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WO2024233471A1 - Systèmes, procédés et supports pour la détection mobile d'un problème médical et l'actionnement sans fil d'un dispositif d'administration de médicament - Google Patents

Systèmes, procédés et supports pour la détection mobile d'un problème médical et l'actionnement sans fil d'un dispositif d'administration de médicament Download PDF

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Publication number
WO2024233471A1
WO2024233471A1 PCT/US2024/027995 US2024027995W WO2024233471A1 WO 2024233471 A1 WO2024233471 A1 WO 2024233471A1 US 2024027995 W US2024027995 W US 2024027995W WO 2024233471 A1 WO2024233471 A1 WO 2024233471A1
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Prior art keywords
physiological sensor
sensor
signal generator
drug delivery
processor
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English (en)
Inventor
Hyowon Lee
Michael Mclean
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Purdue Research Foundation
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Purdue Research Foundation
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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
    • A61B5/48—Other medical applications
    • A61B5/4845—Toxicology, e.g. by detection of alcohol, drug or toxic products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14552—Details of sensors specially adapted therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G16H20/17—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/67—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/18—General characteristics of the apparatus with alarm
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3306—Optical measuring means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/35—Communication
    • A61M2205/3507—Communication with implanted devices, e.g. external control
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/82—Internal energy supply devices
    • A61M2205/8206—Internal energy supply devices battery-operated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2209/00—Ancillary equipment
    • A61M2209/01—Remote controllers for specific apparatus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/20—Blood composition characteristics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/20—Blood composition characteristics
    • A61M2230/205—Blood composition characteristics partial oxygen pressure (P-O2)

Definitions

  • naloxone a Federal Drug Administration (FDA) approved strong opiate antagonist that counteracts the physiological effects of an opioid-induced cardiorespiratory depression event.
  • FDA Federal Drug Administration
  • Naloxone is an indispensable harm reduction tool in efforts to reduce opioid-related deaths.
  • Most commonly, naloxone has been shown to be effective when administered via nasal inhalation, intramuscular injection, or subcutaneous injection.
  • systems, methods, and media for mobile detection of a medical condition and wireless actuation of a drug delivery device are provided.
  • a system for mobile detection of a medical emergency and wireless activation of a drug delivery device comprising: a power supply; a physiological sensor; a trigger switch; a signal generator; a transmitting coil electrically coupled to the power supply via the trigger switch and the signal generator; and at least one processor that is programmed to: receive signals from the physiological sensor; determine that a triggering event has occurred based on the signals received from the physiological sensor; in response to determining that the triggering event has occurred, cause the trigger switch to provide power to the signal generator, such that power is transmitted by the transmitting coil to wirelessly activate the drug delivery device.
  • the power supply comprises at least one battery, and is configured to provide power at about 7.4 volts.
  • the physiological sensor comprises a near-infrared spectroscopy (NIRS) sensor.
  • NIRS near-infrared spectroscopy
  • the signal generator comprises a zero-voltage switching (ZVS) circuit.
  • ZVS zero-voltage switching
  • the transmitting coil comprises a pancake coil.
  • the transmitting coil comprises a polyamide-insulated copper magnetic wire.
  • the signals comprise values output by a photodetector of the physiological sensor.
  • the at least one processor is further programmed to: estimate oxyhemoglobin (WbO 2 ) and deoxyhemoglobin (HbR) based on the values. [0016] In some embodiments, the at least one processor is further programmed to: estimate a variable R that is indicative of oxygen saturation (SpO 2 ) based on the values.
  • the signals comprise oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (HbR) values output by the physiological sensor.
  • HbO 2 oxyhemoglobin
  • HbR deoxyhemoglobin
  • the signals comprise a variable R output by the physiological sensor.
  • a method for mobile detection of a medical emergency and wireless activation of a drug delivery device comprising: receiving signals from a physiological sensor; determining that a triggering event has occurred based on the signals received from the physiological sensor; in response to determining that the triggering event has occurred, causing a trigger switch to provide power to a signal generator, such that power is transmitted by a transmitting coil to wirelessly activate the drug delivery device.
  • a non- transitory computer readable medium containing computer executable instructions that, when executed by a processor, cause the processor to perform a method for mobile detection of a medical emergency and wireless activation of a drug delivery device comprising: receiving signals from a physiological sensor; determining that a triggering event has occurred based on the signals received from the physiological sensor; in response to determining that the triggering event has occurred, causing a trigger switch to provide power to a signal generator, such that power is transmitted by a transmitting coil to wirelessly activate the drug delivery device.
  • FIG. 1 shows an example of a system for mobile detection of a medical condition and wireless actuation of a drug delivery device in accordance with some embodiments of the disclosed subject matter.
  • FIGS. 2A and 2B show an example of hardware that can be used to implement a wearable device in accordance with some embodiments of the disclosed subject matter.
  • FIG. 3 shows an example of hardware that can be used to implement a light emitting diode (LED) driving circuit in accordance with some embodiments of the disclosed subject matter.
  • FIG. 4 shows an example of hardware that can be used to implement a transimpedance amplifier in accordance with some embodiments of the disclosed subject matter.
  • LED light emitting diode
  • FIG. 5 shows an example of a process for mobile detection of a medical condition and wireless actuation of a drug delivery device in accordance with some embodiments of the disclosed subject matter.
  • FIG. 6 shows an example of components implemented for a benchtop experiment to test functionality of a wearable device implemented in accordance with some embodiments of the disclosed subject matter.
  • FIG. 7 shows an example of a setup for a human experiment to test capabilities of a prototype wearable device implemented in accordance with some embodiments of the disclosed subject matter.
  • FIGS. 8A-F shows an example of components of the prototype wearable device shown in FIG. 7, and the prototype wearable device worn by two different subjects.
  • FIGS. 9A-E shows an example of a setup for a benchtop experiment to test to test functionality of the prototype wearable device shown in FIG. 7.
  • FIGS. 9F-G show results of tests with the benchtop experiment setup of FIGS. 9A- E.
  • FIG. 10 shows examples of peak-peak values of infrared and red intensity recorded during the human experiment described in connection with FIG. 7.
  • FIG. 11 shows examples of averaged R modulation index values recorded during the human experiment described in connection with FIG. 7.
  • FIG. 12 shows examples of peak-peak values of oxyhemoglobin and deoxyhemoglobin changes calculated during the human experiment described in connection with FIG. 7.
  • FIG. 13 shows a table that includes a summary of p-values for the analysis on brachial occlusion during the human experiment described in connection with FIG. 7.
  • FIG. 14 shows a table that includes a summary of p-values for the analysis on breath hold during the human experiment described in connection with FIG. 7.
  • mechanisms (which can, for example, include systems, methods, and media) for mobile detection of a medical condition and wireless actuation of a drug delivery device are provided.
