NZ763474B2 - Rotary motor based transdermal injection device - Google Patents

Abstract

apparatus for injectate delivery includes a cartridge, a linear actuator, a rotary motor mechanically coupled the actuator, and a controller coupled to the motor. The controller controls a linear motion of the actuator by controlling an electrical input supplied to the motor in a first interval during which the motor is stationary with the linear actuator engaged with the cartridge to displace an injectate in the cartridge, a second interval following the first interval during which the controller accelerates the motor from stationary to a first speed selected to create a jet of the injectate from the cartridge with a velocity sufficient to pierce human tissue to a subcutaneous depth, a third interval during which the controller maintains the motor at or above the first speed, and a fourth interval during which the controller decelerates the motor to a second speed to deliver the injectate at the subcutaneous depth.

Description

An apparatus for injectate delivery es a cartridge, a linear actuator, a rotary motor mechanically coupled the actuator, and a controller d to the motor. The controller controls a linear motion of the actuator by controlling an electrical input supplied to the motor in a first interval during which the motor is stationary with the linear actuator engaged with the cartridge to displace an injectate in the dge, a second interval following the first interval during which the controller accelerates the motor from stationary to a first speed selected to create a jet of the injectate from the cartridge with a ty sufficient to pierce human tissue to a subcutaneous depth, a third interval during which the controller maintains the motor at or above the first speed, and a fourth interval during which the controller decelerates the motor to a second speed to deliver the injectate at the subcutaneous depth.

NZ 763474 ROTARY MOTOR BASED TRANSDERMAL INJECTION DEVICE Cross nce to Related Application This ation claims the bene?t of the priority ?ling date of US. Provisional Application No. 62/557381, ?led September 12, 2017, the contents of which are hereby incorporated by reference in their entirety.

Background This invention s to a rotary motor based needle-free transdermal injection Skin serves as a protective barrier to the body. In the ?eld of modern medicine, drugs are often delivered through the skin into the bloodstream of patients. Traditionally, this is lished by insertion of a needle through the patient’s skin and into a target area for an injection. However, the use of needles present signi?cant drawbacks ranging from patient fear and discomfort to safety hazards associated with handling used s.

Needle-free transdermal ion s have been developed as an alternative to needle-based injectors. These devices typically use a high pressure, narrow jet of injectate to penetrate a patient’s skin, obviating the need to pierce the patient’s skin with a needle. However, there remains a need for improved needle-free injection devices.

Summa? In a general aspect, an apparatus for injectate ry includes a cartridge containing a volume of an injectate and an eXit port, a linear actuator con?gured for ry of the injectate from the eXit port of the cartridge, the linear actuator including a linkage, a rotary motor mechanically coupled to the linkage, and a controller coupled to the rotary motor. The controller is con?gured to control a linear motion of the actuator in response to a control signal by controlling an electrical input supplied to the motor in a ?rst interval during which the rotary motor is nary and the linear actuator is engaged with the cartridge to displace the ate therefrom, a second interval immediately following the ?rst interval during which the controller accelerates the rotary motor from stationary to a ?rst speed selected to create a jet of the injectate from the cartridge with a velocity at least suf?cient to pierce human tissue to a subcutaneous depth, a third interval during which the controller maintains the rotary motor at or above the ?rst speed, and a fourth interval during which the controller decelerates the rotary motor to a second speed selected to deliver the volume of the ate at the subcutaneous depth. s may include one or more of the following features.

The controller may be con?gured to deliver a sequence of injections of the injectate from the volume without reverse movement of the rotary motor. The controller may be con?gured to deliver a sequence of injections of the injectate from the volume in close al ity to one r. The volume may be at least one milliliter. The volume may be not greater than about 0.5 milliliters. The volume may be not greater than about 0.3 milliliters. The volume may be a therapeutic amount of the injectate. The injectate may be a biological drug.

The injectate may have a ity of at least three centipoise at a temperature between two degrees and twenty degrees Celsius. The injectate may have a viscosity of about three oise to about two hundred centipoise at a temperature between two degrees and twenty degrees Celsius. A second velocity of the jet of injectate from the cartridge during the second interval may reach at least two hundred meters per second.

The rotary motor may provide suf?cient power to reach the ?rst speed in not more than three ons.

A on of the second interval may be less than hundred milliseconds. A duration of the second interval is less than sixty milliseconds. The second interval may be less than ten milliseconds. The linear actuator may be bidirectionally coupled to the rotary motor and the dge to permit bidirectional cement of contents of the cartridge. The apparatus may include plurality of supercapacitors coupled to the rotary motor and con?gured to provide electrical power to the rotary motor during the second interval, the third interval and the fourth interval. The plurality of supercapacitors may be con?gured to charge in parallel and discharge to power the rotary motor in serial. The rotary motor and the plurality of supercapacitors may be con?gured to deliver a peak power to the linear actuator of at least two hundred Watts.

In another general aspect, an apparatus for injectate delivery includes a cartridge containing a volume of an injectate and an eXit port, a linear actuator con?gured for delivery of the injectate from the eXit port of the cartridge, the linear actuator ing a linkage, a rotary motor mechanically coupled to the linkage, and a controller coupled to the rotary motor. The controller is con?gured to control a linear motion of the actuator in response to a control signal by controlling an electrical input supplied to the motor in a ?rst interval during which the rotary motor is engaged with the cartridge to displace the injectate therefrom, a second al immediately following the ?rst interval during which the controller drives the rotary motor at a ?rst speed selected to create a jet of the injectate from the cartridge with a velocity at least suf?cient to pierce human tissue, a third interval during which the controller continues operating the motor at or above the ?rst speed in order to maintain the jet of the injectate at or above the velocity and create a channel through the human tissue to a subcutaneous depth, and a fourth interval during which the controller decelerates the rotary motor to a second speed selected to deliver the volume of the injectate at the subcutaneous depth.

Aspects may include one or more of the following features.

