WO2014096973A2 - Systèmes et procédés de détection interne d'analytes - Google Patents

Systèmes et procédés de détection interne d'analytes Download PDF

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Publication number
WO2014096973A2
WO2014096973A2 PCT/IB2013/003224 IB2013003224W WO2014096973A2 WO 2014096973 A2 WO2014096973 A2 WO 2014096973A2 IB 2013003224 W IB2013003224 W IB 2013003224W WO 2014096973 A2 WO2014096973 A2 WO 2014096973A2
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WO
WIPO (PCT)
Prior art keywords
antenna
membrane
signal
processor
unit
Prior art date
Application number
PCT/IB2013/003224
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English (en)
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WO2014096973A3 (fr
Inventor
Adi Mashiach
Original Assignee
Adi Mashiach
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Publication date
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Publication of WO2014096973A2 publication Critical patent/WO2014096973A2/fr
Publication of WO2014096973A3 publication Critical patent/WO2014096973A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0015—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system
    • A61B5/0024—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system for multiple sensor units attached to the patient, e.g. using a body or personal area network
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683—Means for maintaining contact with the body
    • A61B5/6832—Means for maintaining contact with the body using adhesives
    • A61B5/6833—Adhesive patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/686—Permanently implanted devices, e.g. pacemakers, other stimulators, biochips

Definitions

  • Embodiments of the present disclosure generally relate to devices and methods for making measurements internal to a body for transmission to a receiver external to a body.
  • Diabetes is a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes may lead to serious complications and premature death, but people with diabetes can take steps to control the disease and lower the risk of complications.
  • Glucose testing is recommended for all diabetes patients, regardless of their insulin use. Traditional glucose testing requires regular bfood drawing and testing, a procedure that many patients find painful, inconvenient, and expensive.
  • Continuous glucose monitors (CGSVI) use a sensor and transmitter attached to the body that communicates with a handheld receiver or an insulin pump. A CGM can transmit the glucose readings every five minutes. CGMs monitor the glucose level more frequently than the person himself would using a traditional meter. Many of these systems are classified as “minimally invasive", where the patient inserts a glucose sensor with a needle through the skin and leaves it there for a period of 5-7 days.
  • CGMs must be calibrated on a regular basis for accurate reading. This calibration is done by testing blood glucose with a standard meter and entering the result into the CGM receiver. Though the number of calibrations varies from one device to another, many require at least two blood tests per twenty four hour period. This type of solution does not free patients from the frequent requirement to draw and test their own blood.
  • Embodiments of the present disclosure involve a two part continuous analyte monitoring system (CAMS).
  • An external unit may include a disposable adhesive patch for attaching to the skin.
  • the patch may contain power storage elements, electronics, and an antenna.
  • the patch may be releasably or integrally connected to a reusable or disposable activation chip.
  • the activation chip may include electronics, including at least one processor, configured to send and receive signals via the antenna.
  • the external unit may further include memory for storage of patient specific parameters.
  • the second part of a CAMS may be an internal unit.
  • the internal unit may include various biological sensors, such as a glucose sensor.
  • the internal unit may also include an antenna to receive and transmit communications to the external unit.
  • the internal unit may contain electronics, including at least one processor, and a power source.
  • the internal unit as disclosed herein, is not required to have all of these components, and various embodiments are discussed below.
  • Figure 1 schematically illustrates an implant unit and external unit, according to an exemplary embodiment of the present disclosure.
  • Figure 2 schematically illustrates a system including an implant unit and an externa! unit, according to an exemplary embodiment of the present disclosure.
  • Figure 3 illustrates an exemplary equilibrium binding biological sensor.
  • Figure 4 illustrates an exemplary embodiment including a dual filter membrane.
  • Embodiments of the present disclosure relate generally to a system including an interna! unit with biological sensors for internally measuring a quantity in a body of a subject and transmitting information about that quantity to an external unit.
  • the internal unit receives substantially all of the power required for its operation from the externa! unit.
  • many of the embodiments discussed herein are described with respect to a system for monitoring blood glucose.
  • the biological sensors of the internal unit may be configured for measuring any quantity in a body of a subject.
  • the invention described herein is not limited to a blood glucose sensor, but encompasses the measurement of many different quantities, some of which are described herein.
  • FIG. 1 illustrates an implant unit and external unit, according to an exemplary embodiment of the present disclosure.
  • An implant unit 1 10 may be configured for impianiation in a subject, in a location that permits it to measure a biological quantity of a subject, such as blood glucose.
  • External unit 120 may be configured for location external to a patient, either directly contacting, or close to the skin 112 of the patient. External unit 120 may be configured to be affixed to the patient, for example, by adhering to the skin 112 of the patient, or through a band or other device configured to hold external unit 120 in place. Adherence to the skin of externa! unit 120 may occur such that it is in the vicinity of the location of implant unit 110.
  • the suitability of placement locations may be determined by
  • External unit 120 may further be configured to be affixed to an alternative location proximate to the patient.
  • the external unit may be configured to fixedly or removably adhere to a strap or a band that may be configured to wrap around a part of a patient's body.