  • mechanisms described herein can be used to implement a sensor capable of rapidly detecting an opioid-induced respiratory depression. Additionally, in some embodiments, mechanisms described herein can be used to implement a closed-loop system that can deliver a burst amount of naloxone in response to detection of an opiod-induced respiratory depression, serving as a tool to keep an opioid user alive until specialized medical care can be provided, especially for patients residing in rural areas and places with low availability of healthcare centers.
  • a wearable device for mobile detection of a medical condition e.g., an opioid-induced low oxygen level
  • wireless actuation of a drug delivery device can include various components, such as: (i) a near-infrared spectroscopy (NIRS) sensor, (ii) a metal-oxide semiconductor field-effect transistor (MOSFET) dual switch, and (iii) a modified zero-voltage switching (ZVS) circuit.
  • NIRS near-infrared spectroscopy
  • MOSFET metal-oxide semiconductor field-effect transistor
  • analog-digital fdters and signal data processing resources can be incorporated into a device implemented in accordance with mechanisms described herein to reduce noise induced by user movements and the most relevant sources of artifacts that worsen the signal quality of the NIRS system.
  • the device can be further miniaturized and the electronics can be further optimized, reducing the size of the device as much as possible to improve usability.
  • mechanisms described herein can be used to help mitigate the devastatingly deadly rates of opioid overdose and in other potential emergency life-threatening drug delivery applications.
  • mechanisms described herein can be used to facilitate rapid deployment of subcutaneous medication to treat other medical events, such as anaphylaxis (e.g., with low oxygenation being an indicator of severe anaphylaxis), pediatric nocturnal hypoglycemia (e.g., using a sensor(s) configured detect blood sugar levels, in addition to, or in lieu of, oxygenation).
  • anaphylaxis e.g., with low oxygenation being an indicator of severe anaphylaxis
  • pediatric nocturnal hypoglycemia e.g., using a sensor(s) configured detect blood sugar levels, in addition to, or in lieu of, oxygenation.
  • a wrist- wearable system referred to as the Q-sensor was the first wristwearable system capable of measuring physiological changes including skin electrodermal activity (EDA), skin temperature, and 3D locomotion to establish correlations with an opioid-overdose event.
  • EDA skin electrodermal activity
  • 3D locomotion to establish correlations with an opioid-overdose event.
  • EDA skin electrodermal activity
  • locomotion were not strongly statistically valid to confirm correlations with an opioid-related drug overdose.
  • a closed-loop proof- of-concept wearable injector system of naloxone was developed.
  • the wearable system measured opioid-induced apnea events and respiratory depression, implementing a pair of body accelerometers and administering naloxone through a commercial injector system.
  • the system was relatively bulky and can be easily perceived through a wearer’s garments.
  • the invasiveness of having an injector system may increase the risk of infections and other side effects.
  • mechanisms described herein can utilize optical sensors to detect opioid-induced apnea and cardiorespiratory depression events.
  • PPG photoplethysmography
  • PPG can be used as a noninvasive approach that uses the absorbance property of oxygenated and deoxygenated hemoglobin to calculate the respiratory rate and collect electrocardiographic information.
  • PPG can be implemented using a light transmitter to propagate through the tissue and a photodetector to perceive changes in the emitted light.
  • opioid- induced cardiorespiratory events were detected with 90% accuracy in one study.
  • a wrist-mounted PPG biosensor referred to as Empatica E4 was implemented for the detection and recovery process of opioid-related overdose use.
  • mechanisms described herein can use a subset of PPG, such as NIRS, which is an optical technique that can be used to detect cardiopulmonary activity of the body using red and infrared LEDs.
  • PPG such as NIRS
  • NIRS is an optical technique that can be used to detect cardiopulmonary activity of the body using red and infrared LEDs.
  • NIRS peripheral capillary oxygen saturation levels
  • mechanisms described herein were used to design, fabricate, and evaluate a prototype wearable device with a closed-loop to detect a medical event (e.g., opioid- induced cardiorespiratory depression) and to deliver a burst of medication (e.g., naloxone).
  • a medical event e.g., opioid- induced cardiorespiratory depression
  • a burst of medication e.g., naloxone
  • a wrist-wearable device for sensing change in oxygenation level can include three stages: (i) a sensor based on NIRS technology to detect cardiopulmonary depression events; (ii) a MOSFET switch to activate the actuator; and (iii) an electromagnetic field generator based on the Zero Voltage Switching (ZVS) circuit to deliver the live-saving antidote as quickly as possible.
  • ZVS Zero Voltage Switching
  • a closed-loop wearable device for the detection of cardiorespiratory depression and the delivery of the life-saving medication (naloxone) is described.
  • a wrist wearable device has the potential to improve usability with more compact electronics, specifically in terms of size reduction of at least 26% approximately for the electromagnetic field generator than a previous technology.
  • mechanisms described herein can include three well-defined electronic stages: (i) a NIRS sensor for the detection of an induced low peripheral oxygenation event, (ii) a MOSFET dual switch to couple the instrumentation circuit to the electromagnetic field generator, and (iii) a modified compact ZVS electromagnetic field generator circuit, serving as an actuator to activate the delivery process of naloxone through a minimally invasive implantable capsule (e.g., as described in Dhowan et al., "Simple minimally-invasive automatic antidote delivery device (a2d2) towards closed-loop reversal of opioid overdose," Journal of Controlled Release, 306:130-137 (2019), and in Lee et al., U.S.
  • Patent 11,439,747 which is hereby incorporated by reference herein in its entirety [0044]
  • UOD opioid use disorder
  • mechanisms described herein can be used implement a reliable closed-loop fully wearable device to detect an opioid overdose-induced cardiorespiratory event, capable of delivering a burst dose of naloxone as quickly as possible.
  • Results described below showed that the electromagnetic actuator is capable of releasing the drug within 12.28 ⁇ 1.38 seconds (s) at 1 centimeter (cm) away when a corresponding remotely actuated drug reservoir is implanted under the skin.
  • FIG. 1 shows an example of a system for mobile detection of a medical condition and wireless actuation of a drug delivery device in accordance with some embodiments of the disclosed subject matter.
  • a wearable device 102 can be configured to perform any suitable functions described herein, such as monitoring one or more physiological signals, detecting onset of a medical emergency (e.g., an emergency that indicates a timely dose of a drug or other therapeutic is needed), activation of a remote heating system, etc.
  • a medical emergency e.g., an emergency that indicates a timely dose of a drug or other therapeutic is needed
  • activation of a remote heating system etc.
  • wearable device 102 can communicate with one or more other devices over a communication network 130.
  • such communications can be received from any suitable device, such as a remote physiological sensor, a server, a smartphone, a tablet computer, etc., and/or sent to any suitable device, such as a remote physiological sensor, a server, a smartphone, a tablet computer, etc.
  • wearable device 102 can include a processor 104, one or more physiological sensors 106, a trigger switch 108, memory 110, a remote heating system 112, one or more communication systems 114, one or more inputs and/or displays 116, and/or one or more power sources 118 (e.g., one or more batteries).
