Delivery devices for therapeutic substances

Abstract

To provide a novel method for loading a therapeutic substance in a delivery device.SOLUTION: A delivery device for delivering substance includes: a needle having a needle lumen; a first translation screw fitted to the needle and positioned in a passage with a first thread; a plunger configured to move through the needle lumen; and a second translation screw fitted to the plunger and positioned in a second passage with thread. Operation of a device actuator causes the first passage with thread and the second passage with thread to rotate. Thus, a first translation screw translates through the first passage with thread to move the needle, and a second translation screw translates through the second passage with thread to move the plunger through the needle lumen.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] Cross-Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 009,572, filed on April 14, 2020. The entire disclosure of U.S. Provisional Application No. 63 / 009,572 is incorporated herein by reference.

[0002] The disclosed embodiments relate to delivery devices and related methods of use. Background Art

[0003] Therapeutic agents are administered to patients through a variety of methods. A variety of administration routes are available, including oral routes, inhalation routes, topical routes, intravascular routes, intramuscular routes, subcutaneous routes, intraperitoneal routes, rectal / vaginal routes, transluminal routes, and more tissue-specific routes (e.g., intrathecal routes, intraventricular routes, and intraarticular routes).

[0004] Cell-based therapeutics are generally administered using conventional delivery devices, such as needles and syringes, or balloon dilatation catheters. Injection of cell-based therapeutics through the skin or mucosa can help bypass a portion of the body's defensive barriers and can enable delivery of the cell-based therapeutic to a specific site. Summary of the Invention Means for Solving the Problems

[0005] In some embodiments, a delivery device is provided. The delivery device may include a device actuator, a needle having a needle lumen, and a plunger configured to move through the needle lumen. The actuation of the device actuator may cause the needle to move backward through the shaft lumen, and may cause the plunger to move forward through the needle lumen, the backward direction being opposite to the forward direction.

[0006] In some embodiments, a delivery device is provided. The delivery device may include a device actuator, an outer shaft having a shaft lumen, and a needle having a needle lumen. The needle may be configured to move through the outer shaft lumen. The delivery device may also include a plunger configured to move through the needle lumen. Actuation of the device actuator may cause the needle to move a first distance relative to the outer shaft, and may cause the plunger to move a second distance relative to the outer shaft, the first distance being different from the second distance.

[0007] In several embodiments, a delivery device is provided. The delivery device may include a device housing, a device actuator rotatably mounted to the device housing, a needle having a needle lumen, and a plunger configured to move through the needle lumen. Rotation of the device actuator may cause the plunger to move through the needle lumen.

[0008] In some embodiments, a method for delivering a substance through a delivery device is provided. The method may include the step of rotating a device actuator by at least 10 full rotations, resulting in the delivery of a certain volume of substance through the exit of a needle, wherein the volume is between 1 microliter and 50 microliters.

[0009] In some embodiments, a method is provided for loading cells into a delivery device. The method may include the steps of moving the cells into a needle lumen through the delivery end of a needle, venting air out of the needle lumen through a vent in the needle as the cells are moved into the needle lumen, and closing the fluid communication through the vent after the cells have been moved into the needle lumen.

[0010] In several embodiments, a delivery device is provided. The delivery device may include a device housing and a needle. The needle may include a delivery end, a shaft, and a needle lumen extending through the shaft. The delivery device may also include a plunger configured to move through the needle lumen. The needle may also include a vent in the shaft, which is spaced apart from the delivery end.

[0011] In several embodiments, a delivery device is provided. The delivery device may include a device actuator, an outer shaft having a shaft lumen, and a needle having a needle lumen. The needle lumen may have a diameter between 0.1 mm and 0.7 mm (including 0.1 mm and 0.7 mm), and the needle may be configured to move through the shaft lumen. The delivery device may also include a plunger configured to move through the needle lumen, the plunger having a travel distance of at least 100 mm relative to the outer shaft.

[0012] In some embodiments, a method for delivering cells through a delivery device is provided. The method may include the step of moving the needle of the delivery device to a target site so that the needle occupies a certain volume of space at the target site. The method may also include the step of activating a device actuator to cause the needle to retract from the volume of space, causing a plunger to move through the needle lumen of the needle toward the volume of space, and simultaneously delivering cells into the volume of space as the needle retracts from the volume of space.

[0013] In several embodiments, a delivery device is provided. The delivery device may include a device actuator, a needle having a needle lumen, a plunger configured to move through the needle lumen, and an indicator having a marker indicating the dose to be delivered. The indicator may be mechanically coupled to the device actuator, so that the operation of the device actuator causes the marker of the indicator to move physically without electrical input.

[0014] In several embodiments, a delivery device is provided. The delivery device may include a device housing and a needle having a needle lumen. The needle lumen may have a constant diameter throughout its entire length. The delivery device may also include a plunger configured to move through the needle lumen and a therapeutic substance completely contained within the needle lumen.

[0015] This disclosure is not limited in this respect, and it should be recognized that the concepts described above, and the additional concepts discussed below, may be arranged in any suitable combination. Furthermore, other advantages and novel features of this disclosure will become apparent from the following detailed description of various non-limiting embodiments, when considered together with the accompanying figures.

