from first circumferential location  170 , and second electrode surface  154  is disposed on ring  132  at a third circumferential location less than 45 degrees (e.g., less than 30 degrees, such as less than 15 degrees) clockwise from first circumferential location  170 . For example, first circumferential location  170 , the second circumferential. location, and the third, circumferential location may be at 12 o&#39;clock, 11:55, and 12:05, respectively. As shown in  FIG. 8B , ring  132  is configured to open and become straighter upon dissolving at first circumferential location  170 , which brings first and second electrode surface  152  and  154  farther from, each other than when in the initial configuration shown in  FIG. 8A . In other words, first and second electrode surfaces  152  and  154  are disposed, at a closest initial-configuration distance D 1  from each other, as shown in  FIG. 8A , and a closest expanded-configuration distance D 2  that is greater than closest initial-configuration distance D 1 , as shown in  FIG. 8B . For some applications, closest expanded-configuration distance D 2  equals at least 5 (e.g., at least 10, or at least 20) times closest initial-configuration distance D 1 , and/or at least 12 mm and/or no more than 31 mm. 
     For some applications, ring  132  is configured to become straighter upon dissolving at first circumferential location  170 , because housing  130  and/or first and second electrodes  151  and  153  comprise a material having a shape memory (e.g., Nitinol). 
     Reference is now made to  FIGS. 9A-B , which are schematic illustrations of still another configuration of sensing apparatus  120 , in accordance with an application of the present invention.  FIGS. 8A and 8B  show ring  132  respectively in (a) an initial unexpanded configuration, in which it is attached to drug tablet  122 , and (b) an expanded configuration, in which it has become detached from drug tablet  122  (although drug tablet  122  is shown intact in the latter state, it may in practice have partially or completely dissolved by the time that ring  132  reaches the latter state). 
     In this configuration, ring  132  comprises a hydrogel  180  that is configured to undergo expansion upon contact with a liquid (e.g., having a pH of 3 (such as gastric acid)), and to increase a closest distance between first and second electrode surfaces  152  and  154  upon expansion. In other words, first and second electrode surfaces  152  and  154  are disposed at a closest initial-configuration distance from each other, as shown in  FIG. 9A , and a closest expanded-configuration distance that is greater than the closest initial-configuration distance, as shown in  FIG. 9B . For some applications, the closest expanded-configuration distance equals at least 1.5 times (e.g., 2 times) the closest initial-configuration distance. This configuration may implement any of the features described hereinabove with reference to  FIG. 7 . 
     Reference is now made to  FIGS. 10A-B , which are schematic illustrations of another sensing apparatus  220  for use with an oral dosage form  222 , in accordance with an application of the present invention. For example, oral dosage form  222  may comprise a drug capsule or a drug tablet, which, comprises a drug or a placebo. Sensing apparatus  220  comprises a sensor  250 , which is configured to assume compressed and expanded configurations, as shown in  FIGS. 10A and 10B , respectively. For some applications, sensor  250  is configured to transition from the compressed configuration to the expanded configuration upon contact with a liquid (e.g., having a pH of 3 (such as gastric acid). Sensing apparatus  220  may implement any of the techniques described hereinabove for sensing apparatus  20  and/or sensing apparatus  120 , mutatis mutandis. 
     Sensor  250  is initially coupled to oral dosage form  222  when in the compressed configuration. For example, for applications in which oral dosage form  222  comprises a drug capsule (e.g., a hard-shelled or soft-shelled capsule), sensor  250  may, for example, be disposed within the drug capsule; for applications in which oral dosage form  222  comprises a drug tablet, sensor  250  may, for example, be attached to an external surface of the drug tablet. 