  • a processor 104 one or more physiological sensors 106, a trigger switch 108, memory 110, a remote heating system 112, one or more communication systems 114, one or more inputs and/or displays 116, and/or one or more power sources 118 (e.g., one or more batteries).
  • processor 104 can be any suitable hardware processor or combination of processors, such as a microcontroller, a central processing unit (CPU), an accelerated processing unit (APU), a graphics processing unit (GPU), a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), etc.
  • processors such as a microcontroller, a central processing unit (CPU), an accelerated processing unit (APU), a graphics processing unit (GPU), a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), etc.
  • physiological sensor(s) 106 can include any suitable physiological sensor or combination of physiological sensors, such as a NIRS sensor (e.g., utilizing IR and red light), a PPG sensor (e.g., using green and/or red light).
  • processor 104 can be configured to control physiological sensor(s) 106, for example, by controlling operation of physiological sensor(s) 106 and/or controlling an operational state of physiological sensor(s) 106.
  • processor 104 can be configured to provide control signals to physiological sensor(s) 106.
  • processor 104 can be configured to control an operational state of physiological sensor(s) 106, and physiological sensor(s) 106 can include logic and/or circuits that control operation of physiological sensor(s) 106.
  • trigger switch 108 can include any suitable logic, hardware, and/or software configured to activate a remote heating system 112 in response to a signal from processor 104 and/or physiological sensor(s) 106.
  • trigger switch 108 can be configured to provide power to a ZVS circuit in response to a signal from processor 104 (e g., implemented with a microcontroller).
  • memory 110 can include any suitable storage device or devices that can be used to store instructions, values, etc., that can be used, for example, by processor 104 to control operation of wearable device 102, record physiological signals and/or physiological data (e.g., HbO 2 , HbR, SpO 2 , etc.), to communicate with another device via communications system(s) 114, etc.
  • Memory 110 can include any suitable volatile memory, nonvolatile memory, storage, or any suitable combination thereof.
  • memory 110 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc.
  • memory 110 can have encoded thereon a program (e.g., a computer program) for controlling operation of wearable device 102.
  • processor 104 can execute at least a portion of the program to record physiological signals, physiological data, receive information from another device, transmit information to another device, etc.
  • remote heating system 112 can include any suitable components capable of transmitting power to a remotely actuated drug reservoir that is in relatively close proximity to remote heating system 112 (e.g., within about 1 cm when the remotely actuated drug reservoir is implanted under the skin of a human).
  • remote heating system 112 can include magnetic field generator and/or high frequency amplifier, such as a ZVS circuit coupled between trigger switch 108 and a coil configured to wirelessly transmit power to the remotely actuated drug reservoir.
  • remote heating system 112 can be electrically coupled to power source 118 via trigger switch 108, such that remote heating system 112 is electrically isolated from power source 118 while trigger switch 108 is in an open state.
  • communications systems 114 can include any suitable hardware, firmware, and/or software for communicating information over communication network 130 and/or any other suitable communication networks.
  • communications systems 114 can include one or more transceivers, one or more communication chips and/or chip sets, etc.
  • communications systems 114 can include hardware, firmware and/or software that can be used to establish a Bluetooth connection, Wi-Fi connection, a cellular connection, a universal service bus (USB) connection, an Ethernet connection, etc.
  • USB universal service bus
  • input(s)/display(s) 116 can include any suitable input device(s) and/or sensor(s) that can be used to receive user input, such as one or more buttons, a touchscreen, a microphone, etc. Additionally or alternatively, in some embodiments, input(s)/display(s) 116 can include any suitable display device(s), such as a touchscreen, one or more indicator lights (e.g., implemented with LEDs) to signal an operational and/or power status of wearable device 102, etc.
  • suitable input device(s) and/or sensor(s) that can be used to receive user input, such as one or more buttons, a touchscreen, a microphone, etc.
  • input(s)/display(s) 116 can include any suitable display device(s), such as a touchscreen, one or more indicator lights (e.g., implemented with LEDs) to signal an operational and/or power status of wearable device 102, etc.
  • power supply 118 can include any suitable source of power and/or any suitable power electronics to provide adequate power for operation of other components of wearable device 102.
  • power supply 118 can include one or more batteries, a voltage regulator, etc.
  • communication network 130 can be any suitable communication network or combination of communication networks.
  • communication network 130 can include a peer-to-peer network (e.g., a Bluetooth network), a WiFi network (which can include one or more wireless routers, one or more switches, etc.), a cellular network (e.g., a 3G network, a 4G network, a 5G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, 5GNR, etc.), a wired network, etc.
  • a peer-to-peer network e.g., a Bluetooth network
  • WiFi network which can include one or more wireless routers, one or more switches, etc.
  • a cellular network e.g., a 3G network, a 4G network, a 5G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, 5GNR, etc.
  • communication network 130 can be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of network, or any suitable combination of networks.
  • Communications links shown in FIG. 1 can each be any suitable communications link or combination of communications links, such as Bluetooth links, Wi-Fi links, cellular links, wired links, fiber optic links, etc.
  • FIGS. 2A and 2B show an example of hardware that can be used to implement a wearable device (e.g., the wearable device 102) in accordance with some embodiments of the disclosed subject matter.
  • a wearable device e.g., the wearable device 102
  • FIG. 2A shows an electronic drug delivery system 200 in accordance with some embodiments of the disclosed subject matter.
  • three electronic systems of the wearable device or drug delivery system 200 may include: an NIRS sensor 202, a MOSFET switch 204, and an electromagnetic ZVS actuator 206.
  • FIG. 2A, panel (a) shows a block diagram of principal electronic elements of the NIRS sensor 202;
  • FIG. 2A, panel (b) shows a block description of the MOSFET switch 204 (e.g., a Dual MOSFET trigger switch 204); and
  • panel (c) shows a circuit design of a ZVS actuator 206 (e.g., a ZVS electromagnetic field generator 206, also referred to as a ZVS driver or ZVS circuit).
  • system 200 also includes a remotely actuated drug reservoir 208.
  • the remotely actuated drug reservoir 208 may be a passive drug delivery device, an active drug delivery device, or a combination of a passive and active drug delivery device (e.g., controllable as a passive device and also as an active device).
  • the NIRS sensor 202 may be an example of the physiological sensor(s) 106
  • the microcontroller 212 may be an example of the processor 104 (e.g., the microcontroller 212 may serve as both the processor 104 and also as part of the NIRS sensor 202)
  • the power supply 222 may be an example of the battery 118
  • the dual MOSFET trigger switch 204 may be an example of the trigger switch 108
  • the ZVS actuator 206 (including coil 224) may be an example of the remote heating system 112.
  • FIG. 2A, panel (a) illustrates electronic components involved in an implementation of the NIRS sensor 202.
  • each LED can be pulsed out of phase (e.g., using LED driver 210).
  • each LED can be pulsed out of phase at a frequency of 14.05 hertz (Hz)), establishing an on-time pulse of 15 milliseconds (ms) to yield a duty cycle of 0.21.
