Methods and systems for monitoring an injection site reaction

Abstract

Provided herein are devices, systems, and methods for monitoring one or more health or physiological parameters. In some embodiments, the one or more health or physiological parameters may be indicative of a presence, a likelihood, or a severity of an injection site reaction in a subject. The determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on measurements of the one or more health or physiological parameters of the subject over an extended period of time. The one or more health or physiological parameters are selected from the group consisting of rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, and reflectance of the body or portion thereof.

Description

METHODS AND SYSTEMS FOR MONITORING AN INJECTION SITE REACTIONCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 667,580, filed July 3, 2024, which is entirely incorporated herein by reference.

[0002] The subject matter of this patent application is related to the subject matter in Patent Cooperation Treaty Application No. PCT / US2019 / 069142, U.S. Patent No. 11,109,800, U.S. Patent No. 11,571,164, and U.S. Patent No. 11,786,173, each of which is entirely incorporated herein by reference.BACKGROUND

[0003] Injection site reactions (ISRs) are a local phenomenon at or around a site of injection after an injection of drugs, vaccines, or any other substances, for example through a needle or a cannula to a tissue, such as subcutaneous tissue. ISRs can come in different forms, including pain, swelling, itching, rash, bleeding, or redness at or around the site of injection. Medical professionals often advise patient to stay in proximity to the medical professionals after the injection for the observation of any potential ISRs. If any ISRs occur, the medical professionals can attend to such ISRs immediately. More recently developed self-inj ection devices can enable the patient to administer the injection from locations that do not have immediate access to medical professionals. In these instances, it would be crucial to have an easy and reliable method and apparatus to notify the patient and / or healthcare providers of any potential ISRs developed so that the injection can be ceased or adjusted to minimize the risk of additional severe adverse events.SUMMARY

[0004] Recognized herein is a need for new and / or improved apparatuses, systems, and methods for monitoring one or more health or physiological parameters or attributes before, during, and / or after the administration of medicaments (e.g., drugs), with such one or more physical parameters being indicative of the presence or the likelihood of injection site reactions (ISRs). Such apparatuses or systems can be useful, for example, in self-inj ections, clinical and / or regulatory procedures, and patient monitoring.

[0005] The present disclosure provides apparatuses, systems, and methods that can be used for a subject to monitor one or more health or physiological parameters or attributes before, during and / or after the administration of a substance (e.g., a medicament). In some embodiments, the one or more health or physiological parameters may be indicative of the presence or the likelihood of injection site reactions.

[0006] In an aspect, the present disclosure provides a method for detecting an injection site reaction in a subject, the method comprising: (a) securing a patch comprising a sensor to a body or portion of the subject; and (b) using the sensor of the patch to measure one or more health or physiological parameters from the subject. In some embodiments, the one or more health or physiological parameters are indicative of one or more of a presence, a likelihood, or a severity of the injection site reaction. In some embodiments, the one or more health or physiological parameters are selected from the group consisting of rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, and reflectance of the body or portion thereof.

[0007] In some embodiments, the body or portion thereof comprises skin. In some embodiments, the swelling is measured by an increase in skin surface area. In some embodiments, the method further comprises determining the one or more of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on measurements of the one or more health or physiological parameters of the subject over an extended period of time. In some embodiments, the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on measurements of the one or more health or physiological parameters of a third party individual over an extended period of time. In some embodiments, the measurements of the one or more health or physiological parameters of the third party individual are provided from a database of the one or more health or physiological parameters of the third party individual. In some embodiments, the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on one or more of a trend of the measured one or more health or physiological parameters or a metric derived from the measured one or more health or physiological parameters of the subject. In some embodiments, an injector is coupled to the patch. In some embodiments, the injector is removably coupled to the patch. In some embodiments, the injector is an autoinjector. In some embodiments, the injector comprises a reservoir comprising a substance, wherein the reservoir is in fluid communication with a cannula. In some embodiments, the method further comprises, subsequent to (a), directing the substance through the cannula into the body of the subject. In some embodiments, (b) occurs subsequently to the directing of the substance through the cannula into the body.

[0008] In some embodiments, the method further comprises receiving data from the patch and / or the injector. In some embodiments, data from the patch is received subsequent to (b).

[0009] In some embodiments, the method further comprises transmitting data indicative of the presence, the likelihood, or the severity of the injection site reaction to an electronic device in communication with a communication interface of the patch. In some embodiments, the communication interface comprises a wireless communication interface. In some embodiments, the electronic device comprises a mobile device. In some embodiments, the mobile device further comprises a mobile application. In some embodiments, the method further comprises, subsequent to (b), displaying the presence, the likelihood, or the severity of the injection site reaction on the mobile application. In some embodiments, the method further comprises using a processor of the electronic device to process the data indicative of the presence, the likelihood, or the severity of the injection site reaction.

[0010] In some embodiments, the sensor measures the one or more health or physiological parameters on a surface of the body of the subject. In some embodiments, the method further comprises notifying the subject of the one or more of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the notifying of the subject is performed automatically.

[0011] In another aspect, the present disclosure provides a system for detecting an injection site reaction in a subject, the system comprising: a patch comprising a sensor, the patch being configured to be secured to a body or portion of the subject, wherein the sensor is configured to measure one or more health or physiological parameters from the subject, wherein the one or more health or physiological parameters are indicative of a presence, a likelihood, or a severity of an injection site reaction; wherein the one or more health or physiological parameters are selected from the group consisting of rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, and reflectance of the body or portion thereof.

[0012] In some embodiments, the body or portion thereof comprises skin. In some embodiments, the sensor is configured to measure swelling by measuring an increase in skin area. In some embodiments, the system is configured to determine the one or more of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on measuring the one or more health or physiological parameters of the subject over an extended period of time. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on measurements of the one or more health or physiological parameters of a third party individual over anextended period of time. In some embodiments, the measurements of the one or more health or physiological parameters of the third party individual are provided from a database of the one or more health or physiological parameters of the third party individual. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on one or more of a trend of the measured one or more health or physiological parameters or a metric derived from the measured one or more health or physiological parameters of the subject.

[0013] In some embodiments, the system further comprises an injector configured to be coupled to the patch. In some embodiments, the injector is configured to be removably coupled to the patch. In some embodiments, the injector is an autoinjector. In some embodiments, the injector comprises a reservoir comprising a substance, wherein the reservoir is in fluid communication with a cannula. In some embodiments, the cannula is configured to direct the substance therethrough into the body of the subject. In some embodiments, the cannula is configured to direct the substance into the body before the sensor of the patch measures the one or more health or physiological parameters. In some embodiments, the injector comprises a receiver for receiving data from the patch. In some embodiments, the receiver of the injector is configured to receive the data from the patch before the sensor of the patch measures the one or more health or physiological parameters.

[0014] In some embodiments, the patch comprises a communication interface configured to transmit data indicative of the presence or the likelihood of the injection site reaction to an electronic device. In some embodiments, the communication interface comprises a wireless communication interface. In some embodiments, the electronic device comprises a mobile device. In some embodiments, the mobile device further comprises a mobile application. In some embodiments, the mobile application is configured to display the presence or the likelihood of the injection site reaction on the mobile application after the sensor of the patch measures the one or more health or physiological parameters. In some embodiments, the electronic device comprises a processor and a memory coupled to the processor and storing instructions for the processor to process the data indicative of the presence or the likelihood of the injection site reaction.

[0015] In some embodiments, the sensor of the patch is configured to measure the one or more health or physiological parameters on a surface of the body of the subject. In some embodiments, the patch is configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the patch is configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction automatically.

[0016] Additional aspects and advantages of the present disclosure will become readilyapparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0017] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” or “FIG.” herein), of which:

[0019] FIG. 1 shows a cross-section view of an exemplary injector attached to the body (e.g., skin) with the button up in a pre-fire state, according to many embodiments;

[0020] FIG. 2 shows a cross-section view of the injector attached to the body (e.g., skin) with button down in a first fired state, according to many embodiments;

[0021] FIG. 3 shows a cross-section view of the injector attached to the body (e.g., skin) with button down in a dispense state, according to many embodiments;

[0022] FIG. 4 shows a perspective view of an exemplary injector, according to many embodiments;

[0023] FIG. 5 shows a cross-section of the injector showing the injector with the button in the first position, according to many embodiments;

[0024] FIG. 6 shows a cross-section of the injector showing a dislodgment sensor nonengaged and the cannula locked in the dispense position, according to many embodiments;

[0025] FIG. 7 shows a cross-section of the injector showing a dislodgment sensor engaged and the cannula and button retracted to post-fire position, according to many embodiments;

[0026] FIG. 8 shows an exploded view of the injector and patch, according to many embodiments;

[0027] FIG. 9 shows a top side perspective view of the printed circuit board (PCB) chip of an exemplary patch, according to many embodiments;

[0028] FIG. 10 shows a bottom side perspective view of the PCB chip of the patch, according to many embodiments;

[0029] FIG. 11 shows another example of an exemplary patch, according to many embodiments;

[0030] FIG. 12 shows a perspective view of an exemplary patch with a pierceable membrane and an autoinjector the patch is configured to couple to, according to many embodiments;

[0031] FIG. 13 shows top side and bottom side perspective views of the patch with a pierceable membrane coupled to the autoinjector, according to many embodiments;

[0032] FIG. 14 schematically illustrates an example workflow of a mobile application, according to many embodiments;

[0033] FIG. 15 shows a computer system that is programmed or otherwise configured to implement methods provided herein, according to many embodiments;

[0034] FIG. 16 illustrates schematically an example workflow of the method of detecting a health or physiological parameter (e.g., an injection site reaction), according to many embodiments; and

[0035] FIG. 17 illustrates schematically an example workflow of the method of detecting an injection site reaction (ISR), according to many embodiments.DETAILED DESCRIPTION

[0036] While various embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions can occur to those skilled in the art without departing from the scope of the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein can be employed.

[0037] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0038] Whenever the term “no more than,” “less than,” or “less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than,” or “less than or equal to” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0039] The term “subject,” as used herein, generally refers to a user of a device, system, or method of the present disclosure, or an individual on which a device, system, or method of the present disclosure is being used. The subject can be a patient (e.g., a patient that is being treated or monitored by a physician or healthcare provider). As an alternative, the subject may not be a patient. The subject can have or be suspected of having a disease or disorder. As an alternative, the subject can be asymptomatic with respect to a disease or disorder. The subject can be a vertebrate, a mammal (e.g., human or animal), a non-human primate, etc. The subject can be an animal, such as a rodent (e.g., rat or mouse), a canine (e.g., dog), a feline (e.g., cat), a bovine, or other animal.

[0040] The term “medicament,” “drug,” “substance,” or “medication,” as used interchangeably herein, generally refers to a substance that is used for treating a health or physiological state or condition of a subject (e.g., medical treatment). The medicament can be a drug or therapeutic agent. The medicament can be a solid, semi-solid, liquid, gas, or combinations thereof. The medicament can be an aerosol, pill, tablet, capsule, pastille, elixir, emulsion, effervescent powder, solution, suspension, tincture, liquid, gel, dry powder, vapor, droplet, ointment, or a combination or variation thereof. A medicament can be used to treat an illness, ailment, or disease, or can be used as a health supplement (e.g., vitamins, minerals, probiotics, etc.).

[0041] The term “injection,” “delivery,” or “infusion,” as used interchangeably herein, generally refers to a process to inject a medication to a subject.

[0042] The present disclosure provides devices, methods, and systems for delivering a substance (e.g., a medicament) to a subject and monitoring the subject prior to, concurrently with, and / or subsequent to delivering the substance. In some embodiments, the present disclosure provides devices, methods, and systems for monitoring one or more health or physiological parameters prior to, concurrently with, and / or subsequent to delivering the substance. In some embodiments, the present disclosure provides devices, methods, and systems for monitoring an injection site reaction concurrently with and / or subsequent to delivering the substance. In some embodiments, the present disclosure provides devices, methods, and systems for monitoring an injection site reaction during and / or following delivering the substance. A device of the disclosure can be an injector that delivers the medicament. Alternatively, or inaddition to, the device can be a patch that is configured to monitor the subject and / or communicate with the injector. In some embodiments, the injector and patch may be separate devices (e.g., separable from each other). In some embodiments, the injector and patch may be removably coupled to each other. As an alternative, the injector and patch can be part of a single device (e.g., not separable from each other).