  • the external unit may be configured to remain in a desired location external to the patient's body without adhering to that location.
  • the external unit 120 may include a housing.
  • the housing may include any suitable container configured for retaining components.
  • the housing may be any suitable size and/or shape and may be rigid or flexible.
  • Non-!imiting examples of housings for the externa! unit 100 include one or more of patches, buttons, or other
  • the housing may include a flexible materia! such that the external unit may be configured to conform to a desired location.
  • the external unit may include a skin patch, which, in turn, may include a flexible substrate.
  • the material of the flexible substrate may include, but is not limited to, plastic, silicone, woven natural fibers, and other suitable polymers, copolymers, and combinations thereof. Any portion of externa! unit 120 may be flexible or rigid, depending on the requirements of a particular application.
  • external unit 120 may be configured to adhere to a desired location.
  • at least one side of the housing may include an adhesive material.
  • the adhesive materia! may include a biocompatibie materia! and may ai!ow for a patient to adhere the external unit to the desired location and remove the externa! unit upon completion of use.
  • the adhesive may be configured for single or multiple uses of the external unit. Suitable adhesive materials may include, but are not limited to biocompatible glues, starches, elastomers, thermoplastics, and emulsions.
  • Figure 2 schematically illustrates a system including external unit 120 and an implant unit 1 10.
  • interna! unit 110 may be configured as a unit to be implanted into the body of a patient
  • external unit 120 may be configured to send signals to and/or receive signals from implant unit 1 10.
  • various components may be included within a housing of externa! unit 120 or otherwise associated with externa! unit 120.
  • at least one processor 144 may be associated with externa! unit 120.
  • the at least one processor 144 may be located within the housing of external unit 120.
  • the at least one processor may be configured for wired or wireless communication with the externa! unit from a location externa! to the housing.
  • the at least one processor may include any electric circuit that may be configured to perform a logic operation on at least one input variable.
  • the at least one processor may therefore include one or more integrated circuits, microchips, microcontrollers, and microprocessors, which may be all or part of a central processing unit (CPU), a digital signal processor (DSP), a field programmable gate array (FPGA), or any other circuit known to those skilled in the art that may be suitable for executing instructions or performing logic operations.
  • CPU central processing unit
  • DSP digital signal processor
  • FPGA field programmable gate array
  • Figure 2 illustrates that the external unit 120 may further be associated with a power source 140.
  • the power source may be removably coupiabie to the external unit at an exterior location relative to external unit.
  • power source 140 may be permanently or removably coupled to a location within external unit 120.
  • the power source may further include any suitable source of power configured to be in electrical communication with the processor.
  • the power source 140 may include a battery.
  • the power source may be configured to power various components within the external unit. As illustrated in Figure 2, power source 140 may be configured to provide power to the processor 144. In addition, the power source 140 may be configured to provide power to a signal source 142.
  • the signal source 142 may be in communication with the processor 144 and may include any device configured to generate a signal (e.g., a sinusoidal signal, square wave, triangle wave, microwave, radio-frequency (RF) signal, or any other type of e!ectromagnetic signal).
  • Signal source 142 may include, but is not limited to, a waveform generator that may be configured to generate alternating current (AC) signals and/or direct current (DC) signals.
  • signal source 142 may be configured to generate an AC signal for transmission to one or more other components.
  • Signal source 142 may be configured to generate a signal of any suitable frequency.
  • signal source 142 may be configured to generate a signa! having a frequency of from about 6.5 MHz to about 13.6 MHz.
  • signal source 142 may be configured to generate a signal having a frequency of from about 7.4 to about 8.8 MHz.
  • signa! source 142 may generate a signai having a frequency as low as 90 kHz or as high as 28 MHz.
  • Signai source 142 may be configured for direct or indirect electrical communication with an amplifier 146.
  • the amplifier may include any suitable device configured to amplify one or more signals generated from signai source 142.
  • Amplifier 146 may include one or more of various types of amplification devices, including, for example, transistor based devices, operational amplifiers, RF amplifiers, power amplifiers, or any other type of device that can increase the gain associated one or more aspects of a signai.
  • the amplifier may further be configured to output the amplified signals to one or more components within external unit 120.
  • the external unit may additionally include a primary antenna 150.
  • the primary antenna may be configured as part of a circuit within externa! unit 120 and may be coupled either directly or indirectly to various components in external unit 120.
  • primary antenna 150 may be configured for communication with the amplifier 146.
  • the primary antenna may include any conductive structure that may be configured to create an electromagnetic field.
  • the primary antenna may further be of any suitable size, shape, and/or configuration. The size, shape, and/or configuration may be determined by the size of the patient, the placement iocation of the implant unit, the size and/or shape of the implant unit, the amount of energy required to modulate a nerve, a location of a nerve to be modulated, the type of receiving electronics present on the implant unit, etc.
  • the primary antenna may include any suitable antenna known to those skilled in the art that may be configured to send and/or receive signals. Suitable antennas may include, but are not limited to, a long- wire antenna, a patch antenna, a helical antenna, etc.