The apparatus may include a sensor system con?gured to detect when the apparatus is properly positioned to r the injectate to a patient, wherein the controller and the rotary motor are con?gured to initiate delivery of the injectate without substantial observable latency when the apparatus is properly positioned. The sensor system may detect a contact of the apparatus with a skin of the t. The sensor system may detect an angle of the cartridge relative to a skin of the patient. The sensory system may detect a position of the eXit port relative to a body of the t.

The capacitive energy storage t may e one or more supercapacitive energy storage ts. The one or more apacitive energy storage elements may include a plurality of supercapacitive energy storage elements and the supply try is con?gured to switch the plurality of supercapacitive energy storage elements into a parallel con?guration during a charging ion and to switch the plurality of supercapacitive energy storage elements into a serial con?guration for an injection operation. The capacitive energy storage element may include a plurality of capacitors.

The supply circuitry may be con?gured to switch the plurality of capacitors into a parallel con?guration with the battery during a charging ion and to switch the plurality of capacitors into a serial con?guration for an injection operation.

The supply circuitry may include a direct current to direct current (DC/DC) converter disposed between the battery and the tive energy storage element. The DC/DC converter may be con?gured to boost a e supplied by the battery by a factor in a range of 5 - 20. Substantially all of an electrical power supplied to the rotary motor during the second time interval and the third time interval may be supplied from the capacitive energy storage element. The injection controller may be red to prevent multiple injectate delivery operations within a ermined minimum injection cycle time. In some examples, the supply circuitry includes a DC/DC converter disposed between the capacitive energy storage element and the rotary motor.

The third time interval may be in a range of two to twenty times as long as the second time interval. The second time interval may have a first duration of between 30 milliseconds and 100 milliseconds and third time al has a second duration of between 100 milliseconds and 1000 milliseconds.

The apparatus may include a cartridge removably and replaceably coupled to the apparatus, the cartridge containing an injectate and the dge including an eXit port with a predetermined shape for ejecting the ate in a stream. The electrical input supplied during the second time interval may be selected to drive the rotary motor at a speed sufficient to drive the stream from the eXit port at a velocity to pierce human skin, and wherein a duration of the second time interval is selected to pierce the human skin with the stream to a subcutaneous depth. The electrical input supplied during the third time interval may be selected to deliver additional injectate from the cartridge at the subcutaneous depth.

Aspects may have one or more of the following advantages.

Use of an actively controlled rotary motor to drive a plunger into a cartridge allows for a rapid acceleration of the r into the cartridge. By rapidly accelerating the plunger into the cartridge, a piercing jet with high ty is quickly attained. Use of apacitors in the power supply supports the rapid acceleration of the plunger since supercapacitors have capacitance values much higher than other capacitors and are able to store 10 to 100 times more energy per unit volume or mass than electrolytic capacitors.

Supercapacitors can also accept and deliver charge much faster than batteries, and tolerate many more charge and discharge cycles than rechargeable batteries.

Other features and advantages of the invention are apparent from the following description, and from the .

Description of Drawings is a schematic m of a controllable, -free transdermal injection device. is a cut-away diagram of a ball screw actuator. is a block diagram of the controllable, needle-free transdermal injection device of is a detailed block diagram of the controllable, needle-free transdermal injection device of is a detailed block diagram of the power supply of the controllable, needle- free transdermal ion device of is a target displacement pro?le. is a rotary motor speed pro?le ated with the target displacement pro?le of is an injectate jet ty pro?le associated with the target displacement pro?le of In the following nt, references to items in the singular should be understood to include items in the plural, and vice versa, unless explicitly stated ise or clear from the text. Grammatical conjunctions are intended to express any and all disjunctive and conjunctive combinations of conjoined clauses, sentences, words, and the like, unless ise stated or clear from the context. Thus, the term "or" should generally be understood to mean "and/or" and so forth.

Recitation of ranges of values herein are not intended to be limiting, referring instead individually to any and all values falling within the range, unless otherwise indicated, and each separate value within such a range is incorporated into the speci?cation as if it were individually recited herein. The words "about," "approximately" or the like, when accompanying a numerical value or physical ty, are to be construed as indicating a deviation as would be appreciated by one of ordinary skill in the art to operate satisfactorily for an intended purpose. Similarly, words of approximation such as "approximately" or "substantially" when used in reference to physical characteristics, should be tood to contemplate a range of deviations that would be appreciated by one of ordinary skill in the art to operate satisfactorily for a corresponding use, function, purpose or the like. Ranges of values and/or numeric values are ed herein as es only, and do not constitute a limitation on the scope of the described embodiments unless explicitly stated otherwise. The use of any and all examples, or ary language ("e.g.,77 (L such as," or the like) ed herein, is intended merely to better nate the embodiments and does not pose a limitation on the scope of the embodiments. No language in the speci?cation should be construed as indicating any med element as essential to the practice of the embodiments.

In the following description, it is understood that terms such as "?rst,77 (L second," "top," "bottom," "up," "down," and the like, are words of convenience and are not to be construed as limiting terms. 1 Needle-Free Transdermal Injection Device Referring to a controllable, needle-free transdermal injection device 100 for erring an injectate (e.g., a drug or a vaccine in any one of a number of states such as a liquid state or a powder state) through the skin of a patient includes a needle- free transdermal injector head 104 extending from a housing 102. The injector head 104 includes a chamber 106 for holding the injectate and a nozzle 108 disposed at a distal end 110 of the injector head 104. The nozzle 108 includes a head 112 and an opening 114 from which a jet of the injectate is discharged from the chamber 106. In operation, the opening 114 is placed near or against the skin 115 when the injectate is discharged.