[0043] In an aspect, the present disclosure provides a method for monitoring one or more health or physiological parameters. In some embodiments, the present disclosure provides a method for monitoring injection site reactions (ISRs). The method can comprise (a) securing a patch comprising a sensor to a body or a portion of the body of a subject, and (b) using the sensor to measure one or more health or physiological parameters from the subject. In some embodiments, the one or more health or physiological parameters is indicative of one or more of a presence, a likelihood, or a severity of an injection site reaction (ISR). In some embodiments, the patch can be secured to the body or the portion of the body of subject at or near an injection site. In some embodiments, the measuring one or more health or physiological parameters can be accomplished from at or near the injection site of the body or the portion of the body of the subject. In some embodiments, the measuring one or more health or physiological parameters can be accomplished not at or near the injection site of the body or the portion of the body of the subject.

[0044] ISRs can come in different forms, including pain, swelling, itching, rash, bleeding, or redness at or around the site of injection. Medical professionals often advise patient to stay in proximity to the medical professionals after the injection for the observation of any potential ISRs. If any ISRs occur, the medical professionals can attend to such ISRs immediately. In some cases, the physician medical professionals might be reluctant to let the patient self-administer at home because of potential adverse reactions. If a system is able to monitor for any potential complications (ISRs, heart rate, respiration, temperature, etc.), and transmit a signal to the medical professionals in cases of anything unusual, it might give the medical professionals confidence to send the patient home for injections or let the patient self-administer. In an outcome-based healthcare model, there is a significant benefit to the system knowing that the patient is improving with the therapy with quantitative data as evidence. In the instance where the patient’s health is acutely changing or over the long-term, the ability for a treating medical professional to get involved earlier through notification based on trends of continuously accumulated data and intervene has long term benefit to the patient and overall outcome.

[0045] This type of detachable monitoring patch can also be useful in clinical studies. The patients could be monitored for a variety of parameters during the study that could increase compliance and reduce complications and could even make enrollment easier. For example, if apatient is required to remain in a physician’s office for a few hours after each injection to monitor for ISRs, they might be able to eliminate this wait with the patch monitoring, which could result in improved recruitment. Moreover, such a device can allow for longitudinal studies that measure patient compliance and that provide for increased accuracy of data transmission (e.g., by obviating the need for manual recording of data).

[0046] In some embodiments, the method can further comprise providing an injector to deliver a medicament. In some embodiments, the injector can be coupled to the patch. In some embodiments, the injector can be removably coupled to the patch. An injector can be any suitable injector, for example, a syringe, a wearable autoinjector, or an autoinjector pen. In some embodiments, the injector can be any injector as disclosed in PCT / US2019 / 069142, PCT / US2021 / 039545, or PCT / US2018 / 034486, all of which are incorporated by reference herein in their entirety.

[0047] In some embodiments, the injector can comprise a reservoir comprising a substance, e.g., a medicament. In some embodiments, the reservoir can be in fluid communication with a cannula. In some embodiments, the injector can use the cannula to transfer / deliver the substance to the body of the subject. In some embodiments, the injector can direct the substance through the cannula to the body of the subject prior to, concurrently with, or subsequent to using the sensor to measure one or more health or physiological parameters from the subject.

[0048] FIGS. 1-3 show an example injector 7. FIG. 1 shows a cross-section view of an exemplary injector attached to the body (e.g., skin) with the button up in a pre-fire state. Referring to FIG. 1, the injector 7 can comprise a reservoir 71 for storage of a substance and the reservoir 71 may be in fluid communication with a cannula 85. The injector 7 can comprise an actuator or button 77 that the subject or user depresses on the injector 7 to start the injection.The button 77 can be configured to be an on / off switch, i.e., to have two states, open and closed such as a light switch. Once activated, button 77 can direct the cannula 85 rapidly into a body or a portion of the body of a subject, e.g., a skin 99, independent of the user manipulation of the button 77. Alternatively or in conjunction, the button 77 can have a continuous motion, allowing the user to slowly direct the cannula 85 into skin 99. The button 77 can preferably be directly coupled to the cannula 85 by using adhesive 104.

[0049] FIG. 2 shows a cross-section view of the injector attached to the body (e.g., skin) with button down in a first fired state. Upon actuation of the button 77, the cannula initially advances to a first position or depth as shown in FIG. 2 and may then retract slightly to a second position of depth, in some cases automatically, as shown in FIG. 3. The first depth shown in FIG. 2 can be achieved from an over advancement of the button 77 during actuation. The first depth can be controlled by features 105 in the button 77 in direct contact with the base 106 ofthe injector 7. The final depth of the cannula 85 may be suitable for subcutaneous injections. Alternatively or in conjunction, the final depth of the cannula 85 can be reduced for intradermal injections. Alternatively or in conjunction, the final depth of the cannula 85 can be increased for intramuscular injections. FIG. 3 shows a cross-section view of the injector attached to the body (e.g., skin) with button down in a dispense state. Upon reaching the first depth, the cannula 85 can retract away from the body of the subject to a second depth as shown in FIG. 3. The retraction distance of the cannula to the second depth can be in the range of 0.1-2 millimeters (mm). This retraction feature can be used, in such cases, to prevent the cannula 85 from being blocked by tissue during the initial insertion process. This tissue blockage could require a very high pressure to overcome and prevent the injector 7 from delivering the drug. The retraction of the cannula 85 from the first position to a second position can generate an open pocket ahead of the cannula tip 107, which may allow reduced pressure for initiation of flow of drug from the cannula 85. This reduced pressure for initiation of the flow of drug from the cannula may be necessary, in some instances, for the injector 7 to maintain a relatively constant pressure, to direct the substance through the cannula during injection.

[0050] The injector 7 can include a cannula 85 with a side opening 108. As shown in FIG. 3, once the button 77 on the injector 7 is fully depressed, the cannula 85 may be fully inserted into the skin 99 through the dispense port 82 and the injector 7 can begin dispensing of the substance. Until the button 77 is fully depressed, the side opening 108 and therefore the internal lumen of the cannula 85 may not be in communication with the fluid channel 86 of the dispense port 82. Both the side opening 108 and cannula tip 107 can be retained within a septum 109. With the side opening 108 and cannula tip 107 being retained within the septum 109, the entire drug path may be kept sterile until the time of use. When the button 77 is fully depressed and the cannula 85 is in the dispense position, the side opening 108 in the cannula 85 may be put in communication with the fluid channel 86 of the dispense port 82 and the injection of the substance (e.g., injectable medicament or fluid) can begin.

[0051] The septum 109 can provide the advantage of sealing the cannula tip 107 as well as the side opening 108 from the substance (e.g., injectable medicament or fluid) before and after dispensing. Sealing the cannula tip 107 and the side opening 108 of the cannula 85 at the end of the injection may have a particular advantage to prevent dripping of the substance (e.g., injectable liquid) from the injector 7 after end of dispense and / or after it is removed from the skin surface. It can also prevent contaminants from entering the hollow cannula prior to being actuated into the skin. The septum 109 can comprise a pierceable membrane that can be made of any suitable material to allow for sealing once the cannula 85 has punctured it. The material composition of septum 109, or of the pierceable membrane, can comprise silicone.Alternatively or in conjunction, the material composition of the septum 109, or pierceable membrane, can also be a blend of different materials including but not limited to bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, PTFE, natural rubber and silicone. Alternatively or in conjunction, the fluid pathway 86 including the dispense port 82 could comprise a rigid plastic with a silicone injected over mold to produce the septum previously described.

[0052] The septum 109 at the dispense port 82 can protrude slightly from the underneath surface into the skin surface 99 of the injector 7 to provide for pressure on the skin surface 99 at the injection site. This pressure on the skin surface 99 by the dispense port 82 after the cannula is retracted could eliminate the substance from coming out of the injection site commonly referred to as blowback.

[0053] The injector 7 can include a set of spring tabs 110 that interface with the button 77 to perform locking functions. A spring tab 110 may be biased to lock into an undercut 111 in the button 77 to keep the button 77 in a first up position or pre-fire position as shown in FIG. 10. The geometry of the undercut 111 and spring tab 110 may help to produce the light switch actuation force described previously. This light switch actuation may be accomplished by the translation of the button 77 relative to the spring tab 110 and the geometry of the mating undercut 111 surfaces.

[0054] The injector 7 can include a spring tab 112 that interact with the button 77 in the injector 7 to perform locking functions such that when the button 77 is actuated to the first depth and retracts slightly back to the second depth or dispense position, undercut features 113 in the button 77 allow a spring tab 112 to hold the button 77 in the dispense position until the injector 7 has completed dispensing.

[0055] In some embodiments, the patch may comprise a membrane that is not pierced during injection. The membrane may comprise an opening (e.g., slit, hole) through which the cannula of the injector may pass when the cannula is directed from the injector to the body of the subject, and the opening may close following retraction of the cannula. The opening of the membrane may be pre-formed, or the opening may be generated (e.g., via piercing of the membrane). For instance, the membrane may be provided in an “open” configuration, in which the membrane is stretched by a mechanism (e.g., a “tissue tent” structure) on the patch and providing the opening. When the injector is separated from the patch, the mechanism may toggle to a “closed” configuration (e.g., via removing the “tissue tent” structure from the patch, thereby biasing the membrane to the closed configuration), and the membrane may return to the state prior to stretching. In some embodiments, the membrane may adhere or otherwise be secured to the body of the subject. In some embodiments, the membrane may comprise an absorbent material,e.g., to absorb bodily fluids (e.g., blood, sweat, etc.) from the subject. It will be appreciated that any of the above-described embodiments may comprise a patch comprising one or more sensors (e.g., on the PCB chip), and alternatively or in addition to, the patch may comprise the membrane, which may comprise an absorbent material.

[0056] In some embodiments, the patch comprises a bandage, which may be deposited on the body of the subject. The bandage may be deposited prior to or following injection. The bandage may comprise one or more polymeric materials. The polymeric materials may be naturally occurring or may be synthetic. Non-limiting examples of polymeric materials include poly vinyl chloride (PVC), polyethylene, polyurethane. In some embodiments, the bandage may further comprise an adhesive layer (e.g., acrylate, methacrylate, epoxy diacrylate, or other vinyl resins, etc.). In some embodiments, the bandage comprises a self-healing polymer or elastomeric material. In some embodiments, the bandage includes an opening, e.g., hole or slit that is configured to form a seal in the absence of the cannula directed through the opening. In some embodiments, the bandage may include an opening that is not configured to seal in the absence of the cannula directed through the opening. The opening may be any suitable shape, e.g., a slit, triangular, square, rectangular, rhombus, pentagonal, hexagonal, heptagonal, octagonal, polygonal, ellipsoid, annular, circular, etc. In some embodiments, the bandage comprises an absorbent material, e.g., cotton, rayon, nylon, a polymer, a polymer blend, etc. In some embodiments, the bandage can collect bodily fluids (e.g., sweat, blood, etc.) from the body of the subject. In some embodiments, the bandage may comprise an oxygen-permeable material, which may allow for exposure of the body of the subject, or portion thereof, to the ambient air. In some embodiments, the bandage may comprise a medicament (e.g., analgesic or medicament for treating pain).

[0057] When administering an injection with a syringe or cannula that is meant to be infused under the skin, it can be desirable to know if the cannula is properly placed within the skin or improperly placed within a blood vessel. It is common for a user performing an intradermal (ID), subcutaneous (SC), or intramuscular (IM) injection to aspirate the syringe by pulling back on the plunger to create a pressure drop within the syringe to see if any visible blood comes up the cannula into the syringe. Blood being visualized means the tip of the cannula is in a blood vessel. A number of injectable drugs meant for infusion under the skin specifically indicate not to inject into a blood vessel. Blood aspiration using a syringe and cannula can be performed by anyone with adequate training. In some cases, an autoinjector can be used, and the autoinjector can comprise a mechanism for determining whether the autoinjector is properly placed.

[0058] Referring to FIG. 4 and FIG. 5, the injector 7 can have a cannula 85 with a side opening (e.g., hole) 108 in operative engagement with the button 77 slidable within a septum109 advancing into the skin 99. The button 77 can have a viewing window 160 on the button top 103 that is in fluid communication with the proximal end 161 of the cannula 85. The button top 103 can comprise a cavity 162 for blood 159 to accumulate and be seen through the button window 160 by a user. The cavity 162 can include a center hole 163 that allows fluid communication with the proximal end 161 of the cannula 85 via cannula lumen 165. The outer walls 164 of the cavity 162 may be formed by the button top 103. Additionally, a portion of the outer walls 164 can include a hydrophobic filter 166. In this configuration, the proximal end 161 of the cannula 85 may be at atmospheric pressure. If fluid 14 or blood 159 travels up the internal lumen 165 of the cannula 85, it may exit the proximal end 161 of the cannula 85 and fills the cavity 162. The air 167 in the cavity 162 can be easily displaced through the hydrophobic filter 166 until all of the air 167 has been displaced from the cavity 162 and it is full of fluid 14 or blood 159. At this point, the flow of fluid 14 or blood 159 may stop as the fluid 14 or blood 159 cannot penetrate the hydrophobic filter 166 and can be easily viewed through the window 160 of the button top 103 by the user thus providing a method for determining if the cannula 85 is in a blood vessel 158.