  • primary antenna 150 may include a coil antenna.
  • a coil antenna may be made from any suitable conductive materia! and may be configured to include any suitable arrangement of conductive coils (e.g., diameter, number of coils, layout of coils, etc.).
  • a coil antenna suitable for use as primary antenna 150 may have a diameter of between about 1 cm and 10 cm, and may be circular or oval shaped. In some embodiments, a coil antenna may have a diameter between 5 cm and 7 cm, and may be oval shaped.
  • a coil antenna suitable for use as primary antenna 150 may have any number of windings, e.g. 4, 8, 12, or more.
  • a coil antenna suitable for use as primary antenna 150 may have a wire diameter between about 0.1 mm and 2 mm.
  • implant unit 110 may be configured to be implanted in a patient's body ⁇ e.g., beneath the patient's skin), implant unit 1 10 may be formed of any materials suitable for implantation into the body of a patient. In some
  • implant unit 110 may include a carrier 161 , which may include a flexible, biocompatible material and may include a rigid biocompatible material.
  • a carrier 161 may include, for example, silicone, po!yimides,
  • Implant unit 110 may further include circuitry including conductive materials, such as gold, platinum, titanium, or any other biocompatible conductive material or combination of materials. Implant unit 110 and carrier 161 may also be fabricated with a thickness suitable for implantation under a patient's skin.
  • implant unit 1 10 may include a secondary antenna 152 mounted onto or integrated with carrier 161. Similar to the primary antenna, the secondary antenna may include any suitable antenna known to those skilled in the art that may be configured to send and/or receive signals.
  • the secondary antenna may include any suitable size, shape, and/or configuration. The size, shape and/or configuration may be determined by the size of the patient, the placement location of the implant unit, the amount of energy required to modulate the nerve, etc. Suitable antennas may include, but are not limited to, a long-wire antenna, a patch antenna, a helical antenna, etc.
  • secondary antenna 152 may include a coil antenna having a circular shape or oval shape.
  • a coil antenna may be made from any suitable conductive material and may be configured to include any suitable arrangement of conductive coils (e.g., diameter, number of coils, layout of coils, etc.).
  • Implant unit 110 may additionally include one or more biological sensors 158a, 158b, discussed in greater detail below.
  • the sensors may include any suitable shape and/or orientation for measuring a quantity of the body, for example, an analyte concentration, on the implant unit.
  • sensors 158a and 158b may be implanted into the body of a subject in a location suitable for measuring a quantity of the body.
  • a biological sensor for use in a glucose monitoring application may utilize equilibrium binding as a means of measurement.
  • Equilibrium binding methods rely on reversible bonding between molecules based on the concentration of an analyte. Such methods may not require reagents. Because reagents may not be required, there may be no consumables, and an implant device may last significantly longer. Furthermore, because there may be no reagent to be consumed, it may not be necessary to frequently recalibrate to the new level of reagent. Thus, an equilibrium binding measurement sensor may require less frequent calibration.
  • Biological sensor 158a may include a dual membrane (discussed in greater detail with below and with respect to Fig. 4 ⁇ including a first membrane 410 and a second membrane 420 bias separating a portion of the sensor 158a containing a glucose bonding substance 503 from surrounding tissue containing glucose molecules 505..
  • the openings in membrane 410 may be sized to permit the passage of glucose molecules 505 and the openings in membrane 420 are sized larger than the openings in membrane 410 to permit the free flow of glucose molecules 505.
  • glucose bonding molecules 504 are too large to pass through membrane 420.
  • glucose bonding molecules 504 of glucose bonding substance 503 may bind to the glucose, in portions determined by the concentration of glucose outside the membrane. As glucose bonding molecules 504 bind to the glucose, those molecules no longer interact with the remaining portion of glucose bonding substance 503. As glucose bonding molecules 504 are removed from interaction with glucose bonding substance 503, properties of glucose bonding substance 503 may be altered. These changes in properties may then be detected by a detecting portion 502 of sensor 158a located inside in contact with glucose bonding substance 503. Greater or lesser concentrations of glucose external to membrane 410 may be reflected in the measurements of sensor 502.
  • glucose bonding substance 503 may include a hydrogel, such as a dextran hydroge!
  • glucose bonding molecules 504 may include molecules that may bind or link with both glucose and the hydrogel, depending on their respective
  • a giucose bonding molecule 504 may include concavalin A.
  • membranes 410 and 420 may be used to encapsulate the entirety of implant unit 110, of which biological sensors 158a and 158b are only a portion.
  • biological sensors 158a and 158b may each include an additional membrane, with hole sizes appropriate for an anaiyte to be detected.
  • membrane 410 may encapsulate an the entirety of implant unit 110 while membrane 420 is provided to permit fluid access to the interior of biological sensors 158a and 158b.
  • First and second membrane 410 and 420 are discussed in greater detail with respect to Figure 4,
  • Alternative equilibrium binding sensors may also be suitable for use with implant unit 1 10.
