Precision injector system and methods of using the same

Abstract

In some embodiments, the transdermal injection device may be used to inject an injectate including one or more doses of a treatment under tissue of a subject. The injection device may include a syringe assembly including a syringe coupled to a needle. The injection device may include a plunger configured to move through an inner volume of the syringe. The injection device may include a first actuator configured to actuate the syringe assembly and a second actuator configured to actuate the plunger to eject injectate. The needle may include a geometry configured to improve repeatability across injections and reduce trauma to the skin. The system may include one or more features to balance the torque and impulse of the system during injection. The system can further include an alignment mechanism to align a position of the needle relative to the subject.

Description

Docket No.: RHTK-003 / 01WO 352653-2018PRECISION INJECTOR SYSTEM AND METHODS OF USING THE SAMECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 63 / 696,051, filed September 18, 2024, entitled, "‘Precision Injector System and Methods of Using the Same,” the disclosure of which is incorporated herein by reference in its entirety.BACKGROUND

[0002] Embodiments described herein relate to delivering injections to a subject. More specifically, the embodiments described herein relate to an injector system and methods of using the injector system.

[0003] There is a rising demand for injectable treatments and / or the like such as botulinum neurotoxin (such as BOTOX®), dermal filler, and / or injectable immunizations, for example. Manual needle injection methods have many disadvantages including safety and handling concerns, patient discomfort, targeted delivery, precise control of the injectable treatment, and / or the like. Precision injection systems are a promising avenue for administering injectables. However, current automatic and / or precision needle injectors still face challenges including, for example, lack of (i) fine-tuned control over needle trajectory during injection and dispersion of inj ectate, (ii) precise depth and volume control of injection, (iii) resilient needle design, (iv) and / or light weight and easy-to-use hardware. Accordingly, a need exists for improved injector systems and methods of using the same.SUMMARY OF THE INVENTION

[0004] In some embodiments, an apparatus comprises a syringe assembly including a syringe defining an inner volume configured to receive an inj ectate, the syringe including a needle coupled to a distal end thereof a plunger, at least a portion of the plunger movably disposed in the inner volume of the syringe; a first actuator coupled to the syringe; and a second actuator coupled to the plunger. The first actuator and the second actuator have a first configuration in which the first actuator and the second actuator collectively advance the syringe assembly a predetermined distance such that a distal end of the needle advances to a predetermined depth under a skin surface of a subject. The first actuator and the second actuator configured to transition to a second configuration in which a ratio of a velocity of the second actuator to aDocket No.: RHTK-003 / 01WO 352653-2018 velocity of the first actuator increases to cause the plunger to move distally through the inner volume of the syringe to ej ect the inj ectate from the needle under the skin surface of the subj ect.

[0005] In some embodiments, an apparatus comprises a syringe assembly including a syringe defining an inner volume configured to receive an inj ectate, the syringe including a needle coupled to a distal end thereof; and aplunger, at least aportion of the plunger movably disposed in the inner volume of the syringe; an actuator coupled to the syringe assembly, the actuator configured to transition from a first configuration in which the actuator advances the syringe assembly distally such that a distal end of the needle advanced to a predetermined depth under skin of a subject to a second configuration in which the actuator causes a portion of the plunger to move distally through the inner volume of the syringe to eject the inj ectate through the needle; and a balancing mass coupled to the actuator and configured to accelerate with an equal and opposite magnitude to the syringe assembly when the actuator is in the first configuration, the balancing mass having a center of gravity that is colinear with a line of motion of a center of gravity of the syringe assembly.

[0006] In some embodiments, an apparatus comprises a syringe assembly including a syringe defining an inner volume configured to receive an inj ectate, the syringe including a needle coupled to a distal end thereof; a plunger, a portion of the plunger disposed in the inner volume of the syringe, the syringe assembly coupled to at least one sensor, the at least one sensor configured to collect measurements including at least one of an electrical signal of a surface of the skin or an optical signal of a marker disposed on the syringe assembly; and an actuator coupled to the syringe assembly, the actuator in a first configuration configured to advance the syringe assembly distally, the actuator in a second configuration configured to move the plunger through the inner volume to eject the inj ectate through the needle; and a controller coupled to the syringe assembly. The controller is configured to receive the measurements from the at least one sensor; determine aposition of the distal end of the needle relative to the surface of the skin based on the measurements; and control a velocity of the actuator based on the position of the distal end of the needle relative to the surface of the skin.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 is a schematic diagram of an injector device, according to an embodiment.Docket No.: RHTK-003 / 01WO 352653-2018

[0008] FIG. 2 is a schematic diagram of an injector system, including the injector device of FIG. 1. according to an embodiment.

[0009] FIG. 3 is a flow chart of an example method of using an injector system, according to an embodiment.

[0010] FIGS. 4A-4D are schematic diagrams of an injector device, each according to a different embodiment.

[0011] FIGS. 5A-5B show an alignment system for an injector device, according to an embodiment.

[0012] FIGS. 6A-6C show various needle hub clamping mechanisms of an alignment system for an injector device, according to different embodiments.

[0013] FIGS. 7A-7B show a side view and a front view, respectively, of a syringe clamping mechanism of an alignment system for an injector device, according to an embodiment.

[0014] FIGS. 8A-8B show side views of at least a portion of an injector device without a motion balancing mechanism, according to an embodiment.

[0015] FIG. 8C shows a side view of at least a portion of an injector device with a motion balancing mechanism, according to an embodiment.

[0016] FIGS. 9A-9B show side views of at least a portion of an injector device without a motion balancing mechanism, according to an embodiment.

[0017] FIGS. 9C-9D show side views of at least a portion of an inj ector device with a balancing mass, according to an embodiment.

[0018] FIG. 9E-9F show side views of at least a portion of an injector device including a mechanism to produce a pre-load force on a portion of an injector device during injection, according to an embodiment.

[0019] FIG. 10A shows a side view of at least a portion of an injector device including a pair of motors configured to balance acceleration, according to an embodiment.

[0020] FIG. 10B shows a side view of at least a portion of an injector device including a balancing mass to balance acceleration, according to an embodiment.

[0021] FIGS. 11 A-l 1C show at least a portion of an injector device including a plunger with a detachable proximal portion, according to an embodiment in a first, second, and third configuration, respectively.Docket No.: RHTK-003 / 01WO 352653-2018

[0022] FIGS. 1 ID-1 IE show at least a portion of an injector device including plunger driver(s) to reduce a total length of the injector device, according different embodiments.

[0023] FIGS. 12A-12C show a needle of an injector device, according to an embodiment.

[0024] FIGS. 13A-13B show a needle of an injector device, according to an embodiment.

[0025] FIGS. 14A-14B show a needle of an injector device, according to an embodiment.

[0026] FIGS. 15A-15C show a needle of an injector device, according to an embodiment.

[0027] FIGS. 16A-16D show a needle of an injector device, according to an embodiment.

[0028] FIGS. 17A-17D show a needle of an injector device, according to an embodiment.

[0029] FIGS. 18A-18C show a needle of an injector device, according to an embodiment.

[0030] FIGS. 19A-19C show a needle of an injector device, according to an embodiment.

[0031] FIGS. 20A-20C show a needle of an injector device, according to an embodiment.

[0032] FIGS. 21A-21D show a needle of an injector device, according to an embodiment.

[0033] FIG. 22 A shows a method of determining a depth of a needle of an injector system relative to a surface of skin of a subject, according to an embodiment.

[0034] FIG. 22B is a graph of measurements from a sensor disposed on a needle of an injector system configured to determine a depth of the needle relative to the surface of the skin, according to an embodiment.

[0035] FIGS. 23A-23B show a needle of an injector device including one or more markers for determining a depth of the needle, according to an embodiment.

[0036] FIGS. 24A-24C show needles including one or more openings defined in a sidewall of a needle for injectate to flow through, according to an embodiment.

[0037] FIGS. 25A-25B show a shroud of an injector device for applying a force to the skin during injection to reduce pain, according to an embodiment.

[0038] FIGS. 2 A-26B show diagrams of alignment systems including optical pathways for determining a position of the needle relative to skin of a subject, according to an embodiment.

[0039] FIGS. 27A-27C show needle covers configured to prevent cross-contamination, according to an embodiment.Docket No.: RHTK-003 / 01WD 352653-2018

[0040] FIGS. 28A-28B show needle covers configured to prevent cross-contamination, according to an embodiment.

[0041] FIGS. 29A-29B show a robotic injector for placing the injector device relative to the skin, according to an embodiment.

[0042] FIGS. 30A-30C show method of using an injector system, according to an embodiment.DETAILED DESCRIPTION

[0043] Existing transdermal injection technology has disadvantages in that the systems are either bulky and inconvenient to use, or they lack control over the trajectory and / or depth precision of the inj ectate injected. Among other things, the embodiments described herein provide systems and / or methods for delivering an inj ectate that address these drawbacks.

[0044] Embodiments described herein provide an injection device configured to provide precise and reliable injections. The injection device may be configured to inject one or more doses of an injectate (e.g.. a botulinum neurotoxin such as BOTOX®, subdermal filler, vaccination, etc.) under a subject’s skin. In some embodiments, the transdermal injection device may include a syringe coupled to a needle at a distal end thereof and configured to receive at least a portion of a plunger at a proximal end thereof. In some embodiments, an actuator may be configured to control movement of the plunger through the syringe to eject the injectate from the synnge with a predetermined velocity and at a predetermined depth into an injection site along the skin of the subject. In some embodiments, the transdermal injection device may include one or more actuators (including the same type or different t pes of actuators) to precisely control movement of the plunger through the syringe, while also keeping the device lightweight and power efficient.

[0045] In some embodiments, the injection devices described herein may include an alignment mechanism to ensure a straight and linear trajectory of the needle during injection, thereby reducing likelihood of damaging tissue at the injection site. The injection devices may further include one or more motion balancing mechanisms to counteract torque and linear forces acting on the actuators. Balancing the motion in the injection device can further promote proper alignment during the injection.

[0046] In some embodiments, the transdermal injection devices described herein may include a depth sensing mechanism including one or more sensors and a depth detection circuit. In some embodiments the sensors may include a contact sensor configured to detect first contactDocket No.: RHTK-003 / 01WO 352653-2018 between the needle and the skin surface. In some embodiments, the sensors may include encoders coupled to the actuator(s) of the injection device to determine a distance the needle has traveled. In some embodiments, the one or more sensors may be configured to measure a position and / or movement of components in the transdermal injection device and communicate this information to a controller. The controller can control one or more portions of the actuator based on the position information obtained by the sensors. The depth sensing mechanism may further include one or more optical elements configured to reflect light off of the needle such that a distal end of the needle can be visualized. In some embodiments, the injection system may be compatible with a robotic injector or a machine-controlled injection system. The robotic injector may promote accurate targeting of injection sites.

[0047] The needles described herein may include a tip geometry configured to withstand consecutive injections without dulling or deforming, thereby reducing pain at the injection site and / or tissue damage. The needles may further include one or more openings defined in a sidewall thereof to improve control over horizontal dispersion of injectate.

[0048] Embodiments described herein provide benefits that may include, but are not limited to, better control of the volume of the injectate injected (e.g., accurate dosing); achieving a straight needle travel path during injection; easy and reliable delivery of sequential doses of injectate; reliable and precise control of injection depth; fine-tuned control of dispersion of injectate; reducing medication waste; reduced discomfort of injection; reduced injury in tissue surrounding the injection; light-weight and easy-to-maneuver device; and more.

[0049] FIG. 1 is a schematic of a transdermal injection device 110 (hereinafter, “the injector device 110”), according to an embodiment. The injector device 110 may be configured to administer injections to tissue (e.g., skin) of a patient or subject 102 (e.g., animal or human). The injector device 110 may include a syringe 112 defining an inner volume configured to receive an injectate. The injectate may include a liquid, a semi-liquid, and / or a semi-solid. The injectate may include a treatment, medication, vaccination, and / or any other suitable injectable substance to be injected underneath the skin of the subject 102 such as, for example, botulinum neurotoxin, dermal filler, vaccines, immunizations, etc. In some embodiments, the distal end of the syringe 112 may be coupled to a needle 120. and a proximal end portion of the syringe 112 may be configured to receive at least a portion of a plunger 114. In some embodiments, the needle 120 may be fixed to a needle hub that can be coupled to a distal end portion of the syringe 112. The needle hub can therefore connect the needle 120 to the distal end portion of the syringe 112.Docket No.: RHTK-003 / 01WO 352653-2018

[0050] The needle 120 may include a distal end configured to puncture the skin of the subject 102 and may define an inner lumen configured to receive fluid (e.g.. injectate). For example, the distal end of the needle 120 may include a specific geometry to penetrate the skin of the subject 102 with minimal tissue damage and / or to otherwise reduce pain felt by the subject 102. The geometry of the distal tip may be configured to maintain mechanical strength of the needle 120 and / or to prevent dulling, thereby limiting and / or substantially preventing tissue damage and pain felt by the subj ect 102 after consecutive inj ections . The distal end may include any suitable geometry such as, for example, a diamond-shaped tip, a beveled tip, a cone-shaped tip, a tapered tip, a conventional cutting tip, a reverse cutting tip, a taper cut tip, etc. In some embodiments, the needle 120 may be cone shaped. In some embodiments, the distal end of the needle 120 may include materials and / or be heat treated for procedures in which multiple penetrations are used (e.g., sutures intended for multiple penetrations). The needle 120 may include any suitable material such as, for example, stainless steel and / or any other suitable biocompatible material.

[0051] The distal end of the needle 120 may be open or solid. With an open distal end, fluid may be dispersed from the lumen of the needle 120 through the distal opening alone or fluid can be dispersed through the open distal end and any number of openings 124 along a sidewall of the needle 120. In some embodiments, the shape, size, and / or configuration of the openings (e.g., the distal opening and / or the opening(s) along the sidewall of the needle 120) can be selected to provide a desired dispersion pattern or flow' of injectate into the body of the subject 102. Alternatively, the distal end of the needle 120 may be filled or solid (e.g., a fully filled cone shape) and injectate may be dispersed through the one or more openings 124 (e.g., ports, holes, etc.) defined in a sidewall of the needle 120 proximal to the closed / solid distal tip. In some embodiments, the openings 124 may be disposed around the circumference of the needle barrel such that fluid can be horizontally dispersed under the skin of the subject 102 during injection. The solid distal end may increase mechanical strength of the needle 120 and / or prevent dulling of the needle 120 over time, thereby reducing tissue damage after consecutive injections. In some embodiments, the needle 120 may include any suitable number of openings 124. For example, the needle may include between 1-12 holes, inclusive of all ranges, subranges, and / or values therebetween. The openings 124 may have any suitable shape such as, for example, circular, elliptical, square, rectangular, diamond. In some embodiments, a number of openings 124 and / or a size of the openings 124 may be larger than low er thresholdsDocket No.: RHTK-003 / 01WO 352653-2018 such that horizontal dispersion of the inj ectate is achieved, while being below upper thresholds such that the mechanical integrity of the needle is maintained.

[0052] In some embodiments, the needle 120 with the closed, filled, and / or solid distal end or tip can be and / or can be based on a modified conventional needle in which a lumen of the needle extends through the beveled distal end (e.g., an open distal end). For example, a conventional needle may be modified by filling or plugging the opening or lumen at the distal tip with any suitable material such as, for example, epoxy, resin, silicone, metal(s), etc. In addition, any number of holes may be drilled (e.g., laser drilled) along the sidewall proximal to the filled distal end of the needle.

[0053] In some embodiments, the needle 120 (or portion of the injector device 110) may include a mechanical stop at a predetermined location along a length of the needle 120 to stop the needle 120 from penetrating into the skin beyond the predetermined location. In some embodiments, the mechanical stop may include a sleeve disposed around a needle such that a distal end of the sleeve forms a ledge or surface extending from the needle 120. The predetermined location on the needle 120 may correspond to a predetermined depth of penetration into the skin. In some embodiments, an outer diameter of a portion of the needle 120 may increase at the predetermined location (e.g., stepwise) to form the mechanical stop. In some embodiments, the needle 120 may include one or more markers 126 (e.g.. laser etchings, indicators, etc.) positioned along the needle 120 at predetermined locations and / or in a predetermined pattern on the needle 120 to indicate a depth and / or position of the needle 120 relative to the skin of the subject 102. The needle 120 may include any suitable number of markers. For example, the needle may include between 1-20 markers, inclusive of all ranges, subranges, and / or values therebetween. As described in further detail herein, the injector device 110 or other device operatively coupled to the injector device 110 may include a depth sensing mechanism 140 and / or the like configured to detect a depth of the needle 120. For example, the depth sensing mechanism 140 can be and / or can include an optical sensing system configured to detect the markers 126 along the needle 120, which in turn, can be used to determine an injection depth of the needle 120. In some embodiments, the depth sensing mechanism 140 can include a processor configured to determine the injection depth of the needle 120 and send a signal to one or more actuators 116 of the injector device 110 to stop actuation of the needle 120.