[0059] Alternatively or in conjunction, a sensor can detect if the cannula 85 is in a blood vessel 158. In some embodiments, the cannula 85 can comprise a transparent or semitransparent portion that a source of light can pass through. If the cannula 85 is in a blood vessel 158, blood can backflow to the cannula. A sensor can detect a presence of a fluid in the cannula or detect a color change within the cannula. In some embodiments, infrared sensors can be embedded in the injector to detect the fluid in the cannula. Once such fluid is detected, the sensor can show or send an indication to the subject or the user. In some embodiments, the indication could be in the form of a visual indictor, audible sound, mechanical movement, or a combination thereof. In some embodiments, the injector can comprise a response mechanism to retract the cannula from the body of the subject so as to be retracted from the blood vessel. Alternatively or in combination, the user can retract the injector manually.

[0060] In some embodiments, the sensor can be secured to a body or a portion of the body of the subject. In some embodiments, the portion of the body can comprise a trunk, a torso, or an arm of the subject. In some embodiments, the portion of the body comprises skin.

[0061] In some embodiments, using the sensor to measure one or more health or physiological parameters from the subject can occur subsequent to the directing of the substance to the body of the subject. In some embodiments, the measurement can initiate immediately after injection starts, e.g., the substance is directed to the body of the subject. In some embodiments, the measurement can initiate about 0.1 min, about 0.5 min, about 1 min, about 1.5 min, about 2 min, about 3 min, about 4 min, about 5 min, about 6 min, about 7 min, about 8 min,about 9 min, about 10 min, or more, after the substance is directed to the body of the subject.

[0062] In some embodiments, the sensor can measure one or more health or physiological parameters on a surface of the body or the portion of the body of the subject. In some embodiments, the sensor can measure one or more health or physiological parameters underneath a surface of the body or the portion of the body of the subject.

[0063] When performing self-inj ections with automatic injectors, protecting the user from accidental cannula sticks is a beneficial requirement for the device. Typically, the cannula is retracted within the device before and after use, preventing the user from accessing the cannula. However, during the injection, the cannula can be extended outside of the device. In some embodiments, the automatic injector can comprise a skin dislodgement sensor to automatically retract a cannula if the device becomes dislodged from the skin during the injection.

[0064] Referring to FIGS. 6-7, a skin dislodgement sensor 179 can be in operative engagement with a flexible latch 181 of the button 77 and slidable within the lower housing 180 of the injector 7. Referring to FIG. 6, when the injector 7 is attached to the skin surface 99, the skin dislodgement sensor 179 is forced into a first or up position 182 inside the injector 7. When the button 77 is actuated to a fired state or second position or dispense position (exposing the cannula 85), the flexible latch 181 may be forced into a lock position 187 by the skin dislodgement sensor 179 under the latch board 183. The latch board 183 can hold the button 77 at the latch board surface 184 on the button 77 down in the fired state or dispense position until the end of dispense. At the end of dispense, the latch board 183 may translate away from the latch board surface 184 on the button 77, allowing the button 77 and cannula 85 to retract to a post fire position where the cannula 85 is contained within the injector 7. Referring to FIG. 7, in the event that the injector 7 becomes dislodged from the skin surface 99 during injection, the skin dislodgement sensor 179 may extend to a second or down position 185 out of the injector 7. This extension may allow the flexible latch 181 to spring back to an unlocked position and disengage from the latch board 183. This disengagement may allow the button 77 and cannula 85 to retract to a post fire position where the cannula 85 is contained within the injector 7.

[0065] In some embodiments, the system for measuring a health or physiological parameter (e.g., an injection site reaction) can comprise an injector and a patch removably coupled to each other, wherein the patch comprises a sensor. The cannula of the injector can be configured to extend towards or retract away from the body of the subject. In some examples, the cannula extends towards the body of the subject to deliver the substance into the body of the subject (e.g., across a skin of the subject). Subsequent to delivery of the substance, the cannula can retract away from the body of the subject. The cannula can be connected to the reservoir via a fluid flow path. The cannula can extend to and / or retract from the body using a variety ofmechanisms, e.g., mechanical, electrical, etc. The means for cannula extension and retraction can comprise pumps, springs, gears, diaphragms, screws, or other means to move the cannula, or variations or combinations thereof.

[0066] The patch can comprise a first housing, and the injector can comprise a second housing. In some embodiments, the first and second housing can be removably coupled. In some embodiments, the first housing of the patch can be mechanically coupled to the second housing of the injector using one or more fastening mechanisms. In some cases, the first housing and / or the second housing can comprise magnets that allow for removable coupling. In some embodiments, the first housing and the second housing can be adhered, e.g., using adhesive tape. The adhesive force of the first housing and the second housing can be modulated based on desired properties. In some embodiments, it can be desirable to maintain the patch on the body of the subject while removing the injector. In some embodiments, an adhesive layer can be added to the patch that can facilitate securing of the patch to the body of the subject. This bodyadhering adhesive layer can have a stronger adhesive force between the patch and the body of the subject than the adhesive force between the patch and injector. In some embodiments, the first housing and the second housing can be mechanically coupled, e.g., using interlocking geometries of the first housing and the second housing. For example, the first housing can comprise threads (e.g., screw threads, internal threads, etc.) and the second housing can comprise complementary threads that can engage with the threads of the first housing. In conjunction or alternatively, the first housing and / or the second housing can comprise snap-fit joints (e.g., cantilever snap fits, annular snap fits, etc.) that allow for interlocking of the first housing to the second housing. Alternatively, or in conjunction, the first housing and / or the second housing can comprise components that allow for interference fits, force fits, shrink fits, location fits, etc. Other examples of fastening mechanisms can include, in non-limiting examples, form-fitting pairs, hooks and loops, latches, threads, screws, staples, clips, clamps, prongs, rings, brads, rubber bands, rivets, grommets, pins, ties, snaps, Velcro, adhesives (e.g., glue), tapes, vacuum, seals, a combination thereof, or any other types of fastening mechanisms. Alternatively, the injector can be permanently attached to the patch. For example, the first housing can be connected to the second housing or can be monolithically built into the second housing, or vice-versa.

[0067] In some embodiments, the patch and the injector can be fastened to each other via complementary fastening units. For example, the patch and the injector, or the housing of the patch and the housing of the injector, can complete a form-fitting pair. The patch can comprise a form-fitting male component and the injector can comprise a form -fitting female component, or vice versa. In some instances, an outer diameter of a protrusion-type fastening unit of thepatch can be substantially equal to an inner diameter of a depression-type fastening unit of the injector, or vice versa, to form an interference fit. Alternatively, or in addition, the patch and the injector can comprise other types of complementary units or structures (e.g., hook and loop, latches, snap-ons, buttons, nuts and bolts, magnets, etc.) that can be fastened together. Alternatively, or in addition, the patch and the injector can be fastened using other fastening mechanisms, such as but not limited to staples, clips, clamps, prongs, rings, brads, rubber bands, rivets, grommets, pins, ties, snaps, Velcro, adhesives (e.g., glue), magnets or magnetic fields, tapes, a combination thereof, or any other types of fastening mechanisms.

[0068] In some embodiments, the patch and the injector can be fastened to each other via an intermediary structure. In some embodiments, the intermediary structure can be fastened to one or both of the patch and the injector through one or more of any of the fastening mechanisms described herein. The intermediary structure can comprise a solid material, semi-solid material, liquid material (e.g., a resin that is configured to solidify), or multiple material types. In some embodiments, the intermediary structure can undergo phase transitions (e.g., liquid to solid for an adhesive). For example, the intermediary structure can comprise a fluid adhesive that solidifies to achieve the fastening. In some embodiments, the intermediary structure can be capable of transforming from a first phase to a second phase, such as from liquid to solid or from solid to liquid, upon application of a stimulus (e.g., thermal change, pH change, pressure change, applied force, etc.) to achieve fastening or unfastening (or both). In some embodiments, the patch and / or the injector can comprise the intermediary structure. For example, the intermediary structure can be integral to the patch and / or the injector.

[0069] The fastening between the patch and the injector can be temporary, such as to allow for subsequent fastening and unfastening of the patch and injector without damage (e.g., plastic deformation, shear deformation, wear, compression deformation, etc.) to the patch or injector. Alternatively, the fastening can be permanent, such as to allow for subsequent unfastening of the two patches from the injector. In some cases, it can be desirable to deform either the patch or injector, and either the patch or injector can temporarily or permanently be deformed (e.g., stretched, compressed, etc.) and / or disfigured (e.g., bent, wrinkled, folded, creased, etc.) or otherwise manipulated when fastened to the injector or patch. The opening can comprise a pierceable membrane. The pierceable membrane can be pierced by the cannula to generate the opening. The pierceable membrane can be formed of a polymeric material, or the pierceable membrane can be formed of multiple polymeric materials. The polymeric materials can be naturally occurring or can be synthetic. Non-limiting examples of polymeric materials include poly vinyl chloride (PVC), polyethylene, polyurethane. In some cases, the pierceable membrane can further comprise an adhesive layer (e.g., acrylate, methacrylate, epoxy diacrylate, or othervinyl resins, etc.). In some cases, the pierceable membrane can comprise a self-healing polymer or elastomeric material, such that the opening that is introduced by the cannula can be closed, e.g., after cannula retraction. In such cases, the pierce-able membrane can include an opening, e.g., hole or slit that is configured to form a seal in the absence of the cannula directed through the opening. In some examples, the pierceable membrane can include an opening that is not configured to seal in the absence of the cannula directed through the opening. Alternatively, the opening may not comprise a pierce-able membrane and the opening can be configured to be in direct line of sight with the body of the subject. The opening can be any suitable shape, e.g., a slit, triangular, square, rectangular, rhombus, pentagonal, hexagonal, heptagonal, octagonal, polygonal, ellipsoid, annular, circular, etc. In some cases, the pierceable membrane comprises an absorbent material, e.g., cotton, rayon, nylon, a polymer, a polymer blend, etc. In such cases, the pierceable membrane can be used as a bandage and can collect bodily fluids (e.g., sweat, blood, etc.) from the body of the subject. In some instances, the pierceable membrane can comprise an oxygen-permeable material, which can allow for exposure of the body of the subject, or portion thereof, to the ambient air. In some cases, the pierceable membrane can comprise a medicament (e.g., analgesic or medicament for treating pain).

[0070] In some embodiments, the patch can be coupled to the injection via a latch. The latch can be coupled to the injector using a press-fit mechanism and subsequent pushing or applying force to the latch can result in detachment of the patch from the injector. Alternatively or in addition to, the latch can comprise a hook that can adhere to the housing of the injector. The latch can then be actuated by pressing or applying a force on the latch and pulling the latch away from the housing of the injection, which allows for detachment of the patch from the injector. In some embodiments, the patch can be coupled to the injector via flanges and a ring. The ring can comprise a rubber or other elastomeric material. The ring can couple to the injector by fitting into the grooves of the flanges. In some embodiments, the housing of the patch can partially surround the housing of the injector. The patch can comprise winged feature allowing for better grip of the subject or for positioning the device.

[0071] In some embodiments, a dimension of the patch (e.g., the width or diameter) can be substantially similar as the diameter of the injector. In some embodiments, a dimension of the patch can be smaller than the diameter of the injector.

[0072] In some embodiments, the reservoir can be secured to the injector. In some embodiments, the reservoir is removable from the injector. In some embodiments, the reservoir can comprise a container or be a part of a container. The reservoir container can be removably coupled to the injector (e.g., attach and detach from the housing of the injector). The housing can contain fasteners to secure the reservoir. Alternatively, or in conjunction, the geometry of theinjector can be designed to fit the reservoir or reservoir container. In some embodiments, the reservoir can be part of the injector (i.e., not removable). In some embodiments, a medicament reservoir can be provided in the housing and can be in fluid communication with the injection cannula. In some embodiments, the injection cannula can be moveable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir. The reservoir can be configured to contain a formulation having the substance.

