KR20220024506A - Mechanical coupling of analyte-selective sensors and injection systems - Google Patents

Abstract

Disclosed herein are a device ( 2000 ) and a method ( 1300 ) for coupling an analyte selective sensor ( 20 ) and an injection system ( 800 ) into a single body worn device ( 2000 ). Following coupling, information and/or power is exchanged between the two aspects (analyte selective sensor 20 and injection system 800 ) by a wireless electromagnetic transmission or electrical connector. The analyte selective sensor 20 is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte. The infusion system 800 penetrates the stratum corneum and is configured to deliver the therapeutic agent in solution.

Description

Mechanical coupling of analyte-selective sensors and injection systems

FIELD OF THE INVENTION The present invention relates generally to therapeutic delivery mechanisms, analyte selective sensors and methods for their construction.

Continuous delivery of therapeutics remains an important technology in modern medical devices. The most important example of such medical devices is an insulin pump, also known as a continuous subcutaneous insulin infusion (CSII) system, which is widely used by patients with insulin-dependent diabetes mellitus. Insulin pumps were developed in the 1980s and commercialized in the 1990s to provide a more physiological method of insulin delivery than infrequent subcutaneous injection of insulin by syringe and subcutaneous needle. and Complication Trial (DTTT), which was further recognized in the publication results, showed that intensive insulin treatment dramatically reduced the incidence and severity of long-term complications of diabetes. More recently, insulin pumps have been configured to automatically stop insulin infusion in case of actual or impending hypoglycemia as determined by a continuous glucose monitoring system. Insulin pumps were also configured to continuously modulate insulin delivery in response to glucose levels as measured by continuous glucose monitoring systems. In such scenarios, the analyte sensing and treatment delivery modalities both involve two separate removable devices worn on the body. However, in accordance with the goals for the integration of sensing treatment systems and the demand for miniaturization of body worn devices, integrating both analyte sensing and treatment delivery components into a single wearable device is an active area of development. However, a major hurdle for many patients in using these techniques is to install two separate body mounted devices as shown in FIG. 2 where two devices 205 and 210 are positioned on a user 215 . will be using With the goals for the integration of sensing treatment systems and the demand for miniaturization of body worn devices, the coexistence of both analyte sensing and treatment delivery components into a single wearable device is an active area of development. As mentioned above, the integration of sensing and treatment conditions presents its own unique challenges, namely, a robust method for mechanical coupling and electrical interface between these two removable components configured to operate as a single body worn device. suggest developing them. In view of the challenges associated with the integration of two elements that can be coupled into a single body worn device using different methods, the sensing and transmitting components have usually been implemented by separate non-coupleable components. In such embodiments, the user is delegated to apply and wear the discrete components at spatially distinct locations on the body.

Prior art solutions primarily consist of operating both sensing and delivery systems as separate body worn entities that are spatially separated to a sufficient extent to avoid the challenges associated with insertion of two cannulas physically attached to a single integrated device. was related In addition, implementing the analyte sensing and treatment delivery modalities as physically separate devices so that these conditions can be worn in different areas addresses the challenge of unwanted interaction between the two systems. This interaction can take many forms - crosstalk, interference, contamination, and dilution - which affect the performance, accuracy, and reliability of the sensing routine. Prior art embodiments of an analyte sensing aspect include cannula-assisted, subcutaneously implanted wire-based sensors configured to quantify an analyte using electrochemical transformation techniques; Continuous glucose monitoring systems are an example. Prior art embodiments of a treatment delivery aspect include cannula based patch pumps and infusion sets configured to deliver a therapeutic agent to subcutaneous adipose tissue (subcutaneous tissue) by applying pressure on a reservoir containing the treatment in solution phase; Insulin infusion systems are an example. 1A is a prior art needle/cannula based analyte selective sensor 110 with a user interface device 115 and mobile phone 105 configured for quantification of glucose in subcutaneous adipose tissue. 1B is a prior art needle/cannula based analyte selective sensor 130 and a user interface device 125 configured for quantification of glucose in subcutaneous adipose tissue. 1C is a prior art needle/cannula based analyte selective sensor 150 and a user interface device 145 configured for quantitation of glucose in subcutaneous adipose tissue. Although more recent prior art has directed the coexistence of both sensing and transmission modalities within a single body worn device, both aspects in this prior art are inseparable. In this way, when the supply of therapeutic agent within the treatment delivery conditions is exhausted, the entire system comprising the analyte sensing modality must be removed and replaced despite the fact that the analyte sensing modality may still result in a remaining useful life of several days. do. In another embodiment, the analyte selective sensor may be replaced at the same frequency as the infusion system by reducing the sensor to a minimum number of components while utilizing the circuitry and power source resident in the infusion system.

Current needle and cannula-based infusion systems configured for delivery of solution-phase therapeutics (ie, insulin) are usually paired with needle or cannula-based sensor systems configured for continuous quantitation of an analyte (ie, glucose). Although these systems are configured to operate as one piece and operate as separate components (sensing and transmitting), both systems must still be implemented as a single body worn device. This is due in part to the challenges associated with the insertion of two cannulas physically attached to a single integrated device, but the main challenge arises from the mechanical coupling of the two systems while simultaneously supporting a method for information transfer between them. . However, current treatment delivery mechanisms, such as insulin infusion systems, can only accommodate a three-day supply of on-board therapeutic, suggesting that treatment delivery conditions will require replacement long before the end of the functional lifetime of the analyte selective sensor. In all embodiments, information and power are considered to constitute an electromagnetic quantity. In addition, current advances in analyte selective sensors, such as continuous glucose monitors, have enabled the commercialization of devices characterized by a wear life of 7 to 14 days. However, current treatment delivery mechanisms, such as insulin infusion systems, can only accommodate a three-day supply of on-board therapeutic, suggesting that the therapeutic delivery adjunct will require replacement long before the end of the functional lifetime of the analyte selective sensor. As suggested in the prior art, if both systems are to be integrated into a single body worn condition, this would require both systems to be simultaneously removed from the skin and replaced to replenish the internal supply of therapeutic agent within the treatment delivery integration stage, thereby avoiding the This imposes a burden on the useful life created by the analyte selective sensor. There is a need for a solution to the problem of inadequate duration of use of current glucose sensors and insulin infusion systems.