[0054] As shown in FIG. 1, at least a portion of the plunger 114 is or is configured to be movably disposed in the inner volume of the syringe 112. The plunger 114 may be configuredDocket No.: RHTK-003 / 01WO 352653-2018 to move through the inner volume of the syringe 112 to push the inj ectate through the syringe 112, through the inner lumen of the needle 120, and eject the inj ectate under the skin of the subject 102. At least a portion of the plunger 114 may form a tight seal with an inner surface of the body of the syringe 112 such that as the plunger 114 moves through the inner volume of the syringe 112, the plunger 114 forces the injectate through the needle 120.

[0055] The plunger 114 may be coupled to one or more actuators 116 configured to move the plunger distally 114 through the inner volume of the syringe 112. In some embodiments, the injector device 110 can have a first configuration in which the actuator(s) 116 advance the syringe assembly and a second configuration in which the actuator(s) 116 advance the plunger distally through the inner volume of the syringe 112. In some embodiments, the actuator(s) 116 can be coupled to the syringe assembly having a first configuration in which the actuator(s) 116 advance the syringe assembly distally such that the distal end of the needle 120 is advanced to a predetermined depth under the skin of the patient. The actuator(s) 116 can have a second configuration in which the actuator(s) 116 causes at least the portion of the plunger 114 to move distally through the inner volume of the syringe 112 to eject injectate through the needle 120.

[0056] In some embodiments, the actuator(s) 116 may include any suitable number of actuators and / or any suitable type of actuator including, for example, a rotary motor (e.g., direct current (DC) rotary motor) and / or a voice coil. For example, in some embodiments, the actuator(s) 116 can include a first actuator coupled to the syringe 112 and / or the plunger 114. In some embodiments, the actuator(s) 116 can include a second actuator coupled to the plunger 114. In some embodiments, the second actuator may be coupled to the plunger 114 and not the syringe 112. In some embodiments, the injector device 110 may include a first housing or holder (e.g., clamp, extension, sheath, case, cover, etc.) in which the syringe 112 is at least partially disposed to form a syringe assembly. The injector device 110 may further include a second housing or holder (e.g., clamp, extension, sheath, case, cover, etc.) coupled to a portion of the plunger 114. For example, the injector device 110 can include the second housing in which a proximal portion of the plunger 114 may be disposed. In some embodiments, the first actuator and the second actuator may be coupled to the syringe 112 via the first housing or holder. The first actuator may be coupled to the proximal end of the plunger via the second housing or holder. Therefore, the first actuator and the second actuator may be configured to move portions of the injector device 110 together or relative to one another.Docket No.: RHTK-003 / 01WO 352653-2018

[0057] In some embodiments, the first actuator and / or the second actuator may include a threaded elongate member (e.g., a lead screw, a threaded rod, etc.) coupled thereto. For example, the first actuator may include a first motor coupled to a first lead screw and the second actuator may include a second motor coupled to a second lead screw. In some embodiments, the actuator(s) 116 may be coupled to one or more sensors (e.g., an encoder) to encode a position of the syringe 112 (or syringe assembly) and the plunger 114 to monitor a distance and / or speed of the syringe 1 12 (or syringe assembly) and / or the plunger 114. For example, the actuator(s) 116 can include a first encoder configured to monitor movement of the first actuator and / or a second encoder configured to monitor movement of the second actuator. In some embodiments, at least one of the syringe or the plunger can include a sensor (e.g., an encoder) configured to monitor movement (e.g., speed, distance travelled, acceleration, impulse, etc.) of at least one of the syringe or the plunger.

[0058] The first actuator and the second actuator are collectively configured to advance the syringe assembly a predetermined distance such that the distal end of the needle 120 advances to a predetermined depth under the subject’s skin. In some embodiments, one of the first actuator or second actuator may be configured to cause injection of the inj ectate by actuating the plunger 114. In some embodiments, the second actuator may be configured to actuate the plunger 114 to inject the medication. In some embodiments, the first actuator can be configured to actuate syringe 112 and not the plunger 114. In some embodiments, the second actuator can be configured to actuate the plunger 114 and not the syringe 112. In some embodiments, the first actuator and the second actuator can have a first configuration in which the first actuator and the second actuator collectively advance the syringe assembly a predetermined distance such that the distal end of the needle advances the predetermined depth under the skin surface of the patient. In some embodiments, the first actuator and the second actuator can be configured to transition to a second configuration in which a ratio of a velocity of the second actuator to a velocity of the first actuator can increase to cause the plunger to move distally through the inner volume of the syringe (e.g., with a predetermined velocity). For example, the first actuator and the second actuator in the first configuration can be activated to cause the syringe and the plunger to be advanced with an equivalent velocity. The first actuator and the second actuator in the second configuration can be configured to cause the plunger to be advanced with a velocity larger than a velocity of the syringe 112 such that the plunger 114 moves distally through the inner volume of the syringe 1 12. In some embodiments, when the first actuator and the second actuator are in the second configuration, the first actuator can beDocket No.: RHTK-003 / 01WO 352653-2018 paused, stopped, deactivated, or slowed while the second actuator advances the plunger 114. In some embodiments, when the first actuator and the second actuator are in the first configuration, the second actuator can be paused, stopped, deactivated, or slowed while the first actuator advances the syringe 112 and the plunger 114. In some embodiments, the syringe 112 can remain stationary7(e.g., the first actuator can be deactivated) while the plunger 114 is configured to move distally (e.g., the second actuator is activated).

[0059] In some embodiments, both lead screws may be rotated or turned contemporaneously and / or overlapping in time. In some embodiments, both the actuator(s) 116 may move the first lead screw and the second lead screw with equivalent velocity and / or in sync to move the needle 120 without dispensing the injectate. To dispense fluid (even while moving the needle 120) the actuator(s) 116 are actuated to turn the lead screws at different speeds. For example, a ratio of a speed of the first actuator and a speed of the second actuator may correspond to a velocity and / or acceleration with which the plunger 114 advances through the syringe 112, and therefore a velocity and / or acceleration with which the injectate is ejected from the needle. In some embodiments, a ratio in the speed or velocity7of the first actuator to the second actuator may increase to eject the injectate from the needle 120. In some embodiments, the arrangement of the actuators 116 and / or the lead screws thereof may reduce a total weight and mechanical complexity of the injector device 110 relative to other methods of actuating the syringe 112.

[0060] In some embodiments, the first housing may define a threaded through hole configured to receive a portion of a first threaded elongate member of the first actuator such that rotation of the first threaded elongate member causes linear motion of the first housing. The second housing may define a threaded through hole configured to receive a portion of a second threaded elongate member of the second actuator such that rotation of the second threaded elongate member causes linear motion of the second housing. In some embodiments, the first threaded elongate member and the second threaded elongate member can have threading with opposite directionality. In some embodiments, the first threaded through hole and the second threaded through hole may have threading with opposite directionality. In some embodiments, the first actuator may be configured to rotate the first threaded elongate member in a first direction and the second actuator may be configured to rotate the second threaded elongate member in a second direction opposite the first direction. The opposite threading of the first and second threaded elongate members causes the syringe 112 and the plunger 114 to be actuated in the same direction (e.g., distally) when the threaded elongate members rotate in opposite directions. The threaded elongate members rotating in opposite directions can helpDocket No.: RHTK-003 / 01WO 352653-2018 balance impulse of the injector device 100. For example, a portion of the first actuator configured to rotate (e.g., the threaded elongate member) can have a first mass and can be configured to rotate in the first direction with a first acceleration. A portion of the second actuator configured to rotate (e.g., the threaded elongate member) can have a second mass and be configured to rotate in the second direction with a second acceleration. Therefore, the forces imparted on a portion of the injector device by the first actuator and the second actuator can be neutralized.

[0061] Components configured to move proximally and / or distally may be referred to herein as part of '‘the moving mass,” wherein components configured to remain stationary are referred to herein as “the stationary mass.” In some embodiments, the moving mass may include the syringe 112 and / or syringe assembly. In some embodiments, the moving mass may include a weight below the threshold such that a size of the actuator(s) 116 may be reduced and / or a power supply for operating the device may be reduced. The reduction in the moving mass can also reduce an overall device mass. In some embodiments, the moving mass may have weight below a threshold to reduce an acceleration force. The reduction in the moving mass may reduce a reactionary acceleration (e.g., impulse, torque, torsional acceleration), making the injector device easier to use. In some embodiments, the stationary mass can include one or more portions of the actuator configured to remain axially stationary. In some embodiments, the stationary' mass can include one or more portions of the housing that do not move with the syringe assembly such as a handle or portion to be gripped by the user. The dual lead screw actuators can minimize moving mass by keeping stationary’ both the actuator and the lead screw that drives syringe plunger motion (e.g.. axially stationary).

[0062] Additionally or alternatively, the first actuator may include a motor, and the motor may include a shaft (e.g., a spline shaft or a slotted shaft) and a slot or groove (e.g., a keyway) configured to receive the shaft. To advance the syringe assembly distally, the second actuator may be actuated. To move the plunger 114 distally, the first actuator may actuate the lead screw to turn such that the lead screw and shaft also advances distally through the slot. Movement of the first lead screw may reduce complexity' of controlling the actuator(s) 116 because actuation of the needle and syringe assembly and actuation of the plunger 1 14 is decoupled. Including the shaft and slot may increase a mass of the moving mass relative to the actuator without the shaft and keyway due to increased weight from the lead screw, screw supports, and keyway section. However, because the first lead screw is now moving rather than stationary, the controlDocket No.: RHTK-003 / 01WO 352653-2018 of movement and dosing may be decoupled, and therefore, controlling the velocity and acceleration of the injection may be simplified.

[0063] Additionally or alternatively, the second actuator (e.g., the actuator that moves the syringe assembly) may include a voice coil and linear encoder. In some embodiments, the voice coil may be coupled to the first housing (e.g., coupled to the syringe assembly). To advance the syringe assembly distally, a current may be applied through a coil such that the coil is drawn towards the magnet. In some embodiments, the voice coil may be coupled to a power pack via a wired connection. Advancement and retraction mechanisms may be used, which may include a variable valve lift mechanism, to control insertion depth or movement of the syringe 112 and / or plunger 114. The voice coil, solenoid, or the like may be fitted with and / or otherwise include position measurement devices including, for example, oscillatory position control systems, devices, mechanisms, etc. In some embodiments, sensor(s) coupled to the second actuator may include a hall effect sensor (e.g., XY hall effect sensor) to measure a magnetic field of a magnet disposed in the first housing (e.g., axially in the first housing). The hall effect sensor may be configured to output an electrical output corresponding to a distance the syringe assembly has traveled based on the change in magnetic field measured by the hall effect sensor. In some embodiments, the voice coil may provide precise control over small needle movements (e.g., movements around 10 mm). However, the voice coil may increase a total weight of the device compared to a rotary motor.

[0064] The injector device 1 10 may further include a motion balancing mechanism 150 coupled to a portion of the injector device 110 (e.g., one or more of the actuators 116) and configured to balance or neutralize torque and / or impulse caused by accelerating a portion of the injector device 110 toward the subject 102. The motion balancing mechanism 150 may include features to prevent reactionary acceleration of the stationary mass during acceleration of the moving mass (e.g., prevent acceleration of a handle assembly the user holds). In order to move the needle 120, components connected to the needle (e.g., needle hub, syringe, plunger) are moved as well, which causes a reaction force at or along the actuator 116. Straight travel is affected by the relative position of the moving mass of the injector device 110 and the stationary mass of the injector device 110. When the center of gravity of the moving mass is not vertically aligned with the center of mass of the stationary mass, the syringe assembly and / or the actuator 116 may rotate. The acceleration force can create a net rotation torque on the injector device 110 (e.g., a portion between where there the moving mass and the stationary mass meet) which can cause non-straight needle motion and can cause more damage to tissueDocket No.: RHTK-003 / 01WO 352653-2018 / increase pain for the subject 102. To achieve straight needle motion, the line of travel of the center of gravity of the moving mass may be coincident or colinear with the center of gravity of the stationary mass. In some embodiments, straight travel of the syringe assembly can be determined relative to a travel axis (or an injection axis). For example, the travel axis may be a desired axis of injection relative to a surface of the skin. In some embodiments, the travel axis may be perpendicular to the surface of the skin. In some embodiments, the travel axis is not perpendicular to the surface of the skin. In some embodiments, the injection may be more effective and accurate when the needle follows a travel path that is co-linear with the travel axis (e.g., without curving or rotating relative to the travel axis).

[0065] While aligning the center of mass can reduce rotational acceleration, there can still be inline acceleration that can impact accuracy of the distance traveled by the needle 120 and therefore the depth of the injection. The acceleration (e.g., reactionary’ acceleration) may be linear in an opposite direction than the acceleration of the needle 120 (e.g., proximally towards the user and away from the skin of the subj ect 102). In some embodiments, a ratio of the moving mass to the stationary' mass may be below a threshold (e.g., 1 :1, 2: 1, 3: 1, 4: 1, 5:1, 6: 1, 7: 1, 8: 1, 9: 1, 10: 1, or more) to reduce the linear back-acceleration during injection.

[0066] In some embodiments, a balancing mass may be used to reduce torque (impulse, or torsional acceleration). In some embodiments, a mechanical counterweight may be used (e.g., an open loop approach). In some embodiments, a second driven mass that is lighter in weight may be used (e.g., an open loop approach). In some embodiments, an active second driven mass with accelerometer may be used (e.g., a closed loop approach). In some embodiments, the balancing mass may accelerate with an equal and opposite magnitude to the moving mass (e.g., the syringe assembly) to cancel out force imparted on the stationary mass, thereby keeping the stationary mass in the same position during injection. The balancing mass can be configured to accelerate or be accelerated with an equal and opposite magnitude to the syringe assembly when the actuator(s) 116 are in the first configuration (e.g., when the syringe assembly is advanced distally). The balancing mass (e.g.. the second driven mass) can have a lower mass than the moving mass and can be accelerated with a larger acceleration than the moving mass to achieve an equal and opposite amount of force acting on the stationary mass. In some embodiments, the balancing mass may have an equal mass to the moving mass and can be accelerated with an acceleration equal in magnitude and opposite in direction to the moving mass with the center of gravity of the moving mass travelling colinearly with the center of gravity of the balancing mass. The motion of the balancing mass capable of keeping theDocket No.: RHTK-003 / 01WO 352653-2018 stationary mass from moving can be calculated using the following equation: F == m2a2, where mi is the moving mass, ai is the acceleration of the moving mass, m2 is the balancing mass, and a2 is the acceleration of the balancing mass. In some embodiments, the balancing mass can have a center of gravity that is colinear with a line of motion of a center of gravity of the syringe assembly such that the syringe assembly does not rotate relative to a longitudinal axis of the syringe assembly when the syringe assembly is advanced distally.

[0067] To balance the impulse and / or reduce torsional acceleration, the actuator(s) 116 may include lead screws having threading with opposite directionality. For example, the first lead screw of the first actuator may have a threading having a first direction (e.g., left-handed threading) and the second lead screw of the second actuator may have threading having a second direction of threading (e.g., right-handed threading). Therefore, when the first lead screw and the second lead screw are accelerated and turned at the same rate during the syringe assembly motion, the resulting torque can be equal to zero and / or near zero (e.g., cancelled out, neutralized, etc.).

[0068] The second lead screw having the second direction of threading may be referred to herein as the reverse lead screw. In some embodiments, the balancing mass may include a counterweight including a reverse lead screw with weight. In some embodiments, the balancing mass may be coupled to the second actuator. For example, the balancing mass may be coupled to a proximal end of the second lead screw. The second actuator and balancing mass may be moved faster to get more reaction force with less weight. In some embodiments, a velocity of the counterweight may depend on a velocity of the lead screw and / or a mass of the weight. When the first actuator and lead screw assembly rotate in a first direction (e.g., clockwise (CW)). a second mass may be rotated with equal inertia and in an opposite direction (e.g.. counterclockwise (CCW)). In some embodiments, the second mass may be rotated using a pair of gears. For example, the first motor (e.g., the plunger motor) can be connected to a plunger lead screw using a gear train (planetary, spur, etc.) such that the plunger lead screw rotates in a first direction (e.g., CCW) while the first motor is rotating in a second direction (CW). The rotational inertia of the plunger motor side of the drive train should be equal to the rotational inertia of the lead screw side of the drive train so there is zero or close to zero torsional acceleration imparted on the stationary mass. In some embodiments, a rotational balancing mass may be used to balance torsional acceleration of any rotating masses using the formula torque = moment of inertia * angular acceleration. In some embodiments, torsional balancing mass may concentrate mass away from the pivot point to maximize moment of inertia w hileDocket No.: RHTK-003 / 01WO 352653-2018 minimizing total mass (e.g., a flywheel with thin spokes and a thick rim at a distal end of the lead screw).

[0069] In some embodiments, the stationary mass may be preloaded against the skin with a force that is greater than the acceleration force. For example, the injector device 110 may be preloaded against the subject 102 with a force sufficient to prevent detrimental motion of the device relative to the subject 102. Acceleration force should be greater than the applied preload force to cause any net motion. The injector device 110 may be disposed against the subject with a spring or load cell (or other similar means) so that the user knows sufficient preload has been applied to compensate for the expected acceleration. In some embodiments, the device 110 may electronically detect preload via one or more sensor(s) (e.g., a sensor such as a force sensor) and only activate / inject if sufficient pre-load force is applied. In some embodiments, a level of sufficient preload may be changed depending on velocity settings chosen to compensate for ejection profiles that create more or less reaction force (e.g., different injectates. different amounts of injectate, different depths of injection, etc ). In some embodiments, the preload mechanism may be configured for rapid ejection. For example, the device may fire when sufficient preload is detected, then fire again when sufficient preload is detected again. However, the preload mass may result in a higher overall weight of the injector device 110 in cases where high needle acceleration is used.