  • the LEDs may be part the LED driver 210, as illustrated with respect to FIG. 3.
  • the logic of the system or NIRS sensor 202 can be handled using a microcontroller 212 (e.g., a SAMD21G18AU microcontroller available from Microchip Technology, Inc.).
  • Two analog components of the NIRS sensor can include: a light-emitting diode (LED) driver 210 and a transimpedance amplifier (TIA) 214.
  • Further supporting systems may include, for example, a low-pass filter 216, an anal og-to-digi tai converter (ADC) 218, a voltage regulator 220, a power supply 222, and miscellaneous sub-circuits to facilitate a suitable operation of the system.
  • ADC anal og-to-digi tai converter
  • a commercial dual high- power SWITCH 204 e.g., implemented using a dual MOSFET Tigger Switch 0 - 20 kilohertz (kHz) PMW, procured from Amazon.com, Inc
  • the switch can be connected to the ZVS circuit 206 and activated by the microcontroller 212 as illustrated in FIG. 2 A.
  • a compact version of a commercial ZVS (e.g., a Yooso ZVS Driver Circuit, procured from Amazon.com, Inc) can be implemented.
  • the circuit can be based on the driver electromagnetic field generator implemented in Dhowan et al., "Simple minimally- invasive automatic antidote delivery device (a2d2) towards closed-loop reversal of opioid overdose," Journal of Controlled Release, 306: 130-137 (2019), in order to reduce the size of the device as much as possible.
  • a ZVS circuit 206 implemented herein can incorporate smaller choke inductors, which can be used to block high-frequency voltage signals.
  • FIG. 2A, panel (c) and FIG. 2B show the implemented electronic circuit of the ZVS driver 206.
  • the printed circuit board (PCB) shown in FIG. 8D was designed with licensed specialized program (from Altium) and manufactured by JLCPCB, Inc.
  • a coil 224 used to transmit energy to heat the implanted drug reservoir 208 can include a 9 turn pancake copper coil, implemented using a commercial polyamide-insulated magnetic wire (for example, a Magnet Wire MW35-C HY), which can improve ZVS performance in terms of heat transfer.
  • the inductance of the package coil was measured using a commercial LCR meter (an IM3535 LCR meter available from Hioki).
  • a 1 millimeter (mm) layer of Ecoflex 00-30 can be placed over the top surface of the circuits.
  • all the elements can be packed inside a wrist case (e g., as described below to be used for the benchtop experiments).
  • sample data can be acquired with the 14.05 Hz sampling rate of the LEDs using the microcontroller 212 and the ADC 218 (e.g., an ADS115 16-bit resolution analog-to-digital converter, available from Texas Instruments, Inc).
  • the ADC 218 e.g., an ADS115 16-bit resolution analog-to-digital converter, available from Texas Instruments, Inc.
  • only 15 bits of the ADC 218 can be used due to a slight drop in the negative values of the signal, resulting in a minor modification of 0.1 mV resolution on a 3.3 V instrumentation- powered system.
  • the acquired data was saved as a text file for further processing in Python.
  • the acquired data can be stored in memory and/or provided to a processor (e.g., a microcontroller) for processing to determine physiological signals (e.g., HbO 2 and HbR) and/or to determine whether a wearer is experiencing a medical emergency.
  • a processor e.g., a microcontroller
  • physiological signals e.g., HbO 2 and HbR
  • the raw data was acquired from the wearable device and digitally processed on a computer.
  • the raw data can be processed on a processor within the device (e g., by the microcontroller 212).
  • processing of the NIRS data can include any suitable processing techniques.
  • three principal filters can be applied to process the data.
  • a fifth order finite impulse response (FIR) low pass filter can be applied to smooth the raw data.
  • a third order infinite impulse response (IIR) Butterworth filter can be applied with a cutoff frequency (/ c ) of 0.25 Hz to eliminate the low frequency movement effects and the DC offset.
  • the peak-to-peak voltages values for a 40- sample epoch can be extracted and placed into an array.
  • a five-sample sliding medial filter can be applied.
  • both AC and DC data from the red and infrared color channels can be used, calculating the intermediate variable R using EQ. (1).
  • R can be used as a proxy for SpO 2 , for example using a suitable reference curve.
  • EQS. (2) and (3) represent this modified mathematical model.
  • HbO 2 or HbR can be used alone, or in combination. In some embodiments, using both measurements can provide redundancy and/or improve accuracy of detecting a low oxygenation state.
  • FIGS. 2A and 2B illustrate and are described with respect to a particular example of the system 200.
  • other types of components or controls are implemented.
  • the LED driver 210 may pulse the LEDs using another suitable driving scheme (e.g., at a different frequency and/or duty cycle).
  • FIG. 3 shows an example of hardware that can be used to implement a light emitting diode (LED) driving circuit 300 in accordance with some embodiments of the disclosed subject matter.
  • LED light emitting diode
  • an LED driver circuit 300 can include MOSFETS 302 and resistors 304.
  • the LED driver circuit 300 is an example of the LED driver 210 of FIG. 2A.
  • FIG. 3, panel (a), shows a 7.4 volt (V) power supply 306, which can be implemented using 2 lithium batteries in series.
  • FIG. 3, panel (b) shows 3 LEDs 308 of different colors for the NIRS approach.
  • FIG. 3, panel (c) shows control signals handled by a microcontroller 310.
  • an LED driver circuit 300 can be implemented based on a configuration of MOSFETS 302 and resistors 304 (e.g., as shown in FIG. 3).
  • a processor e.g., a microcontroller 310
  • a processor can be configured to pull in a high level gate voltage (3.3 V) of an N-channel MOSFET, causing the MOSFET's drain-source resistance to drop to a negligible value. This can be followed by current flow from the positive terminal of the power supply (7.4 V) through the LEDs 308. The current can be limited by a resistor to connect the system to the ground.
  • the resistance values can be calculated to establish the maximum current ratings for each LED color channel.
  • the resistors 304 can be tuned to acquire a similar output of the photocurrent at the photodiode.
  • Each color output channel can be set to the same bit value to avoid over- and under-saturation issues.
  • FIG. 3 illustrates and is described with respect to a particular example of the LED driver circuit 300.
  • other types of components or controls are implemented.
  • different types or sizes of MOSFETS 302 and resistors 304 may be used in some examples, and a power supply of a different voltage may be used in some examples.
  • FIG. 4 shows an example of hardware that can be used to implement a transimpedance amplifier (TIA) 400 in accordance with some embodiments of the disclosed subject matter.
  • the TIA 400 is an example of the transimpedance amplifier 214 of FIG.
  • the TIA 400 can be used to convert light changes detected by a photodiode into readable voltage values for output to an ADC (e.g., the ADC 218 of FIG. 2A), whose output may then be provided to a microcontroller (e.g., the microcontroller 212).
  • ADC e.g., the ADC 218 of FIG. 2A
  • microcontroller e.g., the microcontroller 2112.