The present invention teaches methods for coupling of divisible analyte sensing and treatment delivery modalities that are assembled by a user to create a single body worn device configured with open loop or closed loop embodiments. The coupling action is performed in a simple manner by the user either prior to application to the user's skin, or sequentially following application of one of the modalities (sensing or delivery). Following coupling, information and/or power is exchanged between the two aspects by means of a wireless electromagnetic transmission or electrical connector. Alternatively, information may be transferred between the two aspects by electromagnetic interaction with an intermediary electronic device. The intermediary electronic device, in one embodiment, maintains both analyte sensing and treatment delivery modalities, and in another embodiment, is a physically separate device such as a smartphone, smartwatch, tablet, computer, or other body worn device. Configure individual information processing devices. Embodiments of the overall system provide an open-loop system in which the wearer regulates administration of a therapeutic intervention based on the level of an analyte or multiple analytes, and a control algorithm autonomously administers the therapeutic intervention or multiple therapeutic interventions. It includes a closed-loop system regulated by The invention disclosed herein allows for replacement of treatment delivery conditions, such as insulin infusion systems, while the analyte sensing condition remains undisturbed and the sensing operation continues. In this way, the user can realize the full functional life of the analyte sensor, but not the treatment delivery conditions. The present invention directs an facile method for the mechanical coupling and decoupling of therapeutic delivery conditions from analyte selective sensors, while simultaneously facilitating electromagnetic interfaces therebetween for information or power transfer.

One aspect of the present invention is a method for coupling an analyte selective sensor and an injection system into a single body worn device. The method includes first placing an analyte selective sensor on the wearer's skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. The selective approach is to mitigate the noxious signal contribution conferred by cycling together endogenous (i.e., metabolites, ions, proteins) and exogenous (i.e., pharmacological agents, therapeutics) electroactive compounds occupying the biological environment while at least one It is generally understood to mean the ability of an analyte selective sensor to measure an analyte. The method also includes secondly placing the injection system on the wearer's skin. The infusion system pierces the stratum corneum and is configured to deliver in a controlled manner the solution phase therapeutic agent or therapeutic agent aggregate to the physiological compartment below the dermis. Controlled mode is generally understood to mean the ability of an infusion system to deliver a particular dosage, concentration or amount of therapeutic agent; This may include bolus delivery in which the therapeutic agent is given within a short duration of time, or basal delivery in which the therapeutic agent is given over an extended duration of time. Positioning requires mechanical retention between the injection system and the analyte selective sensor to form a single body worn device. The method also finally includes transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system.

Another aspect of the invention is a method for coupling an analyte selective sensor and injection system into a single body worn device. The method includes first placing an injection system on the wearer's skin. The infusion system pierces the stratum corneum and is configured to deliver in a controlled manner the solution phase therapeutic agent or therapeutic agent aggregate to the physiological compartment below the dermis. The method also includes, secondly, positioning the analyte selective sensor on the wearer's skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. Positioning requires mechanical retention between the analyte selective sensor and the injection system to form a single body worn device. The method also finally includes transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system.

Another aspect of the present invention provides an analyte selective sensor configured to penetrate the stratum corneum to access the living epidermis or dermis and to selectively measure the presence of an analyte or a plurality of analytes, and an analyte selective sensor configured to penetrate the stratum corneum and sub-dermis physiology A method for coupling an infusion system configured to deliver a solution phase therapeutic agent or aggregate of therapeutic agents in a controlled manner to a therapeutic compartment. The method includes first engaging a mechanical retention mechanism between an analyte selective sensor and the injection system to form a single device. The method also includes, secondly, placing the single device on the wearer's skin. The method also finally includes transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system.

Another aspect of the present invention provides an analyte selective sensor configured to penetrate the stratum corneum to access the living epidermis or dermis and to selectively measure the presence of an analyte or a plurality of analytes, and an analyte selective sensor configured to penetrate the stratum corneum and sub-dermis physiology A method for coupling an infusion system configured to deliver a solution phase therapeutic agent or aggregate of therapeutic agents in a controlled manner to a therapeutic compartment. The method includes first engaging a mechanical retention mechanism between the analyte selective sensor and the injection system and an intermediary device to form a single device. The method also includes, secondly, placing the single device on the wearer's skin. The method also finally includes transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system. It is generally understood that the intermediary device or device consists of two geometric features on which the analyte selective sensor and the injection system are held or otherwise mechanically coupled to provide the two devices in a fixed position relative to each other. do. In one embodiment, the intermediary device is purely a mechanical device for coupling the analyte selective sensor and injection system into a single integrated device; No embedded electronic system is featured in the intermediary device. In another embodiment, the intermediary device comprises an embedded electronic system capable of transferring electromagnetic energy (ie, power, data) between the analyte selective sensor and the injection system.