[0073] In some embodiments, the substance can comprise a medicament. In some embodiments, the medicament may be any suitable medicament therapeutically effective when delivered subcutaneously. In some embodiments, the medicament can be a solution or a mixture. In some embodiments, the medicament can be used for treating diseases in a range of therapeutics areas including but not limited to cardiovascular, musculoskeletal, gastrointestinal, dermatology, immunology, ophthalmology, hematology, neuroscience, oncology, endocrinology / metabolic and respiratory. The medicament can be used to treat discomfort or pain of the subject. For instance, the medicament can comprise an analgesic, non-steroidal inflammatory drug (NSAID), or other pain-reducing, pain-alleviating, or other pain management substance. In some embodiments, the medicament can comprise a drug for treating diabetes. In some embodiments, the medicament can comprise insulin. In some embodiments, the medicament can comprise an incretin. In some embodiments, the medicament can comprise glucagon-like peptide-1 (GLP-1) agonists, e.g., dulaglutide (Trulicity), bydureon bcise, exenatide (Byetta), Semaglutide (Ozempic), Liraglutide (Victoza, Saxenda), and Lixisenatide (Adlyxin). In some embodiments, the medicament can comprise a drug to reduce blood clotting. In some embodiments, the medicament can comprise heparin. In some embodiments, the medicament can comprise a low molecular weight heparin, e.g., enoxaparin. In some embodiments, the medicament can comprise a human growth hormone, e.g., somatropin. In some embodiments, the medicament can comprise a fertility drug, e.g., ganirelix, menotropins, and human chorionic gonadotropin. In some embodiments, the medicament can comprise a drug to treat allergic reactions, e.g., epinephrine. In some embodiments, the medicament can comprise a drug for immunotherapies. In some embodiments, the medicament can comprise interferons or monoclonal antibodies, e.g., adalimumab, omalizumab, mepolizumab, and reslizumab.

[0074] In some embodiments, the housing of the patch and / or the housing of the injector can comprise one or more polymer or plastic materials. Non-limiting examples of polymers include polyamides, polycarbonate, polyester, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyvinylidene chloride, acrylonitrile butadiene styrene, polymethyl methacrylate, polytetrafluoroethylene, polyimide, polylactic acid, phenolics, polyetheretherketone, or derivatives thereof (e.g., highly cross-linked, high density, etc.). Thehousing of the patch and / or the housing of the injector can comprise a single polymer type (e.g., a homopolymer) or more than one polymer type (e.g., a copolymer) and comprise a random or arranged organization of monomers. For example, a polymer can be a block polymer, an alternating copolymer, periodic copolymer, statistical copolymer, stereoblock copolymer, gradient copolymers, branched copolymers, graft copolymers, etc.

[0075] As illustrated in FIG. 8, a device for injecting a substance and measuring an injection site reaction can comprise an injection 402 and a patch 412. The patch 412 can comprise a sensor 422, a printed circuit board (PCB) chip 424, and a sensor adhesive layer 426. The PCB chip 424 and the sensor adhesive layer 426 can be secured to the sensor 422 by adhesive or other fastening mechanisms. The sensor adhesive layer 426 can comprise a central window 428 through which, after assembly, the extension 414 protrudes. The downward facing surface 430 of the sensor adhesive layer 426 is provided with an adhesive for securing the patch to the skin of a user.

[0076] In some embodiments, the injector 402 and the patch 412 may be configured so that the patch is applied to the body (e.g., skin, digits) of a subject (e.g., user) as the injector is attached. In some embodiments, the patch 412 may remain attached to the body after the injector 402 is removed. In some embodiments, a number of permanent magnets 432 may be positioned and secured within the housing of the injector 402. In some embodiments, the magnets can be secured within corresponding recesses 434 formed within the injector housing by adhesive, interference fit or other attachment arrangements, as described elsewhere herein. The top side of the sensor 422 features a metallic disk portion 436 so that the patch is secured to the bottom of the injector via magnetic attraction. The adhesive on surface 430 of the sensor adhesive layer 426 provides a holding force with the user’s skin that is greater than the magnetic force holding the patch to the injector. As an alternative to disk portion 436 being metallic, the disk portion can be provided with metallic portions that correspond to and attract the magnets of the injector. In an alternative embodiment, the metallic portion(s) of the patch can be provided with other shapes. In some embodiments, a single ring-shaped metallic portion could also be used.

[0077] As illustrated in FIG. 9 and FIG. 10, the PCB chip 424 may comprise a circuitry including a Bluetooth module with microcontroller / microprocessor 444 that is connected to a battery 442 and antenna 448. In addition, the Bluetooth module 444 may be attached to sensor 422. The battery 442 provides for the stored energy to power the system. The Bluetooth module 444 may have an integrated microcontroller / microprocessor. An example of a suitable Bluetooth module is Dialog Semiconductor Part number DA14580-01UNA. In alternative embodiments, the Bluetooth module can be separate from the microcontroller / microprocessor.In some embodiments, direct communication to the cloud can be used, such as, e.g., via cellular or other communication technologies.

[0078] In some embodiments, the system may comprise one or more sensors disclosed herein. In some embodiments, the system may comprise one or more controllers to activate the one or more sensors. In some embodiments, a first sensor may be activated to measure a first health or physiological parameter. In some embodiments, a second sensor may be activated to measure a second health or physiological parameter. In some embodiments, the first sensor and the second sensor may be activated at the same time. In some embodiments, the first sensor may be activated prior to the second sensor. In some embodiments, the second sensor may not be activated if the first sensor has provided sufficient information of the subject that the second health or physiological parameter is not needed. In some embodiments, the second sensor may be activated only if the first sensor does not provide sufficient information of the subject that the second health or physiological parameter is needed.

[0079] As illustrated in FIG. 11, the injector 402 may be provided with one or more sensors (e.g., 450a and 450b) that communicate with the Bluetooth module 444 via Bluetooth. The sensors 450a and 450b can include transmitters and can receive power from a battery also positioned within the injector housing. Alternatively, each sensor can have its own battery. Sensors 450a and 450b can also be passive sensors that do not require battery power. The sensors 450a and 450b can be chosen to provide a variety of alternative functions. In some embodiments, the sensors 450a and / or 450b can be configured to measure one or more device parameters, e.g., a dosage of the substance that is administered, a flow rate of dispensing of the substance, a duration of substance administration or injection, a volume of the substance that is administered, an occlusion of the cannula, and contact of the cannula into the body of the subject. In some embodiments, the sensors 450a and 450b can be configured to measure one or more health or physiological parameters as disclosed herein. In some embodiments, the sensors 450a and / or 450b can be a temperature sensor, humidity sensor, flow rate sensor, button position sensor, strain sensor, force sensor, pressure sensor, image sensor, durometer, vibration sensor, audible sensor, or skin sensor.

[0080] In alternative embodiments, communication between the sensors 450a and 450b of the injector and the module 444 of the PCB chip 424 of the patch can be accomplished by alternative wireless communication arrangements know in the art. In further alternative embodiments, the sensors 450a and 450b can communicate with the module 444 of the PCB chip 424 via wire connect! on(s) that automatically disconnect when the injector is removed from the patch and patient.

[0081] In some embodiments, the Bluetooth module 444 may enable the patch to transmitdata collected from sensors 422, 450a and 450b to a remote receiver such as a personal data device (such as a smart phone), a computer system or network or the cloud. The remote receiver can collect the received data within, and build, a database.

[0082] In the illustrated embodiments, the patch 412 may have multiple functions. First, it may sense and transmit the state of the injector to a remote receiver (such as a personal data device, for example, a smart phone, a computer network, or the cloud), i.e., has the injector been activated so that the injection is being given or has the injection been completed. Secondly, the patch may transmit the state of the patient via data collected from the sensors to the remote receiver. This transmission can be done before, during or after the injection and before, during or after attachment and or removal of the injector. The patch may transmit to a receiver the one or more health or physiological parameters detected by the sensor 422 during and after the injection. This feature can be useful to notify a patient, a caregiver, or a staff, e.g., during a selfinjection or a clinical study, if there is an ISR, and it could quantify the ISR based on the one or more health or physiological parameters. Thirdly, the patch could interact directly with the injector based on data received from the injector and / or data received from the patient and / or data received from itself (e.g., the sensor). The patch could interact with the injector as a control mechanism including adjustment of the flowrate (faster, slower, or pause), vibrate for user notification and / or pain management, provide an audible sound to provide direction or notification to the user, visual indicators to indicate change, alerts, notifications or information to the user, or mechanical interactions to cause a change in state of the injector including but not limited to retraction of the button to stop the delivery in the instance of data from the patient (for example, pain) or data from the device (for example, premature removal or fall-off).

[0083] Alternatively, the patch could be applied independently of the injector and placed on the patient to monitor baseline conditions (e.g., a baseline physiologic parameter) before the start of the administration / inj ection of drug or drugs. The injector could then be coupled to the patch prior to start of the injection.

[0084] In some examples, the patch can be configured to couple to an autoinjector. FIG. 12 shows an example patch comprising a pierceable membrane coupled to an autoinjector 9307. The patch 9301 includes an adhesive layer 9303. The patch can also comprise a sensor (not shown) that can adhere to the adhesive layer 9303. The adhesive layer 9303 can be used to secure the patch 9301 to the body of the subject, and in some cases, the adhesive layer 9303 can be secured to the body of the subject. In such cases, the adhesive layer 9303 comprises an absorbent material (e.g., bandage pad) and will remain on the body of the subject following injection. The patch 9301 can be configured so that the patch 9301 is applied to the body of the subject, which can be secured separately from the autoinjector 9307. Alternatively, or inaddition to, the autoinjector 9307 and the patch 9301 can be coupled prior to securing the patch 9301 to the body of the subject, as shown in FIG. 13. The patch can also comprise an opening 9321, which can be a part of a pierceable membrane 9323. In some cases, the opening 9321 is a slit, and the material of the pierceable membrane 9323 comprises a self-healing elastomer (i.e., the opening closes after the cannula is retracted away from the body of the subject). The adhesive layer 9303 of the patch 9301 can comprise a feature 9311 (e.g., tab), which can allow for separation of the adhesive layer 9303 of the patch 9301 from the autoinjector. In some instances, the patch 9301 can also comprise a sensor unit 9305, which can comprise a PCB chip.

[0085] Embodiments of the disclosure provide a combination of reporting both the injector and the patient state during and after the injection. The patch and associated battery and circuitry may be initially physically coupled to the injector. In an alternative embodiment, the patch could be applied and allow for connection of the one or more injectors. The patch circuit can communicate, e.g., via a communication interface, to the receiver the one or more parameters of the injector before being secured to the patient. Once the patch / injector is secured to the patient, the patch can communicate both the patient and injector states. When the injector is removed, the patch remains on the patient directly on the injection site to transmit the state of the injection site. The patch could remain there for a few minutes to a few hours to ensure no reaction has occurred, or the patch can remain until the next injector / patch is applied. In some embodiments, upon completion of an injection, a patient can remove the injector and keep the patch on. The patch can continue to provide data (up to several days) until the next administration where it is replaced.

[0086] In alternative embodiments, a sensor can detect if another patch is transmitting, or the existing patch was removed. The patch could be clear to allow the patient to see the injection site, and it would be as unobtrusive as possible so the patient could wear the patch and continue to conduct daily activities (shower, swim, etc.).

[0087] In some embodiments, the patch may comprise one or more sensing elements. In some embodiments, the injector may comprise one or more sensing elements. In some embodiments, sensing elements of the patch and / or injector can be provided that can measure device attributes including presence of skin (cannula retraction or fall-off sensing), delivery indicator tracking (including fill and dispense), occlusion detection, drug temperature, device status (On / Off Transfer Base, On / Off Patient, Button Status, Pause Events, etc.), flowrate, internal injector pressure / inj ection pressure, adhesive adhesion.

[0088] In some embodiments, the sensor can measure the one or more health or physiological parameters prior to the injection starts. In some embodiments, the one or more health or physiological parameters measured prior to the injection can be used as a baseline inthe determination of the injection site reaction.

[0089] In some embodiments, the sensor can measure the one or more health or physiological parameters during and / or after the injection. In some embodiments, a change in the one or more health or physiological parameters during and / or after the injection may indicate an injection site reaction. In some embodiments, the change in the one or more health or physiological parameters may occur before a patient feels any symptoms of an ISR, leading to a potential to predict the onset of an ISR earlier than relying on patient symptoms.

[0090] In some embodiments, the one or more health or physiological parameters can comprise a temperature of the body or portion thereof, a color of the body or portion thereof, skin rigidity of the body or portion thereof, induration of the body or portion thereof, swelling of the body or portion, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, reflectance of the body or portion thereof, an impedance of the body or portion thereof, and / or a heart rate of the body.

[0091] In some embodiments, the one or more health or physiological parameters can comprise a temperature of the body or portion thereof. In some embodiments, the temperature of the skin at the injection site can be detected via a temperature monitor during and after the injection. In some embodiments, if an ISR occurs, a temperature of the body or portion thereof can be increased by at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 30%, or more, compared with the temperature of the body or portion thereof before the injection (baseline). In some embodiments, a change of the temperature of the skin of at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 30%, or more may indicate a presence or likelihood of an ISR.