  • FIG. 4, panel (a) shows a 3.3 V supply 402 from a voltage regulator;
  • FIG. 4, panel (b) shows a ferrite bead 404 and decoupling capacitor 406 that can stabilize the power supply signal;
  • FIG. 4, panel (c) shows a lowpass filter 408 to smooth the signal;
  • FIG. 4, panel (d) shows power supply 410 (e.g., from one or more lithium batteries and/or power supply 222 of FIG. 2A).
  • power supply 410 e.g., from one or more lithium batteries and/or power supply 222 of FIG. 2A.
  • the TIA 400 can include: (i) a low-noise and low quiescent current, precision operational amplifier 414 (e.g., an OPA376, available from Texas Instruments, Inc), (ii) a combination of gain-setting resistors, (iii) a feedback capacitor, and (iv) a ferrite bead 404.
  • the output of the operational amplifier 414 (also referred to as an op-amp 414) may be provided as the output of the TIA 400 (e.g., which may be received by the ADC 218).
  • the gain-setting resistors and feedback capacitor may be part of the low pass filter 408.
  • a light sensor of the device e.g., photodiode 412) can be reserved biased by 4.1 V.
  • This voltage value can obtained from the power drop due to the interaction between the two system batteries 410 (7.4 V) and a voltage regulator 402 (3.3 V).
  • the anode from the photodiode 412 can be electrically coupled (e.g., directly connected via a wire and/or other conductive material, such as a wire trace of a circuit board) to the input of the TIA to ensure a current flow from the photocurrent toward the main circuit.
  • Rl 180 kiloohms (kfl)
  • FIG. 5 shows an example of a process 500 for mobile detection of a medical condition and wireless actuation of a drug delivery device in accordance with some embodiments of the disclosed subject matter.
  • the system 100 can monitor one or more physiological signals.
  • the wearable device 102 can receive output from a physiological monitor 106 (e.g., a photodiode or an NIRS sensor 202, an output of the NIRS sensor 202, etc.) at the processor 104 (e.g., the microcontroller 212), and analyze the output to estimate one or more physiological signals, such as HbO 2 , HbR, and/or SpO 2 (e.g., as described above in connection with EQS. ( 1 )-(3)).
  • the wearable device 102 e.g., the processor 104
  • the wearable device 102 may drive a light emitting diode (or diodes) of the NIRS sensor (see, e.g., diodes 308 of FIG. 3); may sense, with a photodetector of the NIRS sensor, light output by the LED of the NIRS sensor (see, e.g., photodetector 412 of FIG. 4); and generate the signals to be output by the physiologic sensor based on the light sensed with the photodetector (see, e.g., output of the opamp 414 in FIG. 4).
  • the system 100 can attempt to detect an onset of a medical emergency (or any other suitable triggering event) that may necessitate timely administration of a drug that is available via a remotely actuated drug reservoir 208.
  • the processor 104 can determine, based on a physiological signal and/or a combination of physiological signals received from the physiological monitor 106, that a low oxygenation event is occurring, potentially due to an opioid overdose.
  • processor 104 determines that SpO 2 has fallen below a threshold (e g., indicated by a value of R increasing by a threshold amount) for a predetermined amount of time, processor 104 can determine that a low oxygenation event is occurring (e.g., as described below in connection with FIG. 11).
  • a threshold e g., indicated by a value of R increasing by a threshold amount
  • processor 104 can determine that a low oxygenation event is occurring (e.g., as described below in connection with FIG. 12).
  • processor 104 can use other physiological signals to determine whether a medical emergency is occurring, such as signals from a remote physiological monitor. Such signals can be used, for example, to corroborate symptoms of an ongoing opioid overdose.
  • the system 100 includes additional types of sensors to facilitate detecting a medical emergency (e.g., a low oxygenation event).
  • the physiological sensor(s) 106 of the wearable device 102 may further include an inertial motion unit (IMU) configured to measure a position or movement of a user.
  • IMU inertial motion unit
  • the processor 104 may determine or infer, based on an output of the IMU, whether the user of the wearable device 102 is motionless (e g., moving below a threshold amount), has limited movement, is upright, has fallen to the ground, is moving above a threshold amount, etc.
  • the processor 104 may use this determination based on the IMU output as an additional source of sensor information to augment the information provided by the NIRS sensor 202.
  • the processor 104 may detect a medical emergency in response to both detecting a low oxygenation event based on the output of the NIRS sensor 202 (as described above) and that the user is motionless or has fallen based on the IMU output.
  • the processor 104 may determine that user is not actually suffering from a low oxygenation event.
  • the wearable device 102 may include a microphone or auditory sensor to sense sound from a user that may be used in a similar manner to corroborate or dismiss a suspected low oxygenation event. Such additional sensor information used for corroboration can reduce false positive detections of medical events by the wearable device 102.
  • process 500 can return to block 502 and the system 100 (e.g., the processor 104 of the wearable device 102) can continue to monitor physiological signals from the physiological sensor(s) 106. Otherwise, if processor 104 determines that a medical emergency is occurring ("YES" at block 506), process 500 can move to block 508, and processor 104 can activate a remote heating system 112 to actuate a remotely actuated drug reservoir 208 to dispense drugs (e g., subcutaneously).
  • the system 100 e.g., the processor 104 of the wearable device 102
  • process 500 can move to block 508, and processor 104 can activate a remote heating system 112 to actuate a remotely actuated drug reservoir 208 to dispense drugs (e g., subcutaneously).
  • processor 104 can cause a signal to be transmitted to a trigger switch (e.g., trigger switch 108, the dual MOSFET trigger switch 204, etc.) to cause the switch to provide power to a remote heating system (e g., remote heating system 112, the ZVS circuit 206 and coil 224, etc.).
  • a trigger switch e.g., trigger switch 108, the dual MOSFET trigger switch 204, etc.
  • a remote heating system e.g., remote heating system 112, the ZVS circuit 206 and coil 224, etc.
  • the process 500 involves the system 100 generating an alarm an audible, tactile, and/or visual alarm (e.g., via display 116) to indicate when an event is detected at block 506.
  • Such an alarm can alert the user and/or nearby individuals in advance of or in parallel with dispensing of drugs via the remotely actuated drug reservoir 208.
  • the alarm may be audible, tactile, or visual.
  • a speaker on or in communication with the wearable device 102 may generate an alert sound (e.g., loud and/or intermittent sounds or beeps)
  • a vibration device on or in communication with the wearable device 102 may generate an alert vibration
  • a light device on or in communication with the wearable device 102 e.g., one or more light emitting diodes, the display 116, etc.
  • an alert light e.g., bright and/or flashing light(s)
  • the wearable device 102 may transmit a message (e.g., via the communication network 130) to cause a phone call, text, or other communication to emergency personnel or services and/or a person of choice (e.g., indicated via emergency contact information that a user has previously stored in the memory 110).
  • a message e.g., via the communication network 130
  • a person of choice e.g., indicated via emergency contact information that a user has previously stored in the memory 110.