1A is a prior art needle/cannula based analyte selective sensor.
1B is prior art needle/cannula based analyte selective sensors.
1C is prior art needle/cannula based analyte selective sensors.
2 is a prior art embodiment of a sensor device (left) and an injection system (right).
3 shows a prior art needle/cannula-based analyte selective sensor and a microneedle array-based analyte selective sensor (right).
4 is a diagram illustrating an injection system and an analyte selective sensor.
Figure 5a is the integration of the sensor into the infusion set.
5B is the integration of the sensor into the patch pump.
6A is the integration of the sensor into the patch pump.
6B is the integration of the sensor into the patch pump.
Fig. 6c is an isolated view of the circle 6c of Fig. 6b.
7A is a top perspective view of a sensor with six electrical pads.
7B is a top plan view of a sensor with six electrical pads.
7C is a side view of the sensor.
7D is a bottom view of the sensor.
7E is a bottom perspective view of the sensor.
8A is a top plan view of a therapy delivery system featuring a cavity designed to hold and electromagnetically interface with the analyte selective sensor (not shown) shown in FIGS. 7A-7E .
8B is a side view of a therapy delivery system.
8C is a bottom plan view of the therapy delivery system.
8D is a bottom plan view of a therapy delivery system.
9A is a side perspective view of a therapy delivery system.
9B is a front view of a therapy delivery system.
9C is a side perspective view of a therapy delivery system.
9D is a rear view of a therapy delivery system.
10 is a diagram of application of an analyte selective sensor to the skin of a wearer.
10A is a schematic of application of a therapy delivery system on the posterior side of an analyte selective sensor.
10B is a diagram of a mechanically and electromagnetically coupled analyte selective sensor and therapy delivery system on a wearer's skin.
11 is a side perspective view of a mechanically and electromagnetically coupled analyte selective sensor and therapy delivery system.
12 is a flow diagram of a method for coupling an analyte selective sensor and injection system into a single body worn device.
13 is a flow diagram of a method for coupling an injection system and an analyte selective sensor into a single body worn device.
14 is a flow diagram of a method for coupling an analyte selective sensor and injection system into a single body worn device prior to skin application.
15 is a flow diagram of a method for coupling an analyte selective sensor and an injection system, enabled by an intermediary device, prior to skin application.
16 is a flow diagram of a method of an open loop embodiment.
17 is a flowchart of a method of a closed loop embodiment.
Fig. 18 is a block/process flow diagram showing the inputs, outputs, and main components under the open loop embodiment.
19 is a block/process flow diagram illustrating inputs, outputs, and main components under a closed loop embodiment.
20 is a cross-sectional view of an intermediary device for coupling an injection system and an analyte selective sensor into a single body worn device.
21 is a cross-sectional view of an injection system and an analyte selective sensor and an intermediary device integrated into a single body worn device.
22 is a cross-sectional view of an alternative embodiment of an intermediary device for coupling an injection system and an analyte selective sensor into a single body worn device.

The technology disclosed herein juxtaposes an analyte sensor system and a therapy delivery system to operate in different physiological compartments while maintaining minimal spatial separation between the two. This is accomplished by providing an analyte sensor in the living epidermis or dermis of the wearer, whereby the system is configured to quantify the analyte or plurality of analytes present therein. Conversely, the therapy delivery system is provided in the subcutaneous region. The lateral separation of both sensing and delivery modalities, confining the sensing routine to the living epidermis or dermis and the delivery routine to subcutaneous adipose tissue, allows for the isolation of both routines, which must coexist in a given physiological compartment; mitigate the potential for cross-talk, interference, contamination, and local dilution of the analyte to be detected. In a preferred embodiment of the present invention, the system operates under an open loop paradigm whereby therapy is administered by the user and guided by measurements from the sensor. Alternatively, the system includes a control algorithm for autonomously delivering a therapeutic intervention in response to a sensor reading or plurality of readings. This paradigm is expected to have profound implications for diabetes management and especially those receiving intensive insulin therapy.

The present invention provides mechanical coupling and concomitant coupling of an analyte selective sensor and therapy delivery modalities, while enabling an electromagnetic interface (for information and/or power transfer) between the analyte selective sensor and the therapy delivery modalities. A simplified method for release is disclosed. In this way, the therapy delivery condition (ie, the insulin infusion system) can be removed and replaced, but the analyte selective sensor condition continues to operate without weakening.

Body worn analyte selective sensors (eg, continuous glucose monitors) are sensitive electrochemical systems configured to detect an analyte or a plurality of analytes in a selective manner with high accuracy. Likewise, body worn therapy delivery mechanisms (eg, an insulin infusion system) are also configured to deliver a therapeutic intervention in a controlled manner in response to circulating levels of an analyte or a plurality of analytes. In the present invention, the analyte sensor and the injection system are configured to be mechanically and electromagnetically coupled to each other to create a single body worn device composed of these two divisible aspects.

The mechanical coupling constitutes a mechanical retention mechanism and takes the form of an interference fit, a gap fit, or a transition fit, in particular for positioning both the sensing and transmitting modalities in an invariant position relative to each other. The user engages the coupling to retain the two aspects and similarly disengages the coupling to separate the two aspects. In alternative embodiments, a third “intermediate” element is employed to locate and maintain both the analyte sensor and therapy delivery components in fixed and invariant positions. Under these embodiments, the user is still able to mechanically couple and uncouple the analyte sensing and therapy delivery modalities as desired.

In the first embodiment, the user first applies the analyte selective sensor to the skin, so that the sensing element penetrates the stratum corneum to access the living epidermis or dermis to perform the analyte detection operation. In one particular embodiment, the sensor device is an electrical circuit board having lock-and-key features to enable proper spatial orientation when mated with a therapy delivery mechanism, such as a patch pump or other insulin infusion system. It consists of an analyte selective sensor mounted on it. The top of the sensor device may also feature electrical contact pads or connector for mounting to the bottom of the injection system, thereby providing a path for electrical transmission of an electromagnetic quantity that enables power or signal transmission. A sensor device mounted on the bottom of the therapy delivery system in this way utilizes the built-in electrical subsystems within the therapy delivery system, thereby significantly lowering the article cost for the sensor element.

The user then applies the therapy delivery mechanism to the skin, the action of which causes a cannula or needle to pierce the three upper layers of the skin (stratum corneum, epidermis and dermis) to access subcutaneous adipose tissue, such that the therapy delivery mechanism By allowing them to be mechanically coupled with an analyte selective sensor, they form a single, invariant body-worn responsive treatment system.

In a second embodiment, the user first applies the therapy delivery mechanism to the skin, causing the delivery element to penetrate the outer layers of the skin to access the subcutaneous adipose tissue to perform the therapy delivery action. The user then applies the analyte-selective sensor to the skin, the action of which causes the microneedle or microneedle array to penetrate the stratum corneum and access the living epidermis or dermis, so that the analyte-selective sensor interacts with the therapy delivery mechanism and mechanical By allowing them to be coupled to each other, they form a single, invariant body-worn responsive treatment system.