     Sensor  250  comprises (a) first and second electrodes  251  and  253 , which comprise first and second electrode surfaces  252  and  254 , respectively, and (b) circuitry  256 , which is electrically coupled to first and second electrode surfaces  252  and  254 . Sensor  250  is: 
     configured such that when sensor  250  is in the compressed configuration, such as shown in  FIG. 10A , first and second electrode surfaces  252  and  254  are disposed at a closest compressed-configuration distance D 3  from each other, and 
     configured such that when sensor  250  is in the expanded configuration, first and second electrode surfaces  252  and  254  are disposed at a closest expanded-configuration distance D 4  from each other, the closest expanded-configuration distance D 4  equal to at least 2 times (e.g., at least 3 times, or at least 4 times) the closest compressed-configuration distance D 3 , no more than 8 times (e.g., no more than 5 times) the closest compressed-configuration distance D 3 , and/or between 2 and 8 times (e.g., between 3 and 5 times) the closest compressed-configuration distance D 3 , and 
     configured to drive a current between first and second electrode surfaces  252  and  254 , as described hereinabove regarding sensing apparatus  20  with reference to  FIGS. 1A-B ,  2 , and  3 A-B, when sensor  250  is in the expanded configuration, such as shown in  FIG. 10B . 
     The driving of the current between first and second electrode surfaces  252  and  254  emits a detectable signal, such as described hereinabove with reference to  FIGS. 1A-B ,  2 , and  3 A-B. Circuitry  256  and/or electrodes  251  and  253  may be configured as described hereinabove with reference to  FIGS. 1A-B ,  2 , and  3 A-B regarding circuitry  56  and/or electrodes  51  and  53 , mutatis mutandis. For some applications, sensor  250  comprises a plurality of sets of first and second electrodes  251  and  253 , as shown, and, optionally, separate circuitry  56  for each set. For example, all of first electrodes  251  may comprise anodes, and all of second electrodes  253  may comprise cathodes, or vice versa. 
     For some applications, sensor  250  is constrained when in the compressed configuration, and unconstrained when in the expanded configuration. 
     For some applications, first and second electrode surfaces  252  and  254  have shape memories, which are configured to transition sensor  250  from the compressed configuration to the expanded configuration. 
     For some applications, sensor  250  comprises a hydrogel  244 , which is configured to undergo expansion upon contact with a liquid (e.g., having a pH of 3 (such as gastric acid)), thereby transitioning sensor  250  from the compressed configuration to the expanded configuration, and increasing a closest distance between the first and the second electrode surfaces from the closest compressed-configuration distance D 3  to the closest expanded-configuration distance D 4 . 
     For some applications, first and second electrodes  251  and  253  further comprise first and second elongate support structures  262  and  264 , respectively. 
     First elongate support structure  262  is coupled to circuitry  256  at a first-structure coupling site  263  along first elongate support structure  262 . First electrode surface  252  is (A) electrically coupled to circuitry  256  via first elongate support structure  262 , and (B) disposed at a first electrode site  267  along first elongate support structure  262 ; when sensor  250  is in the expanded configuration, first electrode site  267  is disposed (x) within 2 mm of an end of first elongate support, structure  262 , measured along first elongate support structure  262 , and (y) at least 3 mm from first-structure coupling site  263 , measured along first elongate support structure  262 . For some applications, first electrode  151  comprises a partially insulated wire, an insulated portion of which serves as first elongate support structure  262 , and a non-insulated portion, of which serves as first electrode surface  252 . 
     Second elongate support structure  264  is coupled to circuitry  256  at a second-structure coupling site  265  along second elongate support structure  264 , Second electrode surface  254  is (A) electrically coupled to circuitry  256  via second elongate support structure  264 , and (B) disposed at a second electrode site  269  along second elongate support structure  264 ; when sensor  250  is in the expanded configuration, second electrode site  269  is disposed, (x) within 2 mm of an end of second elongate support structure  264 , measured along second elongate support structure  264 , and (y) at least 3 mm from second-structure coupling site  265 , measured along second elongate support structure  264 . For some applications, second electrode  153  comprises a partially insulated wire, an insulated portion of which serves as second elongate support structure  264 , and a non-insulated portion of which serves as second electrode surface  254 . 