[0016] The attached drawings are not intended to be drawn to scale. In the drawings, identical or nearly identical components shown in different drawings may be represented by similar numbers. For clarity, not all components may be labeled in all drawings. [Brief explanation of the drawing]

[0017] [Figure 1] This is a schematic diagram of a delivery device that generates a backflow of therapeutic substances during injection. [Figure 2] Figure 1 is a schematic diagram of one embodiment of a delivery device according to the embodiments described herein, in which the potential backflow problem experienced by the delivery device can be reduced. [Figure 3A] This is a perspective view of one embodiment of a delivery device. [Figure 3B] Figure 3A is a partial cutaway view of one embodiment of the delivery device, with a detailed view of the cannula portion of the delivery device. [Figure 4A] A perspective view of the needle of a delivery device, with the needle indicated by phantom lines to show the plunger of the delivery device. [Figure 4B] Figure 4A is a schematic diagram of the plunger having a plunger seal. [Figure 4C] This is a perspective view of a needle in another embodiment of a delivery device, which is retractably positioned inside the cannula portion of the delivery device. [Figure 4D] Figure 4C is a cross-section diagram of the needle. [Figure 5]It is a partial cutaway view of a needle translation screw of one embodiment of a delivery device connected to a needle. [Figure 6] It is a partial cutaway view of a plunger translation screw of one embodiment of a delivery device connected to a plunger. [Figure 7A] It is a partial cutaway view of the delivery device of Figure 3A in a pre-delivery configuration. [Figure 7B] It is a view showing the delivery device of Figure 7A in a post-delivery configuration. [Figure 8] It is a perspective view of a planetary gear system of one embodiment of a delivery device. [Figure 9] It is another perspective view of the planetary gear system of Figure 8, with some components hidden from view. [Figure 10A] It is a cross-sectional view of a delivery device undergoing a loading process, according to one embodiment. [Figure 10B] It is a cross-sectional view of the delivery device of Figure 10A undergoing a flushing process, according to one embodiment. [Figure 10C] It is a cross-sectional view of the delivery device of Figure 10B in a loaded and primed state. [Figure 11] It is a perspective view of an indicator assembly according to one embodiment. [Figure 12] It is a view showing a stereotactic frame for use with a delivery device, according to one embodiment. [Figure 13] It is a flowchart of a method for preparing and priming a delivery device for use, according to one embodiment. [Figure 14] It is a flowchart of a method for using a delivery device, according to one embodiment. DETAILED DESCRIPTION OF EMBODIMENTS

[0018] In some conventional delivery devices, the device is inserted into the tissue, reaches the target site, the therapeutic substance is dispensed from the device into the target site, and then the device is withdrawn from the target site. As discussed in more detail below, the inventors have recognized that some of these conventional delivery devices experience unwanted backflow of the therapeutic substance from the target site when it is injected into the target site. The inventors have also recognized that in some conventional cell delivery devices, the cells delivered in the fluid solution held within the device experience a "cell sedimentation" effect, in which cells may aggregate within the device, for example, due to gravity. Cell sedimentation can result in the delivery of cells at non-uniform concentrations, which can cause fluctuations in cell seeding density. The inventors have also recognized that some conventional delivery devices do not restrict the user from rapidly dispensing the therapeutic substance. The inventors have recognized that a rapid dispensing rate can have adverse effects on the therapeutic substance. For example, in cell delivery, a fast discharge rate can reduce cell viability, for instance, due to damage to cells through shear stress. The inventors also recognize that a fast discharge rate can cause unnecessary tissue trauma. In some conventional delivery devices, the therapeutic substance is backloaded into the device. The inventors also recognize that backloading may require the therapeutic substance to traverse a long path through the device before reaching the delivery end. Due to the long travel distance, some of the therapeutic substance may remain trapped within the delivery device's path instead of being delivered, potentially resulting in waste of the therapeutic substance. Furthermore, in some conventional devices, the path may include changes in diameter and / or non-smooth transitions, either of which could expose the therapeutic substance to adverse effects.

[0019] The inventors recognized the need for a delivery device that addresses some or all of the problems of conventional delivery devices described above.

[0020] Some embodiments described herein include a delivery device for delivering a therapeutic substance via a volumetric transfer configuration, in which a plunger moves through a needle lumen and ejects the therapeutic substance out of the needle. In some embodiments, the therapeutic substance to be delivered is cells or other particles having a specific diameter. However, it should be recognized that the therapeutic substance is not limited to cells or particles. Wherever discussed hereafter, “cells” may be replaced with any other therapeutic substance as appropriate.

[0021] In one embodiment, the delivery device may be configured to reduce backflow of the therapeutic substance from the target site to the outside of the target site during the injection of the therapeutic substance into the target site. In some embodiments, the needle may be positioned to retract while the plunger advances. The needle is capable of creating a cavity in the tissue for the therapeutic substance. As the therapeutic substance is discharged from the needle, the needle retracts, thereby providing a certain volume of space in the created cavity for the therapeutic substance to reside.

[0022] Figure 1 illustrates this backflow concept via a delivery device 400 having an outer cannula 410 and a needle 500. The outer cannula 410 and needle 500 of the delivery device are inserted into tissue 210, and the needle 500 forms a cavity 211 within the tissue 210. The therapeutic substance 180 is being delivered to a target site 215. Since the target site 215 is occupied by the needle 500, the therapeutic substance 180 may be pushed upward 183 between the tissue cavity 211 and the delivery device 400 (instead of occupying the target site 215).

[0023] In contrast, Figure 2 is a schematic diagram of one embodiment of a delivery device according to the embodiments described herein, in which the potential backflow problem described above can be reduced. The delivery device includes an outer shaft 40, a needle 50 movable within the outer shaft 40, and a plunger 60 movable within the needle 50. As the plunger 60 advances distally 201, discharging the therapeutic substance 180 out of the needle 50 toward the target site 215, the needle 50 can simultaneously retract proximal out of the cavity 211 202. Although we do not wish to be constrained by theory, the withdrawal of the needle while discharging the therapeutic substance from the needle can create a space of a certain volume for the therapeutic substance to occupy, which can help reduce backflow of the therapeutic substance out of the target site 215.

[0024] In one embodiment, the delivery device may be configured to help reduce cell or particle sedimentation within the needle lumen. In some embodiments, the diameter of the needle lumen is less than 1 mm. In some embodiments, the ratio of the needle lumen diameter to the cell or particle diameter is less than 100:1.

[0025] In one embodiment, the delivery device may be configured to help the user control the dispensing rate of the therapeutic substance. For some therapeutic substances (e.g., certain types of cells), a slower dispensing rate may help reduce shear or other harmful effects on the cells, which may result in a higher viability of the delivered cells. A slower dispensing rate may also reduce the risk of brain tissue injury. In some embodiments, the device actuator is a rotary actuator. In some embodiments, multiple full turns of the rotary actuator are required to deliver the total target volume.