[0070] The injector device 110 may also include a spring or spring system that pushes the needle 120 and / or a needle holding assembly forward. When retracting the needle 120, the system can store energy in the spring. When inserting the needle 120, the spring helps accelerate the system and the needle forward. The system may also accelerate the needle 120 for a distance in the air before the needle 120 contacts the skin to increase initial penetration velocity given a fixed maximum acceleration force.

[0071] In some embodiments, the injector device 110 may be configured to reduce pain and / or tissue damage of the subject during injection. In some embodiments, the injector device 110 may include a contact foot extending therefrom and configured to apply tension to the skin prior to injection. For example, the foot may splay apart as it contacts the skin, thereby pulling the skin taut. The injector device 110 may further include a shroud 121 configured to improve depth precision during injection. In some embodiments, the shroud 121 may be configured to apply a suction or vacuum force on the skin (e.g., via a shroud 121 disposed around a distal portion of the syringe 112 or needle hub) to pull the skin taut. In some embodiments, the injector device 110 may be configured to actuate the needle 120 at a high velocity and / orDocket No.: RHTK-003 / 01WO 352653-2018 acceleration to reduce pain. In some embodiments, the injector device 110 may be configured to actuate the plunger 114 at a high velocity and / or acceleration relative to the needle 120 such that fluid ejection is fast, thereby minimizing pain.

[0072] In some embodiments, the shroud 121 may include a medium that is air permeable (e.g., ridged open cell foam, disk with small holes, a porous polymer, etc.). The skin may be drawn against the medium (e.g., via vacuum force), setting the needle 120 to a consistent depth. In some embodiments, when the injector device 110 detects a seal with the skin (e.g., when the vacuum is drawn down), then the injection may be triggered (e.g., automatically without user input). For example, a controller may be configured to receive a signal that the skin is drawn against the medium, and the controller may send a signal to the actuator 116 to begin the injection. In some embodiments, the shroud 121 may include a sensor (e.g., an electrode, a force sensor, a light sensor, etc.) configured to detect when skin is drawn against the shroud 121 (e.g.. via capacitance, force, light, etc.).

[0073] In some embodiments, the injector device 110 may be configured to reduce pain by stimulation of the target tissue (e.g., via the shroud 121). For example, the injector device 110 may be configured to perform at least one of the following: heat an area of tissue, cool an area of tissue, electrically stimulate nerves or muscles in an area of tissue, vibrate an area of tissue, apply friction to an area of tissue, vibrate the needle (e.g.. during insertion and / or withdrawal) to reduce a penetration force, or pulse the ejected fluid. In some embodiments, the area may be heated with radiant heat and / or an infrared light-emitting diode (LED). In some embodiments, the area may be cooled before injection (e.g., a topical substance and / or cooling device). In some embodiments, a Peltier device may be used to cool the skin. In some embodiments, electrical stimulation of the nerves may "‘distract” or “occupy” the nerves and therefore reduce perceived pain in the subject. In some embodiments, the foot coupled to the injector device may be configured to vibrate, thereby vibrating the area of tissue. In some embodiments, a distal end of the injector device housing may oscillate. In some embodiments, vibration maybe in a range between about 20 Hz and about 270 Hz, inclusive of all ranges, subranges, and / or values therebetween.

[0074] In some embodiments, stimulating the area of tissue (e.g.. via electrical stimulation, temperature, and / or vibration) may be performed with randomized timing such that the user can not anticipate the stimuli. In some embodiments, a timing betw een the stimulation and the injection may be randomized to avoid body building patterns. In some embodiments, the timing may be randomized in a window between about 0.0 milliseconds (ms) to about 200 ms,Docket No.: RHTK-003 / 01WO 352653-2018 inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, the second actuator (e.g., the second rotary motor) may be used to vibrate the needle during injection and / or ejection.

[0075] The surface of the skin is soft, and when pierced with a needle, the skin can deform a small distance from its relaxed position. The deformation associated with the piercing can create challenges for achieving precise, shallow (e.g., about 0.2 mm), needle insertion depths. In some embodiments, the injector device 110 may include a depth sensing mechanism 140 (also referred to herein as a "contact sensing mechanism” or “contact sensing circuit”) configured to detect the needle position and / or an initial skin position of the subject 102. The needle 120 may then be actuated a predetermined distance based on the position of the needle 120 relative to the skin. In some embodiments, contact sensing mechanism 140 may be configured to detect first contact with the skin. A position of the needle 120 when the needle first contacts the skin may be recorded as the initial position of the needle 120.

[0076] In some embodiments, the contact sensing mechanism 140 may be configured to detect an initial contact of the needle 120 with the skin (e.g., the needle initial position) and / or an initial position of the skin, and then detect a skin tented position. The skin tented position is a position of the skin when the skin is at maximum deformation before the needle 120 begins to penetrate the skin. In some embodiments, an initial position of the needle 120 for penetration purposes may be adjusted based on an initial position of the skin (e.g.. wi th a manual jog). In some embodiments, the depth sensing mechanism 140 may be configured to detect if the needle 120 extends over a desired distance beyond the injector device 110. In some embodiments, the skin may be held in a position (e.g., via the vacuum shroud) to a depth reference portion of the injector device 110 (e.g., a depth reference foot extending therefrom). In some embodiments, the injector device 110 may include a depth sensing mechanism 140 (or circuit) coupled to one or more sensors disposed on the needle 120, needle hub, and / or syringe 112 and configured to detect contact between a portion of the injector device and the skin of the subject 102. In some embodiments, the depth sensing mechanism 140 may be configured to determine a position of the needle 120, a position of the surface of the skin, and / or a depth the needle 120 has traveled.

[0077] The injector device 110 may include a skin contacting surface on which the sensor is disposed. The skin contacting surface may extend from the injector device 110 to contact the skin. For example, the skin contacting surface may be disposed on the foot or extension that extends from the injector device 110 towards the skin. In some embodiments, the skin contacting surface may include a portion of the body of the injector device 110 that isDocket No.: RHTK-003 / 01WG 352653-2018 configured to contact the skin (e.g., the shroud 121). In some embodiments, the skin contacting surface may include an electrical lead (e.g.. an adhesive back lead, a strap hat, and / or a band holding the lead against the skin). In some embodiments, the skin contacting surface may include a conductive material and may be electrically connected to the skin contact detection circuit. In some embodiments, the conductive material may be any suitable conductive material such as, for example, a metal, conductive polymer, metal alloy, or a suitable combination thereof. For example, the conductive material can be a metal for low electrical resistance, or an electrostatic discharge (ESD) shielding plastic to reduce cost and weight (e g., relative to metal materials).

[0078] In some embodiments, the depth sensing mechanism 140 can be configured to perform vacuum-based skin detection to determine a position of one or more portions of the inj ector device 110 relative to the skin surface. For example, the shroud 121 can include a soft, disposable skirt configured to form a vacuum chamber over the skin surface. The shroud 121 can be coupled to a valve (e.g., a slit duck-bill valve) to allow the needle 120 and / or the needle hub to translate while the seal is maintained by the shroud 121 over the skin. Upon skin contact, a vacuum source can be configured to apply a vacuum force to the shroud 121. In some embodiments, the vacuum source can include a pump (e.g.. a diaphragm pump) configured to impart mild negative pressure (e.g., -10 kPa) within the chamber defined by the shroud 121 over the skin. The mild negative pressure can flatten the skin surface and prevent tenting of the skin (as described in FIG. 22B). In some embodiments, the injector device 110 can include a sensor (e.g., as described in FIG. 25 A) such as a pressure sensor configured to monitor seal integrity between the shroud 121 and the skin. Therefore, if the pressure measured within the vacuum chamber defined by the shroud 121 falls below a pressure threshold, the controller of the injector device 110 can be configured to auto-pause injection and / or alert the user. The vacuum force applied by the shroud 121 can also reduce lateral shifting of the injector device 110 during injection, thereby providing a more stable injection platform. The shroud 121 configured to apply the vacuum force can facilitate oblique angle injections by stabilizing the injector device 110 and reducing movement of the injector device 110 relative to the skin during injection.

[0079] In some embodiments, the needle 120 may be coupled (e.g., electrically connected) to the depth sensing circuit of the depth sensing mechanism 140. In some embodiments, a conductive portion (e.g.. including metal material) of the needle 120 may be clamped and / or in physical contact with the conductive element to make electrical contact. In some embodiments,Docket No.: RHTK-003 / 01WO 352653-2018 a spring contact may be disposed on or against a barrel of the needle (e.g., a pogo pin, leaf spring, or the like). In some embodiments, the needle barrel may be clamped with a conductive clamp (e.g., a V-block, a collet, or the like). In some embodiments, the needle hub may include a conductive material. In some embodiments, the needle hub may include the skin contacting surface. For example, the needle hub may include a conductive plastic and / or any suitable conductive element. In some embodiments, the needle hub may include a metal insert or and or may include a conductive plastic. In some embodiments, the needle hub may be molded from conductive plastic. In some embodiments, the depth sensing circuit may be configured to detect when the needle 120 first contacts the skin. For example, when the needle 120 contacts the skin, a circuit may be created by connecting the metal shaft of the needle on one side and the subject's body on the other side. In some embodiments, depth sensing circuit may detect contact between the needle and the skin based on at least one of direct current (DC) resistance, alternating current (AC) resistance in one or more frequencies of Electrochemical Impedance Spectroscopy (EIS), capacitance, or a suitable combination thereof.

[0080] In some embodiments, the depth sensing mechanism 140 may include one or more optical components to visualize and / or determine a location of a distal tip of the needle 120. In some embodiments, the exact location of the distal end of the needle may be used to determine a depth of the needle 120. In some embodiments, at least one of a beam break and / or a laser diode may be used to determine the position of the distal tip of the needle 120. The beam break and / or laser diode may reflect off at least a portion of the needle 120 (e.g., the distal tip) and this reflection can be measured. In some embodiments, the optical system may include a plurality of beam break pairs. The plurality of beam break pairs may enable the user to use lower precision to still reflect light off of the needle 120. In some embodiments, the depth sensing mechanism 140 can include an optical sensor including a light emitter and a light detector pair configured to configured to detect optical signals of one or more markers on a portion of the injector device 110. In some embodiments, the optical sensor can be separate from the injector device 1 10. The one or more markers can be disposed on the needle, the needle hub, the syringe, and / or any suitable portion of the injector device 110. The one or more markers can include laser-etched markers, color-coded markers, striped markers, etc. The controller can be configured to determine a position of the one or more markers relative to the surface of the skin based on the measurements collected by the light detector. In some embodiments, the optical sensor can include, for example, a vertical-cavity surface-emitting laser (VCSEL) and dual photodiodes. For example, the needle 120 may include one or moreDocket No.: RHTK-003 / 01WD 352653-2018 laser-etched markers (such as in FIGS. 23A-23B), and the VCSEL may be configured to emit light such that the photodiodes can detect the one or more laser-etched markers on the needle 120. The laser-etched markers may be a size on the scale of about 10pm to about 1000 pm, inclusive of all values and subranges therebetween. The laser-etched markers may be at the about 100 pm scale. The light detector (e.g., the dual photodiodes) may be configured to read the laser-etched markers through a sealed window (e.g.. a sapphire / zirconia window). In some embodiments, the light detector (e.g., the dual photodiodes) may be configured to detect movement of a point of intersection between the needle hub and the needle 120. In some embodiments, the measurements from the optical sensor can be filtered, resulting in less than 0. 1 mm accuracy over 1 mm to 4 mm of travel of the needle 120. The measurements collected by the optical sensor can be communicated to the controller and / or the actuator(s) (e.g., the VCA’s linear encoder and depth logic circuit) such that a divergence greater than a predetermined threshold triggers at least one of an auto-pause to actuation or an alert. In some embodiments, the predetermined threshold can be about 0.2 mm.

[0081] In some embodiments, the optical sensor can include an infrared light emitting diode (IR LED) (e.g., light emitter) and a Complementary' Metal-Oxide-Semiconductor (CMOS) sensor (e.g., light detector). The IR LED and CMOS sensor can be configured to track one or more markers disposed on a portion of the needle 120 (e.g., a proximal portion). In some embodiments, the one or more markers can be color-coded and striped markings on the injector device 110. The CMOS can track strip motion to compute depth. In some embodiments, the controller may be configured to determine a depth of the needle 120 based on measurements collected from the CMOS sensor and the encode of the actuator(s). For example, a Kalman filter can be used to merge the CMOS sensor data and the encoder data, resulting in an accuracy of about 0.2 mm.

[0082] In some embodiments, the optical sensor can be disposed proximal to a sterile barrier of the injector device 110 (e.g., proximal to barriers shown in FIGS. 27A-28B). The optical sensor can be configured to tolerate routine cleaning and can provide continuous depth verification. The optical sensor can be configured to pause or halt injection if optical confidence drops below a threshold.

[0083] In some embodiments, the controller of the injector device 110 can be configured to integrate outputs from the optical sensor and the pressure sensor coupled to the shroud 121. For example, the needle insertion and / or dose delivery can be paused or slowed if the controller determines the needle 120 has deviated from a desired travel path based on measurementsDocket No.: RHTK-003 / 01WO 352653-2018 collected from the optical sensor. The pressure sensor can ensure (e.g., simultaneously) stable contact between the shroud 121 and the skin to increase reliability of the measurements collected by the optical sensor such that the controller can more accurately update actuation of the actuator(s). In some embodiments, if sensor readings (e.g., by the optical sensor) indicate significant deviation of the needle 120 from the desired travel path, the controller may be configured to cause retraction and / or repositioning of the needle 120 to achieve the desired depth before continuing injection.

[0084] In some embodiments, the depth sensing mechanism 140 may be user triggered. An example method of using the depth sensing mechanism 140 may include the following steps. In some embodiments, the user may select the needle insertion depth. The user may provide input to begin injection (e.g., actuates a button, taps a surface, etc ). The needle 120 may be advanced with the actuator 116 (e.g., DC motor, lead screw, and / or linear encoder). As the needle 120 is advanced, a position of the needle 120 may be measured by the encoder. For example, a rotary encoder on the DC motor may measure a position of the needle 120. When first contact between the needle 120 and the skin is detected, the position of the needle 120 is detected by the encoder. In some embodiments, the needle 120 may be advanced to the desired insertion depth, beyond the point of initial contact. The displacement of the skin surface as the needle 120 applies force to the skin (e.g., before puncture) is referred to herein as the skin tenting error. In some embodiments, after the needle 120 can be advanced to the depth, the skin may not slide up the needle 120 to return to the initial skin position. Therefore, the needle 120 may be oscillated (e.g., distally I proximally). The needle 120 may be oscillated at the desired insertion depth to allow the skin to relax to its initial position and minimize and / or remove the skin tenting error. In some embodiments, the device 110 may measure height of the initial skin tenting error by measuring a distance of needle advancement while having relatively constant capacitance and / or resistance. A sharp change in capacitance and / or resistance may indicate that the skin surface has been puncture whereas a relatively constant capacitance and / or resistance may indicate the skin has not been punctured (and is tenting) In some embodiments, the depth sensing mechanism 140 may include a safety feature configured to abort the injection if no contact with the skin is detected after the needle 120 has been advanced the preset distance. In some embodiments, if contact is not detected, the device 110 may be set for a maximum extension that should make contact. In some embodiments, the injector device 110 may be configured for auto ejection on insertion and / or during withdrawal.Docket No.: RHTK-003 / 01WO 352653-2018

[0085] In some embodiments, the depth sensing mechanism 140 may be contact triggered (e.g., triggered without use input). For example, the device may be transitioned into a contact trigger mode. In the contact trigger mode, the injector device 1 10 may perform steps including the following. In some embodiments, with the needle 120 partially extended and when contact with skin is detected, the injector device 110 may automatically execute a rapid extension, ejection, and retraction. In some embodiments, the injector device 110 may retract farther than the initial contact detection position so that the needle 120 is not at risk of scratching the skin and / or so that the needle 120 is removed from any bulge created in the skin surface by the deposited fluid. In some embodiments, the user may then push a button to reset the position. In some embodiments, the user can select a time delay to reset the needle 120 to a partial extended position. In the contact triggered mode, the user may touch the needle tip against the skin and the injector device may perform the preset ejection at the moment of contact (e.g., in response to the contact).

