Patent Application
20210393201
Not Applicable
The technology described herein relates to methods and devices for application of analyte-selective microneedle sensors to the skin of a wearer for physiological sensing of analytes.
The presentation of circulating biomarkers in a timely fashion remains a key aim in modern medical devices and chronic disease management, in particular. The most pertinent example of the need for low-latency biomarker or analyte quantification resides within the diabetes management domain and is addressed with continuous glucose monitoring systems (CGM or CGMS), which are widely used by individuals with insulin-dependent diabetes mellitus in order to inform dosing decisions involving the delivery of insulin or other pharmacologic agents.1 Indeed, efficacy of CGM has been substantiated over the past decade in a multitude of clinical trials and end-user studies wherein noteworthy improvements in glycemic management (in contrast with self-monitoring of blood glucose via periodic fingerstick blood sampling) have been elucidated. However, surprisingly, uptake of these systems has been tepid and in direct contradiction to the strong outcomes-based evidence would suggest.2 Tanenbaum and colleagues3 have explored the barriers to adherence and use of CGM in managing diabetes mellitus and have come to the conclusion that it is high system cost, meager reliability, and the overall poor user experience that limit widespread adoption of this transformational technology for diabetes management. Accordingly, enabling capabilities that aim at addressing these obstacles would position CGM for widespread adoption. One of these enabling capabilities that is ideally positioned to reducing cost, improving reliability, and augmenting the user experience resides in the devices and methods employed for application of CGM and analyte sensors, in general, to the skin of a wearer.
Current subcutaneously-implanted analyte-selective sensors are configured to execute the analyte sensing operation in the subcutaneous layer beneath the dermis, known as the subcutaneous adipose tissue. Likewise, intradermal analyte sensors, often embodied as microneedle arrays, execute the sensing operation more superficially, in the viable epidermis or dermis (papillary dermis or reticular dermis). In order to penetrate the skin and position the sensing element found within the analyte-selective sensor in the desired anatomical region (or strata), a mechanical applicator mechanism is often employed. These applicators typically contain stored potential energy in the form of a compressed mechanical element (i.e. spring, deformable material) or gas that is transferred to kinetic energy upon actuation by a user, causing the analyte-selective sensor retained within the said applicator to be applied to the user's skin at a defined force, velocity, displacement, momentum, and/or inertia. Penetrating to the desired strata of the skin is tantamount to proper analyte quantification, especially within the domain of microneedle-mediated analyte sensing. Indeed, the proper insertion of microneedle array-based analyte-selective sensors requires an extreme level of precision and, to date, has required the use of a spring- or piston-driven mechanical mechanism in order to store the requisite energy required for microneedle penetration of the skin in the form of potential energy. Indeed, the implementation of mechanical applicators is in direct contradiction to current efforts aimed at reducing system cost to increase accessibility of the technology, improving reliability, and reducing the level of complexity required to apply a sensor to enhance the user experience. A microneedle array analyte-selective sensor capable of application and subsequent insertion to the desired strata of the skin with only user-provided force would make substantial inroads to greater and more widespread adoption of CGM and body-worn analyte sensing, in general.
The prior art includes the following:
U.S. Pat. No. 9,789,249 for a Microneedle array applicator device and method of array application, which discloses an applicator device including a housing, an impactor for impacting a microneedle array and accelerating the microneedle array toward the target site, wherein the impactor is capable of moving along an arcuate path to move the microneedle array toward the target site.
U.S. Pat. No. 8,821,446 for Applicators for Microneedles which discloses a microneedle applicator is provided which has two roughly concentric portions which may be, for example, a solid disk and an annulus surrounding it.
U.S. Pat. No. 8,267,889 for a Low-profile microneedle array applicator, which discloses an applicator used to apply microneedle arrays to a mammal. In particular, an application device for applying a microneedle device to a skin surface comprising a flexible sheet having a raised central area attached to the microneedle device and a supporting member at or near the periphery of the flexible sheet, wherein the flexible sheet is configured such that it will undergo a stepwise motion in the direction orthogonal to the major plane of the sheet.
U.S. Pat. No. 9,687,640 for Applicators for microneedles, which discloses an applicator for a microprojection array is described. In one embodiment, the applicator comprises an energy-storing element.