The dimensions of the nozzle 108 may be adapted to control a shape and pressure pro?le of a stream of injectate exiting the nozzle 108. For example, the inner diameter of the opening 114 may be in a range of 50 pm to 300 um, and may employ a taper along the longitudinal axis 122 toward the opening to shape an exiting stream of injectate. It will also be appreciated that the geometry of the chamber 106 relative to the opening 114 may affect how linear motion of a plunger or the like within the chamber 106 translates into an exit velocity or pressure by an ate through the opening 114. An outer diameter of the head 112 of the nozzle 108 may narrow to the opening 114, or may remain m or may expand to provide a suitable resting surface for the head 112 of the nozzle 108. The nozzle 108 may have a length along the longitudinal axis 122 of about 500 um to about 5 mm. Similarly, the chamber 106 may have any suitable length along the longitudinal axis for containing an ate, and for cing the injectate through the opening 114 in one or more needle-free injections.

The chamber 106 may have a al end 116 and a distal end 110. An actuator (i.e., a piston or plunger 120) may be slidably ed within the chamber 106.

Movement of the plunger 120 along a longitudinal axis 122 in either direction can affect the pressure within chamber 106. In some embodiments, the chamber 106 is integral to the device 100. In other embodiments, the r 106 is separately attachable to device In some examples, the injection device 100 includes a sensor 107 (e.g., a mechanical sensor or a capacitive sensor) for detecting a contact between the apparatus and the skin of a patient. In some examples, the sensor 107 is con?gured to detect an angle of the dge relative to the skin of the patient. In some examples, the sensor 107 is con?gured to detect a position of the injection opening relative to the patient’s skin 115 or body. In some examples, the sensor 107 communicates with the injection controller 100 to t injection from occurring when the tus is not in contact with the patient’s skin 115 or when an angle or position of the apparatus relative to the patient is incorrect. 1.1 Rotary Motor The injection device 100 may include an electromagnetic rotary motor 126 that applies a force to the plunger 120 via a linkage 130 to inject the injectate in the chamber 106 through the skin 115. The linkage may include a ball screw actuator 130, and the linkage may also or d e any other suitable mechanical coupling for transferring a rotary force of the rotary motor 126 into a linear force suitable for displacing injectate from the chamber 106. For example, the linkage may include one or more of lead screws, linear motion bearings, and worm drives, or another other suitable mechanical components or ation of ical components. As noted above, linear motion may usefully be inferred from rotation of a lead screw or the like, and the injection device 100 may be instrumented to monitor rotation in order to provide ck on a position of the plunger 120 to a controller during an injection.

Referring to one example of a ball screw actuator 130 includes a screw 332 and a nut 334 (which is coupled to the housing 102 in , each with matching helical grooves 336. The ball screw actuator 130 may include a recirculating ball screw with a number of miniature balls 338 or similar bearings or the like that recirculate through the grooves 336 and e rolling t between the nut 334 and the screw 332. The nut 334 may include a return system 333 and a de?ector (not shown) which, when the screw 332 or nut 334 rotates, de?ects the miniature balls 338 into the return system. The balls 338 travel through the return system to the opposite end of the nut 334 in a continuous path. The balls 338 then exit from the ball return system into the grooves 336. In this way, the balls 338 continuously recirculate in a closed circuit as the screw 332 moves relative to the nut 334.

In some examples, the rotary motor 126 is of a type ed from a variety of rotational electrical motors (e.g., a brushless DC motor). The rotary motor 126 is con?gured to move the screw 332 of the ball screw actuator 130 back and forth along the longitudinal axis 122 by applying a torque (i.e., TM ) to either the screw 332 or the nut 334 of the ball screw actuator. The torque causes rotation of either the screw 332 or the nut 334, which in turn causes an input force FM (I) which is proportional to the torque applied by the motor, to be applied to the screw 332.

The torque TM d to the screw 332 causes application of a force FP to the plunger 120 which in turn causes movement of the r 120 along the longitudinal axis 122. The force Fp is determined according to the ing equation representing an idealized relationship between torque and force for a ball screw actuator: TM27W F _ P where Fpis a force applied to the plunger 120 by the screw 332, TM is a torque applied to the screw 332, 77is an efficiency of the ball screw actuator 130, and P is a lead of the screw 332. 1.2 Control Loop ing again to the transdermal injection device 100 may include a displacement sensor 140, an injection controller 135, and a three-phase motor controller 141. In general, the displacement sensor 140 measures a displacement x(t) of the screw 332 of the ball screw actuator 130 and/or the plunger 120. The displacement sensor 140 may, for example, measure an incremental displacement of the screw 332 by storing an initial cement value (i.e., x(0)) and ring a deviation from the starting value over time. In other examples, the displacement sensor 140 measures an absolute displacement of the screw 332 relative to a position of the displacement sensor 140 or some other fixed reference point. In another aspect, the displacement sensor 140 may be d to a nut or other component of a ball screw that controls linear movement. In this configuration, the displacement sensor 140 can measure rotation of the screw drive, and rotational motion may be computationally converted into linear displacement for purposes of controlling operation of the device 100.

The displacement x(t) measured by (or calculated using data from) the displacement sensor 140 may be provided as input to the injection controller 135. As is described in greater detail below, the injection controller 135 processes the displacement x(t) to determine a motor control signal y(t). The motor control signal y(t) is provided to the three-phase motor ller 141 which, in conjunction with a power supply 143, drives the rotary motor 126 according to the motor control signal y(t). The motor 126 causes the torque TM (I) to be d to the screw 332. The motor torque, TM (I) causes movement of the screw 332 (or any other suitable linear or) in a direction along the longitudinal axis 122. 1.3 System Diagram Referring to a schematic diagram of the system of shows the rotary motor torque TM being applied to the ball screw 130 in step 344. Application of the rotary motor torque, at a given time t1 by the rotary motor causes application of a force, FM(t1) to the screw 332 of the ball screw 130 as shown in step 345, which in turn causes a displacement of the screw 332 in step 348.

The displacement of the screw 332 of the ball screw 130 is measured by the displacement sensor 140 and is fed back to the injection controller 135. As is bed in greater detail below, the injection controller 135 ses the measured displacement to provide sensor feedback 348 to determine a motor control signal 3200 which is supplied to the three-phase motor controller 141. The three-phase motor controller 141 drives the rotary motor 326 according to the motor control signal y(t1), causing the motor 126 to apply a torque TM (t2) to the screw 332 of the ball screw 130 at a time Q.