[0086] In some embodiments, the injector device 110 may be further configured to detect insertion of the needle 120 into a blood vessel. In some embodiments, the needle 120 may be conductive and / or coupled to a conductive portion of the needle hub. In some embodiments, the needle hub may have a conductive portion separate from the needle 120. In some embodiments, the needle hub may include an electrode. In some embodiments, electrodes may be placed on the body of the subject 102. When the needle 120 is disposed in a blood vessel, electrical signals from the heart of the patient may be detected through the blood. For example, the electrical resistance may change in the EIS pathway as the needle contacts blood. In some embodiments, the injector device 110 may be configured to automatically withdraw the needle upon detection of blood. In some embodiments, the syringe may be withdrawn proximally. In some embodiments, the blood in the needle 120 may be measured electrically during withdrawal of the needle 120. In some embodiments, blood in the needle hub may have a different conductivity than injectate including medication may have. In some embodiments, the needle 120 and / or conductive portion of the needle hub may detect the difference in conductivity. For example, an electrical signal (e.g., impedance, EIS, etc.) may be detected.

[0087] In some embodiments, the needle hub may include a second metal insert to create an electrical contact to the fluid separate from the needle 120. In some embodiments, the needle hub may include a conductive plastic. In some embodiments, no electrode on the needle hub is included. The conductive plastic may include an insulating plastic mold, an over mold, and / or an insert mold.Docket No.: RHTK-003 / 01WD 352653-2018

[0088] Alternatively or additionally, the position of a vessel may be determined optically and / or with ultrasound. In some embodiments, presence of a blood vessel may be detected and / or confirmed optically. For example, the injector system may include an LED (e.g., a green LED) and a sensor configured to measure light reflectance from the skin. The injector device 110 may be configured to determine an optical density measurement based on the reflected light. In some embodiments, the injector device 110 may be configured to detect blood acoustically. For example, a sound of blood from blood stream can be detected by a microphone contact within the needle shaft, needle hub, and / or the syringe body.

[0089] The injector device 110 may be configured to dispense accurate doses of injectate. In some embodiments, a position of the injectate in the inner volume of the syringe 112 and / or a position of the distal end of the plunger 114 in the inner volume of the syringe 112 may be measured and monitored. In some embodiments, a zero position of loaded disposable may be determined. For example, when the injector device 110 is loaded with the syringe 112, the injector device 110 may be configured to determine a location of the plunger 114 (e.g., a location of the proximal end and / or a location of the distal end). In some embodiments, the actuator 116 may be advanced until in contact with a portion of the plunger 114. In some embodiments, contact may be detected by detecting a load on the actuator 116. In some embodiments, the contact can be detected when the actuator 116 approaches the plunger 114 at high speed to get a high resistance force. In some embodiments, the contact between the plunger 114 and the actuator 116 may be determined optically and / or with a small contact switch.

[0090] In some embodiments, the actuator 116 may detect contact to one side of the plunger 114, and a second actuator may clamp the plunger 114. In some embodiments, the syringe plunger may slide into a slot or other passive clamping mechanism. The position of the slot may be automatically changed as the syringe 112 is brought closer to the slot to ensure it lines up without moving the plunger 114 when the plunger is snapped into place. In some embodiments, the position may be monitored with an optical sensor (e.g., a camera). The syringe body may be clamped with the slot clear of the plunger 114.

[0091] The injector device 110 may include a power supply 115 configured to supply power to the one or more components of the injector device 110 (e.g., the actuators 116, sensors, electrical or electronic components, etc.).Docket No.: RHTK-003 / 01WO 352653-2018

[0092] FIG. 2 is a schematic block diagram of an injector system 200 including an injector device 210 (e.g., similar to and / or substantially the same as the injector device 110 described in FIG. 1). As shown, the injector device 210 is configured to be coupled to an alignment system 230, a controller 280, a memory 282, and a machine-controlled injector 290 (e.g., a robotic injector). In some embodiments, the injector device 210 can be configured to be coupled to one or more depth sensing mechanisms (e.g., similar to the depth sensing mechanism 140). In some embodiments, the alignment system 230 may further reduce pain and minimize tissue damage be promoting a straight travel path of the needle of the injector device 210. In some embodiments, the needle of the injector device 210 may be at least partially disposed in a housing such that the needle of the injector device 210 is not visible before, during, and / or after the procedure. The needle being hidden can reduce psychological impact, as the user may not anticipate the pain. In some embodiments, the housing may further include a smooth and / or comfortable distal tip for further comfort of the patient (e.g., physically and psychologically). In some embodiments, the needle geometry may reduce pain and minimize damage. For example, a cone geometry of the distal tip may prevent dulling over multiple uses, thereby reducing pain due to dulling.

[0093] The alignment system 230 may include one or more components coupleable to one or more portions of the injector device 210. In some embodiments, the alignment system 230 can include one or more clamping mechanisms configured to hold one or more portions of the syringe and needle such that the syringe and needle are straight relative to a desired travel axis of the syringe assembly. In some embodiments, the alignment system 230 can include a needle clamp, a synnge clamping mechanism, and / or aneedle hub clamping mechanism. For example, the alignment system 230 may include a needle clamp configured to be disposed around a barrel of the needle. In some embodiments, the barrel of the needle may be clamped to improve precision associated with moving the needle straight. Holding the needle hub or the syringe without clamping the barrel of the needle may not result in precisely straight needle motion due to manufacturing tolerances in the syringe body or needle hub. Conversely, clamping the metal barrel of the needle provides for straight movement and reduces an effect of manufacturing variation on straightness of motion. In some embodiments, the injector device 210 may include a custom needle including a needle hub that is easy to grab. In some embodiments, the needle of the injector device 210 may be precisely located relative to the needle hub (e.g., a concentric arrangement).Docket No.: RHTK-003 / 01WO 352653-2018

[0094] The syringe clamping mechanism can be configured to be disposed around a barrel of the syringe. In some embodiments, the syringe clamping mechanism may include a first clamping point configured to clamp a first portion of the syringe and a second clamping point configured to clamp a second portion of the syringe. In some embodiments, the syringe clamping mechanism may include one adjustable clamping point and one fixed clamping point. In some embodiments, the first clamping point may be adjustable, and the second clamping point may be a fixed clamping point. In some embodiments the adjustable clamping point may be distal on the syringe, and the fixed clamping point may be proximal. In some embodiments, the adjustable clamping point may be proximal, and the fixed clamping point may be distal. In some embodiments, the syringe clamping mechanism may be configured to automatically (e.g., without user input) adjust position of the syringe to align a needle axis with the travel axis. For example, the adjustable clamping point can be adjusted along at least one axis such that the longitudinal axis of the syringe is straight relative to the travel axis.

[0095] In some embodiments, the syringe clamping mechanism may measure an angle of tilt of the syringe using a sensor (e.g., a non-contact sensor). The sensor may include any suitable sensor such as, for example, a beam break, machine vision, charge coupled device (CCD), array of proximity sensors, etc. In some embodiments, the syringe clamping mechanism may adjust a position of the adjustable clamping point. The adjustable clamping point can move along at least two orthogonal axes (e.g., vertically, horizontally, and / or rotationally about a vertical axis) to align the needle axis (e.g., the longitudinal axis of the needle) to the axis of travel. The angle of the syringe can be adjusted such that the longitudinal axis of the syringe is colinear with the needle axis. In some embodiments, the needle clamp and the syringe clamping mechanism can be configured such that the longitudinal axis of the syringe and the needle axis are positioned at a predetermined angle relative to the surface of the skin (e.g., perpendicular). In some embodiments, the sensors may be configured to determine an angle of tilt between the two orthogonal axes that match and / or correspond to the adjustable clamping point. In some embodiments, the syringe clamping mechanism may be configured to align a plurality of needles and syringes with different dimensions and manufacturing tolerances. In some embodiments, the syringe clamping mechanism may include self-centering clamps disposed at a first location and a second location of the syringe to compensate for any taper of the syringe barrel. In some embodiments, the syringe barrel may be clamped using half collets clamping at two locations.Docket No.: RHTK-003 / 01WO 352653-2018

[0096] In some embodiments, the alignment system 230 may further include a needle hub clamping mechanism configured to grip a needle hub of the injector device 210 (e.g., similar to the needle hub described with respect to FIG. 1. The needle hub clamping mechanism may include a tubular member including an inner diameter and an outer diameter. The tubular member may define a first set of openings along a length of the tubular member such that needle hub clamping mechanism may be configured to apply a uniform clamping pressure along a length of the needle hub. The needle hub clamping mechanism may be similar to a collet. The needle hub clamping mechanism may be configured to automatically adjust for expected variation in the needle hub design and can adjust for taper in the shape of the needle hub. If the needle hub is concentric with the needle, this provides straight motion with a simple clamping mechanism. In some embodiments, the needle hub clamping mechanism and the needle clamp can be positioned such that the longitudinal axes of the needle and the needle hub are colinear.

[0097] In some embodiments, the syringe may include a guide mechanism configured to guide the needle, needle hub, and syringe distally through the clamping mechanisms such that the needle and needle hub may be guided distally without the needle contacting the needle hub clamping mechanism and / or the syringe clamping mechanism to maintain sterility. In some embodiments, the needle hub clamping mechanism may include two portions (e.g., a split clamping mechanism). For example, the needle hub clamping mechanism may include a first “C’ shaped portion and a second “C” shaped portion configured to collectively define an opening with a circular cross section when the needle hub clamping mechanism is in a closed configuration. The needle hub may be configured to be disposed through the opening. For example, the first section may be configured to rotate relative to the second section. In some embodiments, the needle hub clamping mechanism may transition from the open configuration to the closed configuration by moving the (e.g., rotating) first section and the second section toward one another. In some embodiments, the needle hub clamping mechanism may transition from the open configuration to closed configuration by rotating the second “C” shaped portion about the longitudinal axis of the needle hub clamping mechanism. In some embodiments, the structure described as the needle hub clamping mechanism may also be used to clamp the barrel of the syringe. In other words, the syringe clamping mechanism may have the same structure or similar structure as the needle hub clamping mechanism.

[0098] The injector device 210 may optionally include and / or may be in communication with a controller 280 configured to control movement of the injector device 210 and / or controlDocket No.: RHTK-003 / 01WO 352653-2018 movement of the plunger relative to the syringe. In some embodiments, the controller 280 may be on board the injector device 210 and / or may be coupled to or in communication with the injector device 210. The controller 280 can control one or more portions of an actuator of the injector device 210 based on the position information obtained by sensors coupled to or included in the injector device 210. In some embodiments, the controller 280 may control current or power to rotary motors of the actuator to control a speed of each rotary motor. In some embodiments, the controller 280 may be configured to control a current flow through a coil of a voice coil actuator to modulate the electromagnetic field generated to control one or more characteristics associated with the movement of the magnet (e.g., direction, velocity7, acceleration, etc.). In some embodiments, the memory 282 (e.g., of the controller 280) may be configured to store information relating to an injection such as parameters for injection (e.g., depth under skin, velocity of injection, dose of injection, etc.). In some embodiments, the memory 282 may be configured to track or store data related to use cycles of the injector device 210. In some embodiments, the memory 282 may be onboard the injector device 210 (e.g., as a component of the controller 280 or independent of the controller 280).

[0099] FIG. 3 is a flow chart diagram of an example method 300 of using the injector system, according to embodiments. The method 300 may include disposing an injector device near a tissue surface of a subject, the injector device including a syringe defining an inner volume configured to receive an inj ectate and a portion of a plunger, at 302. The syringe includes a needle coupled to a distal end thereof. In some embodiments, the syringe and the needle maybe at least partially disposed in or coupled to a housing. At 304, the method may include activating a first actuator coupled to the syringe and the needle to collectively advance the syringe and the needle distally a predetermined distance such that the needle penetrates the tissue surface to a predetermined depth. In some embodiments, the first actuator may include a rotary motor, a voice coil, and / or any other suitable actuator coupled to a lead screw. The lead screw may be configured to extend through a through hole defined in the first housing including threads. In some embodiments, activating the first actuator may include activating the rotary' motor to rotate the lead screw such that the lead screw engages the threads defined in the first housing to move the first housing including the syringe and the needle distally.

[0100] In some embodiments, the method 300 includes, while keeping the syringe and the needle stationary, activating a second actuator coupled to the plunger with a predetermined velocity, at 304. In some embodiments, the plunger may be at least partially disposed in or coupled to a second housing defining a through hole including threads. In some embodiments,Docket No.: RHTK-003 / 01WO 352653-2018 the second actuator may include a rotary motor coupled to a lead screw. The lead screw may be configured to extend through the through hole of the first housing and through the through hole of the second housing. In some embodiments, the second actuator may be configured to engage both the threading on the first housing and the threading on the second housing. The second actuator may be activated contemporaneously or overlapping in time with the first actuator to cause movement of the plunger relative to the syringe and needle. In some embodiments, the method 300 may optionally include adjusting a relative velocity of the first actuator and the second actuator such that the plunger advances distally through the inner volume of the syringe with a predetermined and / or desired set of characteristics, at 306. In other embodiments, the lead screw of the second actuator may be configured to not engage the threading on the first housing, and therefore, the step of adjusting the relative velocity of the first actuator and the second actuator may be omitted.

[0101] The method 300 further includes continuing to activate the second actuator until a predetermined amount of injectate is dispersed under the tissue surface, at 308. While activating at least one of the first actuator and the second actuator, a mass coupled to the first actuator and / or the second actuator may be moved in an opposite direction of a moving portion of the first and / or second actuator to balance an impulse of the first actuator and / or the second actuator, at 310. For example, as described above with reference to the injector device 110, the device can include a balancing mass or the like that may be moved in an opposite (e.g., proximal) direction to at least partially balance a force or impulse associated with the moving mass of the actuators and / or injector device. Reducing an impulse associate with actuating the device can facilitate use and / or can increase an accuracy associated with dose delivery. At 312. the method 300 may include withdrawing the syringe and the needle from the tissue surface of the subject. In some embodiments, the withdrawing the syringe and the needle may include reverse activation of the first actuator such that the lead screw rotates in an opposite direction to withdraw the first housing, and therefore the syringe and needle, proximally.

[0102] FIG. 4 A shows an injector device 410 that includes or is configured to receive a syringe 412 coupled to a needle 420 at a distal end of the syringe 412 via a needle hub 428. The syringe 412 may define an inner volume through which a plunger 414 is configured to move. The syringe 412, the needle hub 428, and the needle 420 may collectively form the syringe assembly. The syringe assembly may be coupled to, disposed in, and / or formed in part by a first housing 432 (holder, clamp, etc.) and the plunger 414 may be coupled to. disposed in, and / or formed in part by a second housing 433 (holder, clamp, etc.). The first housing 432 mayDocket No.: RHTK-003 / 01WO 352653-2018 be configured to move with the syringe assembly, and the second housing 433 may be configured to move with the plunger 414. The first housing 432 and the second housing 433 may be configured to move relative to one another to allow the plunger 414 to move through the inner volume of the syringe 412.

[0103] The injector device 410 includes a first actuator (e.g., a first rotary motor 416a coupled to a first lead screw 418a) and a second actuator (e.g., a second rotary motor 416b coupled to a second lead screw 418b), referred to herein as a dual lead screw actuator system. The first lead screw 418a may be coupled to the first housing 432. The second lead screw 418b may be coupled to the first housing 432 and the second housing 433. In some embodiments, the first housing 432 may define a through hole configured to receive a first portion of the first lead screw 418a such that rotation of the first lead screw 418a causes linear motion of the first housing 432. For example, the first lead screw 418a or at least a portion thereof can be threaded and an inner surface of the first housing 432 that defines the through hole can be similarly threaded. Thus, rotation of the first threaded lead screw 418a results in a linear motion of the first housing 432.

[0104] The through hole of the first housing 432 may be a first through hole (e.g., a threaded through hole), and the first housing 432 may further include a second through hole without threading through which a first portion of the second lead screw 418b is configured to be disposed. The second housing 433 may define a through hole with threading configured to receive a second portion of the second lead screw 418b proximal to the first portion such that rotation of the second threaded lead screw 418b causes linear motion of the second housing 433 (e.g., relative to the first housing 432). As shown, the components shown in white are moving masses of the injector device 410, and the components shown in dark grey are stationary masses of the injector device 410.

[0105] In some embodiments, the second lead screw 418b, when rotated, can be configured to move through first housing 432 (without engaging the first housing 432), but can be configured to engage the second housing 433. To perform an injection, the first rotary motor 416a and the second rotary motor 416b may be activated synchronously to advance the syringe assembly a predetermined distance under the subject’s skin. The first rotary motor 416a and the second rotary motor 416b may be activated such that the plunger 414 does not change position relative to the syringe 412. Once the needle 420 penetrates the skin to a predetermined depth, a relative speed of rotation of the second lead screw 418b to the first lead screw 418a may be adjusted such that the second lead screw 418b moves the plunger 414 distally to inject the inj ectate. ForDocket No.: RHTK-003 / 01WO 352653-2018 example, a ratio of the velocity of the second lead screw 418b to the velocity of the first lead screw 418a may increase such that the second lead screw 418b causes the second housing 433 to advance distally faster than the first housing 432 advances. Therefore, a distance between the second housing 433 and the first housing 432 may decrease such that the plunger 414b moves distally through the inner volume of the syringe. The first rotary motor 416a and the second rotary’ motor 416b may be coupled to a first encoder 417a and a second encoder 417b, respectively. The second encoder 417b may be configured to measure movement (e.g.. velocity, acceleration, distance traveled, position, etc.) of the plunger 414 and the first encoder 417a may be configured to measure movement (e.g., velocity, acceleration, distance traveled, position, etc.) and / or position of the syringe assembly.