[0026] In one embodiment, the delivery device may be configured to improve dose assurance. In some embodiments, the therapeutic substance is contained within a needle lumen, which is relatively small and has a constant diameter. In the case of cells, such an arrangement can help the cells move in conjunction with their fluid solution, which can help ensure delivery of a larger portion of the cells. In some embodiments, such an arrangement can help reduce cell sedimentation.

[0027] In one embodiment, a delivery device may be configured to help reduce the waste of therapeutic material that may occur during loading of the material into the delivery device. The inventors have recognized that in some delivery devices in which the material is backloaded, a portion of the material may be lost due to the long travel distance required from the loading end of the device to the discharge end of the device. The inventors have recognized that frontloading the delivery device instead can help reduce the waste of therapeutic material. Therefore, in some embodiments, the delivery device is configured to be frontloaded with the therapeutic material. In some embodiments, the delivery device may include an air vent configuration to enable frontloading. In some embodiments, the delivery device may include a configuration for priming the system after the therapeutic material has been loaded in order to remove air from the delivery device before use in order to prevent the injection of air into the target site.

[0028] According to one embodiment, the delivery device may include an indicator comprising only mechanical components. Such an arrangement can make the delivery device more portable and easier to sterilize due to the absence of electrical components.

[0029] In one embodiment, the delivery device is used in conjunction with a stereotactic frame (for example, for neurosurgical applications). In some embodiments, the delivery device may be sized and shaped to fit with an existing stereotactic frame.

[0030] Looking at the exemplary embodiments in the figures, Figure 3A is a perspective view of one embodiment of the delivery device 1, and a partial cutaway view with the internal components of the delivery device is shown in Figure 3B. The delivery device has a cannula portion 9 (through which the substance is extruded), a housing 10, a handle 20, and a device actuator 30. As can be seen in the detailed view in Figure 3B, the cannula portion 9 can include multiple components housed in each other. Moving from the outermost component to the innermost component of the cannula portion 9, the cannula portion 9 can include an outer shaft 40, a needle 50 within the outer shaft 40, and a plunger 60 within the needle 50.

[0031] The outer shaft 40 has a shaft lumen 41 through which the needle 50 is movable. The needle 50 has a needle lumen 51 through which the plunger 60 is movable. The operation of the device actuator 30 can cause the plunger 60 to move distally 8 through the shaft lumen 41. When the therapeutic material is loaded into the needle lumen 51, the movement of the plunger 60 distally 8 through the needle lumen 51 actively displaces the therapeutic material out of the needle lumen 51 and thus delivers the therapeutic material.

[0032] As seen in Figure 3A, the outer shaft 40 may include a plurality of segments having stepped outer diameters arranged sequentially along the longitudinal axis 4 of the device. The stepped outer diameters of the plurality of segments increase along the longitudinal axis 4 of the device from the distal end to the proximal end of the outer shaft 40. In one embodiment, one of the plurality of segments may have a first outer diameter or a first range outer diameter. Furthermore, another of the plurality of segments, adjacent to and located proximal to one of the plurality of segments, may have a second outer diameter or a second range outer diameter, where the second outer diameter is greater than the first outer diameter, and the second range outer diameter is greater than the first range outer diameter and does not overlap with the first range outer diameter. Furthermore, the outer shaft 40 may include end faces that define a step between one of the plurality of segments and another of the plurality of segments. The end faces may project radially outward from the longitudinal axis 4 of the device. Alternatively, the end face may be formed as a chamfered surface that protrudes in the proximal direction of the device at an angle of less than 90 degrees from the longitudinal axis 4 of the device.

[0033] The outer shaft 40 may be formed from a material such as stainless steel. Other materials may be used to form the outer shaft 40. For example, the outer shaft 40 may be formed from an MRI-compatible material (e.g., ceramic, glass, or rigid polymer). Alternatively, the outer shaft 40 may also be formed from a non-MRI-compatible material if such compatibility is not required during the use of the device and / or if other factors such as cost and reusability take precedence.

[0034] As can be seen in Figure 4A (Figure 4A shows the distal portions of the needle 50 and plunger 60), the needle 50 includes a needle tip 55 that defines a needle opening 58 through which the therapeutic material is discharged. The needle tip 55 may be formed to have a chamfered outer surface that connects the plane containing the needle opening 58 to a portion of the needle 50 proximal to the needle tip 55 along the longitudinal axis 4 of the device. The needle 50 may be formed from a material such as stainless steel, glass, ceramic, or rigid polymer.

[0035] Figure 4C is a perspective view of the needle 50 according to another embodiment. Figure 4D is a cutaway view of the needle 50. The needle tip 55 of the needle 50 may be formed to have a flat end face defining the needle opening 58. The flat end face may be positioned on a plane perpendicular to the longitudinal axis 4 of the device. Although not shown in Figures 4C and 4D, the end face may be positioned on a plane that forms an angle not perpendicular to the longitudinal axis 4 of the device. Alternatively, the needle tip 55 may be formed to have a chamfered outer surface, as shown in Figure 4A.

[0036] As can be seen in Figure 4D, the needle 50 may include a needle tube 53 defining a needle lumen 51. The needle tube 53 may be formed from a material such as stainless steel, glass, ceramic, or rigid polymer. More specifically, the needle tube 53 may be formed from a material such as polyimide-coated glass. The needle 50 may further include a ferrule 54 attached to a portion of the needle tube 53. The ferrule 54 may be attached to a portion of the needle tube 53 by adhesive or other means. The ferrule 54 may be formed from a material selected to reinforce the portion of the needle tube 53 to which the ferrule 54 is attached. For example, the ferrule 54 may be formed from a material such as stainless steel. Figure 4D shows that the ferrule 54 is attached to a portion of the needle tube 53 that extends along the longitudinal axis 4 from the most distal end of the needle tube 53 to the proximal portion of the needle tube 53. Furthermore, the ferrule 54 may be attached to a portion of the needle tube 53 that extends along the longitudinal axis 4 from a first part of the needle tube 53 proximal to the distal end of the needle tube 53 to a second part of the needle tube 53 proximal to the first part. The length of the ferrule 54 along the longitudinal axis 4 is selected to be longer than the maximum length of the portion of the needle tube 53 that can extend distally along the longitudinal axis 4 beyond the opening of the outer shaft 40 outward from the shaft lumen 41, thereby reinforcing that portion of the needle tube 53.