U.S. patent Ser. No. 10/406,339 for a Force-controlled applicator for applying a microneedle device to skin, which discloses an applicator and method for applying a microneedle device to a skin surface.
U.S. patent Ser. No. 10/300,260 for an Applicator and method for applying a microneedle device to skin which discloses an applicator and method for applying a microneedle device to skin.
U.S. Pat. No. 8,579,862 for an Applicator for microneedle array which discloses a microneedle device which protects microneedle, has an easily portable shape, is free from such problems as breakage of small needles in the step of puncturing the skin with the microneedle, and ensures appropriate skin puncture for administering a drug.
U.S. patent Ser. No. 10/010,707 for an Integrated microneedle array delivery system, which discloses a low-profile system and methods for delivering a microneedle array.
U.S. Pat. No. 9,782,574 for a Force-controlled applicator for applying a microneedle device to skin, which discloses an applicator for applying a microneedle device to a skin surface. The applicator can include a microneedle device, a housing, and a connecting member.
U.S. Pat. No. 9,492,647 for a Microneedle array applicator and method for applying a microneedle array, which discloses a microneedle array applicator is configured to apply a microneedle array in cosmetic and medical applications.
U.S. Pat. No. 9,415,198 for a Microneedle patch applicator system, which discloses a method and apparatus for application of a microneedle patch to a skin surface of a patient includes use of an applicator.
U.S. Pat. No. 9,174,035 for a Microneedle array applicator and retainer, which discloses an applicator that has an elastic band to snap a microneedle array against skin with a predetermined force and velocity.
U.S. Pat. No. 9,119,945 for a Device for applying a microneedle array, which discloses a device for applying a microneedle array to a skin surface.
U.S. Pat. No. 8,758,298 for a Low-profile microneedle array applicator, which discloses an applicator used to apply microneedle arrays to a mammal.
Prior devices and methods to insert microneedle arrays into the dermal strata of a user largely leverage spring- or piston-driven applicator mechanisms to facilitate orthogonal acceleration of an embedded microneedle array towards the skin surface of a user with a specified force, velocity, and displacement profile. Additional previously described embodiments include applicators that comprise of retention of said sensor within a deformable membrane. The user applies a load to the top of the membrane until a set force is reached. Once a requisite force is attained, the deformable membrane collapses and the sensor is accelerated axial to the skin surface of a user. The deformable membrane can be constructed of a material that undergoes plastic deformation once a desired force is attained. In other embodiments, the deformable membrane is constructed from a metal and replicates the function of a dome spring. The geometry and material of said membrane can be modified to tune the desired deformation force and, in some cases, the geometry can be modified to augment said force, such that the force to actuate the membrane is less than the force applied by said membrane. In some embodiments, the membrane may be actuated directly by the user, or by means of a lever or a mating component, further augmenting the force generated by the membrane. In some embodiments, the application of orthogonal forces by the user, are translated into lateral forces by the geometry of the applicator, thus applying tension to the skin of a user in an effort to facilitate access to the desired skin strata.
The current invention teaches of methods and devices enabling the insertion of a microneedle array-based analyte-selective sensors to the desired strata of the viable epidermis or dermis with user-supplied force. The aim of this solution is to provide a method for a user to insert an analyte-selective microneedle array sensor into a desired strata of a user's skin while ensuring that the application force, velocity and insertion angle at impact are controlled. In some embodiments, application is achieved solely with user-supplied force, while in other embodiments, user-supplied force is augmented with force from an energy storage device (i.e. spring). User-supplied force is controlled by a mechanism wherein the sensor or sensor carrier is retained by a gating or detent feature that requires a modest force to overcome. The impact velocity can be controlled by the force required to overcome the gating or detent feature and the travel distance. The angle of insertion is controlled by guide elements found within the application mechanism and/or analyte sensor device. In other embodiments, this solution is enabled by a mechanism wherein an armature retaining a sensor by an interference fit is deployed by a modest user-supplied force and thereby accelerated to a defined impact force and velocity specification. The proximal extremity of said armature is meant to pivot about a hinge, joint, or shaft and may be, optionally, aided by a torsion element such as a spring or elastic member. In some embodiments, the application mechanism is configured to render the skin at the application site immobile or apply tension to the skin at the application site to reduce elasticity and improve reliability of insertion. Advantages of these approaches compared with prior art devices and methods for microneedle application include simplified application process and thereby user experience, lower cost of goods due to reduced bill of materials, reduced package size hence logistics and shelf-space, less waste, and improved reliability due to the reduced count of mechanical components.