  • replacement glucose bonding substance 503 in the sensor described above with a different anaiyte bonding substance and different anaiyte bonding molecules may yield a sensor efficacious for detecting other analytes.
  • Equilibrium binding sensors utilizing wholly different aspects of operation may also be utilized with implant unit 110.
  • implant unit 110 includes a dual filter membrane encapsulation.
  • a dual filter membrane may include a first semi-permeable membrane and a second semi-permeable membrane 420, As illustrated in Figure 4, second membrane 420 may encapsulate at least a portion of implant unit 110. Sn turn, at least a portion second membrane 420 may be encapsulated by first membrane 410.
  • Second membrane 420 may be structurally rigid to provide mechanical strength to implant unit 110, and may include a porous surface to permit the entrance of bodily fluids containing analytes or other quantifies to be measured. Second membrane 420 may be surrounded by first membrane 410, which may include a porous surface to permit the entrance of fluids.
  • first membrane 410 may include holes sized appropriately for an quantify to be measured.
  • the holes in first membrane 410 may be smaller than those of second membrane 420.
  • First membrane 410 may be made of a biomimefic material, such as hyaluronic acid, biomimetic polymer, alginate, chitosan, fibrin, and gelatin. This structure may function as follows.
  • Biomimetic materials are materials that reduce or eliminate the bodily reaction to an implanted device.
  • an implant unit 110 having a first membrane 410 made of a biomimetic material may not elicit a reaction in the body and may not be encapsulated by the body's natural defense mechanisms. This may result in an implant device whose sensors may continue to work after long periods of implantation.
  • the first membrane 410 described herein serves as an environmental barrier, while second membrane 420 provides mechanical strength.
  • the hole in second membrane 420 may be larger, so as not to create an impediment to the flow of fluids for measurement.
  • Embodiments of the present disclosure may utilize a dual filter membrane and biological sensors in various structural arrangements.
  • second membrane 420 may be integrated with the biological sensor, and utilized as the membrane containing an analyte detecting substance including analyte bonding molecules, while the remainder of implant unit 110 is encapsulated by a non- permeable material.
  • implant unit 110 and its accompanying biological sensors may be distinct from first and second membranes 410 and 420, and utilize these only for encapsulation.
  • Other arrangements of the disclosed dual filter membrane and equilibrium binding biological sensors may be realized without departing from the scope of this disclosure.
  • implant unit 110 may include one or more structural elements to facilitate implantation of implant unit 110 into the body of a patient. Such elements may include, for example, elongated arms, suture holes, polymeric surgical mesh, biological g!ue, spikes of flexible carrier protruding to anchor to the tissue, spikes of additional biocompatible material for the same purpose, etc. that facilitate alignment of implant unit 110 in a desired orientation within a patient's body and provide attachment points for securing implant unit 110 within a body.
  • Secondary antenna 152 and sensors 158a, 158b may be mounted on or integrated with carrier 181.
  • carrier 161 may be flexible.
  • Various circuit components and connecting wires may be used to connect secondary antenna with biological sensors 158a and 158b.
  • implant unit 110 may include a protective coating that encapsulates implant unit 110. in some embodiment
  • the protective coating may be made from a flexible material to enable bending along with carrier 181.
  • the encapsulation material of the protective coating may also resist humidity penetration and protect against corrosion.
  • the protective coating may include silicone, polyimides,
  • the protective coating may include a plurality of layers, including different materials or combinations of materials in different layers.
  • External unit 120 may be configured to communicate with implant unit 110, For example, in some embodiments, a primary signal may be generated on primary antenna 150, using, e.g., processor 144, signal source 142, and amplifier 146. More specifically, in one embodiment, power source 140 may be configured to provide power to one or both of the processor 144 and the signai source 142. The processor 144 may be configured to cause signal source 142 to generate a signai (e.g., an RF energy signal). Signal source 142 may be configured to output the generated signal to amplifier 148, which may amplify the signal generated by signal source 142. The amount of amplification and, therefore, the amplitude of the signai may be controlled, for example, by processor 144. The amount of gain or
  • amplification that processor 144 causes amplifier 146 to apply to the signal may depend on a variety of factors, including, but not limited to, the shape, size, and/or configuration of primary antenna 150, the size of the patient, the location of implant unit 110 in the patient, the shape, size, and/or configuration of secondary antenna 152, a degree of coupling between primary antenna 150 and secondary antenna 152 (discussed further below), a desired magnitude of electric field to be generated by biological sensors 158a, 158b, etc.
  • Amplifier 146 may output the amplified signal to primary antenna 150.
  • External unit 120 may communicate a primary signal on primary antenna to the secondary antenna 152 of implant unit 110. This communication may result from coupling between primary antenna 150 and secondary antenna 152. Such coupling of the primary antenna and the secondary antenna may include any interaction between the primary antenna and the secondary antenna that causes a signal on the secondary antenna in response to a signal applied to the primary antenna. In some embodiments, coupling between the primary and secondary antennas may include capacitive coupling, inductive coupling, radiofrequency coupling, etc. and any combinations thereof.