[0037] As seen in Figures 4A and 4B, the plunger 60 includes a plunger seal 68, which provides a seal to the needle lumen 51 while allowing the plunger 60 to move through the needle lumen 51. In some embodiments, the plunger seal 68 has an outer diameter larger than the outer diameter of the rest of the plunger body 61. The length of the plunger seal 68 may be selected to ensure that the therapeutic material loaded into the portion of the needle lumen 51 between the needle opening 58 and the distal end of the plunger seal 68 does not advance proximal beyond the plunger seal 68 into another portion of the needle lumen 51 proximal to the plunger seal 68. Furthermore, the length of the plunger seal 68 may be selected so that when the plunger 60 is advanced to its most distal position in the needle lumen 51, the plunger seal 68 acts to close a vent 59 provided within the wall portion 57 of the needle 50. Such a length of the plunger seal 68 is selected to ensure that when the distal end of the plunger 60 is advanced beyond the vent 59, the vent 59 remains closed by the plunger seal 68, preventing liquid from entering the needle lumen 51 through the vent 59 and from advancing beyond the plunger seal 68 into a portion of the needle lumen 51 distal to the plunger seal 68, as well as preventing liquid in a portion of the needle lumen 51 distal to the plunger seal 68 from advancing beyond the plunger seal 68 and from advancing into a portion of the needle lumen 51 proximal to the plunger seal 68.

[0038] In some embodiments, the distal portion of the plunger body 61 may be housed within a plunger seal 68. The plunger seal 68 may be formed as a heat-shrinkable seal on the plunger body 61. Alternatively, the plunger seal 68 may be formed as a polymer coating through deposition or coating techniques. In other embodiments, the plunger body 61 is not housed within the plunger seal 68, and the two components are connected together. In yet another embodiment, the plunger body 61 and the plunger seal 68 may be formed as separate components.

[0039] In one embodiment, the needle may be positioned to retract while the therapeutic substance is being dispensed from the needle. In some embodiments, during use, the needle is inserted into the tissue and reaches the desired target site. The insertion of the needle can create a cavity within the tissue. As the therapeutic substance is dispensed from the needle, the needle retracts simultaneously, thereby providing a certain volume of space for the therapeutic substance to reside. The inventors have recognized that such a position can help reduce the backflow of the therapeutic substance from the target site back through the channel formed in the tissue by the delivery device.

[0040] In embodiments where the delivery device uses a volumetric transfer delivery configuration (for example, a plunger that moves distally through the needle lumen to expel therapeutic material from the needle), the needle and plunger can move simultaneously in opposite directions in response to the operation of the device actuator. That is, the operation of the device actuator can cause the needle to retract proximal while the plunger advances distally.

[0041] As used herein, the distal end of a delivery device is the end through which the therapeutic substance is delivered. The proximal end of a delivery device is the end of the device opposite the distal end. For illustrative purposes, Figure 3A shows the proximal end 2 and distal end 3 of a delivery device 1.

[0042] As used herein, the proximal direction is the direction pointing from the distal end of the delivery device toward the proximal end. The distal direction is the direction pointing from the proximal end of the delivery device toward the distal end. For illustrative purposes, Figure 3A shows the proximal direction 6 and the distal direction 8.

[0043] In some embodiments, the operation of the device actuator 30 causes the plunger 60 to advance distally 8 and the needle 50 to retract simultaneously proximal 6. In some embodiments, the simultaneous movement of the plunger and needle in opposite directions is achieved through the arrangement of a translation screw mounted in a threaded passage having threads facing opposite directions.

[0044] As shown in Figure 3B, the delivery device 1 may include a needle translation screw 52 attached to a needle 50 and a plunger translation screw 62 attached to a plunger 60. The needle translation screw 52 is mounted in a first threaded passage 56, and the plunger translation screw 62 is mounted in a second threaded passage 66. The threads of the first threaded passage 56 are oriented in the opposite direction to the threads of the second threaded passage 66. For example, the first threaded passage 56 may have a right-hand thread, while the second threaded passage 66 may have a left-hand thread, or vice versa. The device actuator 30 can be operated to impart rotation to each of the first threaded passage 56 and the second threaded passage 66.

[0045] As shown in Figure 3B, the needle translation screw 52 and the plunger translation screw 62 can be mounted on guide rails 151 and 153. The guide rails can extend through the delivery device 1 in a direction parallel to the longitudinal axis 4 of the device and can be fixed to the housing 10. As shown in Figure 5, the needle translation screw 52 can include a guide rail lumen 152, through which the guide rails 151 and 153 pass. The needle translation screw 52 can freely translate linearly along the guide rails 151 and 153. As shown in Figure 6, the plunger translation screw 62 can include a guide rail lumen 162, through which the guide rails 151 and 153 pass. The plunger translation screw 62 can freely translate linearly along the guide rails 151 and 153.

[0046] Guide rails 151 and 153 prevent the needle translation screw 52 from rotating with the first threaded passage 56 when the first threaded passage rotates. As a result, due to the direction of the threads in the first threaded passage 56 and the presence of the guide rails passing over the needle translation screw 52, ​​the rotation of the first threaded passage 56 causes the needle translation screw 52 to translate through the first threaded passage 56. In the exemplary embodiment shown in Figure 3B, the needle translation screw 52 moves in the proximal direction 6 when the device actuator 30 is actuated. With the needle 50 attached to the needle translation screw 52, ​​the proximal movement of the needle translation screw 52 causes the needle 50 to move in the proximal direction 6, and thus causes the needle to retract.