One aspect of the present invention is an applicator device configured for the insertion of an analyte-selective microneedle array sensor into a dermal stratum of a user. The device comprises a body portion configured to be grasped with a hand of said user, a carrier configured to retain said sensor and accelerate sensor during deployment towards the skin surface of said user, a shaft at a proximal end of said carrier configured to enable carrier to undergo radial motion about said shaft, a spring plunger configured to apply an engineering fit to retain carrier in a first position, and a release mechanism configured to deform its shape upon compression by said spring plunger. A user-directed application of a specified force to the carrier causes the spring plunger to retract and the release mechanism to return to its native shape, thereby to effect the acceleration of the microneedle array sensor device in an arc-like motion about said shaft and towards the skin surface of a user with a specified impact force and velocity. The insertion depth beneath the skin surface of a user is dependent on the velocity and mass (momentum) of the microneedle array when it impacts the skin.
Another aspect of the present invention is a method for the insertion of an analyte-selective microneedle array sensor into a dermal stratum of a user. The method includes positioning an applicator mechanism containing said analyte-selective sensor on the skin of a user. The method also includes applying a minimum force on a carrier within said applicator mechanism, thereby causing a spring plunger to retract and a deformed release mechanism to return to its native shape. The decompression of said release mechanism effects the acceleration of the microneedle array sensor device in an arc-like motion about a shaft from a first position within said applicator mechanism and towards the skin surface of said user with a specified impact force and velocity. The insertion depth beneath the skin surface of a user is dependent on the velocity and mass (momentum) of the microneedle array when it impacts the skin.
Yet another aspect of the present invention is a sterile barrier package applicator device. The sterile barrier package applicator device comprises a first aperture, a second aperture, a body portion, an analyte-selective microneedle array sensor retained by an engineering fit in a first position within said body portion, the non-sensing surface of said analyte-selective microneedle array positioned in proximity to said first aperture, and a film disposed over said second aperture of said sterile barrier package, said film configured to be removed by a user. A user-directed application of a minimum force to the non-sensing surface of said analyte-selective microneedle array compromises said engineering fit, thereby to effect the acceleration of the microneedle array sensor device in a linear motion from a first position to a second position and towards the skin surface of a user with a specified impact force, velocity, and angle of insertion. The insertion depth beneath the skin surface of a user is dependent on the velocity and mass (momentum) of the microneedle array when it impacts the skin.
Yet another aspect of the present invention is a method for the insertion of an analyte-selective microneedle array sensor into a dermal stratum of a user by means of a sterile barrier package applicator containing a first aperture, second aperture, and body portion. The method includes removing a film disposed over said second aperture of said sterile barrier package applicator. The method also includes positioning second aperture of said sterile barrier package applicator containing said analyte-selective sensor on the skin of a user. The method also includes applying a minimum force to the non-sensing surface of said analyte-selective microneedle array sensor. The application of a minimum force by a user compromises an engineering fit retaining said analyte-selective microneedle array sensor to said body portion, thereby to effect the acceleration of the microneedle array sensor device in a linear motion from a first position to a second position and towards the skin surface of a user with a specified impact force, velocity, and angle of insertion.
Yet another aspect of the present invention is an applicator device configured for the insertion of an analyte-selective microneedle array sensor into a dermal stratum of a user. The device comprises a body portion configured to be grasped with a hand of said user, a recessed actuation portion configured to be pressed with a finger of said user, a carrier configured to retain said sensor and accelerate sensor during deployment towards the skin surface of said user, a gating feature configured to prevent carrier movement until a minimum force is applied, and a disengagement feature configured to release the sensor upon deployment. A user-directed application of a specified force to the actuation area causes the carrier to overcome the gating feature, thereby to effect the acceleration of the microneedle array sensor device towards the skin surface of a user with a specified impact force and velocity.