In a third embodiment, the user mechanically couples the analyte selective sensor and the therapy delivery mechanism by a third element - an intermediary - prior to application to the body. The intermediary holds the analyte sensor and the delivery means in a fixed position relative to each other, forming a single body-worn responsive treatment system. It should be noted that the analyte selective sensor and treatment system each preferably feature a skin surface adhesive for adhering these devices in a fixed location on the surface of the wearer's body. The single body worn device also preferably includes a skin patch, a dermal patch, an adhesive patch, an infusion set, a patch pump, a responsive treatment system, or an automated therapy delivery system.

The electromagnetic coupling constitutes a means for transferring at least one of information and power between the analyte selective sensor and the therapy delivery mechanism. Delivery can be unidirectional (analyte selective sensor to therapy delivery mechanism or therapy delivery mechanism to analyte selective sensor) or bidirectional (analyte selective sensor to therapy delivery mechanism and from therapy delivery mechanism to analyte selective sensor) is). Information or power transfer is made wirelessly via electromagnetic waves propagating through free space or made possible by an electrical connector featuring at least two conductive pads. In one scenario, the act of mechanically coupling both the analyte selective sensor and the therapy delivery mechanism effectuates the exchange of at least one of electromagnetic information and energy between the two aspects. Uses of wireless transmission include BLUETOOTH, Wi-Fi, NFC, RFID, Cellular Radio, ZigBee, Thread, ANT, Proprietary Radio Technology, Proprietary Microwave Technology, Proprietary Millimeter Wave Technology, Inductive Coupling, Capacitive Coupling, Resonant Coupling , or by light waves.

In another embodiment, both the analyte selective sensor and the therapy delivery mechanism must be paired by an action of the user. Therapeutic delivery modalities usually have a larger spatial extent than analyte sensing conditions, and are therefore designed to house microelectronic systems with a higher level of sophistication (i.e. computational power, wireless capability) as well as batteries with greater charge storage capacity. better positioned. Accordingly, preferred embodiments include an energy source within the therapy delivery mechanism, a housing for the microprocessor, and wireless data transfer capability, and optionally an analog front end responsible for the operation of the analyte selective sensor.

Another embodiment places the analog front end within the analyte selective sensor, with the remaining electronic components (energy source, microprocessor, and wireless data transceiver) housed within the therapy delivery mechanism.

Another embodiment places the analog front end and microprocessor within the analyte selective sensor, with the remaining electronic components (energy source and wireless data transceiver) housed within the therapy delivery mechanism.

Another embodiment places the analog front end, microprocessor, and energy source within the analyte selective sensor, and the wireless data transceiver is housed within the therapy delivery mechanism.

Another embodiment places all electronic components (energy source, microprocessor, wireless data transceiver, and analog front end) within the analyte selective sensor, so that it can operate as a portable device in the absence of a therapy delivery mechanism.

Another embodiment of the disclosed invention is placed on the skin and configured for analyte monitoring for 3 days or more (eg, 7 days, 10 days, or 14 days, as in current continuous glucose monitors). while including the analyte selective sensor, the therapy delivery mechanism is 3 days (as in the case of insulin infusion systems) such that removal of the therapy delivery mechanism does not require removal of, or otherwise perturb, the analyte selective sensor. It is configured to be replaced every time. The analyte selective sensor is preferably configured to measure an endogenous or exogenous biochemical agent, metabolite, drug, pharmacological, biological, or medicament within the skin interstitium indicative of a particular physiological or metabolic state in the physiological fluid of the user. Microneedle array based electrochemical, electrooptical, or all electronic devices. Specifically, the microneedle array comprises a plurality of microneedles having a vertical range from 200 pm to 2000 pm, configured to selectively quantify the level of at least one analyte located within the living epidermis or dermis. The analyte selective sensor is preferably an electrochemical sensor, a chemical sensor, an electrical sensor, a potentiometric sensor, an amperometric sensor, a voltage measuring sensor, a galvanometer measuring sensor, an impedance measuring sensor, a conductivity measuring sensor, or a biosensor. The infusion system or therapy delivery mechanism is preferably via a microneedle, macroneedle, subcutaneous needle, cannula, catheter, or oral delivery route into the dermal interstitium, subcutaneous fat layer, circulatory (venous, arterial, or capillary), or muscular system. A fluid delivery device configured to deliver a therapeutic agent in solution. The solution therapeutic agent is delivered in a controlled manner in response to the metabolic state provided by the analyte selective sensor. The therapeutic agent (also referred to as “therapy”) is preferably a drug in solution, pharmacological, biological, or pharmaceutical.

Another embodiment is a coupled system that integrates a sensor and infusion system (including visceral therapy) with a responsive treatment system. This embodiment is a body worn device that integrates both a sensor and an infusion system to effect delivery of therapy, which occupies a physically separate compartment. Alternatively, the body worn device integrates the sensor, infusion system, and therapy in a single enclosure.

A mechanical coupling mechanism is a mechanism designed to retain the sensor within the injection system housing or vice versa. Alternatively, the body worn device may feature a third element (intermediate) configured to retain both the sensor and the injection system therein. The coupling mechanism may take the form of an interference fit, a gap fit, or a transition fit.

An electromagnetic energy transfer mechanism is an electromagnetic mechanism designed to transfer information and/or power unidirectionally from a sensor to an injection system or in both directions between a sensor and an injection system. Alternatively, an intermediary, such as a third device, may trigger an exchange between the sensor and the injection system. The delivery mechanism may take the form of wireless electromagnetic transmission or electromagnetic communication enabled by the connector device.