[0106] In some embodiments, the syringe assembly (e.g., the moving mass) may have weight below a threshold to reduce an acceleration force to be applied to the syringe assembly for desired the movement, thereby reducing a size of the actuators and a power supply for operating the device. The reduction in the moving mass can also reduce an overall device mass. Moreover, the reduction in the moving mass may reduce a reactionary’ acceleration (e.g., impulse or torque), making the injector device easier to use. The injector device 410 may be structurally and / or functionally similar to the inj ector device 110, and therefore, certain aspects of the injector device 410 are not described herein with respect to FIG. 4A.

[0107] FIG. 4B shows an injector device according to an embodiment. The injector device 510 can be similar to the injector device 410 shown in FIG. 4A but can differ by’ including a dual lead screw actuator system and a counterbalance to balance impulse acting on stationary’ components (components shown in grey). The injector device 510 includes and / or is configured to receive a syringe 512 with a distal end coupled to a needle 520 via a needle hub 528. The syringe 512 defines an inner volume through which a plunger 514 is configured to move. The syringe assembly may be coupled to a first housing 532 (e.g., holder, clamp, etc.) and the plunger 514 may be coupled to a second housing 533 (e.g., holder, clamp, etc.). The first housing 532 may be configured to move with the syringe assembly, and the second housing 533 may be configured to move with the plunger 514. The first housing 532 and the second housing 533 may be configured to move relative to one another to allow the plunger 514 to move through the inner volume of the syringe 512.

[0108] The injector device 510 includes a first actuator including a first rotary' motor 516a coupled to a first lead screw 518a and a second actuator including a second rotary' motor 516b coupled to a second lead screw 518b. The first lead screw 518a may be coupled to the firstDocket No.: RHTK-003 / 01WG 352653-2018 housing 532 and the second lead screw 518b may be coupled to the first housing 532 and the second housing 533. In some embodiments, the second lead screw 518b, when rotated, can be configured to move through first housing 532 (without engaging the first housing 532), but can be configured to engage the second housing 533, as described above with reference to the injector device 410 shown in FIG. 4 A. The first rotary motor 516a and the second rotary' motor 516b may be coupled to a first encoder 517a and a second encoder 517b, respectively, to measure movement of the syringe and the plunger.

[0109] To balance the impulse and / or reduce torsional acceleration, the actuators (e.g., the first rotary motor 516a and the second rotary motor 516b) may include lead screws 518a, 518b having threads with opposite directionality. For example, the first lead screw 518a of the first actuator (and a corresponding through hole of the first housing 532) may have a left-handed threading and the second lead screw 518b of the second actuator (and a corresponding through hole of the second housing 533) may have a right-handed threading. Therefore, when the first lead screw 518a and the second lead screw 518b are accelerated and turned at the same rate during the syringe assembly motion, the resulting torque can be equal to zero and / or near zero (e.g., cancelled out, neutralized, etc.). In some embodiments, the first actuator and the second actuator in a first configuration can be configured to rotate to advance the syringe assembly, and the second actuator in a second configuration can be configured to advance the plunger 514 through the syringe 512. In some embodiments, the first actuator and the second actuator can be configured to have a net zero torque when in the first configuration to prevent rotation of a longitudinal axis of the syringe assembly relative to a travel axis. In some embodiments, the first lead screw 518a may further be coupled to a counterbalance 518c configured to move linearly as the first lead screw 518a is rotated. In some embodiments, the counterbalance 518c can be threaded in a direction that is opposite to the direction of the threading of the first housing 532. Thus, the counterbalance 518 can be moved in an opposite direction as the first housing 532. which in turn, can balance, offset, and / or substantially reduce an impulse (or other forces) associated with the linear movement of the first housing 532. The injector device 510 may be structurally and / or functionally similar to the injector device 110, 410, and therefore, certain aspects of the injector device 110, 410 are not described herein with respect to FIG. 4B.

[0110] FIG. 4C show s an injector device 610 according to an embodiment. The injector device 610 includes and / or is configured to receive a syringe 612 coupled to a needle 620 at a distal end thereof via a needle hub 628. The syringe 612 defines an inner volume through which a plunger 614 is configured to move. The syringe 612, the needle hub 628, and the needle 620Docket No.: RHTK-003 / 01WO 352653-2018 may collectively form the syringe assembly. The syringe assembly may be coupled to a first housing 632 (holder, clamp, etc.) and the plunger 614 may be coupled to a second housing 633 (holder, clamp, etc.). The first housing 632 may be configured to move with the syringe assembly, and the second housing 633 may be configured to move with the plunger 614. The first housing 632 and the second housing 633 may be configured to move relative to one another to allow the plunger 614 to move through the inner volume of the syringe 612.[OHl] The injector device 610 may include a first actuator including a first rotary motor 616a coupled to a threaded lead screw 618a. The injector device 610 may include a second actuator including a second rotary motor 616b including a shaft 609a (e.g., a spline shaft or a slotted shaft) and a slot 609b (e.g., agroove, sleeve keyway, etc.) configured to receive the shaft 609a. The shaft 609a may be coupled to a second threaded lead screw 618b. To advance the syringe assembly distally, the first rotary motor 616a may be actuated. To move the plunger 614 distally, the second rotary motor 616b may actuate the lead screw 618b to turn the lead screw 618a in a manner that advances the shaft 609a distally through the slot 609b and moves the second housing 633 and plunger 614 distally. Including the shaft 609a and slot 609b may increase a mass of the moving mass relative to the stationary mass due to increased weight from the lead screw, screw supports, and keyway section. However, because the second lead screw 618b is now moving rather than stationary, the control of movement and dosing may be decoupled, and therefore, controlling the velocity and acceleration of the injection may be simplified. The injector device 610 may be structurally and / or functionally similar to the injector device 110, 410, 510 and therefore, certain aspects of the injector device 610 are not described herein with respect to FIG. 4C.

[0112] FIG. 4D shows an injector device 710 according to an embodiment. The injector device 710 includes or is configured to receive a syringe 712 coupled to a needle 720 at a distal end thereof via a needle hub 728. The syringe 712 defines an inner volume through which a plunger 714 is configured to move. The syringe 712, the needle hub 728, and the needle 720 may collectively form the syringe assembly. The syringe assembly may be coupled to a first housing 732 (holder, clamp, etc.) and the plunger 714 may be coupled to a second housing 733 (holder, clamp, etc.). The first housing 732 may be configured to move with the syringe assembly, and the second housing 733 may be configured to move with the plunger 714. The first housing 732 and the second housing 733 may be configured to move relative to one another to allow the plunger 714 to move through the inner volume of the syringe 712.Docket No.: RHTK-003 / 01WO 352653-2018

[0113] As shown, a first actuator of the injector device 710 (e.g., the actuator that moves the syringe assembly) may include a voice coil (having a magnet 716a and coil 718a) and a linear encoder 717a. A s econd actuator of the inj ector devi ce 710 includes a rotary motor 716b having a shaft 709a (e.g., a spline shaft or a slotted shaft) and a slot 709b (e.g., a groove, sleeve, keyway, etc.) configured to receive the shaft 709a. The shaft 609a may be coupled to a second threaded lead screw 618b. To advance the syringe assembly distally, a current may be applied through the coil 718a to advance the coil 718a toward the magnet 716a (e.g.. the magnet 716a is stationary) such that the first housing 732 including the syringe assembly moves distally. In some embodiments, the voice coil may be coupled to a power pack 715 via a wired connection. In some embodiments, the injector device 710 may include an advancement and retraction mechanism. The advancement and retraction mechanism may include a variable valve lift mechanism, to control insertion depth or movement of the syringe 712 and / or plunger 714. The voice coil may be fitted with and / or otherwise include position measurement devices including, for example, oscillatory position control systems, devices, mechanisms, etc. In some embodiments, the encoder 717a of the first actuator (voice coil) may include a hall effect sensor (e.g.. XY hall effect sensor) to measure a magnetic field of a magnet 713 disposed axially in the first housing 732. The encoder 717a may be configured to output an electrical signal corresponding to a distance the syringe assembly has traveled based on the change in magnetic field associated with the magnet 713 as measured by the encoder 717a (e.g., the hall effect sensor). In some embodiments, the voice coil may provide precise control over small needle movements (e.g., movements around 10 mm).

[0114] While FIG. 4D shows the lead screw 718b as moving, it should be appreciated that the rotary motor 716b may not be coupled to the shaft 709a or slot 709b and may instead be coupled directly to a lead screw that is linearly stationary (e.g., only rotates). The injector device 710 may be structurally and / or functionally similar to the injector device 110, 410, 510, 610 and therefore, certain aspects of the injector device 710 are not described herein with respect to FIG. 4D.

[0115] FIGS. 5A and 5B show an alignment system 830 for an injector device (not shown) that includes or is configured to receive a syringe 812 coupled to aneedle 820 at a distal end thereof the syringe 812 via a needle hub 828. The syringe 812 defines an inner volume through which a plunger 814 is configured to move. The alignment system 830 may include a syringe clamping mechanism configured to be disposed around a first portion of a barrel of the syringe 812. In some embodiments, the syringe clamping mechanism may include a first clampingDocket No.: RHTK-003 / 01WO 352653-2018 point 832 configured to clamp a first portion of the syringe 812 and a second clamping point 834 configured to clamp a second portion of the syringe 812. In some embodiments, the first clamping point 832 may be adjustable, and the second clamping point 834 may be a fixed clamping point. In some embodiments the adjustable clamping point 832 may be configured to be disposed distal on the syringe 812, and the fixed clamping point 834 may be configured to be disposed proximally to the adjustable clamping point 832. In some embodiments, the adjustable clamping point 832 may be proximal, and the fixed clamping point 834 may be distal to the adjustable clamping point 832.

[0116] In some embodiments, the syringe clamping mechanism may be configured to automatically (e.g., without user input) adjust position of the syringe 812 to align a needle axis N with an axis of travel (e.g., a travel axis T). In some embodiments, the syringe clamping mechanism may measure an angle of tilt using a sensor. The sensor may include any suitable sensor such as. for example, a beam break, machine vision. CCD, array of proximity sensors, etc. The adjustable clamping point 832 can move along at least two orthogonal axes to fully align the needle 820 (e.g., vertically, horizontally, and / or rotationally about a vertical axis) to the axis of travel (e.g., travel axis T) such that the needle axis N (and the syringe axis) are straight and not inclined relative to the travel axis T. In some embodiments, the sensors may be configured to determine an angle of tilt in the two orthogonal axes that match the adjustable clamping point 832. In some embodiments, the syringe clamping mechanism may be configured to align a plurality of needles and syringes with different dimensions and manufacturing tolerances. In some embodiments, the syringe clamping mechanism may include self-centering clamps disposed at a first location and a second location of the syringe to compensate for any taper of the syringe barrel. In some embodiments, the syringe barrel may be clamping using half collets clamping at two locations.

[0117] FIGS. 6A-6C show needle hub clamping mechanisms of an injector device, according to different embodiments. As shown in FIG. 6A, the needle hub clamping mechanism may include a first portion 936a and a second portion 936b configured clamp the needle hub 928 therebetween. For example, the needle hub clamping mechanism may include a collet-like structure that grips a first portion of the needle hub 928 at a proximal end and a second portion of the needle hub 928 at a distal end to account for the tapered shape of the needle hub 928. The needle hub clamping mechanism may include a tubular member including an inner diameter and an outer diameter. The tubular member may define a first set of slits along a length of the tubular member such that needle hub clamping mechanism may be configured toDocket No.: RHTK-003 / 01WO 352653-2018 apply a predetermined clamping pressure along a length of the needle hub 928. The needle hub clamping mechanism may be the same or similar to a collet. The needle hub clamping mechanism may be configured to automatically adjust for expected variation in the needle hub design and can adjust for taper in the shape of the needle hub 928.

[0118] As shown in FIG. 6B, a needle hub clamping mechanism 1036 may include a constricting ring 1035 (e.g., a collet or iris) to grip varying needle hub shapes. A large displacement of the constricting ring 1035 could be used to give a large opening to slide the needle through the opening 1037 without risk of touching the sterile needle. In some embodiments, the alignment system may include a first needle hub clamping mechanism disposed at a first end of the needle hub and a second needle hub clamping mechanism disposed at a second end of the needle hub.

[0119] FIG. 6C shows a needle hub clamping mechanism including a first portion 1236a and a second portion 1236b configured to clamp a portion of the needle hub therebetween. For example, the needle hub clamping mechanism may include a first portion 1236a and a second portion 1236b configured to collectively define an opening 1237 through which a portion of the injector device 1210 (e.g., the needle hub) may be disposed. The shape of the first portion 1336a and the second portion 1336b of the needle hub clamping mechanism may be any suitable shape such as, for example, a “C" shape, a semi-circle shape, a crescent shape, etc. In some embodiments, the first portion 1236a may be configured to rotate relative to the second portion 1236b and / or the second portion 1236b may be configured to rotate relative to the first portion 1236a. In some embodiments, the needle hub clamping mechanism may transition from the open to closed configuration when the second portion 1236b is rotated (e.g., clockwise). In some embodiments, the needle hub clamping mechanism may transition from the open configuration to the closed configuration by moving the (e.g., rotating) first portion 1236a and the second portion 1236b toward one another.

[0120] FIGS. 7A-7B shows a side view and a front view, respectively, of a syringe clamping mechanism of an alignment system for an injector device, according to embodiments. As shown in FIG. 7A, a syringe clamping mechanism may be structurally and / or functionally similar to the needle hub clamping mechanism described in FIGS. 6A-6C. For example, the syringe clamping mechanism may include a first portion 1332a and a second portion 1332b configured to clamp the syringe 1312 therebetween (e.g., a split clamping mechanism). For example, the first portion 1332a and the second portion 1332b collectively define an opening configured to receive the syringe 1312. The shape of the first portion 1332a and the secondDocket No.: RHTK-003 / 01WO 352653-2018 portion 1332b of the syringe clamping mechanism may be any suitable shape such as, for example, a “C” shape, a semi-circle shape, a crescent shape, etc. In some embodiments, the syringe clamping mechanism may transition from an open configuration in which the syringe 1312 can be disposed therethrough to a closed configuration in which the syringe 1312 is clamped between the first portion 1332a and the second portion 1332b. In some embodiments, the syringe clamping mechanism may clamp the syringe at a first clamping point (e.g., near the needle hub 1328) and a second clamping point (e.g., near a proximal end of the syringe 1312) to accommodate any inconsistencies in the syringe 1312. The needle hub 1328 can be configured to be concentric with the needle. The needle hub 1328 being concentric with the needle provides for straight motion with a simple syringe clamping mechanism. In some embodiments, the syringe barrel may include a guide mechanism such that the needle and needle hub may be guided distally without the needle contacting the syringe clamping mechanism to maintain sterility.

[0121] FIG. 8A shows a side view of at least a portion of an injector device 1410 without an impulse control mechanism according to an embodiment. In order to move the needle, all the connected components (e.g., needle hub, syringe, plunger, collectively referred to as the moving mass 1411) are moved, which causes a reaction force at the actuator of the injector device 1410. Straight travel is affected by the relative position of the moving mass 1411 of the injector device 1410 and the stationary mass 1418 of the injector device 1410. If the center of mass of the moving mass 1411 is not axially aligned with the center of mass of the stationary mass 1418 (e.g., not vertically aligned), the syringe and needle and / or the actuator may rotate or pivot. Similarly stated, if the center of mass of the moving mass 1411 is offset by a distance D from the center of mass of the stationary mass 1418, the reaction forces associated with actuating the injector device 1410 may cause the syringe, needle, and / or actuator to rotate or pivot relative to a desired injection axis. For example, as shown in FIG. 8B, the acceleration force may create a net rotation or torque on the injector device 1410 and / or the components thereof, which can cause non-straight needle motion (e g., the needle may rotate or pivot away from a desired travel axis or injection axis) and can cause more damage to tissue 1402 and can increase pain for the subject.

[0122] In contrast, FIG. 8C shows a side view' of at least a portion of an injector device 1510 with an impulse control mechanism according to an embodiment. As described above, to move the needle, the connected components (e.g., needle hub. syringe, plunger, collectively referred to as the moving mass 1511) are moved, which causes a reaction force in the injector deviceDocket No.: RHTK-003 / 01WO 352653-20181510. To achieve straight needle motion, the line of travel associated with the center of mass of the moving mass 1511 may be coincident or colinear with the center of mass of the stationary mass 1518 (e.g., associated with the actuator). For example, a vertical distance D (as shown in FIG. 8C) between the center of mass of the moving mass 1511 and the center of mass of the stationary mass 1518 may be zero or close to zero.