[0092] In some embodiments, the one or more health or physiological parameters can comprise a skin color of the body or portion thereof. In some embodiments, the skin color can be detected via an LED / phototransistor circuit during and after the injection. In some embodiments, a change in skin color may indicate a presence or likelihood of an ISR.

[0093] In some embodiments, the one or more health or physiological parameters can comprise skin rigidity of the body or portion thereof. An inflammation response of the body or portion thereof that occurs with ISR may result in a localized increase of blood flow and / or of retention of body fluids. The increase of blood flow or retention of body fluids may increase the skin rigidity at or around the injection site, therefore allowing either prediction of an impending ISR event or notification of an occurring ISR event. In some embodiments, the skin rigidity ofthe body or portion thereof can be measured by an elasticity sensor. In some embodiments, the skin rigidity of the body or portion thereof can be measured by a strain sensor. In some embodiments, skin rigidity may be measured based on the deformation characteristics of the skin. In some embodiments, skin rigidity may be measured based on elastic and viscoelastic properties of the skin. A negative pressure may be applied to deflect or pull the skin and then release it. A depth of deflection (or displacement) may be measured via a non-contact sensor. The sensor data may be used to calculate two parameters, one of which is a firmness or a resistance of the skin to the negative pressure applied to the skin, and the other is elasticity or an ability of the skin to return to its original position when the negative pressure is released. In some embodiments, if an ISR occurs, a displacement of the skin under the same negative pressure can be reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more, compared with the displacement before the injection (baseline). In some embodiments, a change of displacement of the skin of at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more may indicate a presence or likelihood of an ISR.

[0094] In some embodiments, the one or more health or physiological parameters can comprise an induration of the body or portion thereof. The induration refers to the hardening or thickening of soft tissue in the body or portion thereof. In some embodiments, induration can be caused by the body’s inflammation response. In some embodiments, an indurated tissue is less pliable and more resistant to touch than surrounding areas. In some embodiments, an indurated tissue may appear thicker than normal. In some embodiments, the induration may be measured by an image sensor. In some embodiments, the image sensor may take an image of the body or portion thereof and a processor may analyze an area of the indurated region. In some embodiments, the image sensor may continuously monitor the indurated region. In some embodiments, if the area of the indurated region exceeds a threshold value, an ISR may have occurred. In some embodiments, the induration may be measured by an indentation method. In some embodiments, the indentation method may comprise measuring the skin’s resistance to a deformation when pressed against it. In some embodiments, the indentation method may comprise using an indenter and one or more force sensors. In some embodiments, a change of resistance of the skin to the deformation of at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more may indicate a presence or likelihood of an ISR. In some embodiments, the induration may be measured by a durometer. In some embodiments, measuring by a durometer may comprise measuring a depth of indentation in the skin created by a given force using astandardized pressure indenter. In some embodiments, a change of depth of indentation of at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more may indicate a presence or likelihood of an ISR. In some embodiments, the induration may be measured by a stretchable hardness sensor. The hardness sensor may comprise a strain sensor and / or a pressure sensor. In some embodiments, the strain sensor may comprise a piezoresistive strain sensor. In some embodiments, the pressure sensor may comprise a piezoresistive pressure sensor. In some embodiments, measuring induration with a hardness sensor may comprise applying a force to the skin and measuring a deformation in response to the force. In some embodiments, a change of deformation of at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more may indicate a presence or likelihood of an ISR.

[0095] In some embodiments, the one or more health or physiological parameters can comprise swelling of the body or portion thereof. In some embodiments, swelling can be caused by the body’s inflammation response and local accumulation of body fluids. In some embodiments, swelling may refer to the increasing surface area of the skin as it is stretched from fluid accumulation. In some embodiments, the skin rigidity can be related to swelling of the body or portion thereof. In some embodiments, swelling may or may not change skin rigidity. In some embodiments, swelling may cause doming of the skin surface which may or may not be rigid. In some embodiments, the swollen skin may be soft. In some embodiments, the swollen skin may be rigid. In some embodiments, the swelling of the body or portion thereof can be measured by an increase in skin area. As the skin swells and increases in surface area, transducers, such as strain gauges, can measure the change of the surface area. In some embodiments, if an ISR occurs, the surface area of the skin can be increased by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more, compared with the surface area before the injection (baseline). In some embodiments, an increase of the surface area of the skin of at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or more may indicate a presence or likelihood of an ISR.

[0096] In some embodiments, the one or more health or physiological parameters can comprise oxygen saturation of the body or portion thereof. In some embodiments, if an ISR occurs, the inflammation response of the tissue may lead to a change in the local oxygen saturation. In some embodiments, as the inflammation response increase, local changes in oxygen saturation may occur. In some embodiments, oxygen saturation may be measured usingpulse oximetry. In some embodiments, the oxygen saturation measurement can comprise passing two wavelengths of light through the body or portion thereof and measuring the absorption of the light. The two wavelengths of light may be used to determine both the bound (to hemoglobin) and unbound oxygen concentrations. From these two parameters, a percentage of bound hemoglobin is computed and expressed as a percentage. In some embodiments, the pulse oximetry may be a reflectance pulse oximetry which may measure reflected light from the surface of the skin (not requiring passing light through the skin). The reflectance pulse oximetry allows for measurement on areas of the skin that are not thin or readily accessible. In some embodiments, if an ISR occurs, the oxygen saturation of the body or portion thereof can be reduced by at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more, compared with the oxygen saturation before the injection (baseline). In some embodiments, a reduction of the oxygen saturation of the body or portion thereof of at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more may indicate a presence or likelihood of an ISR.

[0097] In some embodiments, the one or more health or physiological parameters can comprise transepidermal water loss of the body or portion thereof. In some embodiments, if an ISR occurs, the inflammation response of the tissue may lead to a change in skin properties, and the change in skin properties may alter the rate at which the skin loses water. Transepidermal water loss (TEWL) is the measurement of the amount of water which evaporates from the skin surface. Damage to, or changes in, the skin may increase the rate at which water loss occurs. In some embodiments, the TEWL measurement can comprise measuring a local humidity. In some embodiments, the local humidity can be measured with a hygrometer. TEWL may be measured as water weight per unit time per unit skin area, e.g., g / h / m2. In some embodiments, the hygrometer may comprise a sensor to measure the relative humidity. In some embodiments, the hygrometer may comprise a sensor to measure the temperature. In some embodiments, the sensor may measure the density gradient of water evaporation from the skin. In some embodiments, the hygrometer may comprise a chamber above the tested area. In some embodiments, if an ISR occurs, the TEWL of the body or portion thereof can be increased by at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more, compared with the TEWL before the injection (baseline). In some embodiments, an increase of TEWL of the body or portion thereof of at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more may indicate a presence or likelihood of an ISR.

[0098] In some embodiments, the one or more health or physiological parameters can comprise reflectance of the body or portion thereof. In some embodiments, the inflammationresponse of the body during an injection site reaction may cause localized swelling of the tissue which thereby may lead to localized changes in skin melanin and hemoglobin content. In some embodiments, the reflectance of the body or portion thereof can be measured with spectrophotometry. In some embodiments, the reflectance of the body or portion thereof can comprise measuring light reflection properties of the external skin layer. In some embodiments, the reflectance of the body or portion thereof can comprise applying a plurality of wavelengths of light to the skin surface and measuring, via a receiver, the light reflected from the skin surface. In some embodiments, the plurality of wavelengths of light can comprise at least two, at least three, or more wavelengths. In some embodiments, the wavelength can be from 400 nm to 1400 nm. In some embodiments, the light can comprise a red, infrared, near infrared, blue, or green. In some embodiments, the reflectance of the body or portion thereof can comprise quantifying skin components, e.g., melanin and / or hemoglobin content. In some embodiments, the light absorbed can be quantified based on the emitted light and the reflected light. In some embodiments, melanin can be measured by two lights, e.g., red and near infrared. In some embodiments, hemoglobin can be measured by two lights, e.g., green and red. In some embodiments, a content of melanin or hemoglobin may change if an ISR occurs. In some embodiments, if an ISR occurs, the reflectance of the body or portion thereof can be changed by at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more, compared with the reflectance before the injection (baseline). In some embodiments, a change in reflectance of the body or portion thereof of at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or more may indicate a presence or likelihood of an ISR.

[0099] In some embodiments, the patch may comprise a heart rate sensor to obtain a patient electrocardiogram (EKG) signal. In some embodiments, the patch may comprise an electromyogram (EMG) sensor to measure an electrical activity of muscles, at rest or during contraction. In some embodiments, the patch may comprise a strain gauge sensor to detect the skin pressure exerted by the extension 414 (FIG. 8). In some embodiments, patient mobility, position, and location data can be collected by corresponding sensors (such as an accelerometer, light sensor e.g., infrared sensor, machine vision sensor, velocity sensor e.g., sonic or laser Doppler velocity sensor, motion capture sensor, GPS sensor, or the like) incorporated in sensor 422. In some embodiments, the patient mobility, position, and location data can be measured in a single movement metric or a plurality of movement metrics. In some embodiments, the plurality of movement metrics may comprise two or more different movement metrics. In some embodiments, a movement metric may be measured through linear or rotational displacement. In some embodiments, a movement metric may be measured through velocity. In someembodiments, a movement metric may be measured through acceleration. In addition, a couple of electrodes (included in sensor 422) in contact with the skin could detect skin impedance and detect leakage or detachment. Furthermore, the skin contact electrodes could detect a premature removal of the device, i.e., removal of the device before the device has completed its cycle. In some embodiments, the sensor of the patch and / or injector may detect a partial or complete detachment of the patch and / or injector from the body.

[0100] In some embodiments, the patch may comprise a motion sensor. In some embodiments, the motion sensor may comprise an accelerometer, gyroscope, magnetometer, or resistive bend sensor. The motion sensor may detect body postures and / or motions, e.g., lying, standing, moving, or sitting, from the body or portion thereof. In some embodiments, the motion sensor may monitor a posture and / or movement of the body and the period of the physical activity.

[0101] In some embodiments, at least two of the one or more health or physiological parameters can be combined to predict an ISR event. In some embodiments, an increase in skin temperature combined with an indication of swelling would be more indicative of an ISR event than just an increase in temperature alone. In some embodiments, a simple temperature increase could be caused by exposure to the sun, where a combination of parameters would be more predictive of an ISR event.

[0102] In some embodiments, in addition to measured parameters (or signs), an application may also integrate feedback collected from the patient (e.g., symptoms). In some embodiments, the feedback can be collected by the application as questions regarding pain, itching, and other symptoms felt by the patient. In some embodiments, the application can then combine the measured signs and patient-reported symptoms in an algorithm.

[0103] A sensor and / or transducer can comprise one or more sensors or transducers that allows for measuring or monitoring a health or physiological parameter or a plurality of health or physiological parameters or allow for indication of device function to the subject.Alternatively or in conjunction, one or more sensors can allow for measuring of patch or injector parameters. Non-limiting examples of patch or injector parameters include determination of whether the patch is secured (e.g., to a body of the subject), whether the patch or injector is in communication with the communication interface, whether the cannula is in fluid communication with the reservoir, occlusion of the cannula, whether the patch and injector are properly coupled, flow rate of the substance through the cannula, etc. A sensor of the plurality of input transducer / sensors can be selected from the group consisting of a conductivity sensor, impedance sensor, capacitance sensor, charge sensor, humidity and / or moisture sensor, temperature sensor, heart rate sensor, interstitial pressure sensor, resistance sensor, distensionsensor, acoustic sensor, vibration sensor, blood pressure sensor, optical sensors (e.g., color sensor, light sensor, wavelength sensor), chemical sensor, movement and / or activity sensor, and a substance-tracking sensor. A sensor of the plurality of output transducers can be selected from the group consisting of haptic(vibration) transducers, audio transducers or visual transducers. These sensors can be used to detect, in non-limiting examples, the environmental conditions in which the subject is using the injector, the subject’s body temperature, heart rate, blood pressure, interstitial pressure, tissue density, skin distension, bleeding (e.g., internal or external), delivery of the medicament, dosage of the medicament to deliver and / or delivered to the subject, sweat quantity of the subject, a plurality of analyte measurements from the subject (e.g., blood glucose, blood oxygen, etc.), and / or sleep quality measurement. In some embodiments, the sensor comprises an ultrasound transmitter and an ultrasound receiver. In some embodiments, the method for measuring the health or physiological parameter may comprise transmitting an ultrasound signal from the ultrasound transmitter to a location within the body of the subject and using the ultrasound receiver to receive a signal from the same or different location. The signal may be received by the ultrasound receiver and used to measure the health or physiological parameter (e.g., tissue depth, thickness, etc.). One or more measurements can be measured or monitored prior to, contemporaneously, or following securing of the patch. For example, the patch can be configured to measure one or more health or physiological parameters prior to injection to establish a baseline and / or calibration measurement of the one or more health or physiological parameters. The patch can be secured to the body of the subject separately from the injector. For example, the patch can be secured to the body of the subject and one or more measurements can be collected. Subsequent attachment of the injector (e.g., to the patch and / or the body of the user) can then allow for directing a substance to the subject.