The microneedle array sensor is preferably an electrochemical, electrooptical, or fully electronic device. The microneedle array sensor is preferably configured to measure at least one of an endogenous or exogenous biochemical agent, metabolite, drug, pharmacologic, biological, or medicament indicative of a particular physiological or metabolic state in a physiological fluid of a user. The microneedle array sensor preferably contains a plurality of microneedles, each possessing a vertical extent between 200 and 2000 μm. The microneedle array sensor preferably contains a housing containing a power source, electronic measurement circuitry, a microprocessor, and a wireless transmitter. The microneedle array sensor is preferably configured with a skin-facing adhesive intended to adhere the said sensor to the skin surface of the wearer for an intended wear duration.
The dermal stratum is the viable epidermis, papillary dermis, or reticular dermis. The body portion preferably features at least one flange to enhance retention by hand of the user.
The carrier is configured to retain the microneedle array sensor by means of at least one of an interference fit, friction fit, press fit, clearance fit, and a location fit. The shaft is preferably a hinge. Torsion is preferably applied to the shaft, and is preferably achieved by a flexible elastic member. The flexible elastic member is preferably a torsion spring, leaf spring, sprung metal member, or sprung plastic member. The spring plunger is preferably a ball nose spring. An engineering fit is at least one of an interference fit, friction fit, press fit, clearance fit, and a location fit. The first position is preferably recessed within the body portion. The release mechanism is a rigid or elastic member. The release mechanism is preferably configured to further apply retention to the sensor. The user-directed application of a specified force is preferably between 0.3 N and 30 N. The impact force is preferably between 0.3 N and 30 N. The velocity is preferably between 0.15 m/s and 15 m/s.
Having briefly described the present invention, the above and further objects, features and advantages thereof will be recognized by those skilled in the pertinent art from the following detailed description of the invention when taken in conjunction with the accompanying drawings.
Current subcutaneously-implanted analyte-selective sensors have enjoyed much use in continuous physiological monitoring, driven primarily by the challenge of glucose quantification for diabetes applications. Configured to engage in the measurement of physiological analytes in the subcutaneous layer beneath the dermis, these analyte-selective sensors are inserted to this anatomic region by means of spring- or piston-driven applicators, which ensheathes the sensing contingent with a retractable cannula. New developments in the field of dermal sensing, and microneedle-mediated analyte-selective sensing, in particular, facilitate simplified methods of application such that said cannula is no longer required to insert a sensor to the desired anatomical region.
However, owing to the unique dynamics of insertion of microneedles into the skin, the design of these microneedle applicators requires that great care be taken to design the application mechanism to overcome the viscoelastic response of the skin. Inline with this aim, a cohesive set of design requirements must be pursued to achieve a minimum specified impact force and velocity to overcome said viscoelastic response. Furthermore, displacement and angle of incidence are also of fundamental performance in order to ensure access to the desired skin strata of the viable epidermis or dermis.
Indeed, analyte-selective microneedle array sensors comprise of sharp, protruded sensing elements and can be easily deployed just below the surface of the skin, enabling insertion by a user-supplied force (without necessarily requiring an applicator mechanism). However, in order to reliably insert microneedle array-based analyte-selective sensors into the desired skin strata, it is necessary to control one or more critical application parameters including force, velocity, angle of insertion, and skin tension. Due to expected variation among a user population, it is necessary to control one or more of these critical parameters during the application process to ensure reliable application of said sensor and concomitant insertion of sensing elements into the desired skin strata. The noteworthy benefit of these solutions over the prior art include the reduced number of mechanical constituents, which is commensurate with the requirements of a high volume, low cost product. The simplified design reduces the size and complexity of the application mechanism, which is directly related to cost. The current invention also provides for an improved user experience; the user can simply ‘press’ the sensor on the skin surface rather than use a cumbersome applicator for said application. Many of the applicators described in the prior art, such as those shown in
The applicator device 65 and applicator mechanism taught in this disclosure to effect the application of an analyte-selective microneedle array sensor to the skin surface of a user concern the implementation of an armature 71 (otherwise referred to as a ‘carrier’) to which said sensor is retained with an engineering fit. Said armature 71 is configured to undergo a radial or arc-like acceleration upon an actuation or deployment event by a user.