[0123] FIGS. 9A and 9B show side views of at least a portion of an injector device 1610 according to an embodiment. In this embodiment, the injector device 1600 does not include an impulse control mechanism. While aligning the center of mass can reduce rotational acceleration (e.g., as described above with reference to the injector device 1510 of FIG. 8C), there can still be inline acceleration that can impact accuracy of the distance traveled by the needle and therefore the depth of the injection. For example, FIG. 9A shows the injector device 1610 prior to injection. As shown in FIG. 9A, the actuation of the injector device 1610 accelerates the moving mass 1611 with an acceleration al. which causes the needle to pierce the tissue or skin 1602 of a patient. The actuation of the injector device 1610 also causes a reaction force with an acceleration a2. The acceleration a2 may be linear in an opposite direction than the acceleration al of the moving mass 1611 (e.g., proximal towards the user and away from the skin 1602). In some embodiments, a proportion of a mass of the moving mass 1611 relative to a mass of the stationary mass 1618 may be kept below a threshold to reduce the rotational torque and / or linear acceleration (e.g., in a direction opposite the direction of the movement of the moving mass 1611) during injection. Therefore, a moving mass (e.g., syringe assembly) of the injector device 1610 can travel straight relative to a desired travel axis of the syringe assembly when the synnge assembly is advanced distally.

[0124] FIGS. 9C and 9D show side views of at least a portion of an injector device 1710 according to an embodiment. The injector device 1710 includes a balancing mass 1750, which may be used to reduce torque (impulse, or torsional acceleration). In some embodiments, a mechanical counterweight may be used (e.g., an open loop approach). In some embodiments, a second driven mass that is lighter in weight may be used (e.g., an open loop approach). In some embodiments, an active second driven mass with accelerometer may be used (e.g., a closed loop approach). In some embodiments, the balancing mass 1750 may accelerate with an equal and opposite magnitude to the moving mass 1711 to keep the stationary' mass 1718 in the same position during injection. For example, FIG. 9C shows the injector device 1710 prior to injection. As shown in FIG. 9D. the actuation of the injector device 1710 accelerates the moving mass 1711 with an acceleration al, which causes the needle to pierce the tissue or skinDocket No.: RHTK-003 / 01WO 352653-20181702 of a patient. The actuation of the injector device 1710 also causes a reaction force that can move the balancing mass 1750 with an acceleration a2. The balancing mass 1750 (e.g.. the second driven mass) can have a lower mass than the moving mass 1711 and can be accelerated more than the moving mass 1711 to balance the forces associated with the accelerations al, a2. In some embodiments, a force associated with the acceleration a2 of the balancing mass 1750 may be equal in magnitude and opposite in direction to the force associated with the acceleration al of the moving mass 1711, with the center of mass of the moving mass 1711 travelling colinearly (e.g., aligned) with the center of mass of the balancing mass 1750.

[0125] FIGS. 9E and 9F show side views of at least a portion of an injector device 1810 according to an embodiment. The injector device 1810 includes a mechanism to produce a preload force (e.g., a preload mechanism 1850) during injection to prevent an impulse exerted on the stationary mass 1818 of the injector device 1810. In some embodiments, the stationary mass 1818 may be preloaded against the skin 1802 with a force that is greater than the acceleration force al. For example, the injector device 1810 may be preloaded against the subject with a force sufficient to prevent unwanted motion of the device relative to the subject. As shown in FIG. 9E, the injector device 1810 may be disposed against the subject with an extension 1851 (e.g.. contact foot, spring cell, or load cell (or other similar means)) so that the user knows sufficient preload has been applied to compensate for the expected acceleration. In some embodiments, the injector device 1810 may electronically detect preload via one or more sensor(s) (e.g., a sensor such as a force sensor) and only activate / inject if sufficient pre-load force is applied. In some embodiments, a level of sufficient preload may be changed depending on velocity settings chosen to compensate for ejection profiles that create more or less reaction force (e.g., different injectates, different amounts, different depths, etc.). In some embodiments, the preload mechanism 1850 may be configured for rapid ejection. For example, the injector device 1810 may fire when sufficient preload is detected, then fire again when sufficient preload is detected again. The preload mass may result in a higher overall weight of the injector device 1810 in cases where high needle acceleration is used. The device may also include a spring that pushes the needle holding assembly forward. As shown in FIG. 9F, the actuation of the injector device 1810 accelerates the moving mass 1811 with an acceleration al. which causes the needle to pierce the tissue or skin 1802 of a patient. The actuation of the injector device 1810 also causes a reaction force with an acceleration a2. The preloading of the stationary mass 1818 can be sufficient to prevent unwanted motion of the device relative to the subject in response to the accelerations al, a2.Docket No.: RHTK-003 / 01WO 352653-2018

[0126] FIG. 10A shows at least a portion of an injector device 1910 according to an embodiment. The injector device 1910 includes a first actuator and a second actuator configured to balance acceleration of the injector device 1910 and / or components therein. The first actuator may include a first rotary motor 1916a and the second actuator may include a second rotary motor 1916b. The first rotary motor 1916a may be coupled to a first threaded screw 1918a. and the second rotary motor 1916b may be coupled to a second threaded screw 1918b. To balance torsional acceleration of the injector device 1910. the first rotary motor 1916a and the second rotary motor 1916b may turn in opposite directions. For example, the first rotary motor 1916a may turn the first threaded screw 1918a along threading having a first direction (e.g., a right-hand thread), and the second rotary motor 1916b may turn the second threaded screw 1918b along threading having a second direction (e.g., a left-hand thread). To accelerate the needle 1920 forward or backward without ejecting fluid, both the first rotary motor 1916a and the second rotary motor 1916b may turn at the same time to move the plunger 1914 and the syringe 1912 at the same rate. In some embodiments, rotation of the first actuator may impart a first force on the injector device 1910 and rotation of the second actuator may impart a second force on the injector device 1910 that is equal to but in an opposite rotational direction of the first force. Therefore, the net torque acting on the device (e.g., the stationary mass of the device) may be zero or near zero to prevent unwanted motion of the injector device 1910 during injection. Reducing the net torque of the device can prevent the syringe assembly from straying from a desired travel axis during the injection. The stationary mass of the injector device 1910 can include one or more portions of the injector device 1910 configured to remain stationary along a longitudinal axis of the injector device 1910. The stationary mass of the injector device 1910 can include the first actuator and / or the second actuator. In some embodiments, the stationary mass of the injector device 1910 can include a portion of housing configured to be held by the user (e.g., an outer housing).

[0127] In some embodiments, one motor can be smaller than the other and therefore use less power. The second rotary motor 1916b (e.g., the plunger motor) may be larger than the first rotary motor 1916a such that the second rotary motor 1916b can provide sufficient power to push thick liquids. The motor sizes may also be identical (e.g., weight balance) or reversed (e.g., the second rotary motor 1916b may be configured for thin liquids only). In some embodiments, the first threaded screw 1918a may include a flywheel 1919a disposed at a proximal end thereof configured to match the moment of inertia of the first actuator (e.g., the first rotary motor 1916a and the first threaded screw 1918a) to the second actuator (e.g., theDocket No.: RHTK-003 / 01WO 352653-2018 second rotary motor 1916b and the second threaded screw 1918b). The first actuator and the second actuator may further include a first encoder 1917a and a second encoder 1917b coupled to the first rotary motor 1916a and the second rotary motor 1916b, respectively, and configured to measure one or more characteristics of motion of the syringe 1912 and / or the plunger 1914. In some embodiments, the injector device 1910 may include a voice coil actuator in addition to or instead of the first rotary motor 1916a and / or the second rotary motor 1916b.

[0128] FIG. 10B shows at least a portion of an injector device 2010 according to an embodiment. The injector device 2010 includes a balancing mass 2050 to balance acceleration in the injector device 2010. As shown, acceleration of the moving mass (syringe 2012, plunger 2014, needle 2020, threaded screw 2018b, and housing(s) 2032, 2033 (e.g., frame(s), etc.) can be counteracted by the acceleration of the balancing mass 2050. The injector device 2010 can include a first actuator including a first motor 2016a coupled to a first threaded screw including a first threaded portion 2018a and a second threaded portion 2019a. The injector device 2010 may further include a second actuator including a second motor 2016b coupled to a second threaded screw 2018b. The second motor 2016b may be coupled to or include a slot, groove, or sleeve 2009b (e g., a keyway) configured to receive a shaft 2009a (e.g.. a spline shaft or a slotted shaft) disposed on a distal end of the second threaded screw 2018b.

[0129] The balancing mass 2050 can be driven by the second threaded portion 2019a having a first direction of threading (e.g., right-handed) while the moving mass can be driven by the first threaded portion 2018a having a second direction of threading opposite the first direction (e.g., left-handed). For example, a first housing 2032 can define a threaded through hole configured to receive the first threaded portion 2018a such that the first threaded portion 2018a engages the first housing 2032 to drive the first housing 2032 when the first threaded screw is rotated. The balancing mass 2050 can define a threaded through hole configured to receive the second threaded portion 2019a such that the second threaded portion engages the balancing mass 2050 to drive the balancing mass 2050 when the first lead screw is rotated. In some embodiments, the balancing mass 2050 may have an equal mass to the moving mass. In some embodiments, the first threaded portion 2018a and the second threaded portion 2019a may be separate screws coupled together. The balancing mass 2050 center of gravity can be coincident or colinear with the line of motion of the moving mass center of gravity. Mechanically synchronized motion of the moving mass and the balancing mass 2050 could be accomplished by any suitable mechanism such as, for example, e.g. a linkage, a shaft with two cams, etc. In some embodiments, injection may be completed by first activating the first motor 2016a to move theDocket No.: RHTK-003 / 01WO 352653-2018 syringe 2012 and needle 2020 distally and then to activate the second motor 2016b after the first motor 2016 has been activated to move the plunger 2014 distally. In some embodiments, the first motor 2016a and the second motor 2016b can be activated simultaneously to move the syringe 2012 and needle 2020 distally. For example, the first motor 2016a and the second motor 2016b can be activated such that the first housing 2032 and the second housing 2033 are moved distally with an equivalent velocity. As the second housing 2033 (or frame, etc.) moves along the first threaded portion 2018a, the balancing mass 2050 coupled to the second threaded portion 2019a can move along the second threaded portion with an equal and opposite acceleration to balance the acceleration felt by the user. In other words, when the syringe assembly is moved forward, the equal mass is accelerated backward and vice versa reducing the impulse felt due to forward acceleration of the syringe assembly.

[0130] In some embodiments, the injector device 2010 may alternatively or additionally be manually inserted into a predetermined depth under the skin. For example, the needle 2020 may be extended distally, and the needle 2020 may be manually inserted into the patient. In some embodiments, the injector device 2010 may include a manual option for “feathering.” For example, the plunger 2014 may include a third actuator (e.g., a tab, button, slider) coupled thereto that can be actuated (e.g., pushed). In some embodiments, a user can control a volume of inj ectate and change injection rate with pressure sensitive button change. In some embodiments, the injector device may include a slider to push out and pull fluid out.

[0131] The first actuator and the second actuator may further include a first encode 2017a and a second encoder 2017b coupled to the first motor 2016a and the second motor 2016b, respectively, and configured to measure one or more characteristics of motion of the syringe assembly and / or the plunger 2014.

[0132] FIGS. 11 A-l 1C are side views of at least a portion of an injector device 2110 according to an embodiment, shown in a first configuration, a second configuration, and a third configuration, respectively. The injector device 2110 includes a needle 2120 coupled to a distal end of the syringe 2112 via a needle hub 2128. The syringe 2112 defines an inner volume through which a plunger 2114 is configured to move. The inner volume of the syringe 2112 may be configured to receive a fluid 2105 (e.g., from a fluid reservoir 2104). As shown in FIG. 11 A, the injector device has a first configuration in which the plunger 2114 is disposed in the inner volume of the syringe 2112 such that no fluid can flow into the inner volume. The plunger 2114 may be configured to be moved proximally to transition the injector device 2110 to a second configuration in which fluid 2015 can flow into the inner volume of the syringe 2112,Docket No.: RHTK-003 / 01WO 352653-2018 as shown in FIG. 11B. The plunger 2114 may include a distal portion 2114d and a proximal portion 2114p. The injector device 2110 has a third configuration in which the proximal portion 2114p of the plunger 2114 may be removed at a break point such that a total length of the injector device 2110 is reduced, as shown in FIG. 11C. For example, the portion of the plunger 2114 that extends beyond the syringe 2112 can be removed such that a total length of the syringe assembly is equivalent a length of the needle 2120, needle hub 2128, and the syringe 2112. The break point may align with a proximal end of the syringe 2112. In some embodiments, the break point may be disposed at any position along a length of the plunger 2114. In some embodiments, the position of the break point may correspond to a dosage of the inj ectate.

[0133] FIG. 11D shows at least a portion of an injector device 2210 according to an embodiment. The injector device 2210 includes a plunger actuator configured to reduce a total length of the injector device. The injector device 2210 may include a syringe 2212 defining an inner volume holding an inj ectate 2205 and a portion of the plunger 2214 (e g., similar to the plunger 2114 that has been broken at the break point as shown in FIG. 11C). The syringe 2212 is further coupled to a needle hub 2228 and needle 2220 at a distal end thereof. The injector device 2210 includes an actuator including a motor 2216 coupled to an encoder 2217 and a lead screw 2218. The lead screw 2218 can be disposed inside the actuator (e.g., the rotary motor 2216), resulting in a minimum length assembly with the motor 2216 in line with the syringe 2212.

[0134] FIG. HE shows at least a portion of an injector device 2310 according to an embodiment. The injector device 2310 includes a flexible plunger actuator configured to reduce a total length of the inj ector device 2310. The inj ector device 2310 may include a syringe 2312 defining an inner volume holding an injectate 2305 and a portion of the plunger 2314 (e.g., similar to the plunger 2114 that has been broken at the break point as shown in FIG. 11 C). The syringe 2312 is further coupled to a needle hub 2328 and needle 2320 at a distal end thereof. The injector device 2310 includes an actuator including a motor 2316 coupled to an encoder 2317 and a lead screw 2318 coupled to a push / pull cable 2362. The flexible actuator may enable a shorter assembly length. The syringe barrel can be used as additional support for the flexible plunger driver. While shown with the cable 2362 exposed for illustration, a guide 2364 could be placed nearly flush with the syringe 2312 to minimize buckling. In some embodiments, a telescoping rod may be used.Docket No.: RHTK-003 / 01WO 352653-2018

[0135] FIGS. 12A-12C show a needle 2420 of an injector device according to an embodiment. As shown, the needle 2420 includes a surface 2423 (e.g., sidewall) defining an inner lumen 2425 configured to receive an injectate (e.g., from the syringe). The surface 2423 may define one or more openings 2424 (e.g., through holes, apertures, orifices, etc.) such that fluid can flow from the lumen 2425, through the openings 2424, and under the skin of the patient. The openings 2424 may be positioned along a length of the needle 2420 proximal to the distal end 2421. As shown, the needle 2420 includes four openings 2424 positioned around a circumference of the needle 2420. The openings may be positioned equidistance or substantially equidistant around the circumference of the needle 2420. As shown, the openings 2424 are positioned in a single row' around the circumference of the needle 2420. For example, each of the openings are disposed at a distance Lt from a distal end of the needle 2420.

[0136] The needle 2420 includes a distal end 2421 tapering to a point. As shown, the distal end 2421 may be solid (e.g.. fully solid or at least partially filled). The distal end 2421 (or distal tip) may taper to a sharp point to puncture the tissue of the subject. The solid tip may prevent deformation or bending of the distal end 2421 such that the distal end 2421 follows a substantially straight travel path, thereby reducing tissue damage (and / or pain). The needle 2420 may be structurally and / or functionally similar to the needle 120, and therefore, certain details of the needle 2420 are not described herein with respect to FIGS. 12A-12C.

[0137] FIGS. 13A and 13B show a needle 2520 of an injector device according to an embodiment. The needle 2520 includes a beveled distal end 2521. The needle 2520 may include a surface 2523 (e.g., sidewall) defining an inner lumen 2525 configured to receive injectate. The surface 2523 may define one or more openings 2524 proximal to the distal end 2521. The openings may be positioned equidistance or substantially equidistant around the circumference of the needle 2520. As shown, the openings 2524 are positioned in a single row around the circumference of the needle 2520. For example, each of the openings is disposed at an equal distance from the distal end of the needle 2520. The needle 2520 may be structurally and / or functionally similar to the needles 120, 2420. and therefore, certain details of the needle 2520 are not described herein with respect to FIGS. 13A and 13B.

[0138] FIGS. 14A and 14B show a needle 2620 of an injector device according to an embodiment. The needle 2620 includes a beveled distal end 2621. The needle 2620 may include a surface 2623 (e.g., sidewall) defining an inner lumen 2625 configured to receive injectate. The surface 2623 may define a plurality of openings 2624 proximal to the distal end 2621. As shown, the openings 2624 may be disposed at varying distances from the distal endDocket No.: RHTK-003 / 01WO 352653-2018 of the needle 2620. For example, the openings 2624 may be positioned in a first row and a second row proximal to the first row. The first row of openings and the second row of openings may be staggered circumferentially. For example, an opening from the second row of openings may be disposed between a pair of adjacent openings from the first row of openings. The needle 2620 may be structurally and / or functionally similar to the needles 120, 2420, 2520, and therefore, certain details of the needle 2620 are not described herein with respect to FIGS. 14A and 14B.