[0104] The transducer can comprise any useful components, e.g., a solenoid, motor, or micro-electro-mechanical systems (MEMS) actuator. In such cases, the housing of the injector or patch can comprise electrically conductive contacts providing both mechanical attachment and electrical contact of the transducers or sensors, e.g., in an electronic sub-system housed in the injector.

[0105] In some embodiments, the patch can comprise a communication interface for transmitting data indicative of the presence or likelihood of the injection site reaction to an electronic device in communication with the communication interface. In some embodiments, the communication interface can comprise a wireless communication interface. In some embodiments, the electronic device can comprise a mobile device. In some embodiments, the mobile device can comprise a mobile application.

[0106] In some embodiments, the method can further comprise determining the one or moreof the presence, the likelihood, or the severity of the injection site reaction. The determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction can be based on measurements of the one or more health or physiological parameters of the subject over an extended period of time. In some embodiments, the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction can be based on measurements of the one or more health or physiological parameters of a third party individual over an extended period of time. In some embodiments, the measurements of the one or more health or physiological parameters of the third party individual can be provided from a database of the one or more health or physiological parameters of the third party individual.

[0107] In some embodiments, the method can further comprise, using a processor of the electronic device to process the data indicative of the presence or likelihood of the injection site reaction.

[0108] In some embodiments, the method can further comprise notifying the subject of the presence of the injection site reaction. In some embodiments, the notifying can be performed automatically. In some embodiments, the mobile application can display the presence of the injection site reaction on a screen of the mobile application.

[0109] In some embodiments, the patch or the injector can comprise a mechanism to alert the subject, the prescriber, the healthcare provider or another third-party participant a presence of an injection site reaction. In some embodiments, the alert could be in the form of visual indicators, audible sounds, mechanical movements or a combination. The subject, the prescriber, the healthcare provider or another third-party participant can have the need to temporarily stop or pause the injection due to the injection site reaction. This pause in flow of injectable into the injection site, accomplished by removing pressure on the plunger rod of the syringe, can help to reduce the pain at the injection site by allowing the injectable fluid bolus more time to diffuse into the surrounding tissue and thus reducing the local pressure and associated pain and irritation.

[0110] In some embodiments, the injector can receive data from the patch. In some embodiments, the injector can comprise a mechanism for pausing the injection, e.g., automatically or manually. In some embodiments, the injector can comprise a controller (or control mechanism) configured to adjust a flow rate (e.g., injection rate) or pause the injection. In some embodiments, the flow rate may be reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90%. In some embodiments, the sensor may continue monitoring the one or more health or physiological parameters. In some embodiments, the processor may continueprocessing the one or more health or physiological parameters. In some embodiments, the injector may resume the injection or increase a flow rate if the ISR is determined to have disappeared or reduced. In some embodiments, the data may comprise an injection site location on the body or portion thereof, an injection time (e.g., a time during the day), an injection rate, an environment parameter (e.g., temperature, humidity), an injection volume, an injection period, or a combination thereof. In some embodiments, the processor may analyze a correlation between the ISR and the data disclosed herein. In some embodiments, the processor may determine an injection condition for injection that may prevent or reduce the ISR. For example, an ISR may less likely to occur at injection rate below M, the subject may select the injection rate below M to prevent or reduce the ISR. In some embodiments, the historical data including the processed data and correlations may be stored in a data storage device (e.g., an application). In some embodiments, the historical data may be employed to guide a subsequent or future injection.[OHl] In some embodiments, the injector can receive data from the patch. The data may be taken / collected by the sensor during and / or following a delivery of the medicament.

[0112] The patch and / or injector can comprise a communication interface that allows for transmitting and / or receiving data corresponding to the plurality of health or physiological parameters of the subject and / or parameters of the patch or injector. The data can be transmitted to an electronic device in communication with the communication interface. The communication interface can be a wireless communication interface, a Wi-Fi interface, a near-field communication interface, or a Bluetooth interface, as described herein. The electronic device can be a device that can communicate with the communication interface, e.g., a mobile device (e.g., smart phone, tablet, laptop, etc.). Alternatively or in conjunction, the communication interface can be a wired communication interface. In some examples, the patch and / or injector can comprise a port for communication and / or power supply (e.g., universal serial bus (USB), USB-type C, etc.) for connection to the electronic device. The patch and / or injector can include an RFID tag that allows for information to be transferred to and optionally, recorded by the injector and / or patch including but not limited to information about the drug. This can allow data transmitted about the injection to include information about the device and the drug. In some embodiments, the patch may comprise a communication interface and the injector may comprise an additional communication interface. In some embodiments, the communication interfaces may be used to provide information on the other communication interface. For instance, the communication interface of the patch may be able to determine a parameter of the injector (e.g., via the additional communication interface). For example, the communication interfaces may be used to determine a location of the injector or patch and provide one or moreoutputs (e.g., audio, vibrational, or visual signal). In some embodiments, if a subject misplaces the injector or the patch, the patch or the injector (or the electronic device in communication with the patch and / or injector) may be used to track the misplaced item.

[0113] In another aspect, the present disclosure provides a device for monitoring an injection site reaction. The device can comprise: a patch comprising a sensor disclosed herein, wherein the sensor is configured to measure from a subject one or more health or physiological parameters indicative of a presence, a likelihood, and / or a severity of an injection site reaction.

[0114] In another aspect, the present disclosure provides a system for detecting an injection site reaction in a subject. The system can comprise a patch comprising a sensor disclosed herein. The patch may be configured to be secured to a body or portion of the subject. The sensor is configured to measure one or more health or physiological parameters from the subject. The one or more health or physiological parameters may be indicative of a presence, a likelihood, and / or a severity of an injection site reaction.

[0115] In some embodiments, the one or more health or physiological parameters may comprise rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, or reflectance of the body or portion thereof, or any combination thereof.

[0116] In some embodiments, the body or portion thereof comprises skin. In some embodiments, the sensor may be configured to measure swelling by measuring an increase in skin area. In some embodiments, the system or device may be configured to determine the one or more of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction may be determined based on measuring the one or more health or physiological parameters of the subject over an extended period of time. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction may be determined based on measurements of the one or more health or physiological parameters of a third party individual over an extended period of time. In some embodiments, the measurements of the one or more health or physiological parameters of the third party individual may be provided from a database of the one or more health or physiological parameters of the third party individual. In some embodiments, the one or more of the presence, the likelihood, or the severity of the injection site reaction may be determined based on one or more of a trend of the measured one or more health or physiological parameters or a metric derived from the measured one or more health or physiological parameters of the subject.

[0117] In some embodiments, the system or device further comprises an injector disclosed herein. In some embodiments, the injector may be configured to be coupled to the patch. In some embodiments, the injector may be configured to be removably coupled to the patch. In some embodiments, the injector may be an autoinjector. In some embodiments, the injector may comprise a reservoir comprising a substance, wherein the reservoir is in fluid communication with a cannula. In some embodiments, the cannula may be configured to direct the substance therethrough into the body of the subject. In some embodiments, the cannula may be configured to direct the substance into the body before the sensor of the patch measures the one or more health or physiological parameters. In some embodiments, the injector may comprise a receiver for receiving data from the patch. In some embodiments, the receiver of the injector may be configured to receive the data from the patch before the sensor of the patch measures the one or more health or physiological parameters.

[0118] In some embodiments, the patch may comprise a communication interface configured to transmit data indicative of the presence or the likelihood of the injection site reaction to an electronic device. In some embodiments, the communication interface may comprise a wireless communication interface. In some embodiments, the electronic device may comprise a mobile device. In some embodiments, the mobile device may further comprise a mobile application. In some embodiments, the mobile application may be configured to display the presence or the likelihood of the injection site reaction on the mobile application after the sensor of the patch measures the one or more health or physiological parameters. In some embodiments, the electronic device may comprise a processor and a memory coupled to the processor and storing instructions for the processor to process the data indicative of the presence or the likelihood of the injection site reaction.

[0119] In some embodiments, the sensor of the patch may be configured to measure the one or more health or physiological parameters on a surface of the body of the subject. In some embodiments, the patch may be configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction. In some embodiments, the patch may be configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction automatically.

[0120] In some cases, the patch, injector, and / or electronic device can comprise methods for data processing, data storage, and / or one or more feedback loops. In one such example, the patch can monitor one or more physiological parameters of the subject after injection to produce data on the one or more physiological parameters of the subject. The data can be transmitted through the communication interface to the electronic device (e.g., mobile device). In some cases, the mobile device can comprise a method for processing the data and / or storing data (e.g., incomputer readable memory). Examples of processing include measurement of a concentration of an analyte, identification of an analyte, comparing the concentration of an analyte to a standard, calibration of the measurement, summaries of information collected, statistics calculation, trend determination, etc. The processed data can subsequently be used to regulate, e.g., in a feedback loop, to regulate one or more parameters of the patch or injector. The processed data can also be sent directly to a third party for further evaluation. The data can be transmitted to the electronic device, which can further process the data (e.g., calibrate the concentration, compare to a standard, determination if a dosage change is required etc.). Accordingly, the processed data can be used to change a device parameter, e.g., dosage of the substance to be administered, flow rate of dispensing of the substance, etc. The data, processed data, or other signal can then be relayed back to the patch or injector, such that the subsequent injection of the injector is modulated (e.g., the next dosage is higher or lower). In another example, a measurement of the physiologic parameter can measure patient bleeding (e.g., colorimetric, measurement of heme iron of blood, etc.). Detection of bleeding or substance leakage from the site can be used to modulate (e.g., in a feedback loop) the subsequent administration rate or injection. In such examples, presence of patient bleeding can allow for subsequent injections to be delayed, or to change a parameter of the cannula extension toward the body of the subject (e.g., force of injection, speed of injection, etc.). In some cases, an electronic device may not be required, and the patch can be able to communicate with the injector directly or through a communication interface. In such cases, the patch and / or injector can measure a device and / or physiological parameter of the subject and subsequently use the measurement to regulate a parameter of the injector or patch. In one nonlimiting example, the measurement of the parameter (e.g., blood glucose of the patient) can regulate the dosage of a subsequent injection of the injector.

[0121] In some embodiments, the patch can monitor one or more parameters of the patch and / or injector to produce data on the one or more parameters of the injector and / or patch. The data can be transmitted through the communication interface to the electronic device (e.g., mobile device). In some cases, the mobile device can comprise a method for processing the data. Examples of processing include determination if device is properly secured (e.g., if the adhesion force of the patch to the body of the subject is above or below a threshold value), whether the patch is properly connected to the injector, etc. The processed data can subsequently be used to regulate, e.g., in a feedback loop, one or more parameters of the patch or injector. For example, a measurement of the adhesion force of the patch to the body of the subject can be conducted. The data can be transmitted to the electronic device, which can further process the data (e.g., determine insufficient adhesion force). Accordingly, the processed data can be used to change a device parameter, e.g., activation a notification to the subject or other user, as described herein.The data, processed data, or other signal can then be relayed back to the patch or injector, such that a parameter of the patch or injector is adjusted or requires adjustment before proceeding to inject again (e.g., administer another dosage of the substance). In some cases, an electronic device may not be required, and the patch may be able to communicate with the injector directly or through a communication interface. In such cases, the patch and / or injector can measure a parameter of the patch and / or injector and subsequently use the measurement to regulate that parameter or a different parameter of the injector or patch. In one non -limiting example, the measurement of an insufficient adhesion force of the patch can, in a feedback loop, prevent subsequent injection of the injector until the patch is measured as sufficiently adhered to the body of the subject.