In another embodiment that is a closed loop embodiment, the elements are: 200 um to 2000 um, wherein the microneedle array analyte selective sensor is configured to selectively quantify the level of at least one analyte located within the dermal interstitium. It includes a plurality of microneedles having a vertical range of . The therapy delivery mechanism, i.e. the infusion system, preferably comprises the dermal interstitium, subcutaneous fat layer, circulatory system (venous, arterial, or capillary), preferably via a microneedle, macroneedle, subcutaneous needle, cannula, catheter, or oral delivery route; or a fluid delivery device configured to inject a therapeutic agent in solution into the muscular system. A therapeutic agent, ie, therapy, is a drug in solution, pharmacological, biological, or pharmaceutical. A coupled system that integrates a sensor and an infusion system (including visceral therapy) with a responsive treatment system uses both the sensor and infusion system to occupy physically distinct anatomical or physiological compartments to effect delivery of therapy. It is a body worn device that can be integrated. Alternatively, the body worn device integrates the sensor, infusion system, and therapy in a single enclosure. The control algorithm controls administration of the therapeutic agent by controlling the amount delivered, the duration of delivery, and/or the frequency of delivery, based on input from the user or from measurements recorded by the microneedle array analyte selective sensor. A software routine that employs one or more mathematical transformations to control. Said administration can include transient delivery, in which the therapy is delivered at a time, or basal delivery, in which the therapy is delivered over an extended period of time. The mathematical transformation may employ additional inputs provided by the user or automatically incorporated from elsewhere. A mechanical coupling mechanism is a mechanism designed to retain the sensor within the injection system housing or vice versa. Alternatively, the body worn device includes a third element (intermediate) configured to retain both the sensor and the injection system therein. The coupling mechanism preferably takes the form of an interference fit, a gap fit, or a transition fit. An information transfer mechanism is an electromagnetic mechanism designed to transfer information and/or power unidirectionally from a sensor to an injection system or in both directions between a sensor and an injection system. Alternatively, an intermediary, such as a third device, may moderate or mediate the interaction between the sensor and the injection system. The delivery mechanism preferably takes the form of wireless electromagnetic transmission or electromagnetic communication enabled by the connector device.

Another embodiment is a first method embodiment of the analyte selective sensor. In a first step, the user applies the sensor to the skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. In one sub-embodiment, the sensor is configured to precisely match a similar geometry on the bottom of the injection system, such that the injection system fits properly on the sensor and, if necessary, electrically connects appropriately for proper operation of the combined system. It consists of geometric features.

In a next step, the user applies the injection system to the skin while simultaneously coupling the injection system to the sensor by mechanical coupling, thereby forming a single body worn device. The therapy delivery transducer penetrates the stratum corneum and is configured to deliver in a controlled manner a solution phase therapeutic agent or a collection of therapeutic agents to a physiological compartment below the stratum corneum, wherein the positioning comprises the therapy delivery transducer and bloodstream to form a single body worn device. Requires mechanical retention between analyte selective sensors.

In the next step, the transfer of relevant information and/or power between the sensor and the injection system takes place. Electromagnetic signals conveying information and/or power related to the sensor and/or injection system may be transmitted in a unidirectional (sensor to injection system/infusion system to sensor) or bidirectional manner (sensor to injection system) between two conditions. to and from the injection system to the sensor), or as an intermediary (sensor to vehicle to injection system/infusion system to medium to sensor/sensor to vehicle to injection system and from injection system to sensor) is relayed through

Another embodiment is a first method embodiment of a therapy delivery mechanism. In a first step, the user applies the injection system to the skin. The therapy delivery mechanism pierces the stratum corneum and is configured to deliver the therapeutic agent in solution or aggregate of therapeutic agents in a controlled manner to the physiological compartment below the stratum corneum.

The user then applies the sensor to the skin while simultaneously coupling the sensor to the injection system by mechanical coupling, thereby forming a single body worn device. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis, and selectively measure the presence of the analyte or a plurality of analytes, wherein positioning the analyte to form a single body worn device. It requires mechanical retention between the water-selective sensor and the therapy delivery mechanism. The dermis preferably comprises dermal interstitium, dermal interstitial fluid, papillary dermis, reticular dermis, or dermal capillary phase. The analyte or the plurality of analytes preferably contains at least one of glucose, lactate, ketone body, uric acid, ascorbic acid, alcohol, glutathione, hydrogen peroxide, metabolite, electrolyte, ion, drug, pharmacological, biological, or pharmaceutical. include

Next, the transfer of relevant information between the sensor and the injection system takes place. Electromagnetic signals conveying information and/or power related to the sensor and/or injection system may be transmitted in a unidirectional (sensor to injection system/infusion system to sensor) or bidirectional manner (sensor to injection system) between two conditions. to and from the injection system to the sensor), or as an intermediary (sensor to vehicle to injection system/infusion system to medium to sensor/sensor to vehicle to injection system and from injection system to sensor) is relayed through

Another embodiment is a method of coupling an analyte selective sensor to a therapy delivery mechanism. First, the sensor is engaged with the injection system by means of a mechanical coupling. This is a mechanical coupling of an analyte selective sensor and a therapy delivery mechanism to form a single device primed for application to the skin. Optionally, a third element is employed to maintain both the analyte selective sensor and the therapy delivery mechanism prior to application to the skin.

Next, the user applies the coupled sensor and injection system to the skin as a single device. Both an analyte selective sensor and therapy delivery mechanism comprising a single mechanically coupled device are simultaneously applied to the skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. The therapy delivery mechanism pierces the stratum corneum and is configured to deliver the therapeutic agent in solution or aggregate of therapeutic agents in a controlled manner to the physiological compartment below the stratum corneum.

Next, the transfer of relevant information between the sensor and the injection system takes place. Electromagnetic signals conveying information and/or power related to the sensor and/or the injection system may, between two conditions, be unidirectional (sensor → injection system/infusion system → sensor) or bidirectional (sensor ← → injection system) , or via an intermediary (sensor → intermediary ← → injection system/sensor intermediary ← → injection system).

The inputs of the present invention are couplings, which are mechanisms designed to retain the sensor within the injection system housing or vice versa. Alternatively, the body worn device includes a third element configured to retain both the sensor and the injection system therein. The coupling mechanism preferably takes the form of an interference fit, a gap fit, or a transition fit. The outputs of the present invention indicate that electromagnetic signals carrying information and/or power related to the sensor and/or injection system can be transmitted between two conditions, either in a unidirectional manner (sensor to injection system/infusion system to sensor) or in a bidirectional manner (sensor to injection system to sensor). It is a transfer relayed from to the infusion system and from the infusion system to the sensor), or via an intermediate (sensor to intermediate to infusion system/sensor to intermediate to infusion system and from infusion system to intermediate to sensor). .