[0139] FIGS. 15A-15C show side and cross-sectional views of a needle 2720 according to an embodiment. The needle 2720 may include an outer surface (e.g., sidewall) defining an inner lumen configured to allow inj ectate to flow therethrough. The outer surface may define a plurality7of openings 2724 (e.g., four openings) configured to allow7the injectate to flow from the inner lumen out of the needle 2720. As shown, the needle 2720 includes a beveled distal end portion. The openings 2724 may be disposed a distance Lt from a distal-most end of the needle 2720. In some embodiments, the distance Lt may be a short distance (e.g., in a range between about 0.5 millimeters (mm) to about 0.8 mm, inclusive of all ranges, subranges, and / or values therebetween). In some embodiments, an inner diameter ID of the needle 7270 may be in a range between about 0. 15 mm to about 0.25 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, outer diameter of the needle OD may be in a range between about 0.25 mm to about 0.35 mm, inclusive of all ranges, subranges, and / or values therebetw een. In some embodiments, a radius r of each of the openings may be in a range between about 0.12 mm to about 0.16 mm. inclusive of all ranges, subranges, and / or values therebetween.

[0140] FIGS. 16A-16D show side and cross-sectional views of a needle 2820 according to an embodiment. The needle 2820 may include an outer surface (e.g., sidewall) defining an inner lumen configured allow injectate to flow- therethrough. The outer surface may define a plurality of openings 2824 (e.g., eight openings) configured to allow the injectate to flow7from the inner lumen out of the needle 2820. As shown, the needle 2820 includes a beveled distal end portion. The first subset of the openings may be disposed a distance Ltl from a distal-most end of the needle 2820, and a second subset of the openings may be disposed at a distance Lt2 from the distal-most end of the needle 2820. In some embodiments, Ltl may be in a range between about 1.45 mm to about 1.55 mm, inclusive of all ranges, subranges, and / or values therebetw een. In some embodiments, Lt2 may be in a range between about 1.55 mm and about 1.65 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, theDocket No.: RHTK-003 / 01WO 352653-2018 distance Lt may be a short distance (e.g., in a range between about 0.5 mm to about 0.8 mm, inclusive of all ranges, subranges, and / or values therebetween). In some embodiments, an inner diameter ID of the needle 2870 may be in a range between about 0.15 mm to about 0.25 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, outer diameter of the needle OD may be in a range between about 0.25 mm to about 0.35 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range between about 0.08 mm to about 0. 1 mm. inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an angle a defined between center-points of adjacent openings 2724 may be in a range between about 40 degrees and about 50 degrees, inclusive of all ranges, subranges, and / or values therebetween.

[0141] FIGS. 17A-17D show side and cross-sectional views of a needle 2920 according to an embodiment. The needle 2920 may include an outer surface defining an inner lumen configured to allow inj ectate to flow therethrough. The outer surface may define a plurality of openings 2924 (e.g., six openings) configured to allow the injectate to flow from the inner lumen out of the needle 2920. As shown, the needle 2920 includes a beveled distal end portion. The plurality of openings 2924 may be disposed a distance Lt from a distal-most end of the needle 2920. In some embodiments, the distance Ltl may be in a range between about 1.45 mm to about 1.55 mm, inclusive of all ranges, subranges, and / or values therebetw een. In some embodiments, an inner diameter ID of the needle 2970 may be in a range between about 0.15 mm to about 0.25 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, outer diameter of the needle OD may be in a range between about 0.25 mm to about 0.35 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range betw een about 0.08 mm to about 0. 1 mm, inclusive of all ranges, subranges, and / or values therebetw een. In some embodiments, an angle a defined between center-points of adjacent openings 2924 may be in a range between about 55 degrees and about 65 degrees, inclusive of all ranges, subranges, and / or values therebetween.

[0142] FIGS. 18A-18C show a needle 3020 of an injector device according to an embodiment. As shown, the needle 3020 may include an outer surface defining an inner lumen configured to allow injectate to flow therethrough. The outer surface may define a plurality of openings 3024 (e.g., three openings) configured to allow injectate to flow7from the inner lumen out of the needle 3020. The needle 3020 includes a beveled distal end portion. The plurality of openings 3024 may be disposed a distance Lt from a distal-most end of the needle 3020. In some embodiments, the distance Lt may be in a range between about 0.60 mm to about 0.80Docket No.: RHTK-003 / 01WO 352653-2018 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an inner diameter ID of the needle 3070 may be in a range between about 0. 15 mm to about 0.25 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, outer diameter of the needle OD may be in a range between about 0.25 mm to about 0.35 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range between about 0. 10 mm to about 0.20 mm, inclusive of all ranges, subranges, and / or values therebetween.

[0143] FIGS. 19A-19C show side and cross-sectional views of a needle 3120 according to an embodiment. The needle 3120 may include an outer surface defining an inner lumen configured allow inj ectate to flow therethrough. The outer surface may define a plurality of openings 3124 (e.g., nine openings with three openings per row) configured to allow the inj ectate to flow from the inner lumen out of the needle 3120. As shown, the needle 3120 includes a beveled distal end portion. A first set of openings may be disposed a first distance Ltl from a distal-most end of the needle 3120, a second set of openings may be disposed a second distance Lt2 from the distal-most end of the needle 3120, and a third set of openings may be disposed a third distance Lt3 from the distal-most end of the needle 3120. In some embodiments, the distance Ltl may be in a range between about 1.45 mm to about 1.55 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, the distance Lt2 may be in a range between about 1.65 mm to about 1.75 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, the distance Lt3 may be in a range between about 1.80 mm and about 2.0 mm. inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range between about 0. 10 mm to about 0.20 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an angle a defined between center-points of adjacent openings 2924 in a given row (e.g., an angle between center-points of adjacent openings of the first set of openings) may be in a range between about 110 degrees to about 130 degrees, inclusive of all ranges, subranges, and / or values therebetween.

[0144] FIGS. 20A-20B show a side and cross-sectional views of a needle 3220 according to an embodiment. The needle 3220 may include an outer surface defining an inner lumen configured to allow' injectate to flow therethrough. The outer surface may define a plurality' of openings 3224 (e.g., nine openings with three openings per row) configured to allow the injectate to flow from the inner lumen out of the needle 3220. As shown, the needle 3220 includes a beveled distal end portion. A first set of openings may be disposed a first distanceDocket No.: RHTK-003 / 01WO 352653-2018Ltl from a distal-most end of the needle 3220, a second set of openings may be disposed a second distance Lt2 from the distal-most end of the needle 3220, and a third set of openings may be disposed a third distance Lt3 from the distal-most end of the needle 3220. In some embodiments, the distance Ltl may be in a range between about 1.45 mm to about 1.55 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, the distance Lt2 may be in a range between about 1.80 mm to about 2.0 mm. inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, the distance Lt3 may be in a range between about 2.20 mm and about 2.40 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range between about 0.10 mm to about 0.20 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an angle a defined between center-points of adjacent openings 2924 in a given row (e.g., an angle between center-points of adjacent openings of the first set of openings) may be in a range between about 110 degrees to about 130 degrees, inclusive of all ranges, subranges, and / or values therebetween.

[0145] FIGS. 21A-21D show side and cross-sectional views of a needle 3320 according to an embodiment. The needle 3320 may include an outer surface defining an inner lumen configured to allow inj ectate to flow therethrough. The outer surface may define a plurality of openings 3324 (e.g., four openings) configured to allow the injectate to flow from the inner lumen out of the needle 3320. As shown, the needle 3320 includes a beveled distal end portion. The plurality7of openings 3324 may be disposed a distance Lt from a distal-most end of the needle 3320. In some embodiments, the distance Ltl may be in a range between about 1.45 mm to about 1.55 mm. inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an inner diameter ID of the needle 3370 may be in a range between about 0.15 mm to about 0.25 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, outer diameter of the needle OD may be in a range between about 0.25 mm to about 0.35 mm. inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, a radius r of each of the openings may be in a range between about 0.08 mm to about 0.1 mm, inclusive of all ranges, subranges, and / or values therebetween. In some embodiments, an angle a defined between center-points of adjacent openings 3324 may be in a range between about 80 degrees and about 100 degrees, inclusive of all ranges, subranges, and / or values therebetween.

[0146] FIG. 22 A shows a method of determining a depth of a needle 3420 of a depth sensing mechanism of an injector system relative to a surface of skin 3402 of a subject, according toDocket No.: RHTK-003 / 01WO 352653-2018 embodiments. The surface of the skin 3402 can be soft; therefore, when pierced with a needle, the skin 3402 can generally deform a small distance from its relaxed position. This poses a problem for achieving precise, shallow, needle insertion depths (e.g. 0.2mm). In some embodiments, the injector device may be configured to detect an initial position of the needle 3420 and an initial position of the skin 3402. The injector device may be configured to determine a first contact of the needle 3420 with the skin 3402 and use the first contact point as the initial position. In some embodiments, the needle 3420 may be advanced a predetermined distance based on a desired depth. As the needle 3420 advanced, the skin 3402 may tent a distance dl (e.g., the skin tenting error), as shown in FIG. 22A. The distance dl can then be used to adjust a distance traveled by the needle 3420 based on the distance dl. In some embodiments, after piercing, the skin may move up the needle and a distance d2 of the skin after piercing may be determined. As shown, oscillating the needle may allow the skin to slide up the needle to recover its initial position (e.g., position before the first needle contact).

[0147] In some embodiments, the initial position of the needle 3420 may be adjusted based on first contact with skin (e.g., via a manual job). In some embodiments, an optical method to detect where the actual distal end of the needle 3420 is located can be used. For example, a beam break, laser diode, or the like can be used to visualize a position of the needle 3420. In some embodiments, capacitive, magnetic detection can be used in addition to or instead of optical methods. In some embodiments, a depth sensing mechanism (e.g., optical methods and / or capacitive / magnetic methods) may detect when the needle extends too far.

[0148] FIG. 22B is a graph of measurements from a sensor disposed on a needle of an injector system and / or on a needle hub of the injector system. In some embodiments, the sensor may be configured to detect contact and / or piercing of the skin by the needle. In some embodiments, changes in electrical signal can be used to measure how far the skin tents before the needle pierces the skin. For example, an electrical circuit (resistive, capacitive, EIS) from when the needle contacts the subject experiences a detectable change when (A) the needle first contacts the skin, changing from a metal to air to skin connection to a metal to skin connection, and (B) when the needle first pierces the skin, changing from a metal to epidermis connection into a metal to dermis connection. DC resistance, alternating current (AC) resistance in one or more frequencies (EIS), capacitance, or a combination of these is used to detect a step change in signal when (A) the needle first makes contact with the skin and / or (B) when the needle first pemitrates different structures of the skin (epidermis, dermis, etc.). In some embodiments, the needle 3420 and / or a portion of the needle hub or syringe can include a sensor configured toDocket No.: RHTK-003 / 01WO 352653-2018 measure electrical signals from the skin 3402. In some embodiments, the injector device can include or be coupled to a controller configured to receive the measurements from the sensor and determine a position of the distal end of the needle based on the change in electrical signal measured through the sensor. In some embodiments, the controller can be configured to send signals to control a velocity of the actuator (e.g., stop or slow the actuator) from advancing the syringe assembly distally based on the position of the distal end of the needle. For example, an acceleration or activation protocol of the actuator can be adjusted based on the position of the distal end of the needle relative to the skin surface (accounting for tenting). In some embodiments, when the controller determines the distal end of the needle reaches a predetermined depth (e.g., based on the measurements) the controller can deactivate or slow the actuator. In some embodiments, the controller can be configured to: detect initial contact of the needle with the skin surface of the patient (A); determine a second position of the distal end of the needle when the skin is tented a maximum amount without piercing the skin (B); calculate the distance between the first position and the second position; and adjust a travel distance of the needle, by controlling the actuator, based on the distance calculated.

[0149] FIGS. 23A-23B show a needle 3520 of an injector device according to an embodiment. The needle 3520 includes one or more markers 3526 for determining a depth of the needle 3520 in the skin 3502 of the subject. In some embodiments, the markers may be laser etched onto an outer surface of the needle 3520 in a predetermined pattern. In some embodiments, the markers 3526 may be imaged and / or scanned (e.g., using an optical sensor 3542). In some embodiments, the markers 3526 may be used to determine a depth of penetration. In some embodiments, the plurality of markers may correspond to different injections. In some embodiments, the markers 3526 may be step counted (e.g., a relative encoder system). In some embodiments, the markers 3526 can directly correspond to the distance / depth (e.g., absolute encoder). FIG. 23B shows a needle 3620 with one marker 3626 penetrating skin 3602 of a subject. The needle 3620 may be used when one depth is being targeted (e.g., for dermal injection). The marker 3626 can be scanned by an optical device 3642.

[0150] FIGS. 24A shows a needle 3720 according to an embodiment. The needle 3720 includes an opening 3724 defined in a sidewall thereof and includes a distal end tip 3721 configured to taper to a point. The needle 3720 may define an inner lumen 3725 configured to allow fluid to flow therethrough. As fluid is pushed distally through the lumen of the needle 3720. the fluid can disperse horizontally out of the openings 3724. As shown in FIG. 24B, a needle 3820 may include a plurality of openings 3824 to increase a flow of fluid through the needle. As shownDocket No.: RHTK-003 / 01WO 352653-2018 in FIG. 24C, a needle 3920 may include an opening 3924 defined in a sidewall thereof and a distal end tip 3921. The needle 3920 may further include a stopping mechanism 3929 proximal to the opening 3924 and configured to prevent the needle 3920 from moving further distally once the stopping mechanism 3929 contacts skin of the subject. In some embodiments, the stopping mechanism 3929 may be a sleeve disposed around the barrel of the needle 3920 to increase an outer diameter of the needle 3920. In some embodiments, the needle 3920 may increase in thickness (e.g.. stepwise) at a predetermined point along the length of the needle corresponding to a desired depth of injection.

[0151] FIG. 25A shows a shroud 4023 of an injector device for applying a force to the skin 4002 during injection to reduce pain, according to an embodiment. As shown, a needle 4020 including a tapered distal end 4021 and a sidewall defining one or more openings 4024 therein is disposed in the skin 4002 of the subject. The shroud 4023 may be configured to apply a vacuum force to hold the skin 4002 in position prior to penetration. In some embodiments, the shroud 4023 may include an air permeable medium 4027 that allows air flow (e.g. ridged open cell foam, disk with small holes). As shown, the skin 4002 can be drawn against the medium 4027, thereby setting the needle 4020 to a consistent depth. When the injector device 4010 detects a seal with the skin 4002 (e.g.. turn vacuum draw down) then the injector device 4010 triggers the injection (e.g., automatically without user input). In some embodiments, the shroud 4023 can include a sensor configured to detect a seal with the skin 4002, The injector device 4010 can be coupled to a controller configured to receive measurements from the sensor and control an actuator of the injector device 4010 to initiate injection in response to detecting the seal with the skin 4002.

[0152] FIG. 25B show s a shroud 4123 configured to apply a vacuum force to draw the skin 4103 to a known position and / or apply tension to the skin. As shown, the shroud 4123 includes a passage or channel 4107 extending from a distal side of the shroud to a proximal side of the shroud that can be coupled to the vacuum source.

[0153] FIGS. 26A-26B show diagrams of alignment system including optical pathways for determining a position of the needle 4220 and 4320, respectively, relative to a target injection site of a subject, according to embodiments. In some embodiments, the syringe clamping mechanism may measure an angle of tilt using a sensor (e.g., a non-contact sensor). The sensor may include any suitable sensor such as, for example, a beam break, machine vision, CCD, CMOS, array of proximity sensors, etc. The alignment system may include a light source (e.g., beam breaker, laser diode) configured to transmit light. The alignment system may include oneDocket No.: RHTK-003 / 01WO 352653-2018 or more optical components (e.g., objective, mirrors, dichroic mirrors, objective mirrors, lenses) configured to guide the light to reflect off a distal tip of the needle. For example, as shown in FIG. 26A, the optical components may include an objective mirror 4233 configured to reflect light to a secondary mirror 4231, and the secondary mirror 4231 may be configured to reflect light to an eyepiece 4235. In some embodiments, the injector system may include one or more optical components to guide light from the distal tip of the needle to an optical sensor and / or an eyepiece 4235. The light from the beam breaks, minors, and / or laser diode may reflect off at least a portion of the needle 4220 (e.g., the distal tip) and this reflection can be measured (e.g., at the eyepiece 4235).

[0154] In some embodiments, the optical system may include a set of beam break pairs configured to guide light around a portion of the injector device. For example, FIG. 26B shows an optical sensor that includes a set of beam break pairs 4331 (e.g., mirrors or the like), that can direct, divert, and / or guide light reflected off of the needle 4320 around a portion of the injector device 4310. The optical sensor (e.g., a camera such as CDD, CMOS, etc.) may be configured to measure the reflected light signals. The measured reflected light signals can then be used to determine a position of the distal tip of the needle 4320. Additionally or alternatively, the light may be directed to an eyepiece (not shown) for the user to view.