  • Coupling between primary antenna 150 and secondary antenna 152 may depend on the proximity of the primary antenna relative to the secondary antenna. That is, in some embodiments, an efficiency or degree of coupling between primary antenna 150 and secondary antenna 152 may depend on the proximity of the primary antenna to the secondary antenna.
  • the proximity of the primary and secondary antennas may be expressed in terms of a coaxial offset (e.g., a distance between the primary and secondary antennas when central axes of the primary and secondary antennas are co-aligned), a lateral offset (e.g., a distance between a central axis of the primary antenna and a central axis of the secondary antenna), and/or an angular offset (e.g., an angular difference between the centra!
  • a theoretical maximum efficiency of coupling may exist between primary antenna 150 and secondary antenna 152 when both the coaxial offset, the lateral offset, and the angular offset are zero. Increasing any of the coaxial offset, the lateral offset, and the angular offset may have the effect of reducing the efficiency or degree of coupling between primary antenna 150 and secondary antenna 152.
  • a secondary signal may arise on secondary antenna 152 when the primary signal is present on the primary antenna 150.
  • Such coupling may include inductive/magnetic coupling, RF coupling/transmission, capacitive coupling, or any other mechanism where a secondary signal may be generated on secondary antenna 152 in response to a primary signal generated on primary antenna 150.
  • Coupling may refer to any interaction between the primary and secondary antennas, !n addition to the coupling between primary antenna 150 and secondary antenna 152, circuit components associated with implant unit 110 may also affect the secondary signal on secondary antenna 152.
  • the secondary signal on secondary antenna 152 may refer to any and all signals and signal components present on secondary antenna 152 regardless of the source.
  • a signal on primary antenna 150 induced by a secondary signal on secondary antenna 152 may be referred to as a primary coupled signal component.
  • the primary signal may refer to any and all signals or signal components present on primary antenna 150, regardless of source, and the primary coupled signal component may refer to any signal or signal component arising on the primary antenna as a result of coupling with signals present on secondary antenna 152.
  • the primary coupled signal component may contribute to the primary signal on primary antenna 150.
  • implant unit 110 may be configured to respond to external unit 120.
  • a primary signal generated on primary coil 150 may cause a secondary signal on secondary antenna 152, which in turn, may cause one or more responses by Implant unit 110.
  • the response of implant unit 110 may include utilizing the received electrical energy to power biological sensors biological sensors 158a and 158b to perform a biological measurement.
  • Secondary antenna 152 may be arranged in electrical communication with biological sensors 158a, 158b, through biological sensor circuitry 156.
  • Biological sensor circuitry may contain appropriate electronics and circuitry for enabling biological sensors 158a, 158b to operate.
  • biological sensor circuitry 156 may include basic circuit elements such as resistors, capacitors, inductors, transistors and diodes.
  • Biological sensor circuitry 156 may also include more complex elements, such as at least one processor, and a memory element.
  • Biological sensor circuitry 156 may be configured to generate a measurement signal to be transmitted to the external unit 120 through secondary antenna 152.
  • circuitry 154 connecting secondary antenna 152 with biological sensors 158a and 158b may cause a voltage potential across biological sensor circuitry 156 in the presence of a secondary signal on secondary antenna 152.
  • an implant unit 110 may apply a voltage potential to implant biological sensor circuitry 156 in response to an AC signal received by secondary antenna 152.
  • This voltage potential may be referred to as a power providing signal as this voltage potential may provide power to biological sensor circuitry 156
  • the power providing activation signal may include any signal (e.g., voltage potential) applied to biological sensor circuitry 156 that may result in electrical activity occurring within biological sensor circuitry 156.
  • the power providing activation signal may be generated as a result of conditioning of the secondary signal by circuitry 154.
  • circuitry 170 of external unit 120 may be configured to generate an AC primary signal on primary antenna 150 that may cause an AC secondary signal on secondary antenna 152.
  • circuitry 154 in implant unit 110 may include an AC-DC converter.
  • the AC to DC converter may include any suitable converter known to those skilled in the art. For example, in some
  • the AC-DC converter may include rectification circuit components including.
  • implant unit 110 may include an AC-AC converter, or no converter, in order to provide an AC power providing activation signal at biological sensors 158a and 158b.
  • the power providing activation signal may be configured to activate biological sensors 158a and 158b. Sn some instances, the magnitude, energy density, and/or duration of the generated electric field resulting from the power providing may be sufficient to activate biological sensors 158a and 158b. In such cases, the power providing activation signal may be referred to as an activation signal. In other instances, the magnitude and/or duration of the power providing may generate an electric field that does not result in activation of biological sensors 158a and 158b. In such cases, the power providing may be referred to as a sub-activation signal.
  • an activation signal may include a moderate amplitude and moderate duration, while in other embodiments, an activation signal may include a higher amplitude and a shorter duration.