As is noted above, the torque TM applied to the screw 332 causes application of a force FP to the plunger 120 with FP being ined as: TM27W F _ P where Fpis a force d to the plunger 120 by the screw 332, TM is a torque applied to the screw 332, 77is an efficiency of the ball screw actuator 130, and P is a lead of the screw 332.

Referring to in some examples the injection controller 135 includes a target displacement profile 450, a g block 452, and a motor control signal generator 454. Very generally, the injection controller 135 receives a displacement value x(t) at time Zfrom the displacement sensor 140. The time lis provided to the target displacement pro?le 450, which determines a target displacement value xT(t) for the time In some examples, the target displacement pro?le 450 includes a mapping between target displacement values and times ated with an injection cycle (i.e., a range of time over which the plunger 120 of the device moves). For example, in the target cement pro?le 450 shown in the displacement starts at zero at the beginning of an injection cycle (i.e., at time to) and changes (e.g., increases) over time as the injection cycle proceeds, with each instant in time of the ion cycle being associated with a corresponding displacement value. As is described in greater detail below, in some examples the rate of change of the displacement values varies over time, with different time intervals of the injection cycle being associated with different rates of change of displacement values. Control of the r displacement, e.g., according to the target displacement pro?le 450, can be used to perform x injections. For example, in one aspect, the plunger 120 is displaced relatively quickly during an initial piercing phase to penetrate the skin barrier, and in other time intervals the plunger 120 is ced relatively slowly to deliver the injectate through an opening formed during the initial, piercing phase. In another aspect, the target displacement pro?le 450 may control le, sequential injections each having a biphasic pro?le with a piercing phase and a drug delivery phase. In practice, the actual displacement pro?le of the plunger 120 may vary from the ideal target displacement pro?le ing to physical limits of the system and other constraints.

Both the measured displacement value x(t) and the target cement value xT(t) are provided to the summing block 452. The summing block 452 subtracts the measured displacement value x(t) from the target displacement value xT(t) to obtain an error signal XE (t) . The error signal XE (t) is provided to the motor control signal generator 454 which converts the error signal to a motor control signal y(t). The motor control signal y(t) is provided to the three-phase motor controller 141 or other le drive system, which in turn drives the motor 126 according to the motor control signal y(t) .

In some examples, the rotary motor 126 may be a three-phase motor with three windings 447 and three Hall sensors 449, each Hall sensor 449 corresponding to a different one of the three windings 447. Each of the windings 447 is d around a laminated soft iron ic core (not shown) so as to form magnetic poles when _ 10- energized with current. Each of the three Hall s 449 generates a corresponding output signal 456 in response to presence (or lack of) a magnetic ?eld in its corresponding g 447.

The three-phase motor controller 141 includes a switch control module 445 and a switching module 448. The switching module 448 includes three pairs of switches 451 (with siX switches 451 in total), each pair of switches corresponding to a different one of the windings 447 of the rotary motor 126 and con?gurable to place the corresponding winding 447 into ical connection with the power supply 143 (whereby the winding is energized) or with ground. The switch control module 445 receives the motor control signal y(t) from the ion controller 135 and the three Hall sensor output signals 456 as inputs and processes the inputs to generate siX switch control signals 455, each switch control signal 455 con?gured to either open or close a corresponding switch 451 of the switching module 448.

The above-described con?guration implements a feedback control approach to ensure that a combination of the controlled torque applied to the screw 332 of the ball screw 130 due to the motor 126 causes the cement of the plunger to track the target displacement pro?le 450 as the screw 332 is displaced. 1.4 Power Supply Referring to in some examples, the power supply includes a battery 560 (e.g., a Nickel Cadmium battery, a Nickel-Metal Hydride battery, a Lithium ion battery, an alkaline battery, or any other suitable battery type) con?gured to supply a voltage Vlto a DC/DC converter 562 (e.g., a boost converter). The DC/DC ter 562 receives the supply voltage Vlfrom the battery 560 as input and generates an output voltage V2 r than V1. In some examples, the DC/DC converter 562 is con?gured to boost the supply voltage by a factor in the range of 5 to 20. While the y 560 may be rechargeable, the y 560 may also usefully store suf?cient energy for multiple injections, such as two or more one milliliter injections, e.g., from eable single-dose cartridges or from a single, multi-dose cartridge.

The output voltage V2 may be provided in parallel to a supercapacitor 564 and to the switching module 448 of the three-phase motor controller 141 via a diode 566. In operation, the output voltage V2 charges the supercapacitor 564 while the transdermal injection device 100 is inactive. When an injection ion commences, the es 451 of the switching module 448 close (according to the switch control signals 45 5), connecting the windings 447 of the rotary motor 126 to the supercapacitor 564. This results in a discharge of the supercapacitor 564, causing current to ?ow through the windings 447 of the rotary motor 126 and induce rotation of the rotary motor 126.

In some examples, the supercapacitor 564 includes a number of supercapacitors coupled together with a switching network. When the transdermal injection device 100 is ve, the switching network may be con?gured so that the number of supercapacitors is connected in parallel for ng. When an injection is initiated, the switching network may be recon?gured so that the number of supercapacitors are serially connected for discharge. In some examples, the supercapacitor 564 is con?gured to r a peak power of 200 Watts or more to the ball screw 130 via the rotary motor 126.

In general, the supercapacitor may be any high-capacity capacitor suitable for accepting and delivering charge more y than a battery or other source of ical energy. A wide variety of supercapacitor designs are known in the art and may be adapted for use as the supercapacitor 564 plated herein, such as double-layer capacitors, pseudocapacitors, and hybrid capacitors. Similarly, the supercapacitor 564 may usefully include any number and arrangement of supercapacitors suitable for delivering electrical power in an amount and at a rate suitable for driving a rotary motor 126 of an injection device 100 as plated herein. 2 Target Disp_lacement Pro?le Referring to one example of a target displacement pro?le includes a number of injection phases, each associated with a corresponding time interval.