The sensor preferably comprises a plurality of microneedles having a vertical range of 200 gm to 2000 gm, configured to selectively quantify the level of at least one analyte located within the living epidermis or dermis. 3 shows a microneedle array sensor 325 associated with a dime 301 and a needle 305 .

4 is a diagram 40 of a therapy delivery device 25 configured to operate within the subcutaneous tissue 43 and an analyte selective sensor 20 configured to operate within the dermis 42 and through the epidermis 41 . am. It should be noted that both are located in close spatial proximity.

5A shows the integration of a microneedle array based analyte selective sensor 20 into an injection set 500 . 5B, 6A and 6B illustrate the integration of microneedle array based analyte selective sensor 20 into patch pump 525. FIG. 6C shows a microneedle array-based analyte selective sensor 20 and microneedle 25 .

7A, 7B, 7C, 7D and 7E show a microneedle-based analyte selective sensor 20 having a microneedle array and excitation and measurement circuitry (not shown). The microneedle analyte selective sensor 20 preferably comprises a housing member 125, a back plate, an inner pad, a circuit board cover, an outer pad, and an adhesive pad, a front panel, a microneedle 150, and an embedded wireless transceiver. and a printed circuit board including electronic circuitry necessary for converting biochemical signals into digital data that is wirelessly transmitted to an external device through a printed circuit board. The electrochemical analog front end preferably comprises: a Texas Instruments LMP91000 sensor AFE system, a configurable AFE potentiostat for low power chemical sensing applications; Texas Instruments LMP91200 configurable AFE for low-power chemical sensing applications; or an Analog Devices ADuCM350 16-bit precision, Cortex-M3 and low-power on-chip meter with connectivity. The wireless transceiver is preferably a BLUEGIGA BLE-113A BLUETOOTH smart module, or a Texas Instruments CC2540 SimpleLink BLUETOOTH smart wireless MCU with USB. The microneedle 150 penetrates the stratum corneum to access the living epidermis or dermis. The microneedle-based analyte selective sensor 20 also has a plurality of electrical pads 127 for transferring power and/or information between the therapy delivery system and the microneedle-based analyte selective sensor 20 . The microneedle-based analyte selective sensor 20 preferably has two to ten pads 127 , and most preferably six pads 127 .

8A-8C show an interior surface 805 having a port 802 , a button 810 , and a cavity having a plurality of electrical pads 827 for coupling with a microneedle based analyte selective sensor 20 . It shows a therapy delivery system 800 having a body 801 having a 820 . 8D shows a therapy delivery system 800 coupled with a microneedle-based analyte selective sensor 20 and a cannula 803 attached to a port 802 . 9A and 9B show a therapy delivery system 800 with a needle 804 . 9C and 9D show a therapy delivery system 800 having a cannula 803 attached to a port 802 .

10 , 10A and 10B show the process of application of an analyte selective sensor and therapy delivery system, illustrating the operation of mechanical and electromagnetic coupling therebetween. In FIG. 10 , the application of an analyte selective sensor to the skin of a wearer 215 is shown, wherein the analyte selective sensor 20 has six conductive electrical elements for the transfer of electromagnetic energy (power and/or information). It features pads 127 . In FIG. 10A , the application of the analyte selective sensor to the back of the therapy delivery system 800 is shown. 10B shows an analyte selective sensor 20 and therapy delivery system 800 mechanically and electromagnetically coupled on the skin of a wearer 215 .

11 shows a microneedle array of analyte selective sensors 20 and an analyte selective sensor 20 and therapy delivery system mechanically and electromagnetically coupled with a cannula 803 of the therapy delivery system 20 . 800 is shown.

12 depicts a method 1200 for coupling an analyte selective sensor and injection system into a single body worn device. At block 1201, an analyte selective sensor is placed on the wearer's skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. At block 1202, an injection system is placed on the wearer's skin. The infusion system pierces the stratum corneum and is configured to deliver in a controlled manner the solution phase therapeutic agent or therapeutic agent aggregate to the physiological compartment below the dermis. In block 1203, the analyte selective sensor is coupled to the injection system to form a single body worn device. Coupling requires mechanical retention between the analyte selective sensor and the injection system. At block 1204 , electromagnetic energy is transferred between the analyte selective sensor and the injection system. The transfer results in an exchange between the analyte selective sensor and the injection system.

13 depicts a method 1300 for coupling an injection system and an analyte selective sensor into a single body worn device. At block 1301, an injection system is placed on the wearer's skin. The infusion system pierces the stratum corneum and is configured to deliver in a controlled manner the solution phase therapeutic agent or therapeutic agent aggregate to the physiological compartment below the dermis. At block 1302, an analyte selective sensor is placed on the wearer's skin. The analyte selective sensor is configured to penetrate the stratum corneum to access the living epidermis or dermis and to measure the presence of the analyte or a plurality of analytes in a selective manner. At block 1303 , the analyte selective sensor is coupled to the injection system to form a single body worn device. Coupling requires mechanical retention between the analyte selective sensor and the injection system. At block 1304 , electromagnetic energy is transferred between the analyte selective sensor and the injection system. The transfer results in an exchange between the analyte selective sensor and the injection system.

14 shows a flow diagram for a method 1400 for coupling an analyte selective sensor and an injection system prior to skin application. At block 1401 , a mechanical retention mechanism engages between the analyte selective sensor and the injection system to form a single body worn device. At block 1402, a single body worn device is placed on the wearer's skin. At block 1403, electromagnetic energy is transferred between the analyte selective sensor and the injection system.

15 depicts a flow diagram for a method 1500 for analyte selective sensor and injection system coupling, enabled by an intermediary device, prior to skin application. At block 1501 , a mechanical retention mechanism engages between both the analyte selective sensor and the injection system and the intermediary device to form a single body worn device. At block 1502, a single body worn device is placed on the wearer's skin. At block 1503 , electromagnetic energy is transferred between the analyte selective sensor and the injection system.