[0047] Similarly, the guide rails 151 and 153 prevent the plunger translation screw 62 from rotating with the second threaded passage 66 when the second threaded passage rotates. As a result, due to the orientation of the threads in the second threaded passage 66 and the presence of the guide rails passing through the plunger translation screw 62, the rotation of the second threaded passage 66 causes the plunger translation screw 62 to translate through the second threaded passage 66. In the exemplary embodiment shown in Figure 3B, the plunger translation screw 62 moves distally 8 when the device actuator 30 is activated. With the plunger 60 attached to the plunger translation screw 62, the distal movement of the plunger translation screw 62 causes the plunger to move distally 8, thereby expelling the therapeutic material out of the needle opening.

[0048] As shown in detail in Figure 5, the needle 50 is connected to the needle translation screw 52. The needle 50 can extend at least partially into the screw lumen 53. The needle 50 can be attached to the needle translation screw 52 via any suitable arrangement (e.g., adhesive (e.g., epoxy or UV adhesive), mechanical interlock, interference fit, welding the components together, etc.), or the needle 50 and the needle translation screw 52 can be formed integrally with each other.

[0049] As used herein, parts that are "integrally formed" with respect to each other mean that the parts are formed as a single component, thereby being formed from a single monolithic component (for example, being cast simultaneously as a single piece, such as by die casting or injection molding, or being cut from a single material, such as by stamping or die cutting).

[0050] As shown in detail in Figure 6, the plunger 60 is connected to the plunger translation screw 62. The plunger 60 can extend at least partially into the screw lumen 63. The plunger 60 can be attached to the plunger translation screw 62 via any suitable arrangement as discussed above with respect to the needle 50 and the needle translation screw 52.

[0051] In some embodiments, the needle 50 and the needle translation screw 52 attached to the needle 50, and / or the plunger 60 and the plunger translation screw 62 attached to the plunger 60, may be removed from the housing 10 and replaced with another needle and another needle translation screw attached to the other needle, and / or another plunger and another plunger translation screw attached to the other plunger. The other needle and another needle translation screw may be positioned in the housing 10 so as to be translated through a first threaded passage 56, and the other plunger and another plunger translation screw may be positioned in the housing 10 so as to be translated through a second threaded passage 66. The other needle may be a replacement for the needle 50 and have similar physical dimensions (e.g., the same needle lumen size) and similar functionality (e.g., the same amount of advance allowed) as the needle 50. Alternatively, another needle may have different physical dimensions (e.g., different needle lumen sizes) and different functions (e.g., allow for different amounts of advancement) than needle 50.

[0052] Figure 7A shows the delivery device in its pre-delivery configuration, and Figure 7B shows the delivery device in its post-delivery configuration. At the end of delivery, the needle translation screw 52 is translated proximally 6 through the first threaded passage 56, thereby retracting the needle, and the plunger translation screw 62 is translated distally 8 through the second threaded passage 66, thereby advancing the plunger in the deployment direction.

[0053] In some embodiments, after delivery into the volume of space within the tissue generated by the needle, the therapeutic material occupies a portion of the volume of space. In some embodiments, the therapeutic material occupies a therapeutic material volume that is at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, or 60% of the volume of space. In some embodiments, the therapeutic material occupies a therapeutic material volume that is about 70%, 60%, 50%, 40%, 30%, 25%, 20%, 15%, 10%, or 5% or less, or equal to such a volume. Combinations of the ranges referenced above are also possible. In some embodiments, the therapeutic material occupies a therapeutic material volume that is between about 5% and about 60%, about 5% and about 50%, about 5% and about 40%, about 5% and about 30%, or about 5% and about 25% of the volume of space.

[0054] In one embodiment, the diameter of the needle lumen is sized to suit the properties of the therapeutic substance. In some embodiments, the therapeutic substance contains cells or other particles having a specific diameter. In one embodiment, the diameter of the needle lumen is close in size to the diameter of the cells or particles of the therapeutic substance. For example, in some embodiments, the ratio of the needle lumen diameter to the diameter of the cells or particles is less than 100:1. In some embodiments, such an arrangement can help reduce cell or particle sedimentation within the needle lumen. In some embodiments, such an arrangement can help cells move in conjunction with their fluid solution, which can help ensure the delivery of larger portions of the cells. Such an arrangement can help improve dose assurance.

[0055] In some embodiments, the delivery device is configured to deliver cells, which are nerve cells. In some embodiments, the cells can be dopaminergic neurons, and in some embodiments, iPSC-derived dopaminergic neurons. However, the delivery device can deliver to other types of cells (e.g., mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells or induced pluripotent stem cells, erythrocytes, platelets, chondrocytes, skin cells, immune cells (e.g., tumor-infiltrating lymphocytes, viral-reconstituted T cells, dendritic cells, regulatory T cells, macrophages), neural crest stem cells, neurons, glia, smooth muscle, cardiac tissue, chondrocytes, osteocytes, glial restriction progenitor cells, astrocytes, oligodendrocytes, neuroblasts, megakaryoblasts, megakaryocytes, monoblasts, monocytes, macrophages, myeloid dendritic cells, proerythroblasts, erythroblasts, normalblasts, reticulocytes, platelets, myeloblasts, progranulocytes, neutrophilous myelocytes, neutrophilous zonate cells, neutrophils, eosinophilic myelocytes, eosinophilic zonate cells, eosinophils, basophilic myelocytes, basophilic zonate cells, basophils, committed lymphoid progenitor cells) It should be recognized that it may be used to deliver projenitors, pre-NK cells, NK lymphoblasts, NK cells, thymocytes, T-lymphoblasts, T-cells, plasmacytoid dendritic cells, pre-B cells, B-lymphoblasts, B-cells, plasma cells, osteoblasts, chondrocytes, myoblasts, myotubes, fibroblasts, adipocytes, mesoderm, ectoderm, primordial germ cells, sperm, eggs, embryonic endoderm, or any other suitable type of cell.