A ?rst injection phase 670 is ated with a ?rst time interval extending from time to to time Q. In the ?rst injection phase 670, the target displacement of the plunger 120 is at a constant initial position p0 where the plunger 120 is engaged with the ate in the chamber 106. In this phase, the injection device 100 is generally prepared to perform an injection operation. In general, the ?rst injection phase 670 may be preceded by any number of preparatory steps or phases, such as loading of an ate (or a cartridge ning an injected) into the injection device, the removal of bubbles from the injectate as necessary or riate, measuring environmental ions, measuring parameters of an injection site, and any other steps or combination of steps useful for performing, or preparing to perform, a needle-free ion as contemplated herein.

In one aspect, the rotary motor 126 may be mechanically engaged with the ball screw actuator 130 (or any other suitable linear actuator) while the rotary motor 126 is stationary in the ?rst injection phase 670. That is, the rotary motor 126 may be preengaged with the ball screw actuator 130 and preload to remove any mechanical slack in the mechanical components of the system. In this con?guration, a mechanical switch or the like may be used to prevent relative movement of the ents, and/or a gate or seal may be used at the nozzle exit to prevent leakage of drug from the chamber 106. In another , the rotary motor 126 may be slightly spaced apart from engagement with the ball screw or 130. In this latter con?guration, the rotary motor 126 may usefully accelerate (while ed) into engagement with the ball screw actuator 130 at an end of the ?rst injection phase 670 or at a beginning of the second injection phase 672 to facilitate a greater initial velocity of injectate from the . This may, for example, include a single rotation of the rotary motor 126 from ment with the ball screw actuator 130, or a onal rotation suitable to facilitate very high initial rotational acceleration.

A second injection phase 672 is associated with a second time interval ing from time t1 to In the second injection phase 672, movement of the plunger 120 may be initiated. In this phase, the target displacement of the plunger 120 increases at a relatively high ?rst rate to move the plunger 120 from the initial position p0 to a ?rst position p1 .

In l, the motion of the plunger 120 in this phase may cause a jet of injectate to be ejected from the chamber 106 of the injector head 104 (via the opening 114) with a ?rst velocity Vlat least suf?cient to pierce human tissue to a subcutaneous depth. In some examples, the second injection phase 672 spans a time interval less than 100 ms (i.e., the difference between t1 and t2 is less than 100 ms). In some es, the second injection phase 672 spans a time interval less than 60 ms (i.e., the difference between t1 and t2 is less than 60 ms). In some examples, the second injection phase 672 spans a time interval less than 10 ms (i.e., the difference between t1 and t2 is less than 10 More lly, the injection device 100 may be con?gured so that in this second injection phase 672, the plunger 670 transitions from a stationary position to the target velocity at a suf?cient rate for the initial stream of injectate to achieve a piercing velocity substantially instantaneously, e.g., without ntial leakage or loss of injectate at the surface. By con?guring the linear drive system described above to accelerate in this manner from a ?xed position to a piercing velocity, the injection device 100 may advantageously mitigate loss of injectate. As a r advantage, an injection device with this capability can usefully perform multiple sequential injections without requiring any physical recharge or resetting of a mechanical stored energy system.

A third injection phase 674 is associated with a third time interval extending from time t2 to Q. In the third ion phase 674 the target displacement of the plunger ses at a rate substantially the same as the ?rst rate to move the plunger 120 from the ?rst position 1?1 to the second position p2. In this third ion phase 674, the plunger 120 may be moved at a rate to cause the jet of injectate to be ejected from the chamber 106 of the injector head 104 with a second ty V2 greater than or equal to the ?rst velocity V1. While the rate of plunger 120 movement and the velocity of the injectate stream may vary within this third injection phase 674, e.g., according to limitations on control precision, al system components, and so forth, the plunger 120 should generally be driven at a minimum velocity le for piercing tissue at a target site to a desired depth for ry of the injectate. The jet of injectate may also have a maximum velocity selected to avoid over-penetration or other undesirable tissue damage.

A fourth injection phase 676 is associated with a fourth time al ing from time Q to time Q . In the fourth injection phase 676 the target displacement of the plunger 120 increases at a third rate, relatively slower than the ?rst rate, to move the plunger 120 from the third position p3 to a fourth position p4. In this fourth injection 676, the injection device 100 may generally rate the plunger 120 to cause the jet of injectate to eject from the chamber 106 of the injector head 104 with a third velocity V3 less than the ?rst velocity V1, which may generally be any velocity suitable for non- piercing delivery of additional injectate at a current depth of the stream of injectate within the target tissue.

A ?fth injection phase 678 is associated with a ?fth time interval extending from time Q to is. In the ?fth injection phase 678 the target displacement of the plunger 120 continues to increase at the third rate to move the plunger 120 from the fourth position p4 to the ?fth position p5. In the ?fth injection phase 678, the injection device 100 may generally deliver the injectate — typically a majority of the injectate in the chamber 106 — at a subcutaneous depth achieved during the prior, piercing phase. The rate of movement may be generally constant, or may otherwise vary consistent with maintaining aneous drug delivery without further piercing of the tissue.

It will be appreciated that some continued piercing may occur during the ?fth injection phase 678. Provided that any additional piercing does not create a pathway _ 14- below subcutaneous depth within the target tissue that might result in loss or misdelivery of therapeutic dosage, then this additional piercing will not affect the efficacy of transdermal drug delivery. It will also be understood that the total displacement of the plunger 120 will control the volume of drug delivered over the course of an injection, and a duration of the fifth injection phase 678 may correspondingly be selected according to an intended dosage.

Finally, a sixth injection phase occurs after time is. In the sixth injection phase the target displacement of the plunger 120 stops sing, substantially halting the plunger 120 at a sixth position p6. The sixth injection phase is associated with completion of the ion operation. As noted above, from this position, additional injection cycles may be initiated, provided of course that sufficient additional drug remains in the ion device 100 for completing additional injections.