  • processor 104 can continue to monitor one or more physiological signals.
  • processor 104 can receive output from a physiological monitor (e.g., a photodiode 412 or an NIRS sensor 202, an output of the NIRS sensor 202, etc.), and analyze the output to estimate one or more physiological signals, such as HbO 2 , HbR, and/or SpO 2 (e.g., as described above in connection with EQS. ( l)-(3).
  • a physiological monitor e.g., a photodiode 412 or an NIRS sensor 202, an output of the NIRS sensor 202, etc.
  • HbO 2 e.g., HbR, and/or SpO 2
  • processor 104 can attempt to detect whether the medical emergency (or any other suitable triggering event) detected at block 504 has been resolved. For example, processor 104 can determine, based on a physiological signal and/or a combination of physiological signals, whether a low oxygenation event is still occurring after actuation of the drug delivery reservoir 208 at block 508.
  • processor 104 determines that SpO 2 has risen above a reoxygenation threshold and/or is improving at a threshold rate (e.g., indicated by a value of R decreasing by a threshold amount) for a predetermined amount of time, processor 104 can determine that a low oxygenation event has been resolved.
  • a threshold rate e.g., indicated by a value of R decreasing by a threshold amount
  • process 500 can return to block 502 so as to cause the processor 104 to continue to monitor physiological signals, or can end.
  • process 500 can move to block 516, and the processor 104 can activate the remote heating system 112 to actuate another remotely actuated drug reservoir 208 to dispense drugs (e.g., subcutaneously).
  • drugs e.g., subcutaneously
  • processor 104 can cause a signal to be transmitted to a trigger switch (e.g., trigger switch 108, the dual MOSFET trigger switch 204, etc.) to cause the switch to provide power to the remote heating system (e.g., remote heating system 112, the ZVS circuit 206 and coil 224, etc.).
  • a trigger switch e.g., trigger switch 108, the dual MOSFET trigger switch 204, etc.
  • the switch to provide power to the remote heating system (e.g., remote heating system 112, the ZVS circuit 206 and coil 224, etc.).
  • multiple drug reservoirs 208 can be implanted, with a first reservoir configured to release a drug after a single actuation of the remote heating system 112, a second reservoir configured to release a drug after multiple actuations of the remote heating system 112, etc.
  • one or more of blocks 510-516 can be omitted. For example, if only a single drug reservoir 208 is available, one or more of blocks 510-516 can be omitted.
  • FIG. 6 shows an example 600 of components implemented for a benchtop experiment to test functionality of a wearable device implemented in accordance with some embodiments of the disclosed subject matter.
  • FIG. 6 shows a block diagram of components implemented for benchtop experiments described herein, including in panel (a), a schematic of the front side of the NIRS sensor 202. For example, a digital pin of the microcontroller 212 is activated to drive the switch 204 and the ZVS circuit 206.
  • FIG. 6, panel (b) shows a representation of the MOSFET switch driver 204 to integrate the instrumentation circuit to the ZVS driver 206.
  • FIG. 6, panel (c) shows a diagram of an electromagnetic field generator, placed at different height levels to melt a phase change material (PCM) of a remotely actuated drug reservoir 208 (e.g., which can be implanted to deliver the drug subcutaneously).
  • PCM phase change material
  • FIG. 6 illustrates several components involved in the experiment.
  • a highdevel voltage was set to a digital pin on the microcontroller 212 to manually activate the Dual MOSFET switch 204 and the ZVS circuit 206. All components were powered using a DC power supply 222 (e.g., an Agilent E366454A DC Power Supply, available from Agilent Scientific Instrument, Inc).
  • a DC power supply 222 e.g., an Agilent E366454A DC Power Supply, available from Agilent Scientific Instrument, Inc.
  • FIG. 7 shows an example of a setup for a human experiment to test capabilities of a prototype wearable device (e.g., the wearable device 102) implemented in accordance with some embodiments of the disclosed subject matter.
  • FIG. 7 shows a setup 700 for a brachial occlusion trial mimicked with a conventional sphygmomanometer. Signals from the prototype wearable device were recorded during multiple events, including event (1): a low-oxy en event due to breath hold section for a range of 60 seconds; event (2): resting time for 60 seconds; and event (3): low oxygen event due to brachial occlusion at 200 millimeters of mercury (mmHg) of pressure induced through an inflatable cuff.
  • the scale bar of FIG. 7 indicates 2 cm.
  • criteria of participation was established for the test as follows: (i) the participant must be at least 18 years old or older; (ii) the participant must have a no history of any cardiovascular disease or events that compromise the regular functionalities of the respiratory system; (iii) the patient cannot be an opioid user; and (iv) the patient must be conscious and free or any hallucinogens, substances, or medication that compromise the cognitive system during the test.
  • Each test included 3 main events with a total duration of three minutes.
  • Event (1) low oxygen state induced by a breath hold (BH) test. In this event, the subject was asked to hold his/her breath continuously for 60 s. However, in case of discomfort or adverse events, the subject was allowed to take as many breaths as needed and resume the trial until the timer reached the total duration of the trial.
  • Event (2) resting time. During this part of the trial, the subject rested for 60 s, breathing without forced episodes.
  • Event (3) low oxygen state induced by a brachial occlusion test. In the final part of the trial, brachial occlusion (BO) was caused due to a continuous pressure of 200 mmHg on the bracelet cuff for 60 s. After the test was completed, the pressure over the arm was released.
  • BO brachial occlusion
  • FIGS. 8A-F shows example components of the prototype wearable device shown in FIG. 7, and the prototype wearable device worn by two different subjects.
  • FIG. 8A shows a front side of an NIRS PCB sensor (e.g., NIRS sensor 202), including a TIA(e.g., the TIA 214), a microcontroller (e.g., the microcontroller 212), a 16 bit ADC (e.g., the ADC 218), and supplementary subcircuits.
  • FIG. 8B shows a back side of the NIRS PCB sensor, containing the principal optical component of the device (e.g., LED driver 210), denoted by the sensing area enclosed by the white square.
  • FIG. 8C shows a commercial MOSFET switch driver (e.g., the DUAL MOSFET trigger switch 204) without the wire-to-board header components.
  • FIG. 8D shows a modified ZVS board (e.g., the ZVS circuit 206 as described above in connection with FIGS. 2A and 2B).
  • FIG. 8E shows a view of all the electronic parts of the prototype wearable system packed inside a wrist case worn by a first subject.
  • FIG. 8F shows a final version of prototype wearable device on a second subject. All the scale bars represent 5 mm.
  • FIGS. 8E-F shows a prototype of a wearable device as described herein (e.g., wearable device 102), including electronics and a prototype version of a wrist case.
  • FIG. 8 A shows the front side of the PCB of the NIRS sensor, characterized by the inclusion of the principal electronics of the system as follows: a microcontroller (SAMD21G18A), the implemented design of the TIA circuit, a 3.3 V voltage regulator, and a 16-bit ADC (ADS1115). Supplementary electronic components such as a push button to reset the system, a ferrite bead along with a capacitor to decouple the power supply signal, two female plug connectors to connect two lithium batteries, and a set of resistors, capacitors, and an operation amplifier (OPA376) are included in the top side of the PCB in FIG. 8A.