16 is a flow diagram of a method 1600 of an open loop embodiment of the present invention. The method 1600 for performing an open loop embodiment begins at block 1601 in which a microneedle array analyte selective sensor records measurements of an analyte or a plurality of analytes in the dermal interstitial fluid. The circulating level of the analyte within the living epidermis or dermis is quantified by a sensor. Next, at block 1602, the measurement or measurements from the microneedle array analyte selective sensor are displayed to the user. The user receives a reading of the circulating level of the analyte or plurality of analytes on a display or interface. Alternatively, the user is notified that the circulating level of the analyte or plurality of analytes extends beyond a range of predefined criteria or values. Next, at block 1603, the user adjusts administration of the therapeutic agent or multiple therapeutic agents, if necessary. The user manipulates the amount, duration or frequency of infusion of therapy based on measurements of the analyte or plurality of analytes provided by the sensor. Next, at block 1604, a therapeutic agent or a plurality of therapeutic agents is administered to the dermal interstitium, subcutaneous fat layer, circulatory (venous, arterial, or capillary) or muscular system by a therapeutic delivery mechanism. The regimen is delivered to the user via the infusion subsystem and is based on the user's dosage determination taking into account or measurements from the sensor.

17 is a flow diagram of a method 1700 of a closed loop embodiment of the present invention. The method 1700 for performing a closed loop embodiment begins at block 1701 in which a microneedle array analyte selective sensor records measurements of an analyte or a plurality of analytes in the dermal interstitial fluid. The circulating level of the analyte within the living epidermis or dermis is quantified by a sensor. Next, at block 1702, the measurement or measurements from the microneedle array analyte selection sensor are input into the control algorithm; Optionally, the measurement or measurements are displayed to the user. Measurements stored now, and optionally in the past, are used as input or inputs to the algorithm. Alternatively, the user also receives a reading of the circulating level of the analyte or plurality of analytes on the display or interface. Alternatively, the user is notified that the circulating level of the analyte or plurality of analytes extends beyond a range of predefined criteria or values. Next, at block 1703, the control algorithm adjusts, if necessary, administration of the therapeutic agent or plurality of therapeutic agents based on the programmed mathematical transformation. The algorithm autonomously manipulates the amount, duration or frequency of infusion of therapy based on measurements of the analyte or plurality of analytes provided by the sensor. Next, at block 1704, a therapeutic agent or a plurality of therapeutic agents is administered to the dermal interstitium, subcutaneous fat layer, circulatory (venous, arterial, or capillary), muscular system by a therapeutic delivery mechanism. The regimen is delivered to the user via the infusion subsystem and is based on a dosage decision taking into account the output of the algorithm.

An input of circulating levels of an analyte or a plurality of analytes in the living epidermis or dermis is an endogenous or exogenous biochemical agent, metabolite, drug, pharmacology in the living epidermis or dermis, indicative of a particular physiological or metabolic state. enemy, biological, or pharmaceutical.

The output is the administration of a therapeutic agent or multiple therapeutic agents to the circulatory system (venous, arterial or capillary), muscular, or oral routes of delivery. Measurements provided by the sensors are used to effect the release of therapy by the infusion subsystem. In an open loop embodiment, delivery of therapy is controlled by the user. In a closed loop embodiment, an algorithm is used to control the administration, duration and frequency of therapy.

18 is a block/process flow diagram 1800 illustrating inputs, outputs, and key components under an open loop embodiment. At block 1801 , the circulating level of the analyte or plurality of analytes is within the dermal interstitium. At block 1802, the sensor measures the analyte. User 1803 adjusts administration of a therapeutic agent or multiple therapeutic agents, if necessary. User 1803 manipulates the amount, duration, or infusion frequency of therapy 1804 based on measurements of the analyte or plurality of analytes provided by the sensor. At block 1805, a therapeutic agent or a plurality of therapeutic agents is administered to the dermal interstitium, subcutaneous fat layer, circulatory (venous, arterial, or capillary), muscular system by a therapeutic delivery mechanism. The regimen is preferably delivered to the user via the infusion subsystem and is based on the user's dosage determination taking into account or measurements from a sensor.

19 is a block/process flow diagram 1900 illustrating inputs, outputs, and key components under a closed loop embodiment. At block 1901 , the circulating level of the analyte or plurality of analytes is within the dermal interstitium. At block 1902, the sensor measures the analyte. The control algorithm 1903 adjusts the administration of the therapeutic agent or plurality of therapeutic agents based on the programmed mathematical transformations. The algorithm autonomously manipulates the amount, duration, or infusion frequency of therapy 1904 based on measurements of the analyte or plurality of analytes provided by the sensor. Next, at block 1905, the therapeutic agent or plurality of therapeutic agents is administered by a therapeutic delivery mechanism to the subcutaneous fat layer, the circulatory system (venous, arterial, or capillary), the muscular system, or the oral delivery route. The regimen is delivered to the user via the infusion subsystem and is based on a dosage decision taking into account the output of the algorithm.

20 and 21 show an alternative alternative having an injection system 800 ′ and an intermediary device 2010 integrated into a single body worn device 2000 with the analyte selective sensor 20 ′. Intermediary device 2010 includes compartment 2025 for detachable integration with injection system 800', compartment 2020 for detachable integration with analyte selective sensor 20', CPU 2040, memory 2045 , a transceiver 2050 , an interface 2055 , and a communication/connection line 2030 . In this embodiment, the user mechanically couples the analyte selective sensor 20' and the infusion system (therapy delivery mechanism) 800' by means of an intermediary device 2010, preferably prior to application to the body of the wearer. ring it The intermediary device 2010 holds the analyte sensor 20 ′ and the injection system 800 ′ in a fixed position relative to each other, forming a single body worn responsive treatment system 2000 . The single body worn device 2000 also preferably includes a skin patch, a dermal patch, an adhesive patch, an infusion set, a patch pump, a reactive treatment system, or an automated therapy delivery system. In alternative embodiments, the connection line 2030 is not present and the communication between the injection system 800 ′ and the analyte selective sensor 20 ′ is wireless. In a most preferred embodiment, the intermediary device 2010 preferably has a length ranging from 2 centimeters (cm) to 13 cm, a width ranging from 1 cm to 8 cm, and a height ranging from 1 cm to 8 cm. The analyte selective sensor 20' preferably has a diameter in the range of 1 cm to 5 cm and a thickness in the range of 0.1 cm to 3 cm. The injection system preferably has a length ranging from 2 centimeters (cm) to 12 cm, a width ranging from 1 cm to 7 cm, and a height ranging from 1 cm to 7 cm.