In order to quickly achieve a piercing velocity and avoid loss of drug at the surface of an ion site, the second injection phase 672 (where acceleration of the injectate occurs) may be short relative to the piercing phase that is maintained once the piercing ty is achieved. Thus in some es, the time interval associated with the third injection phase 674 is in a range of two to twenty times as long as the time interval associated with the second injection phase 672. In some examples, the time interval associated with the second injection phase 672 has a duration between 30 milliseconds and 100 econds and the time interval associated with the third injection phase 674 has a duration n 100 milliseconds and 1000 milliseconds.

More generally, the duration of each phase may depend on the diameter of the injectate stream, the properties of the injectate, the characteristics of the tissue at the injection site and so forth. Thus, the injection profile may usefully employ any durations suitable for accelerating to a piercing ty suff1ciently rapidly to avoid substantial loss of injectate, maintaining a piercing ty until a target depth (e.g., subcutaneous depth) is achieved, and then ining a non-piercing velocity to deliver a full dose at the target depth.

It will also be tood that, while a single ion cycle is illustrated, the injection device 100 contemplated herein may usefully be con?gured for multiple, sequential injections. As such any number of injection cycles might usefully be performed, and any such multi-injection applications are expressly contemplated by this description. 2.1 Rota? Motor Speed Referring to in the ?rst inj ection phase 670, the injection controller 135 controls the rotary motor 126 to maintain its speed at substantially 0 rotations per minute (RPM) to ensure that the plunger 120 remains stationary at the initial position p0 . may include actively maintaining the rotary motor 126 in a ?xed position, e.g., by monitoring the position and activation the rotary motor 126 in counter-response to any detected motion or drift, or by control a magnetic, mechanical, or electromechanical lock that securely engages the plunger 120 in the initial position p0 . In another aspect, this may include passively maintaining the rotary motor 126 in the ?xed position by withholding control signals or drive signals from the rotary motor 126. It will also be understood that combinations of the ing may advantageously be employed. For example, the plunger 120 may be locked with a mechanical lock during storage or while otherwise not in use, and then the rotary motor 126 may be used to electromechanically and ly lock the position of the plunger 120 when the mechanical lock is disengaged to prepare for an injection. In this manner, power may be ved during long term e, while the position can be securely and controllably locked using the rotary motor 126 in an interval immediately prior to injection in order to prevent, e.g., e of an inj ectate.

In the second injection phase 672, the injection controller 135 may control the rotary motor to rate from 0 RPM to a ?rst rotary motor speed S1 (e.g., 33,000 RPM), causing the plunger 120 to move from the l position p0 to the ?rst position p1. In the third ion phase 674, the injection controller 135 may control the rotary motor 126 to maintain a speed at or above the ?rst rotary motor speed SI, causing the plunger 120 to move from the ?rst on 1?1 to the second position p2. In the fourth injection phase 676, the injection controller 135 may control the rotary motor 126 to decelerate to a second rotary motor speed 52 (e.g., 11,000 RPM) less than the ?rst rotary motor speed SI, causing the plunger 120 to move from the second on p2 to a third position p3. In the ?fth injection phase 678, the injection controller 135 may control the rotary motor 126 to maintain the second rotary motor speed 52, causing the plunger 120 to move from the third position p3 to a fourth position p4 at a substantially consistent rate for delivery of an ate at a target depth for an injection.

In the sixth injection phase, the injection controller 135 may control the rotary motor 126 to decelerate its speed from the second rotary motor speed 52 to 0 RPM, causing movement of the plunger 120 to substantially halt at the fourth position p4. _ 16- While the supercapacitor 564 in the power supply 143 described above may be used during any portion of the injection delivery, the supercapacitor 564 may be particularly advantageous where high mechanical loads are anticipated, e.g., during the initial acceleration and piercing phases, as well as where necessary or helpful to quickly decelerate or stop the plunger l20, e.g., at the fourth position p4. Thus, the supercapacitor 564 may be speci?cally used during the second injection phase 672, the third injection phase 674, and ally the fourth injection phase 676 if high power is required to maintain a target speed even during a deceleration of the injectate to a drug delivery velocity, and/or if high power is required to quickly decelerate or stop the r 120. 2.2 Injectate Velocity Referring to in the ?rst injection phase 670, no injectate is ejected from the chamber 106 (i.e., the initial injectate velocity, Vois 0 m/s). In the second injection phase 672, the injectate velocity ses from 0 m/s to the ?rst velocity, Vlat least suf?cient to pierce human tissue. In some examples, the ?rst velocity V1 is at least 200 m/s. If ng is not ted quickly, then there may be substantial loss or leakage of drug. Thus, in some embodiments, the rotary motor 126 may usefully be con?gured to reach the ?rst velocity V1 for injection from a stationary starting point in not more than three rotations, such as less than two rotations, or less than one rotation.

In the third injection phase 674, the injectate velocity may be maintained at a second velocity V2 greater than or equal to the ?rst velocity V1 in order to continue piercing tissue at a target site. Where the ?rst velocity V1 is a minimum velocity for piercing tissue, then the second velocity V2 is preferably maintained above the ?rst ty V1 in order to continue piercing throughout the third ion phase 674.

However, the ?rst velocity V1 may instead be a m velocity or an optimum velocity to initiate piercing, in which case the second velocity V2 may usefully be any velocity greater than, equal to, or less than the ?rst velocity V1 suitable for uing to pierce tissue to the desired, target depth. Similarly, the second velocity V2 may vary over the duration of the third injection phase 674 provided that the second velocity V2 remains within this window of useful piercing ties.

In the fourth injection phase 676, the injectate velocity may decreases to a third velocity V3 (in a range between a maXimum third velocity [/3ch and a minimum third velocity V3Mm) suf?cient to r the majority of the injectate in the chamber 106 at a WO 55500 2018/050643 subcutaneous depth. In the ?fth injection phase 678, the injectate ty may be substantially maintained at the third velocity V3 while the majority of the injectate in the chamber 106 is red to the subcutaneous depth through the channel created during the third injection phase 674. It will be appreciated that the third velocity V3 may vary over the course of the ?fth injection phase 678 between any values — typically greater than zero and less than a piercing velocity — consistent with delivery of the injectate at the target depth. Finally, in the sixth injection phase 680, the injectate velocity may decrease to 0 m/s as the injection operation completes. 3 Inj ectate In some examples, the volume of injectate in the chamber is at least one milliliter.