  • Various amplitudes and/or durations of power providing signals across biological circuitry 156 may result in activation signals, and whether a power providing signal rises to the level of an activation signal can depend on many factors
  • Whether a power providing constitutes a activation signal or a sub- activation signal may ultimately be controlled by processor 144 of external unit 120. For example, in certain situations, processor 144 may determine that sensor activation is appropriate. Under these conditions, processor 144 may cause signal source 144 and amplifier 148 to generate an activation signal on primary antenna 150 (i.e., a signal having a magnitude and/or duration selected such that a resulting secondary signal on secondary antenna 152 will provide at activation signal at biological circuitry 158).
  • Processor 144 may be configured to limit an amount of energy transferred from external unit 120 to implant unit 110.
  • implant unit 110 may be associated with a threshold energy limit that may take into account multiple factors associated with the patient and/or the implant.
  • Circuitry 154 of implant unit 1 10 may include components having a maximum operating voltage or power level that may contribute to a practical threshold energy limit of implant unit 110.
  • components including diodes may be included in implant unit 110 or in external unit 120 to limit power transferred from the external unit 120 to the implant unit 110.
  • Processor 144 may be configured to account for such limitations when setting the magnitude and/or duration of a primary signal to be applied to primary antenna 150.
  • processor 144 may also determine a lower power threshold based, at least in part, on an efficacy of the delivered power.
  • the lower power threshold may be computed based on a minimum amount of power that enables sensor activation (e.g., signals having power levels above the lower power threshold may constitute activation signals while signals having power levels below the lower power threshold may constitute sub-activation signals).
  • a lower power threshold may also be measured or provided in alternative ways.
  • appropriate circuitry or sensors in the implant unit 110 may measure a lower power threshold.
  • a lower power threshold may be computed or sensed by an additional external device, and subsequently
  • implant unit 110 may be constructed with circuitry 154 specifically chosen to generate signals at the sensors of at least the lower power threshold.
  • an antenna of externa! unit 120 may be adjusted to accommodate or produce a signal corresponding to a specific lower power threshold.
  • biological sensor circuitry 156 may cause the activation of biological sensors 158a and 158b.
  • a measurement signal may be transmitted back to implant unit 110.
  • a measurement signal may be included in a coupled signal on secondary antenna 152 to be received by primary antenna 150 as a primary coupled signal component.
  • a measurement signal may include information about a biological measurement performed by biological sensors 158a and 158b.
  • a measurement signal may be actively generated by components in biological circuitry 156, for example, by at least one processor.
  • a measurement signal may also be generated by altering or otherwise modifying components of the power providing signal received by biological circuitry 156.
  • the measurement signal may transmit information based on various characteristics of the signal, such as frequency, amplitude, duration, pulse length, etc.
  • a detecting portion 502 of biological sensors 158a and 158b may be configured to alter the characteristics of biological circuitry 158 based on detected concentrations of an analyte.
  • Detecting portion 502 may be mechanical in nature, and cause these characteristic changes regardless of whether a power providing activation signal has been received by implant unit 110.
  • thai signal is conditioned or altered by biological circuitry 156 and may constitute a measurement signal included in a coupled signal on secondary antenna 152.
  • the measurement signal may be determined based on a detected concentration of an analyte in the body.
  • implant unit 110 may be capable of sending a measurement signal to external unit without containing any power storage or electrically active components of its own,
  • Processor 144 may also be configured to cause appiication of sub- activation control signals to primary antenna 150.
  • Such sub-activation control signals may include an amplitude and/or duration that result in a sub-activation signal at electrodes 158a, 158b, While such sub-activation control signals may not result in sensor activation, such sub- activation control signals may enable feedback- based control of the sensor system. That is, in some embodiments, processor 144 may be configured to cause application of a sub-activation signal to primary antenna 150. This signal may induce a secondary signal on secondary antenna 152, which, in turn, induces a primary coupled signal component on primary antenna 150. These signals may be used to optimize the performance of implant unit 1 10,
  • external unit 120 may include a feedback circuit 148 (e.g., a signal analyzer or detector, etc.), which may be placed in direct or indirect communication with primary antenna 150 and processor 144, Sub-activation signals may be applied to primary antenna 150 at any desired periodicity. It should be noted that feedback may also be received upon application of activation signals to primary antenna 150, as such activation signals may also result in generation of a primary coupled signal component on primary antenna 150.
  • a feedback circuit 148 e.g., a signal analyzer or detector, etc.
  • the primary coupled signal component may be fed to processor 144 by feedback circuit 148 and may be used as a basis for determining a degree of coupling between primary antenna 150 and secondary antenna 152.
  • the degree of coupling may enable determination of the efficacy of the energy transfer between two antennas.
  • Processor 144 may also use the determined degree of coupling in regulating delivery of power to implant unit 110.
  • Processor 144 may be configured with any suitable iogic for determining how to regulate power transfer to implant unit 110 based on the determined degree of coupling.
  • Processor 144 may, for example, utilize a baseline coupling range, A baseline coupling range may encompass a maximum coupling between primary antenna 150 and secondary antenna 152, A baseline coupling range may also encompass a range that does not include a maximum coupling level between primary antenna 150 and secondary antenna 152.