[0155] FIGS. 27A-27C show disposable devices configured to interface with the injector device 4410 to prevent cross contamination between injections, according to different embodiments. In some embodiments, the injector device 4410 may be configured to enable easy cleanability. For example, the injector device 4410 may be configured such that the entire injector device 4410 can be cleaned in an autoclave. In some embodiments, a distal end of the injector device 4410 may be disposed in a caddy of cleaning solution. In some embodiments, the injector device 4410 can be sterilized with ultrasonic or activate vibrations. In some embodiments, the injector device 4410 may include one or more disposable devices configured to interface with the injector device 4410 such that the same surface is not holding a needle 4420 of the injector device 4410 and / or the needle hub between subjects. In some embodiments, the disposable clamping mechanism may include a disposable cap or cover 4485 including a membrane 4486, as shown in FIG. 27A. The needle 4420 may pierce the membrane 4486 to get to the subject. In some embodiments, the membrane 4486 may maintain the needle 4420 in a sterile environment. The membrane 4486 may be fluid impermeable such that the membrane 4486 prevents splashing of contaminants onto the non-disposable portion of the injector device 4410 (e.g., to isolate the injector device housing from contaminants). In someDocket No.: RHTK-003 / 01WO 352653-2018 embodiments, the disposable cap or cover 4485 may also be configured as a sharp protection cap.

[0156] As shown in FIG. 27B, the needle hub may include a cover (e.g., flange) 4585 coupleable to the needle hub 4528. The cover 4585 may cover the distal end of the injector device 4510 to protect a portion of the injector device 4510 proximal to cover 4585 from contaminants. In some embodiments, the cover 4585 may be removably couplable to the injector device 4510. In some embodiments, the cover 4585 may clip onto the needle hub 4528. In some embodiments, the cover 4585 may be molded plastic configured to be disposed around a portion of a distal portion of the injector device 4510 and / or onto a portion of the syringe 4512 / needle hub 4528. As shown in FIG. 27C, a cover 4685 may include a clam shell clamp or the like including a first portion 4687a and a second portion 4687b configured to clamp together around the needle hub. In some embodiments, the cap or cover 4485, 4585, 4685 may include conductive plastic. In some embodiments, the cap or cover 4485, 4585. 4685 may include a molded polymer such as silicone.

[0157] FIGS. 28A and 28B show injector devices 4710 and 4810, respectively, including needle covers 4785, 4885, respectively, configured to prevent cross-contamination, according to embodiment. In some embodiments, the covers 4785, 4885 may include a disposable rubber cover that can be disposed on or around the needle hub 4729, 4828. In some embodiments, the cover may be coupleable to the distal portion of the injector device. In some embodiments, the cover 4875, 4885 may be flexible to allow needle travel. For example, the cover may include bellows (as shown in FIG. 28B), thin sleeve stretches (as shown in FIG. 28A), etc. In some embodiments, the cover may be a bag or sheet-like covering (not shown) configured to be disposed around a portion of the injector device housing (e.g., to isolate the injector device hosing from contaminants).

[0158] FIGS. 29A-29B show a robotic injector system 4990 for placing the injector device 4910 relative to skin of a subject, according to embodiments. In some embodiments, placement of the injector device 4910 may be automated or machine-controlled (e.g., performed by the robotic injector system 4990). For example, determining a target injection site on the subject and / or an angle of approach of the needle to the surface normal on the patient may be determined without user input. In some embodiments, the robotic injector system 4990 can be configured to align the injector device 4910 along a desired travel axis relative to the skin of the subject and at a predetermined starting distance from the skin of the subject.Docket No.: RHTK-003 / 01WO 352653-2018

[0159] In some embodiments, a user may determine a target injection site on the subject using one or more pre-operative images of a portion of interest of the subject (e.g., CT, MRI). In some embodiments, the user may mark (e.g., draw, tape, etc.) one or more locations (e.g., points, fiducials, etc.) on the skin of the subject. In some embodiments, the one or more locations drawn can be scanned by an optical sensor (e.g., a camera). In some embodiments, the robotic injector system 4990 may be configured to move through a predetermined configuration of points (e.g.. a grid of points, a hexagonal pattern, etc.). In some embodiments, the pattern may be projected with laser light onto the patient to visualize the path of injections. In some embodiments, the robotic injector system 4990 may be configured to detect the fiducials optically and determine how' the skin of the subject moves and / or flexes to reduce discrepancies between the actual movements and the predetermined pattern marked. In some embodiments, results from previous injections may be scanned (e.g., by the camera) to determine whether the pattern of points should be adjusted to achieve a desired bleb pattern.

[0160] In some embodiments, the robotic injector mechanism may include a gantry or a movable arm configured to move the injector device 4910 along two or more axes. In some embodiments, the gantry or movable arm may be configured to move the injector device 4910 along an XY plane parallel to a surface of the skin of the subject. In some embodiments, the robotic injector system 4990 can be configured to hold the injector device 4910 at a predetermined distance from the skin along a Z plane perpendicular to the surface of the skin. In some embodiments, the robotic injector system 4990 can be configured to move the injector device 4910 along the Z plane above the target site and prior to inj ection. In some embodiments, the robotic injector system 4990 may include a frame that rests on a local area of the patient and can cover any point within that frame. In some embodiments, the robotic injector system 4990 may be configured to tilt and / or rotate the inj ector device to a predetermined angle relative to the skin, as shown in FIG. 29B. For example, the robotic injector system 4990 may be able to angle the device to nearly parallel with the surface of the skin for injecting (e.g., for beveled needle tips), as shown in FIG. 29 A.

[0161] FIG. 30A show's a robotic injector 5090 for using an injector device 5010, according to embodiments. As shown, the robotic injector 5090 includes a movable arm 5094 may be coupled to a support arm 5092, the support arm 5092 being coupled to a fixed surface. As shown, the injector device 5010 may be maneuvered relative to the head of the subject 5002 by the movable arm 5094.Docket No.: RHTK-003 / 01WO 352653-2018

[0162] As shown in FIG. 30B, the injector device 5010 may be held directly by a user 5001 for applying injection pattern. In some embodiments, the injector device 5010 can be used to inject any large area of the subject 5002 and / or across a plurality of areas, as shown in FIG. 30C. In some embodiments, the injector system may be used for any living tissue (e.g., animal, human) and can be scaled down for smaller subjects as well (mice, insects, etc.).

[0163] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0164] As used herein, in particular embodiments, the terms “about,’' “approximately,"’ and / or “substantially” when preceding a numerical value(s) and / or geometric structure(s) / relationship(s) indicates the value or characteristic so defined is nominally the valve stated or characteristic described. In some instances, the terms “about,” “approximately,” and / or “substantially” can generally mean and / or contemplate a valve or characteristic stated within a desired tolerance such as. for example, plus or minus a range of 10%. For example, a value of about 0.01 can include 0.009 and 0.011, a value of about 0.5 can include 0.45 and 0.55, a value of about 10 can include 9 to 11, and a value of about 1000 can include 900 to 1100. Similarly, a first surface may be described as being substantially parallel to a second surface when the surfaces are nominally parallel. While a value, structure, and / or relationship stated may be desirable, it should be understood that some variance may occur as a result of. for example, manufacturing tolerances and / or other practical considerations that would be appreciated by one skilled in the art, unless expressly stated otherwise. Accordingly, the terms “about,” “approximately,” and / or “substantially” can be used herein to account for such tolerances and / or considerations.

[0165] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. That the upper and lower limits of these smaller ranges can independently be included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.Docket No.: RHTK-003 / 01WO 352653-2018

[0166] As used herein, the phrase “and / or” should be understood to mean “either or both” of the elements so conjoined, i.e.. elements that are conjunctively present in some cases and disjunctively present in other cases. Conjoining more than two elements with “and / or” should be construed in a similar fashion, i.e., “one or any and all combinations” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B.” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0167] As used herein, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive (i.e., the inclusion of at least one, but also including more than one) of a number or list of elements, and, optionally, additional unlisted items. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by term(s) of exclusivity, such as “either,” “one of,” “only one of.” “exactly one of.” etc., and / or unless otherwise clearly indicated.

[0168] As used herein, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one. A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0169] While specific embodiments and / or implementations of the present disclosure have been outlined above, many alternatives, modifications, and variations will be apparent to thoseDocket No.: RHTK-003 / 01WO 352653-2018 skilled in the art. Accordingly, the embodiments set forth herein are intended to be illustrative, not limiting. Various modifications, changes, and / or variations in form and / or detail may be made without departing from the spirit and scope of the disclosure and / or without altering the function and / or advantages thereof unless expressly stated otherwise. For example, the specific configurations of the various components such as size and / or specification shape may be varied and may be different from the embodiments shown, while still providing the desired functions described herein. In some implementations, the size and / or shape of the various components can be specifically selected for a desired or intended usage. Thus, it should be understood that the size, shape, and / or arrangement of the embodiments and / or components thereof can be adapted for a given use unless the context explicitly states otherwise.

[0170] Likewise, while embodiments and / or features, components, configurations, aspects, etc. thereof may be described above in the context of certain implementations, it should be understood that such implementations are presented by way of example only and not limitation. Any of the embodiments and / or features, components, configurations, aspects, etc. thereof can be used in, and / or adapted for use in, other implementations unless expressly stated otherwise. For example, although various embodiments have been described as having particular features, configurations, and / or combinations of components, other embodiments are possible having a combination of any features, configurations, and / or components from any of the embodiments described herein, except mutually exclusive combinations. Thus any of the embodiments described herein can include various combinations and / or sub-combinations of the functions, components, configurations, and / or features of the different embodiments described. Moreover, functionally equivalent embodiments, implementations, and / or methods, in addition to those described herein, will be apparent to those skilled in the art from the foregoing descriptions and are intended to fall w ithin the scope of the disclosure.

[0171] Where methods and / or steps described above indicate certain events occurring in a certain order, the ordering of certain steps may be modified. Additionally, certain events and / or steps may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above, whether such events and / or steps are performed by a user (a human), a component of a given embodiment (a compute device, a processing device, a processor, etc.), and / or any combination(s) thereof. While methods have been described as having particular steps and / or combinations of steps, other methods are possible having a combination of any steps from any of methods described herein, except mutually exclusive combinations and / or unless the context clearly states otherwise.

Claims

Docket No.: RHTK-003 / 01WO 352653-2018What is claimed is:

1. An apparatus, comprising: a syringe assembly including: a syringe defining an inner volume configured to receive an inj ectate, the syringe including a needle coupled to a distal end thereof; a plunger, at least a portion of the plunger movably disposed in the inner volume of the syringe; a first actuator coupled to the syringe; and a second actuator coupled to the plunger, the first actuator and the second actuator having a first configuration in which the first actuator and the second actuator collectively advance the syringe assembly a predetermined distance such that a distal end of the needle advances to a predetermined depth under a skin surface of a subject, the first actuator and the second actuator configured to transition to a second configuration in which a ratio of a velocity of the second actuator to a velocity of the first actuator increases to cause the plunger to move distally through the inner volume of the syringe to eject the inj ectate from the needle under the skin surface of the subject.

2. The apparatus of claim 1, wherein at least one of the first actuator or the second actuator includes a rotary motor.

3. The apparatus of claim 1, wherein at least one of the first actuator or the second actuator includes a voice coil.

4. The apparatus of claim 1 , wherein the first actuator includes a first threaded lead screw and the second actuator includes a second threaded lead screw.

5. The apparatus of claim 4, further comprising: a first housing coupled to the syringe; and a second housing coupled to a portion of the plunger.Docket No.: RHTK-003 / 01WO 352653-20186. The apparatus of claim 5, wherein the first housing defines a threaded through hole configured to receive a portion of the first threaded lead screw such that rotation of the first threaded lead screw causes linear motion of the first housing, the second housing defines a threaded through hole configured to receive a portion of the second threaded lead screw such that rotation of the second threaded lead screw causes linear motion of the second housing.

7. The apparatus of claim 5, wherein the first threaded lead screw and the second threaded lead screw have threading with opposite directionality such a portion of the first actuator is configured to rotate in a first direction with a first acceleration and a portion of the second actuator configured rotate in a second direction opposite to the first direction with a second acceleration such that a net torque imparted by the first actuator and the second actuator is zero or near zero.

8. The apparatus of claim 1, further comprising: a balancing mass coupled to the syringe assembly and configured to accelerate with an equal and opposite magnitude to the syringe assembly when the syringe assembly is advanced distally.

9. The apparatus of claim 8, wherein the balancing mass has a center of gravity that is colinear with a line of motion of a center of gravity of the syringe assembly such that the syringe assembly does not rotate relative to a desired travel axis of the syringe assembly when the syringe assembly is advanced distally.

10. The apparatus of claim 1, wherein a distal tip of the needle is solid, the needle defining one or more openings in a sidewall thereof such that inj ectate is ejected through the one or more openings during an injection.

11. An apparatus, comprising: a syringe assembly including: a syringe defining an inner volume configured to receive an inj ectate, the syringe including a needle coupled to a distal end thereof; and a plunger, at least a portion of the plunger movably disposed in the inner volume of the syringe;Docket No.: RHTK-003 / 01WO 352653-2018 an actuator coupled to the syringe assembly, the actuator configured to transition from a first configuration in which the actuator advances the syringe assembly distally such that a distal end of the needle advanced to a predetermined depth under skin of a subject to a second configuration in which the actuator causes a portion of the plunger to move distally through the inner volume of the syringe to eject the inj ectate through the needle; and a balancing mass coupled to the actuator and configured to accelerate with an equal and opposite magnitude to the syringe assembly when the actuator is in the first configuration, the balancing mass having a center of gravity that is colinear with a line of motion of a center of gravity of the syringe assembly.

12. The apparatus of claim 11. wherein the actuator includes at least one of rotary motor or a voice coil.

13. The apparatus of claim 11, wherein the actuator includes a first actuator and a second actuator, the first actuator being coupled to the syringe and the second actuator being coupled to the plunger.

14. The apparatus of claim 13, wherein the balancing mass is coupled to the first actuator.

15. The apparatus of claim 13. wherein the first actuator and the second actuator have a first configuration in which the first actuator and the second actuator advance the syringe assembly distally and a second configuration in which a ratio of a velocity of the second actuator to a velocity of the second actuator increases to cause the plunger to move distally through the inner volume of the syringe.

16. The apparatus of claim 14, wherein the first actuator includes a first threaded lead screw coupled to a rotary motor and the second actuator includes a second threaded lead screw coupled to a second rotary motor.

17. The apparatus of claim 1 , further comprising: a first housing coupled to the syringe; and a second housing coupled to a portion of the plunger, ,the first housing defines a threaded through hole configured to receive a portion of the first threaded lead screw such that rotation of the first threaded lead screw causes linear motion of the first housing, theDocket No.: RHTK-003 / 01WO 352653-2018 second housing defines a threaded through hole configured to receive a portion of the second threaded lead screw such that rotation of the second threaded lead screw causes linear motion of the second housing.

18. An apparatus, comprising: a syringe assembly including: a syringe defining an inner volume configured to receive an inj ectate. the syringe including a needle coupled to a distal end thereof, and a plunger, a portion of the plunger disposed in the inner volume of the syringe, the syringe assembly coupled to at least one sensor, the at least one sensor configured to collect measurements including at least one of an electrical signal of a skin surface or an optical signal of a marker disposed on the syringe assembly; an actuator coupled to the syringe assembly, the actuator in a first configuration configured to advance the syringe assembly distally, the actuator in a second configuration configured to move the plunger through the inner volume to eject the inj ectate through the needle; and a controller coupled to the syringe assembly, the controller configured to: receive the measurements from the at least one sensor; determine a position of the distal end of the needle relative to the skin surface based on the measurements; and control a velocity of the actuator based on the position of the distal end of the needle relative to the skin surface.

19. The apparatus of claim 18, wherein the actuator includes at least one of a rotary motor or a voice coil.

20. The apparatus of claim 18, wherein the actuator includes a first actuator and a second actuator, the first actuator being coupled to the syringe and the second actuator being coupled to the plunger.

21. The apparatus of claim 18, wherein a distal tip of the needle is solid, the needle defining one or more openings in a sidewall thereof such that inj ectate is ejected through the one or more openings during an injection.Docket No.: RHTK-003 / 01WO 352653-201822. The apparatus of claim 18, wherein the controller is further configured to: detect initial contact of the distal end of the needle with the surface of the skin; determine a first position of the distal end of the needle during the initial contact; determine a second position of the distal end of the needle when the skin is tented a maximum amount without piercing the skin; calculate a distance between the first position and the second position; adjust a travel distance the needle is advanced for an injection based on the distance; and control the velocity of the actuator such that the needle is advanced the travel distance during the injection.

23. The apparatus of claim 18, wherein the sensor is a conductive material disposed on at least one of the needle or a needle hub coupling the needle to the syringe.

24. The apparatus of claim 18, wherein the at least one sensor includes an optical sensor operatively coupled to the controller, the optical sensor configured to detect the optical signal of the marker, the marker being disposed on at least one of the needle or a needle hub coupling the needle to the syringe.

25. The apparatus of claim 18. further comprising: a shroud coupled to a distal portion of the syringe assembly and configured to define a chamber over the surface of the skin, the shroud coupled to a vacuum source configured to apply a vacuum force within the chamber, the at least one sensor including a pressure sensor operatively coupled to the shroud and the controller, the pressure sensor configured to measure a pressure within the chamber.

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