Thus, in one aspect the injection device 100 may be con?gured to deliver one milliliter of drug subcutaneously in a single dose, or as a number of sequential doses over time, e.g., to different locations or over the course of an extended dosing schedule. Where a large number of sequential doses are intended, or where a larger single dose is intended (e.g., more than one milliliter) the chamber may ly have a greater volume. For multi-dose applications, the contents of the chamber 106 may be conveniently distributed in discrete doses using a rotary motor and linear drive system as contemplated herein. In some examples, the volume of injectate in the chamber is less than or equal to imately 0.5 milliliters. In some examples, the volume of injectate in the chamber is less than or equal to approximately 0.3 milliliters. In some examples, the volume of injectate in the r is a therapeutic amount of injectate.

In some examples, the injectate includes a biological drug. In some examples, the injectate has a viscosity of at least three centipoise at a ature between two degrees and twenty degrees Celsius. In some examples, the injectate has a viscosity of about three centipoise to about two hundred centipoise at a temperature between two degrees and twenty degrees Celsius. Thus, the system described herein may usefully be employed with large le therapeutics or other drugs having relatively high viscosities. 4 Miscellaneous In one aspect, the injection ller may be con?gured to cause the needle-free transdermal ion device 100 to perform a number of sequential injection operations in close temporal proximity to one another. The injection device 100 may usefully be instrumented to support this operation by sensing movement of the injection device 100 and providing tactile, visible, audible or other ck to aid in navigating the user through a injection procedure.

In another aspect, a number of sequential injection operations may be performed without having to reverse the movement of the rotary motor (i.e., to withdraw the plunger). Thus, where additional injectate remains in the injection device 100 at the end of an injection cycle suf?cient for an additional dose, the rotary motor 126 may remain stationary, and a second, complete injection cycle may be initiated from this new starting position. In this context, the rotary motor 126 may be manually locked, or electromagnetically maintained in a ?xed location in order to prevent leakage or other loss of therapeutic product.

In some examples, the linkage (e.g., the ball screw linkage) is bidirectionally coupled to the rotary motor and the plunger such that bidirectional displacement of contents in the chamber is le, e. g. by moving the plunger toward an exit nozzle to eject contents, or moving the plunger away from the exit nozzle to load additional drug into the injection device 100.

In some examples, the transdermal injection device includes a sensor system for detecting when the device is properly positioned for performing an injection operation.

In some examples, once the device is properly positioned, the ion controller is configured to initiate the injection operation without any observable latency. That is, the sensor system may monitor the injection device 100, determine when the injection device 100 is properly positioned and nary, and then initiate an ion. Depending on the duration and feel of the ion, the injection may usefully be preceded by a beep, vibration, or other human-perceptible signal alerting a user that the ion is about to OCCUI.

In some examples, one or more conventional capacitors (e.g., electrolytic capacitors) can be used d of the supercapacitor.

In some examples the injection controller is configured to prevent two or more injection operations within a ermined minimum injection cycle time. Thus, for example, where a dosing regimen speci?es a minimum time before ions, or where an injection is being delivered as a sequence of injections in different but adjacent locations, the injection ller may monitor activation of the injection device 100 to ensure that any rules for a corresponding injection protocol are adhered to.

In some examples, the -free transdermal or head is formed as a removable cartridge for containing injectate. The removable cartridge has an g with a predetermined shape for ejecting the injectate in a stream with a predetermined shape. In some examples, the needle-free transdermal injector includes a movable cartridge door mechanism. A user can interact with the movable cartridge door mechanism to load cartridges into the needle-free transdermal injector and to unload cartridges from the needle-free transdermal injector.

While the above description s primarily to methods and apparatuses for the injection of therapeutics through human tissue to a aneous depth, it is noted that, in some examples the methods and apparatuses described above are used for injection of therapeutics through human tissue to other shallower or deeper depths. For example, the methods and apparatuses can be used for a shallow injection of therapeutics into the dermis, or for a deeper injection though the subcutaneous layer of fat and connective tissue into a patient’s musculature.

It is to be understood that the foregoing description is intended to illustrate and not to limit the scope of the ion, which is de?ned by the scope of the appended claims. Other ments are within the scope of the following claims. _ 20-

Claims (39)

1. An apparatus for injectate delivery, the apparatus comprising: a cartridge containing a volume of an injectate and an exit port; a linear or configured for delivery of the injectate from the exit port of the cartridge, the linear actuator including a linkage; a rotary motor mechanically coupled to the linkage; a controller coupled to the rotary motor; wherein the controller is configured to control a linear motion of the actuator in response to a control signal by controlling an electrical input supplied to the motor in a first interval during which the rotary motor is nary; a second interval ately following the first interval during which the controller accelerates the rotary motor from stationary to a first speed ed to create a jet of the injectate from the cartridge with a velocity at least sufficient to pierce human tissue to a subcutaneous depth, wherein the rotary motor provides ient power to reach the first speed in not more than three rotations; a third interval during which the controller maintains the rotary motor at or above the first speed; and a fourth interval during which the controller decelerates the rotary motor to a second speed selected to deliver the volume of the injectate at the subcutaneous depth.

2. The apparatus of claim 1, wherein the linear actuator is not more than three rotations from engagement with the rotary motor at a beginning of the second al.

3. The apparatus of claim 1, wherein the controller is configured to deliver a sequence of injections of the injectate from the volume without reverse movement of the rotary motor.

4. The tus of claim 1, wherein the ller is configured to deliver a sequence of injections of the injectate from the volume in close temporal proximity to one another.