  • Processor 144 may be configured to determine the baseline coupling range based on a command from a user, such as the press of a button on the patch or the press of a button on a suitable remote device. Alternatively or additionally, processor 144 may be configured to automatically determine the baseline coupling range when external unit 120 is placed such that primary antenna 150 and secondary antenna 152 are within range of each other.
  • processor 144 when processor 144 detects any degree of coupling between primary antenna 150 and secondary antenna 152, it may immediately begin tracking a baseline coupling range. Processor 144 may then determine a baseline coupling range when it detects that the only movement between primary antenna 150 and secondary antenna 152 is caused by a patient's natural movements (i.e., the patient has secured the external unit to an appropriate location on their body). Additionally, processor 144 may be configured such that it measures coupling between the primary antenna 150 and the secondary antenna 152 for a specified period of time after activation in order to determine a baseline coupling range, such as 1 minute, 5 minutes, 10 minutes, etc.
  • processor 144 may determine that secondary antenna 152 has moved with respect to primary antenna 150 (either in coaxial offset, lateral offset, or angular offset, or any combination). Such movement, for example, may be associated with a movement of the implant unit 110, and the tissue that it is associated with based on its implant location. In such situations, processor 144 may determine that adjusting the power of a power providing signal is appropriate. Processor 144 may be configured to determine a degree of coupling between primary antenna 150 and secondary antenna 152 by monitoring one or more aspects of the primary coupled signal component received through feedback circuit 148.
  • processor 144 may determine a degree of coupling between primary antenna 150 and secondary antenna 152 by monitoring a voltage level associated with the primary coupled signal component, a current level, or any other attribute that may depend on the degree of coupling between primary antenna 150 and secondary antenna 152. For example, in response to periodic sub-activation signals applied to primary antenna 150, processor 144 may determine a baseline voltage level or current level associated with the primary coupled signal component. This baseline voltage level, for example, may be associated with an initial relative location of implant unit 110 with respect to external unit 120. As the patient moves and goes about their daily business, the relative location between implant unit 110 and external unit 120 may change, thus affecting the coupling between the two,
  • processor 144 may be configured to determine, in situ, appropriate parameter values for the power providing signal that will ultimately result in sensor activation. For example, by determining the degree of coupling between primary antenna 150 and secondary antenna 152, processor 144 may be configured to select characteristics of the modulation control signal (e.g., amplitude, pulse duration, frequency, etc.) that may provide an activation signal at biological sensor circuitry 156 in proportion to or otherwise related to the determined degree of coupling. In some embodiments, processor 144 may access a lookup table or other data stored in a memory correlating modulation control signal parameter values with degree of coupling. In this way, processor 144 may adjust the applied power providing signal in response to an observed degree of coupling.
  • characteristics of the modulation control signal e.g., amplitude, pulse duration, frequency, etc.
  • processor 144 may access a lookup table or other data stored in a memory correlating modulation control signal parameter values with degree of coupling. In this way, processor 144 may adjust the applied power providing signal in response to an observed degree of coup
  • processor 144 may employ an iterative process in order to select power providing signal parameters that result in a desired response. For example, upon determining that a power providing signal should be generated, processor 144 may cause generation of an initial power providing signal based on a set of predetermined parameter values. If feedback from feedback circuit 148 indicates that biological sensors have been activated, then processor 144 may return to a monitoring mode by issuing sub-power providing signals. If, on the other hand, the feedback suggests that the intended sensor activation did not occur as a result of the intended power providing signal, processor 144 may change one or more parameter values associated with the power providing signal (e.g., the amplitude, pulse duration, etc.). [086] Where no sensor activation occurred, processor 144 may increase one or more parameters of the power providing signal periodically until the feedback indicates that sensor activation has occurred.
  • processor 144 may increase one or more parameters of the power providing signal periodically until the feedback indicates that sensor activation has occurred.
  • processor 144 may be configured to sweep over a range of parameter va!ues until sensor activation is achieved. For example, in circumstances where sensor activation is appropriate, processor 144 may use the last applied sub-power providing signal as a starting point for generation of the power providing signal.
  • the amplitude and/or pulse duration (or other parameters) associated with the signal applied to primary antenna 150 may be iteratively increased by predetermined amounts and at a predetermined rate until the feedback indicates that sensor activation has occurred.
  • processor 144 may take several different steps.
  • external unit 120 may be provided with a display unit to provide measurement information to a user.
  • External unit 120 may be provided with an alarm to alert a user to a measurement outside of certain threshoids, for example, a too-low or too-high glucose level.
  • External unit 120 may also be configured to communicate with a user's device.
  • the user's device may include a dedicated device for the display, logging, and storage of measurements, or may include a user's smartphone, tablet, laptop, PDA, etc., configured to receive data transmitted wirelessly from external unit 120.
  • the users device may, in turn, be configured to display, store, and analyze measurements received from implant unit 110 via external unit 120.
  • the user's device may be configured to continuously or periodically transmit measurement information to a patient's doctor or to a centralized database.
  • the user's device may be configured to alert emergency services or family members if the unit determines that a patient's life may be threatened by an imminent crisis condition.