[0056] In some embodiments, the therapeutic substance contains a cell concentration of at least about 50,000 cells / μL, at least about 100,000 cells / μL, at least about 200,000 cells / μL, at least about 300,000 cells / μL, at least about 400,000 cells / μL, or at least about 500,000 cells / μL. In some embodiments, the therapeutic substance contains a cell concentration of about 500,000 cells / μL or less, about 400,000 cells / μL or less, about 300,000 cells / μL or less, about 200,000 cells / μL or less, about 100,000 cells / μL or less, or about 50,000 cells / μL or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, the therapeutic substance contains cell concentrations ranging from approximately 50,000 cells / μL to approximately 500,000 cells / μL, or from approximately 100,000 cells / μL to approximately 400,000 cells / μL, or from approximately 200,000 cells / μL to approximately 300,000 cells / μL.

[0057] In some embodiments, the needle lumen can have a diameter of at least about 0.05 mm, at least about 0.1 mm, at least about 0.15 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, or at least about 0.5 mm. In some embodiments, the needle lumen can have a diameter of about 1 mm or less, about 0.95 mm or less, about 0.9 mm or less, about 0.85 mm or less, about 0.8 mm or less, about 0.75 mm or less, about 0.7 mm or less, about 0.65 mm or less, about 0.6 mm or less, about 0.55 mm or less, about 0.5 mm or less, about 0.45 mm or less, about 0.4 mm or less, about 0.35 mm or less, about 0.3 mm or less, about 0.25 mm or less, about 0.2 mm or less, about 0.15 mm or less, or about 0.1 mm or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, the needle lumen can have a diameter of about 0.1 mm to about 1 mm, or about 0.15 mm to about 0.9 mm, or about 0.2 mm to about 0.8 mm, or about 0.2 mm to about 0.7 mm, or about 0.2 mm to about 0.6 mm, or about 0.2 mm to about 0.5 mm, or about 0.2 mm to about 0.4 mm, or about 0.25 mm to about 0.3 mm.

[0058] In some embodiments, the cells or particles of the therapeutic material can have a diameter of at least about 400 nm, at least about 1 micron, at least about 2 microns, at least about 4 microns, at least about 6 microns, at least about 8 microns, at least about 9 microns, at least about 10 microns, at least about 11 microns, at least about 12 microns, at least about 13 microns, at least about 14 microns, at least about 15 microns, at least about 16 microns, at least about 17 microns, at least about 18 microns, at least about 19 microns, at least about 20 microns, at least about 25 microns, at least about 30 microns, at least about 40 microns, at least about 50 microns, at least about 70 microns, at least about 100 microns, at least about 200 microns, or at least about 500 microns. In some embodiments, cells or particles can have diameters of approximately 500 microns or less, approximately 300 microns or less, approximately 200 microns or less, approximately 150 microns or less, approximately 100 microns or less, approximately 90 microns or less, approximately 80 microns or less, approximately 70 microns or less, approximately 60 microns or less, approximately 50 microns or less, approximately 40 microns or less, approximately 30 microns or less, approximately 20 microns or less, approximately 19 microns or less, approximately 18 microns or less, approximately 17 microns or less, approximately 16 microns or less, approximately 15 microns or less, approximately 14 microns or less, approximately 13 microns or less, approximately 12 microns or less, approximately 11 microns or less, approximately 10 microns or less, approximately 9 microns or less, approximately 8 microns or less, approximately 7 microns or less, approximately 6 microns or less, approximately 5 microns or less, approximately 4 microns or less, approximately 2 microns or less, or approximately 1 micron or less. Combinations of the ranges referenced above are also possible.For example, in some embodiments, cells or particles can have diameters of approximately 400 nm to approximately 500 microns, or approximately 1 micron to approximately 200 microns, or approximately 5 microns to approximately 150 microns, or approximately 8 microns to approximately 120 microns, or approximately 8 microns to approximately 100 microns, or approximately 8 microns to approximately 50 microns, or approximately 8 microns to approximately 40 microns, or approximately 8 microns to approximately 30 microns, or approximately 8 microns to approximately 20 microns, or approximately 10 microns to approximately 15 microns.

[0059] In some embodiments, the ratio of needle lumen diameter to cell or particle diameter is at least about 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, 150:1, 200:1, 300:1, 400:1, or 500:1. In some embodiments, the ratio of needle lumen diameter to cell or particle diameter is about 500:1, 400:1, 300:1, 200:1, 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, or 10:1 or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, the ratio of the needle lumen diameter to the cell or particle diameter is about 10:1 to about 500:1, or about 50:1 to about 300:1, or about 60:1 to about 200:1, or about 70:1 to about 150:1, or about 80:1 to about 120:1, or about 90:1 to about 110:1.

[0060] In some embodiments, the entire volume of the therapeutic substance loaded into the delivery device is contained solely within the needle lumen of the delivery device. In some embodiments, the needle lumen has a constant diameter along the entire length of the needle. In the case of cells, such an arrangement can help the cells move in conjunction with their fluid solution, which can help ensure the delivery of a larger portion of the cells. Such an arrangement can help improve dose assurance. In some embodiments, such an arrangement can help reduce cell sedimentation.

[0061] In some embodiments, the density of the fluid solution in which cells and / or particles are supplied is selected to increase the buoyancy acting on the cells and / or particles. For example, the density of the fluid solution may be selected to approach a known density, taking into account the known density of the cells and / or particles to be delivered, thereby increasing the buoyancy acting on the cells and / or particles and making it possible to achieve or approach neutral buoyancy. Furthermore, the density of the fluid solution may be selected to approach a known density, taking into account the known density of the cells and / or particles to be delivered, thereby increasing the buoyancy acting on the cells and / or particles, thereby bringing the concentration of cells and / or particles in the fluid solution discharged by the delivery device closer to a predetermined concentration. In other embodiments, the viscosity of the fluid solution may be selected to reduce cell sedimentation, thereby bringing the concentration of cells and / or particles in the fluid solution discharged by the delivery device closer to a predetermined concentration. In yet another embodiment, both the density and viscosity of the fluid solution may be selected in the manner described above. Such arrangements may further help to reduce cell sedimentation.