This is enabled by means of a shaft 73 or pivot, which provides for the pivot point about which said radial or arc-like motion is effectuated. Said shaft 73 or pivot is optionally torsioned by a spring 75 or elastic member, which serves to store kinetic energy in the form of potential energy. In alternative embodiments, the armature/carrier is maintained at a prescribed distance from the skin surface by a gating feature that can be overcome with a defined force. When the user applies a force that is below the minimum required to reliably insert the sensor, the sensor remains retained within the carrier by the gating feature. Upon application of a minimum force by a user on said armature (actuation or deployment event), said potential energy transfers to kinetic energy as an embedded microneedle array affixed to said armature is accelerated in either an axial or radial/arc-like trajectory from a first position wholly within said applicator mechanism to a second position in which the said analyte-selective microneedle array sensor is applied to the skin to effect the insertion of the microneedle constituents of the said sensor into a user's dermal stratum at a specified impact force, velocity, and angle. In some embodiments, the user's skin is either maintained in a fixed position or tensioned to control that aspect. The dermal stratum can either comprise the viable epidermis or dermis and in the vicinity of the papillary plexus, subpapillary plexus, or dermal plexus.
Applying the sensor 20 using the applicator 65 is shown in
In radial application embodiments, the acceleration a of the sensor to the skin of the user is given by the time-derivative of the velocity v, namely:
wherein t refers to time, θ is the angle between the armature and the skin of a user, ma is the mass of the armature, Fuser is the force applied by the user, ka is the constant of the torsion applied to the shaft at the proximal extremity of the armature, h is the height of the armature above the skin surface, and g is the acceleration due to gravity. This equation may be integrated to yield the time-dependent velocity of the sensor:
Provided that the sensor undergoes radial motion, the instantaneous acceleration may be determined by the formula:
where r is the length of the armature.
Embedded tensioner embodiments:
It is generally accepted in the microneedle development and application industry that skin tensioning/stretching improves the efficacy of microneedle insertion. Other micro-needle application devices typically stretch the skin outside of the perimeter of the microneedle and its carrying housing.
This stretching is typically executed as a preliminary step, before insertion, and the skin is held stretched during the process of insertion. The skin stretching mechanism is typically an independently actuated motion. The displacement of the stretcher, amount of stretch in the skin, can be graphed as a typical stress-strain curve and is a percentage (approximately 30% if stretching on one axis, which is typical for an effective stretch) and therefore the mechanism required to perform the stretching motion around the perimeter of the microneedle housing is relatively large and requires multiple actuating parts. One problem with stretching the skin over this relatively large macro-area outside of the sensor is that it can cause pain, and second problem is that some areas of the body such as the lower arm of a smaller person has such a radius of curvature that a macro-stretcher can be rendered ineffective.
The primary objectives of Embedded tensioner embodiments are: to minimize the total mass and area of the skin to be stretched; to stretch the skin for a very short period of time rather than hold the skin in a stretched (painful) position during insertion; and to auto-stretch the skin with no secondary action required by the applicator's operator.
The invention consists of small elastically deformable protrusions with a living hinge at the base of the protrusions all of which are part of the housing assembly stack and are molded as radial, outwardly angled, protrusions from the housing's lower seal that resides immediately around the perimeter of the microneedle array. These radial, outwardly angled protrusions are slightly longer than the microneedles and just long enough make contact with the skin when the sensor is pressed into the skin immediately before the tips of the microneedles. Due to the outward angle and elasticity of the protrusions, as these radial protrusions apply pressure to the skin they stretch the skin in the small area immediately around the microneedle array only where skin stretching is necessary for effective insertion and do not stretch any skin outside of this contained region. These small molded protrusions are pressured outward while the sensor is pressured downward and stretching is occurring and as they rotate and deform outward on the living hinge at the base they fall into a cavity that is also molded into the seal and connected to the base of the protrusions and living hinge. Once the protrusions are fully in the cavity, the bottom surface of the housing is level (flush) and does not interfere with microneedle insertion. Without these cavities, the protrusions would continue to apply pressure to the skin and potentially pull the microneedles out of the skin after insertion.