[0122] The patch and / or injector can also be in communication or be capable of communication with the subject or other user. In some cases, the communication with the subject or other user can comprise a feedback system or loop. Alternatively, or in conjunction, the patch or injector can be capable of notifying the subject or other user (e.g., physician, nurse, medical practitioner, clinician, etc.) on a device parameter, health, or physiological parameter, or both. For example, the patch or injector can be capable of producing sounds (e.g., to give directions to the subject or other user), producing motion (e.g., vibration), or can comprise visual indicators such as a light (e.g., light-emitting diode), a screen or display (e.g., a liquid-crystal display (LCD), organic light-emitting diode, quantum dot display, or variations or derivatives thereof), or other visual indicator. Alternatively, or in conjunction, the patch or injector can comprise a user interface module. In such examples, the subject or other user can be able to interact with the patch and / or injector. In one of such examples, the patch or injector can comprise a screen or display that can produce a string of characters or sounds that can be used to prompt the subject or other user to respond to a command. In another example, the patch or injector can comprise a screen or display that can produce a string of characters or sounds that can be used to display an output or result, such as the results of the measurement of a physiological parameter. The subject or other user can then be able to input a response or a command, e.g., through a microphone, which can be in the housing of the patch and / or injector, or through a button on the housing of the patch or the injector with which the subject can interact. In some cases, the subject’s input into the patch or injector can result in modulation of a parameter of the patch or injector. In some cases, the subject or other user can input a parameter, e.g., pain, discomfort, etc., that may not be easily measurable or accessible from the patch or injector. These parameters can then be communicated, e.g., through a communication interface, to an external device (e.g., mobile device). In some cases, the patch and / or injector can comprise feedback systems such that the input from the subject or other user can modulate a parameter ofthe patch or injector. For example, input of a pain parameter can result in modulation of the flow rate of the substance through the cannula or the frequency of administered doses of the substance.

[0123] The patch and / or injector can also be configured to communicate with a remote system. In some examples, the patch and / or injector can measure one or more physiological parameters of the subject or one or more parameters of the patch and / or injector to produce data on the one or more physiological parameters of the subject or the one or more parameters of the patch and / or injector. The data can be transmitted to a remote server, a distributed computing network (e.g., for cloud computing). Processing of the data can then occur separately from the patch and / or injector. In some cases, the processed data can then be transmitted to an electronic device (e.g., mobile device). In other cases, the processed data can then be transmitted to the patch and / or injector, for modulation of a parameter of the patch and / or injector. Transmission of data to a remote server and / or to an electronic device can allow for the subject to monitor the one or more physiological parameters, and / or can additionally or alternatively allow for physicians or caretakers to also monitor the one or more physiological parameters of the subject.

[0124] In some embodiments, upon detection of an ISR, the patch or the injector can notify the user or the subject by vibrating, sending sounds, or visual indicators.

[0125] In further embodiments, a lockout for the injector button depression (e.g., for security or preventing drug mis-use) can be provided and activated based on sensing information from injector (drug temperature, etc.), sensing information from patient (skin sensing, etc.), sensing information from the mobile application (e.g., time since last injection, user authentication), or variations or combinations thereof.

[0126] In further embodiments, subcutaneous / transcutaneous electrical neural stimulation (TENS) (e.g., for pain management or bio-absorption) can be provided. In such cases, an electrode element in cannula and / or patch can be activated based on site reaction sensing information, pain information from patient (manual) or pain sensing information, interstitial pressure / site distention information (automatic), or variations or combinations thereof.

[0127] Using embodiments of the disclosure, a person with any number of physical and / or mental conditions treatable with drugs administered with an injector, such as the devices described above, can be monitored to ensure that the injection site reaction is prevented or detected once happens. Data collected during monitoring of the patient and injector attributes can be used by patients, caregivers, providers, payers, and / or drug and device manufacturers to provide feedback to any of the aforementioned parties including confirmation of claims / outcomes and allowing for manual and / or automatic intervention by the patient and / or device to improve the safety and effectiveness of the injection.

[0128] In certain embodiments of the disclosure, the injector or the patch can utilize Bluetooth communications to provide data to the user. Furthermore, embodiments can integrate Bluetooth Low Energy (BLE) into the device. BLE can be designed for low power, low cost applications that require lower data throughput rates than traditional Bluetooth connections such as audio streaming or hands-free phone connections.

[0129] There are two major types of connections defined in the Bluetooth standard: Standard (bonded) mode and Broadcast (also known as “beacon”) mode. In standard or bonded connections, a host (smartphone with installed app) creates a saved connection with a peripheral (i.e., a smart device). In this scenario, through the pairing process, both the host and the peripheral share data to create a permanent connection that allows sharing between only one host and one peripheral. This method has the advantage of a secure connection allowing the exchange of encrypted information that cannot be decoded without the encryption key.

[0130] In broadcast mode (also called a “beacon”), the peripheral sends out data at regular intervals that can be read by any nearby host. In this scenario, the peripheral only broadcasts data; data is never received. There may be several advantages to this mode, e.g., reduced power consumption. In some instances, further power savings can be achieved through lower power ‘sleep’ mode, waking up only when new data needs to be broadcast.

[0131] Additionally, as the peripheral can be configured to be a transmit-only device, enhanced security is provided as the hardware cannot be ‘hijacked’ or loaded with malicious software. This can reduce or eliminate the risk of unauthorized remote control of the device. The software may be loaded onto the device in the factory, preventing unauthorized alteration once deployed.

[0132] In some embodiments, installation of an application, as described elsewhere herein, can be used for securing data privacy. For instance, without proper application installation, the data can simply consist of an unusable list of binary numbers, lacking any text or other readable identifiers. Because of this, the lack of an encrypted connection does not expose any sensitive user information. The data can also exclude patient information - such as names or identification numbers - which could be associated with a specific individual (thereby following HIPAA Compliance).

[0133] An important attribute of the connected healthcare implementation within embodiments of the disclosure can be that it does not affect the essential performance functions of the drug delivery device. In some embodiments, this feature of the device only reports the status of the device and in no way alters the function of the drug delivery device. Even in the event of a critical failure of the Bluetooth components, such as the battery, some embodiments of the device will complete the delivery of the drug and provide the user with visual feedback asto the device status.

[0134] Utilizing the Bluetooth Low Energy broadcast mode and through an electronic chip in the button of the device, some embodiments of the disclosure can deliver real-time device performance information in a small, low cost, convenient package.

[0135] Further embodiments can incorporate patient and device sensing elements to allow for manual and / or automatic intervention (management) on the injector. For example, the flow rate of the injector can be adjusted (e.g., faster, slower, stopped / paused) based on injection site reaction sensing information (automatic), pain information from patient (manual), bioabsorption rate (automatic) or any combination or variations thereof.Mobile Applications

[0136] In another aspect, disclosed herein are systems and methods for generating mobile applications for monitoring one or more health or physiological parameters, wherein the one or more health or physiological parameters is indicative of a presence or a likelihood of an injection site reaction. A mobile application can be generated using a variety of methods, e.g., an application programming interface (API). The mobile application can comprise a plurality of useful features and can be configured to interact with other mobile applications. In some cases, the mobile application can be configured to display the measurements of one or more physiological parameters from the subject or a parameter of the patch and / or injector. The mobile application can comprise feedback systems that allow for subject or other user input, which can allow for modulation of the patch and / or injector (e.g., amount of substance dispensed). The mobile application can also communicate, e.g., through the communication interface, with a remote server. In some cases, the remote server can be a part of or communicate with a separate electronic device (e.g., mobile device, laptop), which can allow for a clinician or physician to monitor the physiological parameters of the subject. In some cases, the mobile application can allow for inputs from the subject of non-measurable parameters (e.g., pain, discomfort, etc.). The mobile application can also comprise software for data processing. Data processing can include, in non-limiting examples, statistical analysis of data, trend plotting and analysis, and graphical representation of the data. In some cases, the mobile application can be capable of interfacing or combining with other mobile applications, such as a lifestyle tracking application (e.g., to monitor diet and activity), or other useful mobile applications, e.g., location tracking, accelerometer, calendars (e.g., to send reminders), etc.

[0137] FIG. 14 illustrates schematically an example workflow of a mobile application for monitoring one or more health or physiological parameters. A mobile device 9700 can be a laptop, a tablet, a phone, or other electronic device (e.g., portable electronic device). Uponopening or selection of the application on the mobile device 9700, a loading screen 9710 can be presented, followed by a menu screen 9720. The menu screen 9720 can provide a plurality of functions 9730. Non-limiting examples of functions 9730 can include starting a new infusion, infusion history, training videos, additional information, and patient profile. Upon selection of a function 9730 (e.g., infusion history), a second screen 9740 pertaining to the function can be presented. In such an example, the subject can be presented with a calendar. In process 9750, the subject can select a second function on the second screen 9740 which presents a third screen 9760. The third screen can display one or more health or physiological parameters of the subject, the device, or the delivery of the substance to the subject (e.g., prescription, time, day of week, regiment, reminders to the patient, alarms, vibrations, etc.). In an example third screen 9980, the calendar can comprise selectable dates that provide information on the one or more health or physiological parameters of the subject on each selected date. In an example fourth screen 9990, the calendar of the mobile application can display additional information, e.g., when the subject has missed an infusion. In an example fifth screen 9790, the calendar of the mobile application can display additional information, e.g., when the subject has received an infusion.

[0138] FIG. 16 illustrates schematically an example workflow of the method of measuring a health or physiological parameter or detecting an injection site reaction. The method 1600 can comprise, at operation 1601, preparing and filling an injector on a base, removing the injector from the base, and attaching the injector and patch to a body of a subject (e.g., a patient). The injection and patch may comprise one or more sensors to monitor one or more functions of the injector and one or more health or physiological parameters. The one or more sensors can comprise one or more electronic components. The method 1600 can further comprise, at operation 1602, performing infusion (injection) while the injector is attached on the body and monitoring the one or more functions of the injector and one or more health or physiological parameters. The method 1600 can further comprise, at operation 1603, removing the injector and leaving the patch on patient for continued monitoring. The method 1600 can further comprise, at operation 1606, disposing the injector. In some embodiments, the injector can be disposable after one single use. In some embodiments, the injector can be reusable. In some embodiments, the injector can be refilled for a subsequent injection. The method 1600 can further comprise, at operation 1604, continuing to monitor the one or more health or physiological parameters on the patient after the injector is removed. The method 1600 can further comprise, at operation 1605, removing the patch. In some embodiments, the patch can be disposable after one single use. In some embodiments, the patch can be reusable. In some embodiments, the patch can be sterilized for a subsequent use. In some embodiments, the injector and / or the patch may be treated after use and prior to re-use. In some embodiments, the injector and / or the patch may be reused atleast 1 time, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 60 times, at least 70 times, at least 80 times, at least 90 times, at least 100 times, at least 500 times, at least 1000 times, or at least 10000 times. The injector or patch or portion thereof that is reusable may be sterilized or cleaned prior to and / or following use. For instance, the subject or a user (e.g., the subject, a healthcare provider, clinician, etc.) may sterilize or clean the injector or patch or portion thereof. The injector or patch or portion thereof may be sterilized using, in non-limiting examples, chemical sterilization (e.g., using bleach, alcohol, hydrogen peroxide, acids, bases, or other chemical agents), radiation treatment (e.g., gamma or UV irradiation), heat (e.g., autoclave, microwave, etc.), or a combination thereof.

[0139] The patch, the injector, or both the patch and injector may comprise reusable parts and may be configured to couple to a docking or recharging station. For instance, the patch or portion thereof may be reusable, and the patch may comprise a rechargeable battery. The rechargeable battery may be removed from the housing of the patch and coupled to the docking or charging station, which may be used to recharge the battery. In some embodiments, the entire patch may be coupled to the docking or charging station. In some embodiments, the docking or charging station comprises a communication interface, which may be used, for instance, to transmit or upload data from the patch, the injector, or both. The docking station may also be used for providing software updates to the patch, the injector, or both. In some embodiments, the docking station may be configured to couple to multiple patches or injectors to facilitate use or to avoid wait times or latencies (e.g., due to duration of recharging), or to simplify workflows for the subject or user.