[0062] In one embodiment, the volume of space through which the plunger travels in response to device operation (and / or the volume of therapeutic material discharged by the delivery device) is close to or substantially the same as the volume of space through which the needle travels during needle retraction. In some embodiments, the volume of space through which the plunger travels (and / or the volume of therapeutic material discharged by the delivery device) is within at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, or 50 percent of the volume of space through which the needle travels. In some embodiments, the volume of space through which the plunger travels (and / or the volume of therapeutic material dispensed by the delivery device) is among 50, 40, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 percent of the volume of space through which the needle travels. Combinations of the ranges referenced above are also possible. In some embodiments, the volume of space through which the plunger travels (and / or the volume of therapeutic material dispensed by the delivery device) is among 1 to 50 percent, 1 to 40 percent, 1 to 30 percent, 1 to 25 percent, 1 to 20 percent, 1 to 15 percent, 1 to 10 percent, or 1 to 5 percent of the volume of space through which the needle travels.

[0063] In volumetric transport configurations, the inventors recognized that the plunger travel distance can determine the delivered volume. However, in embodiments where the needle retracts as the plunger advances, the inventors recognized that the needle travel distance may not necessarily match the plunger travel distance in all embodiments. In some embodiments, the needle travel distance can be determined by the anatomical structure of the target site.

[0064] In one embodiment, the needle and plunger can experience different travel distances during delivery. Such an arrangement can allow the plunger to travel a specific distance to deliver a desired volume of therapeutic material, while simultaneously allowing the needle to travel a distance appropriate to the target anatomical structure.

[0065] In some embodiments, different travel distances for the plunger and needle are achieved via differences in the number of threads per inch of the threaded passage associated with the translation screw, or via a gear system, or, in some embodiments, via a combination of both.

[0066] In the exemplary embodiment shown in Figure 3B, the first threaded passage 56 (the passage through which the needle translation screw 52 translates) has a first number of threads. The second threaded passage 66 (the passage through which the plunger translation screw 62 translates) has a second number of threads different from the first number of threads. In some embodiments, such as the embodiment shown in Figure 3B, the needle travel distance is shorter than the plunger travel distance. To achieve this difference in travel distance, the first threaded passage 56 has a greater number of threads than the second threaded passage 66 (for example, a higher number of threads per inch). Thus, the actuation of the device actuator 30 causes the plunger translation screw 62 to translate a greater distance than the needle translation screw. As a result, the plunger travels a greater distance than the needle.

[0067] In some embodiments, the ratio of the number of threads in the first screw thread to the number of threads in the second screw thread is at least about 1.5:1, at least about 1.6:1, at least about 1.7:1, at least about 1.8:1, at least about 1.9:1, at least about 2:1, at least about 2.1:1, at least about 2.2:1, at least about 2.3:1, at least about 2.4:1, at least about 2.5:1, at least about 2.6:1, at least about 2.7:1, at least about 2.8:1, at least about 2.9:1, at least about 3:1, at least about 3.1:1, at least about 3.2:1, at least about 3.3:1, at least about 3.4:1, at least It is possible to have a ratio of approximately 3.5:1, at least approximately 3.6:1, at least approximately 3.7:1, at least approximately 3.8:1, at least approximately 3.9:1, at least approximately 4:1, at least approximately 4.2:1, at least approximately 4.4:1, at least approximately 4.6:1, at least approximately 4.8:1, at least approximately 5:1, at least approximately 6:1, at least approximately 7:1, at least approximately 8:1, at least approximately 9:1, at least approximately 10:1, at least approximately 11:1, at least approximately 12:1, at least approximately 13:1, at least approximately 14:1, at least approximately 15:1, at least approximately 16:1, at least approximately 18:1, or at least approximately 20:1. In some embodiments, the ratio of the number of threads in the first screw thread to the number of threads in the second screw thread is approximately 20:1 or less, approximately 18:1 or less, approximately 16:1 or less, approximately 14:1 or less, approximately 12:1 or less, approximately 10:1 or less, approximately 9:1 or less, approximately 8:1 or less, approximately 7:1 or less, approximately 6:1 or less, approximately 5:1 or less, approximately 4.5:1 or less, approximately 4:1 or less, approximately 3.9:1 or less, approximately 3.8:1 or less, approximately 3.7:1 or less, approximately 3.6:1 or less, approximately 3.5:1 or less, and approximately 3.4:1. The following ratios are possible: approximately 3.3:1 or less, approximately 3.2:1 or less, approximately 3.1:1 or less, approximately 3:1 or less, approximately 2.9:1 or less, approximately 2.8:1 or less, approximately 2.7:1 or less, approximately 2.6:1 or less, approximately 2.5:1 or less, approximately 2.4:1 or less, approximately 2.3:1 or less, approximately 2.2:1 or less, approximately 2.1:1 or less, approximately 2:1 or less, approximately 1.9:1 or less, approximately 1.8:1 or less, approximately 1.7:1 or less, approximately 1.6:1 or less, or approximately 1.5:1 or less. Combinations of the ranges referenced above are also possible.For example, in some embodiments, the ratio of the number of threads in the first screw thread to the number of threads in the second screw thread can be approximately 1.5:1 to approximately 20:1, or approximately 1.6:1 to approximately 14:1, or approximately 1.7:1 to approximately 10:1, or approximately 1.8:1 to approximately 9:1, or approximately 1.9:1 to approximately 8:1, or approximately 2:1 to approximately 7:1, or approximately 2.1:1 to approximately 6:1, or approximately 2.2:1 to approximately 5:1, or approximately 2.3:1 to approximately 4:1, or approximately 2.4:1 to approximately 3:1, or approximately 2.5:1 to approximately 2.7:1.