Additively, the living hinge is designed in a way that is applies pressure on the protrusions from the attachment point to keep the protrusions in the cavity. This is achieved with an arc shaped living hinge that adds a camming force as the protrusion travels from the extended position to the retracted position effectively holding the protrusion in the extended, or retracted position naturally and now allowing the protrusion to rest in any position between the extended and retracted position.
One embodiment is micro-stretching protrusions could be molded as separate part rather than one part with the seal or housing.
Another embodiment is micro-stretching protrusions could be rigid plastic rather that elastic and still actuate via living hinge.
Another embodiment is micro-stretching protrusions could be designed with a classic pivoting hinge rather than living hinge.
Another embodiment is micro protrusions with a texture on the tip designed to engage the skin with improved friction between the protrusions and skin.
Another embodiment is micro protrusions with adhesive on the skin-facing surfaces to engage the skin with improved friction/stiction.
Another embodiment is micro-protrusions actuated by a small spring. Another embodiment is various quantities of micro-protrusions 2, 3, 4, 5, 6, 7, +1, etc.
Another embodiment is micro-protrusions that are outwardly arc shaped and designed to roll on the skin as they rotate outward.
Another embodiment is micro-protrusions with small sharp tips on the end to assist is grabbing the skin for more effective stretching.
It is generally accepted in the microneedle development and application industry that inserting microneedles into the skin requires a prescribed minimum velocity at impact. Mechanically analogous to a nail gun, where the nail is accelerated into a piece of wood relying in inertial forces for effective insertion.
Applicators retain microneedles at some displacement distance away from the skin and then accelerate the microneedles into the skin at a rate fast enough to achieve insertion before the skin can elastically deform. This approach requires linear action slides or radial action pivots that typically increase the profile and surface area of the applicator. This approach to insertion also requires controlled input force to achieve proper impact velocity and has the unfortunate result of startling the subject (user) when the trigger is released and on impact.
The primary objectives of the present embodiments are: to lower the overall profile and surface area required to apply microneedles; To achieve consistent effective insertion with little or no displacement; To avoid startling sounds, slapping, and potential for pain to the user/wearer; To reduce the number of human factors and physics variables involved with the physics of insertion; Reduce the risk of off-perpendicular insertion; Reduce risk of microneedle shear (which can contribute to catastrophic brittle fracture); Reduce effects of small movements from the user; Reduce total impact energy required for insertion.
One aspect of the invention is a device 120 which consists of a mass 122 suspended a small distance above the microneedle array 20 and a metal spring dome 121 between the microneedle array 20 and the mass, as shown in
The analyte-selective sensor (SENSOR) is preferably a microneedle or microneedle array-based electrochemical, electrooptical, or fully electronic device configured to measure an endogenous or exogenous biochemical agent, metabolite, drug, pharmacologic, biological, or medicament in the dermal interstitium, indicative of a particular physiological or metabolic state in a physiological fluid of a user. Specifically, said microneedle array contains a plurality of microneedles, possessing vertical extent between 200 and 2000 μm, configured to selectively quantify the levels of at least one analyte located within the viable epidermis or dermis and in the vicinity of the papillary plexus, subpapillary plexus, or dermal plexus. Said microneedle array is contained and/or mounted to an enclosure or housing containing a power source, electronic measurement circuitry, a microprocessor, and a wireless transmitter. SENSOR is configured with a skin-facing adhesive (sensor adhesive) intended to adhere the said SENSOR for the desired wear duration.
The sensor retainer/carrier (CARRIER) secures the sensor in place and is responsible for accelerating the SENSOR during deployment towards the skin surface of a user.
A user clasps holder (HOLDER) with hand to position SENSOR over desired application area. The base of the holder includes flanges, which are configured to provide additional surfaces for the user to hold the applicator, resulting in increased control of placement on skin and during acceleration of the SENSOR during application.
A shaft/threaded insert (SHAFT) is a pivot axle for the CARRIER and point of attachment of said CARRIER to the HOLDER. It enables the CARRIER to undergo radial motion that follows an arc trajectory.
A torsion spring (SPRING) augments the acceleration of SENSOR once applicator is deployed by the conversion of stored potential energy to kinetic energy.