  • the back side of the PCB NIRS sensor is shown in FIG. 8B, which includes the LED driver (SFH7050). Note that the PCB includes 2 layers, where GND and power supply lines are fully connected through the layers.
  • FIG. 8C depicts the commercial MOSFET driver switch with an absence of the header-wire-to-board, with the aim of the reducing the size of switch to facilitate the packaging of the entire components in a 3D printed wrist case (59 mm X 49 mm X 25 mm).
  • FIG. 8D shows the modified ZVS driver with a volume of 32 mm X 41 mm X 3 mm, which is 26% smaller than a commercially available electromagnetic field generator described in Dhowan et al., "Simple minimally-invasive automatic antidote delivery device (a2d2) towards closed-loop reversal of opioid overdose.”
  • the modified ZVS reached 15 kiloamperes per meter (kA/m) of magnetic field at 195 kHz, delivering the necessary power capabilities.
  • FIGS. 8E- F show the integrated electronic components of the system, packed, and placed inside the wrist case. Note that FIGS. 8E-F illustrate two different subjects to validate the wearability of the device, considering different wrist sizes.
  • the wrist of the first subject in FIG. 8E has a perimeter of approximately 196 mm and the wrist of the second subject in FIG. 8F has a perimeter of approximately 216 mm. Both subjects did not exhibit any signs of discomfort while wearing the wrist case.
  • FIGS. 9A-E shows an example of a setup for benchtop experiments to test functionality of the prototype wearable device shown in FIG. 7.
  • FIGS. 9F-G also shows results of the benchtop experiments.
  • FIG. 9A shows a stainless steel (SS) heating element tube 900;
  • FIG. 9B shows a high-density polyethylene (HDPE) tube 902 and a polytetrafluoroethylene (PTFE) sealing ball 905;
  • FIG. 9C shows a prototype of the drug reservoir 908 sealed with PCM 910;
  • FIG. 9D shows electronic components 915 used during the benchtop experiment;
  • FIG. 9E shows a setup 920 of the wearable device to test the ZVS driver at different high levels above the drug delivery capsule;
  • FIG. 9F shows time for the implantable drug delivery device to reach 42 degrees Celsius (°C) from the electromagnetic field generator at different distances
  • FIG. 9G shows time for the implantable drug delivery device to reach 42 °C from the electromagnetic field generator at a distance of 1 cm.
  • the scale bar for FIG. 9A-C indicates 1 mm
  • the scale bar represents 1 cm and 2 cm, respectively.
  • FIGS. 9A-C illustrate the used implantable device made of four fully commercial biocompatible elements: the SS heater tube 900, the HDPE tube 902, the PTFE ball 905, and the cover side made of PCM 910.
  • FIG. 9D depicts electronics components used for the experiments, before packaging inside the 3D printed case.
  • FIG. 9E shows the configuration of the wearable device at a height level of above the drug delivery capsule in a horizontal position.
  • FIGS. 9F-G depict the quantitative data for the characterization of the heating element.
  • the device is capable of ensuring a rapid delivery of a burst of the life-saving antidote.
  • the system can reach the appropriate temperature (42 °C) to melt the PCM on time, allowing the delivery of the drug relatively quickly.
  • the fast response for the horizontal orientation of the implantable capsule may be due to nonaxial components of the electromagnetic field induced by the ZVS circuit, causing eddy currents over the implantable capsule. Indeed, such a fast-heating process is feasible since a quick response is desirable during an opioid overdose.
  • FIG. 10 shows examples of peak-peak values of infrared and red intensity recorded during the human experiment described in connection with FIG. 7. More particularly, FIG. 10 shows peak-peak values of IR and Red intensity for the 8 subjects during the BH and BO trials. All graphics are normalized with a 95% interval of confidence indicated by the shade regions in each plot.
  • FIG. 10, panel (a) shows IR intensity peak-peak values for the BO trial;
  • FIG. 10, panel (b) shows IR intensity peak-peak values for the BH trial;
  • FIG. 10, panel (c) shows red intensity peak-peak values for the BO experiments; and
  • FIG. 10, panel (d) shows red intensity peak-peak values for the BH experiment.
  • FIG. 10 shows the average normalized results of the intensity of red and IR lights across the 8 subjects for the BH and BO trials with a 95% confidence interval denoted by the shaded regions in each plot.
  • FIG. 10, panel (a) displays the peak-peak values for the intensity of the IR LED data before, during, and after the BO experiment, presenting a minimum peak-peak value of -1 during the experiment and a maximum rise of 2 after releasing the brachial occlusion.
  • panel (b) for the BH experiment presenting evidence of a slight decrease to approximately -1.5 in the intensity of the IR light during the test, followed by an increase in the absorption of the light, reaching values greater than 1.
  • FIG. 11 shows examples of averaged R modulation index values recorded during the human experiment described in connection with FIG. 7.
  • panel (a) shows R values before, during and after the BO trial; and
  • panel (b) shows R data before, during and after the BH trial.
  • the R value is analyzed.
  • FIG. 11 shows the normalized values with a 95% confidence interval highlighted by the shaded regions for the BH and BO experiments.
  • FIG. 11 shows the normalized values with a 95% confidence interval highlighted by the shaded regions for the BH and BO experiments.
  • panel (a) shows the results for R before, during and after the BO test, representing values between -2 and 2 during the resting time and reaching values of 4 during the induced low oxygenation event induced. Note that after the BO test there is a steady decrease in the R values. However, an increase in the R values was expected as a result of the relationship between this parameter and the level of oxygenation in the tissue. Similarly, for the BH trail, the R (FIG. 11, panel (b)) represents a noticeable decrease to -3, indicating a low level of oxygenation in the tissue. It was followed by an increase of the R increase value to positive values, denoting a reoxygenation during resting time.
  • the modulation index (/?) can be used as a parameter to calculate SpO 2 through the implementation of an NIRS system.
  • Results depicted in FIG. 11, panels (a) and (b) show a slight increase in the R values during the BO and BH tests, validating a physiological expectation for low peripheral oxygenation. Note that high values of R are associated with low levels of SpO 2 .
  • FIG. 11, panel (b) shows a sharp decrease in the R values towards the end of the breath hold period. Such decrease can be attributed to brief exasperated breaths taken by participants before the end of the intended breath hold period.
  • FIG. 12 shows examples of peak-peak values of oxyhemoglobin and deoxyhemoglobin changes calculated during the human experiment described in connection with FIG. 7. More particularly, in FIG. 12, peak-peak values of HbO 2 and HbR changes are shown for the 8 subjects during the BH and BO trials. All graphics are normalized with a 95% interval of confidence indicated by the shade regions in each plot.