5. The tus of claim 1, wherein the volume is at least one milliliter.

6. The apparatus of claim 1, wherein the volume is in a range from 0.5 milliliters to 1 iter.

7. The apparatus of claim 1, wherein the volume is not greater than about 0.5 milliliters.

8. The apparatus of claim 1, wherein the volume is not greater than about 0.3 milliliters.

9. The apparatus of claim 1, wherein the volume is a therapeutic amount of the injectate.

10. The apparatus of claim 1, wherein the injectate is a biological drug.

11. The apparatus of claim 1, wherein the injectate has a viscosity of at least three oise at a temperature between two s and twenty degrees Celsius.

12. The apparatus of claim 1, wherein the injectate has a viscosity of about three centipoise to about two hundred centipoise at a temperature between two degrees and twenty degrees Celsius.

13. The apparatus of claim 1, wherein a second velocity of the jet of injectate from the cartridge during the second interval reaches at least two hundred meters per second.

14. The apparatus of claim 1, wherein a duration of the second al is less than d milliseconds.

15. The apparatus of claim 1, wherein a on of the second interval is less than sixty milliseconds.

16. The apparatus of claim 1, wherein the second interval is less than ten milliseconds.

17. The apparatus of claim 1, wherein the linear actuator is bidirectionally coupled to the rotary motor and the cartridge to permit ctional displacement of contents of the cartridge.

18. The apparatus of claim 1, further comprising a plurality of supercapacitors d to the rotary motor and configured to provide electrical power to the rotary motor during the second al, the third interval and the fourth interval.

19. The apparatus of claim 18, wherein the plurality of supercapacitors are configured to charge in parallel and discharge to power the rotary motor in serial.

20. The tus of claim 18, wherein the rotary motor and the plurality of supercapacitors are configured to deliver a peak power to the linear actuator of at least two hundred Watts.

21. An apparatus for injectate delivery, the apparatus comprising: a cartridge containing a volume of an injectate and an exit port; a linear actuator configured for delivery of the injectate from the exit port of the cartridge, the linear actuator including a linkage; a rotary motor mechanically coupled to the linkage; a controller coupled to the rotary motor; wherein the controller is ured to control a linear motion of the actuator in response to a control signal by lling an electrical input supplied to the motor in a first interval during which the rotary motor is engaged with the cartridge to displace the injectate therefrom; a second interval immediately following the first interval during which the controller drives the rotary motor at a first speed selected to create a jet of the injectate from the cartridge with a velocity at least sufficient to pierce human tissue, wherein the rotary motor provides sufficient power to reach the first speed in not more than three rotations; a third interval during which the controller continues operating the motor at or above the first speed in order to in the jet of the injectate at or above the velocity and create a channel through the human tissue to a subcutaneous depth; a fourth al during which the controller decelerates the rotary motor to a second speed selected to deliver the volume of the injectate at the subcutaneous depth.

22. The apparatus of claim 21, further comprising a sensor system configured to detect when the apparatus is ly oned to deliver the injectate to a patient, n the ller and the rotary motor are configured to initiate delivery of the injectate without substantial observable latency when the apparatus is properly positioned.

23. The tus of claim 22, wherein the sensor system detects contact of the apparatus with skin of the patient.

24. The apparatus of claim 22, wherein the sensor system detects an angle of the cartridge relative to skin of the patient.

25. The apparatus of claim 22, wherein the sensor system detects a on of the exit port relative to a body of the patient.

26. The apparatus of claim 21, wherein the apparatus further comprises a capacitive energy storage element that es one or more supercapacitive energy storage elements.

27. The apparatus of claim 26, wherein the one or more apacitive energy storage elements includes a plurality of supercapacitive energy storage elements and wherein the apparatus further comprises supply circuitry, wherein the supply circuitry is configured to switch the plurality of supercapacitive energy storage elements into a parallel configuration during a charging operation and to switch the plurality of supercapacitive energy storage elements into a serial configuration for an injection operation.

28. The apparatus of claim 21, n the apparatus further comprises a capacitive energy storage t, wherein the capacitive energy storage element includes a plurality of capacitors.

29. The apparatus of claim 28, wherein the tus further comprises a battery and supply circuitry, wherein the supply circuitry is configured to switch the plurality of capacitors into a parallel configuration with the battery during a charging ion and to switch the plurality of capacitors into a serial uration for an injection ion.

30. The apparatus of claim 21, wherein the apparatus further comprises a battery and supply circuitry, wherein the supply circuitry includes a direct current to direct current (DC/DC) converter that is disposed between the battery and the capacitive energy storage element.

31. The apparatus of claim 30, wherein the DC/DC converter is configured to boost a voltage ed by the y by a factor in a range of 5-20.

32. The apparatus of claim 21, wherein the apparatus further comprises supply circuitry and a capacitive storage element, wherein the supply try includes a direct current to direct current (DC/DC) converter disposed between the capacitive energy storage element and the rotary motor.

33. The apparatus of claim 21, wherein the tus further comprises a capacitive energy storage element and wherein substantially all of an electrical power supplied to the rotary motor during the second interval and the third interval is supplied from the capacitive energy storage element.

34. The apparatus of claim 21, wherein the controller is ured to prevent multiple injectate delivery operations within a predetermined minimum injection cycle time.

35. The apparatus of claim 21, wherein the third interval is in a range of two to twenty times as long as the second interval.

36. The apparatus of claim 21, wherein the second interval has a first duration of between 30 milliseconds and 100 milliseconds and the third interval has a second on of between 100 milliseconds and 1000 milliseconds.

37. The apparatus of claim 21, wherein the cartridge is coupled to the remainder of the apparatus in a removable and replaceable manner and n the exit port has a predetermined shape for ejecting the injectate in a stream.

38. The tus of claim 37, wherein the electrical input supplied during the third interval is selected to drive the rotary motor at a speed sufficient to drive the stream from the exit port at a velocity to pierce human skin and wherein a duration of the third interval is selected to pierce the human skin with the stream to a subcutaneous depth.

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