  • an implant unit 110 may have biological sensors to detect creatine kinase and lactate dehydrogenase. These enzymes frequently rise in the body prior to or during a heart attack. Thus, an increase in these enzymes, when detected by implant unit 1 10, may trigger a user's device to contact emergency services.
  • external unit 120 or a users device may be configured to communicate measurement data to a user's medical device.
  • a diabetic user may wear an insulin pump.
  • Measurements from externa! unit 120 may be transmitted directly to the insu!in pump and utilized by the insulin pump to determine an appropriate amount of insulin to dispense.
  • externa! unit 120, or the user's device may determine the appropriate amount of insulin to dispense and direct the insulin pump to do so.
  • the disclosed embodiments may be used in conjunction with a method for regulating delivery of power to an impiant unit.
  • the method may include determining a degree of coupling between primary antenna 150 associated with externa! unit 120 and secondary antenna 152 associated with impiant unit 110, implanted in the body of a patient. Determining the degree of coupling may be accomplished by processor 144 located externa! to impiant unit 110 and that may be associated with external unit 120. Processor 144 may be configured to regulate delivery of power from the external unit to the implant unit based on the determined degree of coupling.
  • the degree of coupling determination may enable the processor to further determine a location of the implant unit.
  • the motion of the impiant unit may correspond to motion of the body part where the implant unit may be attached. This may be considered physiologic data received by the processor.
  • the processor may, accordingly, be configured to reguiate delivery of power from the power source to the implant unit based on the physiologic data.
  • the degree of coupling determination may enable the processor to determine information pertaining to a condition of the implant unit.
  • Such a condition may include location as we!! as information pertaining to an internal state of the implant unit.
  • the processor may, according to the condition of the implant unit, be configured to regulate delivery of power from the power source to the implant unit based on the condition data.
  • implant unit 110 may include a processor located on the impiant.
  • a processor located on implant unit 110 may perform all or some of the processes described with respect to the at least one processor associated with an externa! unit.
  • a processor associated with implant unit 110 may be configured to receive a control signal prompting the implant controller to turn on and cause a activation signal to be applied to the biological sensors for modulating a nerve.
  • Such a processor may also be configured to monitor various sensors associated with the implant unit and to transmit this information back to and external unit.
  • Power for the processor unit may be supplied by an onboard power source or received via transmissions from an external unit.
  • implant unit 110 may be self-sufficient, including its own power source and a processor configured to operate the implant unit 110 with no externa! interaction.
  • the processor of implant unit 110 could be configured to monitor conditions in the body of a subject (via one or more sensors or other means), determining when those conditions warrant modulation of a nerve, and generate a signal to the electrodes to modulate a nerve.
  • the power source could be regenerative based on movement or biological function; or the power sources could be periodically rechargeable from an external location, such as, for example, through induction.

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Abstract

La présente invention concerne des systèmes et des procédés de détection interne d'analytes. Les systèmes de détection interne d'analytes peuvent comprendre un dispositif de détection d'analytes implantable. Un dispositif de détection d'analyte implantable peut être configuré pour communiquer avec un dispositif externe, et peut comprendre des capteurs biologiques de type à liaison à l'équilibre. Les systèmes de détection interne d'analytes peuvent en outre comprendre des dispositifs externes configurés pour communiquer avec des dispositifs de détection d'analytes implantables et autres dispositifs.
PCT/IB2013/003224 2012-12-19 2013-12-19 Systèmes et procédés de détection interne d'analytes WO2014096973A2 (fr)

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US10065038B2 (en) 2013-11-19 2018-09-04 The Cleveland Clinic Foundation System and method for treating obstructive sleep apnea
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JP2021166750A (ja) * 2017-04-04 2021-10-21 エフ ホフマン−ラ ロッシュ アクチェン ゲゼルシャフト 医療用センサシステム、特に、連続グルコースモニタリングシステム
CN110446464A (zh) * 2017-04-04 2019-11-12 豪夫迈·罗氏有限公司 医学传感器系统，特别是连续葡萄糖监测系统
JP7483081B2 (ja) 2017-04-04 2024-05-14 エフ ホフマン－ラ ロッシュ アクチェン ゲゼルシャフト 医療用センサシステム、特に、連続グルコースモニタリングシステム
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US11291842B2 (en) 2019-05-02 2022-04-05 Xii Medical, Inc. Systems and methods for improving sleep disordered breathing
US11420063B2 (en) 2019-05-02 2022-08-23 Xii Medical, Inc. Systems and methods to improve sleep disordered breathing using closed-loop feedback
US11869211B2 (en) 2019-05-02 2024-01-09 Xii Medical, Inc. Systems and methods to improve sleep disordered breathing using closed-loop feedback
US11420061B2 (en) 2019-10-15 2022-08-23 Xii Medical, Inc. Biased neuromodulation lead and method of using same
US11883667B2 (en) 2019-10-15 2024-01-30 Xii Medical, Inc. Biased neuromodulation lead and method of using same
US11691010B2 (en) 2021-01-13 2023-07-04 Xii Medical, Inc. Systems and methods for improving sleep disordered breathing

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