     For some applications, sensor  250  comprises hydrogel  224 , which, as mentioned above, is configured to undergo expansion upon contact with a liquid, thereby transitioning sensor  250  from the compressed configuration to the expanded configuration. First and second elongate support structures  262  and  264  are arranged such that the expansion of hydrogel  224  increases a closest distance between the first and the second electrode surfaces from closest compressed-configuration distance D 3  to the closest expanded-configuration distance D 4 . For some applications, first and second elongate support structures  262  and  264  and circuitry  256  are embedded in hydrogel  224 . For some applications, an expanded volume of hydrogel  224  equals at least 1.5 times a compressed volume of hydrogel  224 , such as at least 3 times the compressed volume. For some applications, hydrogel  224  is generally spherical when sensor  250  is in both the compressed configuration and the expanded configuration. 
     In the applications described with reference to  FIGS. 10A-B , first and second electrodes  251  and  253  (including first and second elongate support structures  262  and  264 , if provided) are typically mechanically-passive, i.e., do not mechanically aid in the expansion of sensor  250  from the compressed configuration to the expanded configuration. 
     The detectable signal emitted by sensor  250  is detected by sensing unit  60 , such as described hereinabove with reference to  FIG. 5 , mutatis mutandis. 
     Reference is now made to  FIGS. 9A-B  and  10 A-B. In some applications of the present invention, apparatus is provided for use with an oral dosage form, the apparatus comprising a sensor, which is configured to assume compressed and expanded configurations, and which comprises (a) first and second electrodes, which comprise first and second electrode surfaces, respectively, and (b) circuitry, which is electrically coupled to the first and the second electrode surfaces. The sensor is: 
     configured such that when the sensor is in the compressed configuration, the first and the second electrode surfaces are disposed at a closest compressed-configuration distance from each other, and 
     configured such that when the sensor is in the expanded configuration, the first and the second electrode surfaces are disposed at a closest expanded-configuration distance from each other, the closest expanded-configuration distance equal to at least 2 times the closest compressed-configuration distance, and 
     configured to drive a current between the first and the second electrode surfaces when the sensor is in the expanded configuration. 
     For some applications, the oral dosage form is drug capsule, while for other applications, the oral dosage form is a drug tablet, such as a disk-shaped drug tablet or a caplet (an oval-shaped tablet in the general shape of a capsule). For some applications, the apparatus further comprises the oral dosage form. 
     For some applications, the sensor comprises a hydrogel that is configured to undergo expansion upon contact with a liquid (e.g., having a pH of 3 (such as gastric acid)), and to increase a closest distance between the first and the second electrode surfaces upon expansion. In other words, the first and the second electrode surfaces are disposed at a closest initial-configuration distance from each other, such as shown in  FIGS. 9A and 10A , and a closest expanded-configuration distance that is greater than the closest initial-configuration distance, as shown in  FIGS. 9B and 10B . For some applications, the closest expanded-configuration distance equals at least 1.5 times (e.g., 2 times) the closest initial-configuration distance. 
     For some applications, the hydrogel is provided as an element of ring  132 , described hereinabove with reference to  FIGS. 9A-B , or as an element of sensor  250 , described hereinabove with reference to  FIGS. 10A-B . Alternatively, the hydrogel is otherwise attached to the oral dosage form. For example, for applications in which the oral dosage form comprises a disk-shaped drug tablet, the hydrogel may be attached to one or both of the major surfaces of the disk-shaped drug tablet, e.g., the hydrogel itself may be disk-shaped. 
     In an application of the present invention, a sensing apparatus is provided for use with an oral dosage form containing an oral drug. The sensing apparatus comprises a piezoelectric crystal and a striking element. The striking element is initially restrained from contacting the piezoelectric crystal by a dissolvable element. The dissolvable element is configured to dissolve upon contact with a target physiological liquid inside a body of a human subject, such as gastric acid, after the oral dosage form has been swallowed with the sensing apparatus attached thereto. Upon release, the striking element strikes the piezoelectric crystal, thereby deforming the crystal. As a result of the deformation, the crystal generates a voltage pulse. The voltage pulse is detectable by a separate sensing unit, which is typically configured to be disposed external the subject&#39;s body. The energy used by the striking element to strike the crystal may be provided, for example, by a loaded spring, or by gas energy developed as a result of a local chemical reaction. This sensing apparatus may be used alone or in combination with any of the sensing apparatus described herein. 
     It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.