22 shows an embodiment having an intermediary device 2010 as a shell for retaining the injection system in recess 2025 and for retaining analyte selective sensor in recess 2020 to form a single body worn device. . In this embodiment, the intermediary device is preferably formed of plastic and contains no electrical components. Recesses 2025 and 2020 may be shaped to hold various shapes of sensors and implant systems.

Claims (20)

A method for coupling an analyte selective sensor and an injection system into a single body worn device, the method comprising: positioning the analyte selective sensor on the skin of a wearer, the analyte selective sensor touching the stratum corneum configured to penetrate through to access the living epidermis or dermis and to measure the presence of an analyte or a plurality of analytes in a selective manner; positioning the infusion system on the skin of the wearer, the infusion system penetrating the stratum corneum and configured to deliver a therapeutic agent in solution or an assembly of therapeutic agents to a physiological compartment below the dermis, wherein the positioning comprises a single body worn device requires mechanical retention between the injection system and the analyte selective sensor to form a; and transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system. The injection system of claim 1 , wherein the analyte selective sensor comprises a geometrical feature configured to mechanically couple with a corresponding structure on a bottom of the injection system during positioning of the injection system on the skin of a wearer. and enable the system to be placed in a suitable spatial orientation on the upper surface of the analyte selective sensor already applied to the skin of the wearer. The method of claim 1 , wherein the analyte selective sensor is first placed on the skin of the wearer. The method of claim 1, wherein the analyte selective sensor is an electrochemical sensor, a chemical sensor, an electrical sensor, a potentiometric sensor, a current measuring sensor, a voltage measuring sensor, a galvanometer measuring sensor, an impedance measuring sensor, a conductivity measuring sensor, or a biometric sensor. a sensor. The method of claim 1 , wherein the infusion system comprises a fluid delivery device configured for infusion via a microneedle, microneedle array, macroneedle, subcutaneous needle, cannula, catheter, or oral delivery route. The method of claim 1 , wherein the single body worn device comprises a skin patch, a dermal patch, an adhesive patch, an infusion set, a patch pump, a reactive treatment system, or an automated treatment delivery system. The method according to claim 1, wherein the analyte or the plurality of analytes is glucose, lactate, ketone body, uric acid, ascorbic acid, alcohol, glutathione, hydrogen peroxide, metabolite, electrolyte, ion, drug, pharmacological, biological, or pharmaceutical A method comprising at least one of The method of claim 1 , wherein the transfer of electromagnetic energy is for transferring at least one of information and energy. The method of claim 1 , wherein the transmission of electromagnetic energy is by means of an electrical connector featuring conductive elements or by wireless transmission. an analyte selective sensor configured to penetrate the stratum corneum to access the living epidermis or dermis and to selectively measure the presence of an analyte or a plurality of analytes; A method for coupling an infusion system configured to deliver an aggregate of therapeutic agents in a controlled manner, the method comprising: engaging a mechanical retention mechanism between the analyte selective sensor and the infusion system to form a single device; positioning the single device on the wearer's skin; and transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system. 11. The method of claim 10, wherein the analyte selective sensor is an electrochemical sensor, a chemical sensor, an electrical sensor, a potentiometric sensor, a current measuring sensor, a voltage measuring sensor, a galvanometer measuring sensor, an impedance measuring sensor, a conductivity measuring sensor, or a biometric sensor. a sensor. The method according to claim 10, wherein the analyte or the plurality of analytes is glucose, lactate, ketone body, uric acid, ascorbic acid, alcohol, glutathione, hydrogen peroxide, metabolite, electrolyte, ion, drug, pharmacological, biological, or pharmaceutical A method comprising at least one of The method of claim 10 , wherein the infusion system comprises a fluid delivery device configured for infusion via a microneedle, microneedle array, macroneedle, subcutaneous needle, cannula, catheter, or oral route of delivery. The method of claim 10 , wherein the single device comprises a skin patch, a dermal patch, an adhesive patch, an infusion set, a patch pump, a reactive treatment system, or an automated treatment delivery system. The method of claim 10 , wherein the transfer of electromagnetic energy is for transferring at least one of information and energy. The method according to claim 10 , wherein the transmission of electromagnetic energy is by means of an electrical connector featuring conductive elements or by wireless transmission. an analyte selective sensor configured to penetrate the stratum corneum to access the living epidermis or dermis and to selectively measure the presence of an analyte or a plurality of analytes; A method for coupling an infusion system configured to deliver an aggregate of therapeutic agents in a controlled manner, the method comprising: engaging a mechanical retention mechanism between the analyte selective sensor and the infusion system and an intermediary device to form a single device; step; positioning the single device on the wearer's skin; and transferring electromagnetic energy between the analyte selective sensor and the injection system to cause an alternating current between the analyte selective sensor and the injection system. The method of claim 17 , wherein the analyte selective sensor is a microneedle or a microneedle array. The method according to claim 17, wherein the analyte or the plurality of analytes is glucose, lactate, ketone body, uric acid, ascorbic acid, alcohol, glutathione, hydrogen peroxide, metabolite, electrolyte, ion, drug, pharmacological, biological, or pharmaceutical A method comprising at least one of 18. The method of claim 17, wherein the infusion system comprises a fluid delivery device configured for infusion via a microneedle, microneedle array, macroneedle, subcutaneous needle, cannula, catheter, or oral route of delivery.

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