  • FIG. 12, panel (a) shows HbO 2 peak-peak concentration values for the BO trial;
  • panel (b) shows HbO 2 peak-peak concentration values for the BH trial;
  • FIG. 12 panel (c) shows HbR peak-peak concentration values for the BO experiments; and
  • panel (d) shows HbR peak-peak concentration values for the BH experiment
  • FIG. 12 illustrates the changes in the HbO 2 and HbR for the BO and BH experiments. Data were averaged and normalized with a 95% confidence interval indicated by the shaded region.
  • panel (a) presents a slight decrease in the HbO 2 data to -1.5 (micro molar) M during the BO trial, followed by a rise in the changes to 2 juM approximately after the experiment. It is also possible to observe that changes in HbO 2 concentration are followed by a slight decrease in HbR values because of the presence of an induced low-oxygen event associated with the BO. A similar trend is observed in FIG.
  • Table 1 contains p-values ⁇ 0.05, except for SpO 2 , which was related to the R modulation index for the three stages of the BO experiments. Similarly, in Table 2 most of the p-values were ⁇ 0.05 besides those related to SpO 2 during the BH experiment, limiting the rejection of the null hypothesis.
  • the groups of interest shown in the tables represent the statistical difference between two stages (e.g., the difference in measurements between the pre-occlusion time period and the occlusion time period is labeled "pre-during occlusion," while the difference in measurements between the pre-occlusion time period and the post-occlusion time period is labeled "pre-post occlusion,” etc. Using multiple signals can provide redundancy in identifying a real risk event.
  • an important aspect is the ability of the device to detect changes in Hb O 2 and HbR concentrations during a simulated opioid- induced overdose event.
  • a decrease in the concentration of oxyhemoglobin can be expected during brachial occlusion (BO) and breath holding (BH) as indicated by a negative derivative (see, e.g., FIG. 12, panels (a) and (b)).
  • the negative derivative indicates a consistent negative value owing to an expected change in the Y axis. This phenomenon is associated with low oxygenation in the tissue, leading to a reduction in HbO 2 on the surrounding capillaries.
  • HbR concentration values for the BO and BH experiments were predicted to rise by a positive derivative.
  • the physiological reasoning behind such an increase in deoxyhemoglobin and a fall in oxyhemoglobin is based on the event of blood supply cutoff, which prompts muscles to use locally available oxygen. As reoxygenated blood becomes reduced, oxygen supply is slowly depleted as a result of continued muscle use. It is important to note that the possible errors in the data can be explained due to the skin tone on the subjects, which is known as a critical topic for research in the field of optical wearable devices. Another important aspect to consider is noise induced by the movements of the subjects, which can strongly affect the signal obtained during the tests.
  • FIG. 13 shows a table that includes a summary of p-values for the analysis on brachial occlusion during the human experiment described in connection with FIG. 7.
  • FIG. 14 shows a table that includes a summary of p-values for the analysis on breath hold during the human experiment described in connection with FIG. 7.
  • any suitable computer readable media can be used for storing instructions for performing the functions and/or processes described herein.
  • computer readable media can be transitory or non-transitory.
  • non-transitory computer readable media can include media such as magnetic media (such as hard disks, floppy disks, etc.), optical media (such as compact discs, digital video discs, Blu-ray discs, etc.), semiconductor media (such as RAM, Flash memory, electrically programmable read only memory (EPROM), electrically erasable programmable read only memory (EEPROM), etc ), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and/or any suitable tangible media.
  • magnetic media such as hard disks, floppy disks, etc.
  • optical media such as compact discs, digital video discs, Blu-ray discs, etc.
  • semiconductor media such as RAM, Flash memory, electrically programmable read only memory (EPROM), electrically erasable programmable read only memory (EEPROM), etc ),
  • transitory computer readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and/or any suitable intangible media.
  • mechanism can encompass hardware, software, firmware, or any suitable combination thereof.
  • the terms “about” and “approximately,” as used herein, should be understandable to one of skill in the art in the context in which they are used. For example, “about” and “approximately” can mean within 10%, within 5%, within 1%, or within 0.5% of the corresponding value. For example, “about 7.4 volts” may mean 7.4 volts +/- 10% (e.g., a voltage between 6.66 volts and 8.14 volts).

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Abstract

L'invention concerne des procédés, des systèmes et des supports permettant une détection mobile d'un problème médical et un actionnement sans fil d'un dispositif d'administration de médicament. Dans certains modes de réalisation, le système comprend : une alimentation électrique ; un capteur physiologique ; un commutateur de déclenchement ; un générateur de signal ; une bobine de transmission couplée électriquement à l'alimentation électrique par l'intermédiaire du commutateur de déclenchement et du générateur de signal ; et au moins un processeur qui est programmé pour : recevoir des signaux provenant du capteur physiologique ; déterminer qu'un événement de déclenchement s'est produit sur la base des signaux reçus de la part du capteur physiologique ; en réponse à la détermination selon laquelle l'événement de déclenchement s'est produit, amener le commutateur de déclenchement à fournir de l'énergie au générateur de signal, de sorte que la puissance est transmise par la bobine de transmission pour activer sans fil le dispositif d'administration de médicament.
PCT/US2024/027995 2023-05-05 2024-05-06 Systèmes, procédés et supports pour la détection mobile d'un problème médical et l'actionnement sans fil d'un dispositif d'administration de médicament Pending WO2024233471A1 (fr)

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US20180034507A1 (en) * 2016-08-01 2018-02-01 Nxp B.V. Nfc system wakeup with energy harvesting
WO2021007351A1 (fr) * 2019-07-10 2021-01-14 Verily Life Sciences Llc Commande d'aiguille pneumatique
US20220273299A1 (en) * 2021-02-26 2022-09-01 Ethicon Llc Adjustable communication based on available bandwidth and power capacity
US20220360109A1 (en) * 2019-07-03 2022-11-10 Verily Life Sciences Llc Systems And Methods For Sealing And Providing Wireless Power To Wearable Or Implantable Devices
WO2022261492A1 (fr) * 2021-06-10 2022-12-15 Northwestern University Systèmes et procédés de surveillance de l'état physiologique d'un sujet vivant et d'administration de substances à cet effet

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180034507A1 (en) * 2016-08-01 2018-02-01 Nxp B.V. Nfc system wakeup with energy harvesting
US20220360109A1 (en) * 2019-07-03 2022-11-10 Verily Life Sciences Llc Systems And Methods For Sealing And Providing Wireless Power To Wearable Or Implantable Devices
WO2021007351A1 (fr) * 2019-07-10 2021-01-14 Verily Life Sciences Llc Commande d'aiguille pneumatique
US20220273299A1 (en) * 2021-02-26 2022-09-01 Ethicon Llc Adjustable communication based on available bandwidth and power capacity
WO2022261492A1 (fr) * 2021-06-10 2022-12-15 Northwestern University Systèmes et procédés de surveillance de l'état physiologique d'un sujet vivant et d'administration de substances à cet effet

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