A ball nose/spring plunger (BALL) applies a prescribed interference to retain CARRIER in the “loaded” position (primed for deployment/application). Adjustments to the tension embodied by the BALL results in a concomitant adjustment to the trigger force of the applicator. Threading SENSOR further into HOLDER manifests increased interference and hence higher trigger force required to deploy SENSOR.
A rubber pad (PAD) imparts additional friction/traction to secure
HOLDER to desired location on the skin of a user and simultaneously decreases the probability of lateral movements during application of SENSOR.
A nylon tip (TIP) secures BALL in desired location; used in conjunction with a set screw.
A set screw (SCREW) secures BALL in desired location; used in conjunction with TIP.
An auto release (RELEASE) secures SENSOR during while the applicator is primed. The RELEASE is characterized by a prescribed degree of compliance/flexibility. In the primed position, BALL applies pressure to the auto-release causing it to deform in a manner which secures SENSOR in an immotile position. Once deployed, the RELEASE returns to its initial position/shape and SENSOR is released.
A method 400 of practicing the invention is shown in
Next, step 402, includes priming of the applicator, as shown in
Next, step 403, includes preparing the SENSOR. With RELEASE engaging/securing SENSOR, user removes adhesive liner from skin-facing surface of said sensor. The applicator is then placed over the desired application site. Flanges on the exterior of HOLDER, in combination with PAD located on the skin-facing surface of the applicator allow for securement of the applicator in the desired location in all three cardinal axes. This feature is necessary due to the stored potential energy in SPRING, which, upon deployment, causes rapid acceleration of HEAD towards the skin of a user. This rapid acceleration may give rise to recoil in the HOLDER that could destabilize the system.
Next, step 404, includes application of the SENSOR. The user activates applicator by depressing CARRIER until required minimum actuation force is achieved, desirably between 0.3 and 30 Newtons. Once the minimum actuation force is exceeded, BALL releases CARRIER The actuation force can be increased or decreased, as desired, by adjusting the amount of engagement of BALL. The application force and velocity is directly related to the actuation force and the strength of SPRING. The sensor is accelerated via SPRING and applied force until it impacts the skin of the user, thereby applying SENSOR. The application force and velocity can be modulated by an appropriate selection of SPRING stiffness/constant. SPRING augments the impact velocity via conversion of stored potential energy to kinetic energy. Furthermore, SPRING improves the consistency of the final impact velocity to compensate for variability in user-applied force to deploy SENSOR. Once CARRIER is deployed, BALL no longer deforms RELEASE and SENSOR is released from CARRIER as interference fit is no longer applied. Under current embodiments, RELEASE exerts loose coupling to SENSOR, even when released, to help stabilize SENSOR AND CARRIER through the acceleration, impact, and application. Following this process, SENSOR is applied to the skin of the user and the applicator can be removed. The securement force of SENSOR to CARRIER is significantly less than the securement force of SENSOR ADHESIVE to skin. This ensures that SENSOR can be easily released from the applicator once applied. In alternative embodiments, applicator is configured to function without SPRING. In the absence of SPRING, the force required by the user is increased to around 30 N to achieve a target velocity of approximately 5 m/s, where with SPRING the same velocity can be achieved with less than a 20 N force applied by the user. These figures depend on the overall mass of SENSOR and CARRIER, constant of SPRING, length of CARRIER, and potentially other variables.
Another method 410 of the invention is shown in
Another method 420, as shown in
Next, step 422, is positioning second aperture of the sterile barrier package applicator, containing the sensor, on the skin of a user. Positioning an applicator mechanism indicates future location of placement of the sensor.
Next, step 423, is applying a minimum force to the non-sensing surface of the sensor. Applying a minimum force compromises an engineering fit retaining the sensor to the body portion.
Next, step 424, is the acceleration of the sensor device in a linear motion from a first position to a second position and towards the skin surface of a user with a specified impact force, velocity, and angle of insertion. The insertion depth beneath the skin surface of a user is dependent on the velocity and mass (momentum) of the microneedle array when it impacts the skin.