[0140] FIG. 17 illustrates schematically an example workflow of the method of detecting an injection site reaction. The method 1700 can comprise, at operation 1701, attaching an injector and a patch to a body of a subject (e.g., a patient). The injector and patch may comprise one or more sensors. In some embodiments, the one or more sensors may detect one or more operation measurements of the injector and / or one or more health or physiological parameters of the subject. In some embodiments, the detection can be performed when the injector is attached to the body and the injector is infusing or injecting a substance to the subject. In some embodiments, after the injection is complete, the injector can be removed or detached from the subject while the patch can remain attached to the subject for continued detection of the one or more health or physiological parameters. In some embodiments, the one or more health or physiological parameters can be indicative of a presence, a likelihood, or a severity of an injection site reaction. In some embodiments, the one or more health or physiological parameterscan comprise a skin color, a skin rigidity, induration of a skin or tissue, swelling of a skin or tissue, temperature of a skin or tissue, moisture of a skin or tissue, heart rate, oxygen saturation of a skin or tissue, water loss of a skin or tissue, reflectance of a skin or tissue, or impedance of a skin or tissue. In some embodiments, the patch can record the measurement data. In some embodiments, the one or more sensors can format the measurement data into Bluetooth packet. In some embodiments, the one or more sensors can comprise a plurality of sensor types. In some embodiments, a sensor can measure a plurality of types of the one or more health or physiological parameters (e.g., more than one health or physiological parameter), e.g., a sensor that can detect both the heart rate and oxygen saturation. The method 1700 can comprise, at operation 1702, transmitting a signal from the patch or injector to a receiver via a wireless transmit, e.g., a Bluetooth or a near field communication (NFC). The method 1700 can comprise, at operation 1703, determining a presence, a likelihood, or severity of an ISR. In some embodiments, the determining can be performed with a mobile device. In some embodiments, the determining can be performed with a smart phone. In some embodiments, the mobile device can comprise a mobile application that uses an algorithm for the determination. In some embodiments, the mobile device can comprise a user interface for the subject to input data or information, e.g., a pain, a comfort, an itching, etc. In some embodiments, the algorithm can determine if the ISR is occurring. In some embodiments, the algorithm can determine if the ISR is likely to occur (e.g., prediction of an ISR). In some embodiments, if an ISR is determined or predicted, the mobile application can send or display a notification to the subject. In some embodiments, if an ISR is determined or predicted, the mobile application can send signal to the injector to change an operation of the injector (e.g., reducing the flow rate of the injection or pausing the injection). Although the above methods 1600 and 1700 show operations of detecting an injection site reaction in accordance with many embodiments, a person of ordinary skill in the art will recognize many variations based on the teaching described herein. In some embodiments, the operations may be completed in a different order. In some embodiments, an operation may be added or deleted. In some embodiments, some of the operations may comprise sub-operations. In some embodiments, many of the operations may be repeated as often as beneficial to the method(s).Computer Systems

[0141] The present disclosure provides computer systems that are programmed to implement methods of the disclosure. FIG. 15 shows a computer system 1501 that is programmed or otherwise configured to transmit and / or receive data, and process data. The computer system 1501 can regulate various aspects of the present disclosure, such as, for example, methods fordata analysis, subject monitoring and measurement of physiological or health parameters, and providing an output of the physiological or health parameters. The computer system 1501 can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0142] The computer system 1501 includes a central processing unit (CPU, also “processor” and “computer processor” herein) 1505, which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system 1501 also includes memory or memory location 1510 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 1515 (e.g., hard disk), communication interface 1520 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 1525, such as cache, other memory, data storage and / or electronic display adapters. The memory 1510, storage unit 1515, interface 1520 and peripheral devices 1525 are in communication with the CPU 1505 through a communication bus (solid lines), such as a motherboard. The storage unit 1515 can be a data storage unit (or data repository) for storing data. The computer system 1501 can be operatively coupled to a computer network (“network”) 1530 with the aid of the communication interface 1520. The network 1530 can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is in communication with the Internet. The network 1530 in some cases is a telecommunication and / or data network. The network 1530 can include one or more computer servers, which can enable distributed computing, such as cloud computing. The network 1530, in some cases with the aid of the computer system 1501, can implement a peer-to-peer network, which can enable devices coupled to the computer system 1501 to behave as a client or a server.

[0143] The CPU 1505 can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions can be stored in a memory location, such as the memory 1510. The instructions can be directed to the CPU 1505, which can subsequently program or otherwise configure the CPU 1505 to implement methods of the present disclosure. Examples of operations performed by the CPU 1505 can include fetch, decode, execute, and writeback.

[0144] The CPU 1505 can be part of a circuit, such as an integrated circuit. One or more other components of the system 1501 can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

[0145] The storage unit 1515 can store files, such as drivers, libraries and saved programs. The storage unit 1515 can store user data, e.g., user preferences and user programs. The computer system 1501 in some cases can include one or more additional data storage units that are external to the computer system 1501, such as located on a remote server that is incommunication with the computer system 1501 through an intranet or the Internet.

[0146] The computer system 1501 can communicate with one or more remote computer systems through the network 1530. For instance, the computer system 1501 can communicate with a remote computer system of a user (e.g., Located at a physician’s office or a physician’s mobile device). Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system 1501 via the network 1530.

[0147] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system 1501, such as, for example, on the memory 1510 or electronic storage unit 1515. The machine executable or machine-readable code can be provided in the form of software. During use, the code can be executed by the processor 1505. In some cases, the code can be retrieved from the storage unit 1515 and stored on the memory 1510 for ready access by the processor 1505. In some situations, the electronic storage unit 1515 can be precluded, and machine-executable instructions are stored on memory 1510.

[0148] The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a precompiled or as-compiled fashion.

[0149] Aspects of the systems and methods provided herein, such as the computer system 1501, can be embodied in programming. Various aspects of the technology can be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code and / or associated data that is carried on or embodied in a type of machine readable medium. Machine-executable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk.“Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which can provide non-transitory storage at any time for the software programming. All or portions of the software can at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, can enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that can bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, throughwired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also can be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0150] Hence, a machine readable medium, such as computer-executable code, can take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as can be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media can take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer can read programming code and / or data. Many of these forms of computer readable media can be involved in carrying one or more sequences of one or more instructions to a processor for execution.

[0151] The computer system 1501 can include or be in communication with an electronic display 1535 that comprises a user interface (UI) 154O.Examples of UFs include, without limitation, a graphical user interface (GUI) and web-based user interface.

[0152] Methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit 1505. The algorithm can, for example, process data, perform statistical analyses, plot or graphically represent data, and provide feedback for one or more systems disclosed herein (e.g., the patch and / or injector).

[0153] While preferred embodiments of the present disclosure have been shown and described herein, such embodiments are provided by way of example only. It is not intended that the disclosure be limited by the specific examples provided within the specification. While the disclosure has been described with reference to the aforementioned specification, thedescriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur without departing from the invention. Furthermore, it shall be understood that all aspects of the disclosure are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the disclosure described herein can be employed in practicing the disclosure. It is therefore contemplated that the disclosure shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method for detecting an injection site reaction in a subject, the method comprising:(a) securing a patch comprising a sensor to a body or portion of the subject; and(b) using the sensor of the patch to measure one or more health or physiological parameters from the subject, wherein the one or more health or physiological parameters are indicative of one or more of a presence, a likelihood, or a severity of the injection site reaction; wherein the one or more health or physiological parameters are selected from the group consisting of rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, and reflectance of the body or portion thereof.

2. The method of claim 1, wherein the body or portion thereof comprises skin.

3. The method of claim 2, wherein the swelling is measured by an increase in skin surface area.

4. The method of any one of claims 1-3, further comprising determining the one or more of the presence, the likelihood, or the severity of the injection site reaction.

5. The method of claim 4, wherein the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on measurements of the one or more health or physiological parameters of the subject over an extended period of time.

6. The method of claim 4 or 5, wherein the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on measurements of the one or more health or physiological parameters of a third party individual over an extended period of time.

7. The method of claim 6, wherein the measurements of the one or more health or physiological parameters of the third party individual are provided from a database of the one or more health or physiological parameters of the third party individual.

8. The method of any one of claims 4-7, wherein the determining of the one or more of the presence, the likelihood, or the severity of the injection site reaction is based on one or more of a trend of the measured one or more health or physiological parameters or a metric derived from the measured one or more health or physiological parameters of the subject.

9. The method of any one of claims 1-8, wherein an injector is coupled to the patch.

10. The method of claim 9, wherein the injector is removably coupled to the patch.

11. The method of claim 9 or 10, wherein the injector is an autoinjector.

12. The method of any one of claims 9-11, wherein the injector comprises a reservoir comprising a substance, wherein the reservoir is in fluid communication with a cannula.

13. The method of claim 12, further comprising, subsequent to (a), directing the substance through the cannula into the body of the subject.

14. The method of claim 13, wherein (b) occurs subsequently to the directing of the substance through the cannula into the body.

15. The method of any one of claims 9-14, further comprising receiving data from the patch and / or the injector.

16. The method of claim 15, wherein data from the patch is received subsequent to (b).

17. The method of any one of claims 1-16, further comprising transmitting data indicative of the presence, the likelihood, or the severity of the injection site reaction to an electronic device in communication with a communication interface of the patch.

18. The method of claim 17, wherein the communication interface comprises a wireless communication interface.

19. The method of claim 17 or 18, wherein the electronic device comprises a mobile device.

20. The method of claim 19, wherein the mobile device further comprises a mobile application.

21. The method of claim 20, further comprising, subsequent to (b), displaying the presence, the likelihood, or the severity of the injection site reaction on the mobile application.

22. The method of any one of claims 17-21, further comprising using a processor of the electronic device to process the data indicative of the presence, the likelihood, or the severity of the injection site reaction.

23. The method of any one of claims 1-22, wherein the sensor measures the one or more health or physiological parameters on a surface of the body of the subject.

24. The method of any one of claims 1-23, further comprising notifying the subject of the one or more of the presence, the likelihood, or the severity of the injection site reaction.

25. The method of claim 24, wherein the notifying of the subject is performed automatically.

26. A system for detecting an injection site reaction in a subject, the system comprising: a patch comprising a sensor, the patch being configured to be secured to a body or portion of the subject, wherein the sensor is configured to measure one or more health or physiological parameters from the subject, wherein the one or more health or physiological parameters are indicative of a presence, a likelihood, or a severity of an injection site reaction; wherein the one or more health or physiological parameters are selected from the group consisting of rigidity of the body or portion thereof, induration of the body or portion thereof, temperature of the body or portion thereof, color of the body or portion thereof, swelling of the body or portion thereof, oxygen saturation of the body or portion thereof, transepidermal water loss of the body or portion thereof, and reflectance of the body or portion thereof.

27. The system of claim 26, wherein the body or portion thereof comprises skin.

28. The system of claim 27, wherein the sensor is configured to measure swelling by measuring an increase in skin area.

29. The system of any one of claims 26-28, wherein the system is configured to determine the one or more of the presence, the likelihood, or the severity of the injection site reaction.

30. The system of claim 29, wherein the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on measuring the one or more health or physiological parameters of the subject over an extended period of time.

31. The system of claim 29 or 30, wherein the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on measurements of the one or more health or physiological parameters of a third party individual over an extended period of time.

32. The system of claim 31, wherein the measurements of the one or more health or physiological parameters of the third party individual are provided from a database of the one or more health or physiological parameters of the third party individual.

33. The system of any one of claims 29-32, wherein the one or more of the presence, the likelihood, or the severity of the injection site reaction is determined based on one or more of a trend of the measured one or more health or physiological parameters or a metric derived from the measured one or more health or physiological parameters of the subject.

34. The system of any one of claims 26-33, further comprising an injector configured to be coupled to the patch.

35. The system of claim 34, wherein the injector is configured to be removably coupled to the patch.

36. The system of claim 34 or 35, wherein the injector is an autoinjector.

37. The system of any one of claims 34-36, wherein the injector comprises a reservoir comprising a substance, wherein the reservoir is in fluid communication with a cannula.

38. The system of claim 37, wherein the cannula is configured to direct the substance therethrough into the body of the subject.

39. The system of claim 38, wherein the cannula is configured to direct the substance into the body before the sensor of the patch measures the one or more health or physiological parameters.

40. The system of any one of claims 34-39, wherein the injector comprises a receiver for receiving data from the patch and / or the injector.

41. The system of claim 40, wherein the receiver of the injector is configured to receive the data from the patch before the sensor of the patch measures the one or more health or physiological parameters.

42. The system of any one of claims 26-41, wherein the patch comprises a communication interface configured to transmit data indicative of the presence or the likelihood of the injection site reaction to an electronic device.

43. The system of claim 42, wherein the communication interface comprises a wireless communication interface.

44. The system of claim 42 or 43, wherein the electronic device comprises a mobile device.

45. The system of claim 44, wherein the mobile device further comprises a mobile application.

46. The system of claim 45, wherein the mobile application is configured to display the presence or the likelihood of the injection site reaction on the mobile application after the sensor of the patch measures the one or more health or physiological parameters.

47. The system of any one of claims 42-46, wherein the electronic device comprises a processor and a memory coupled to the processor and storing instructions for the processor to process the data indicative of the presence or the likelihood of the injection site reaction.

48. The system of any one of claims 26-47, wherein the sensor of the patch is configured to measure the one or more health or physiological parameters on a surface of the body of the subject.

49. The system of any one of claims 26-48, wherein the patch is configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction.

50. The system of claim 49, wherein the patch is configured to notify the subject of the presence, the likelihood, or the severity of the injection site reaction automatically.

Images