The inputs of the invention include a user-directed application of force to the CARRIER. Said application of force, of a minimum specified magnitude, is intended to deploy CARRIER and accelerate SENSOR to the skin of a user at a prescribed velocity and impact force.
The outputs of the invention include application of SENSOR to the skin of a user. A SENSOR applied to the skin surface of a user and retained in the desired position by means of a skin-facing adhesive. Said application process results in the microneedle constituents of said SENSOR penetrating the stratum corneum and accessing the interstitial fluid of the viable epidermis, papillary dermis, or reticular dermis in order to impart the sensing operation of at least one of a circulating endogenous or exogenous biochemical agent, metabolite, drug, pharmacologic, biological, or medicament.
McCanna et al., U.S. Pat. No. 9,933,387 for a Miniaturized Sub-Nanoampere Sensitivity Low-Noise Potentiostat System is hereby incorporated by reference in its entirety.
Windmiller, U.S. patent application Ser. No. 15/177,289, filed on Jun. 8, 2016, for a Methods And Apparatus For Interfacing A Microneedle-Based Electrochemical Biosensor With An External Wireless Readout Device is hereby incorporated by reference in its entirety.
Wang et al., U.S. Patent Publication Number 20140336487 for a Microneedle Arrays For Biosensing And Drug Delivery is hereby incorporated by reference in its entirety.
Windmiller, U.S. patent Ser. No. 10/092,207 for a Tissue Penetrating Electrochemical Sensor Featuring A Co Electrodeposited Thin Film Comprised Of A Polymer And Bio-Recognition Element is hereby incorporated by reference in its entirety.
Windmiller, et al., U.S. patent application Ser. No. 15/913,709, filed on Mar. 6, 2018, for Methods For Achieving An Isolated Electrical Interface Between An Anterior Surface Of A Microneedle Structure And A Posterior Surface Of A Support Structure is hereby incorporated by reference in its entirety.
PCT Publication Number WO2018071265 for an Electro-Deposited Conducting Polymers For The Realization Of Solid-State Reference Electrodes For Use In Intracutaneous And Subcutaneous Analyte-selective Sensors is hereby incorporated by reference in its entirety.
Windmiller et al., U.S. patent application Ser. No. 15/961,793, filed on Apr. 24, 2018, for Heterogeneous Integration Of Silicon-Fabricated Solid Microneedle Sensors And CMOS Circuitry is hereby incorporated by reference in its entirety.
Windmiller et al., U.S. patent application Ser. No. 16/051,398, filed on Jul. 13, 2018, for Method And System For Confirmation Of Microneedle-Based Analyte-Selective Sensor Insertion Into Viable Tissue Via Electrical Interrogation is hereby incorporated by reference in its entirety.
Windmiller et al., U.S. patent application Ser. No. 16/701,784, filed on Dec. 3, 2019, for Devices And Methods For The Generation Of Alerts Due To Rising Levels Of Circulating Ketone Bodies In Physiological Fluids is hereby incorporated by reference in its entirety.
Windmiller et al., U.S. patent application Ser. No. 16/824,700, filed on Mar. 20, 2020, for Devices and Methods For The Incorporation Of A Microneedle Array Analyte-Selective Sensor Into An Infusion Set, Patch Pump, Or Automated Therapeutic Delivery System is hereby incorporated by reference in its entirety.
Windmiller et al., U.S. patent application Ser. No. 16/899,541, filed on Jun. 11, 2020, for a Mechanical Coupling Of An Analyte-Selective Sensor And An Infusion System And Information Conveyance Between The Same is hereby incorporated by reference in its entirety.
From the foregoing it is believed that those skilled in the pertinent art will recognize the meritorious advancement of this invention and will readily understand that while the present invention has been described in association with a preferred embodiment thereof, and other embodiments illustrated in the accompanying drawings, numerous changes modification and substitutions of equivalents may be made therein without departing from the spirit and scope of this invention which is intended to be unlimited by the foregoing except as may appear in the following appended claim. Therefore, the embodiments of the invention in which an exclusive property or privilege is claimed are defined in the following appended claims.
The Present application claims priority to U.S. Provisional Patent Application No. 63/040,295, filed on Jun. 17, 2020, which is hereby incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63040295 | Jun 2020 | US |