[0068] In the exemplary embodiment shown in Figure 3B, a gear system is additionally used to further reduce the needle's travel distance relative to the plunger's travel distance. As shown in Figures 8 and 9, the gear system is a planetary gear system 100 (also known as an epicyclic gear system). The planetary gear system 100 includes a solar gear 160, a planetary gear 114, and a ring gear 110.

[0069] The sun gear 160 is connected to the device actuator 30 and the second threaded passage 66 (which is associated with the plunger translation screw). As shown in Figure 3B, the sun gear 160, the device actuator 30, and the second threaded passage 66 are integrally formed as a single component. Also, one full rotation of the device actuator 30 results in one full rotation of the sun gear 160 and one full rotation of the second threaded passage 66. The planetary gear 114 rotates around the sun gear 160 and rotates within the ring gear 110. As shown in Figure 9, the planetary gear 114 is rotatably mounted on the carrier 150, which is connected to the first threaded passage 56 (which is associated with the needle translation screw). One full rotation of the carrier 150 results in one full rotation of the first threaded passage. The relationship between the sun gear 160 and the planetary gear 114 generates a gear ratio, where multiple rotations of the sun gear are required to achieve a single complete rotation of the carrier. As a result, the operation of the device actuator 30 results in more rotations of the second threaded passage 66 than of the first threaded passage 56, and this results in a greater travel distance of the plunger translation screw 62 and plunger 60 than the travel distance of the needle translation screw 52 and needle 50.

[0070] In some embodiments, the gear ratio between the solar gear 160 and the carrier 150 can be at least about 2:1, at least about 2.5:1, at least about 3:1, at least about 3.2:1, at least about 3.4:1, at least about 3.6:1, at least about 3.8:1, at least about 4:1, at least about 4.1:1, at least about 4.2:1, at least about 4.3:1, at least about 4.4:1, at least about 4.5:1, at least about 4.6:1, at least about 4.7:1, at least about 4.8:1, at least about 4.9:1, at least about 5:1, at least about 6:1, at least about 7:1, at least about 8:1, at least about 9:1, or at least about 10:1. In some embodiments, the gear ratio between the sun gear and the carrier can be approximately 10:1 or less, approximately 9:1 or less, approximately 8:1 or less, approximately 7:1 or less, approximately 6:1 or less, approximately 5:1 or less, approximately 4.9:1 or less, approximately 4.8:1 or less, approximately 4.7:1 or less, approximately 4.6:1 or less, approximately 4.5:1 or less, approximately 4.4:1 or less, approximately 4.3:1 or less, approximately 4.2:1 or less, approximately 4.1:1 or less, approximately 4:1 or less, approximately 3.8:1 or less, approximately 3.6:1 or less, approximately 3.4:1 or less, approximately 3.2:1 or less, approximately 3:1 or less, approximately 2.5:1 or less, and approximately 2:1 or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, the ratio of the solar gear to the carrier can be approximately 2:1 to approximately 10:1, or approximately 2.5:1 to approximately 9:1, or approximately 3:1 to approximately 8:1, or approximately 3.2:1 to approximately 7:1, or approximately 3.4:1 to approximately 6:1, or approximately 3.6:1 to approximately 5:1, or approximately 3.8:1 to approximately 4.8:1, or approximately 3.9:1 to approximately 4.6:1, or approximately 4:1 to approximately 4.5:1, or approximately 4.1:1 to approximately 4.4:1, or approximately 4.2:1 to approximately 4.3:1.

[0071] While planetary gears are used in the delivery device shown in the figure, this embodiment is not so limited, and it should be recognized that other types of gear systems may also be used, such as spur gears, helical gears, rack and pinion gears, bevel gears, miter gears, worm gears, screw gears, helical gears, hypoid gears, helical gears, internal gears, sawtooth gears, clock and pin gears, mutilated gears, hypocycloid gear systems, Geneva gears, or any other suitable gear system.

[0072] In the exemplary embodiment shown in Figure 3B, the delivery device 1 utilizes a combination of a gear system and a pair of threaded passages having different numbers of threads, allowing the plunger and needle to experience different travel distances in response to the operation of the device actuator 30. The combined arrangement results in a travel distance ratio between the plunger and the needle. In other embodiments, the delivery device can utilize a pair of threaded passages (or a gear system) without combining the two.

[0073] In some embodiments, the ratio of the travel distance between the plunger and the needle can be at least about 2:1, at least about 2.5:1, at least about 3:1, at least about 3.5:1, at least about 4:1, at least about 4.5:1, at least about 5:1, at least about 5.5:1, at least about 6:1, at least about 6.5:1, at least about 7:1, at least about 7.5:1, at least about 8:1, at least about 8.5:1, at least about 8.7:1, at least about 9:1, at least about 9.2:1, at least about 9.4:1, at least about 9.6:1, at least about 9.8:1, at least about 10:1, at least about 11:1, at least about 12:1, at least about 13:1, at least about 14:1, at least about 15:1, at least about 16:1, at least about 17:1, at least about 18:1, at least about 19:1, or at least about 20:1. In some embodiments, the ratio of the travel distance between the plunger and the needle is approximately 20:1 or less, approximately 18:1 or less, approximately 16:1 or less, approximately 14:1 or less, approximately 12:1 or less, approximately 11.8:1 or less, approximately 11.6:1 or less, approximately 11.4:1 or less, approximately 11.2:1 or less, approximately 11:1 or less, approximately 10.9:1 or less, approximately 10.8:1 or less, approximately 10.7:1 or less, approximately 10.6:1 or less, approximately 10.5:1 or less, approximately 10.4:1 or less, approximately 10.3: It is possible for the ratio to be 1 or less, approximately 10.2 to 1, 10.1 to 1 or less, approximately 10 to 1 or less, approximately 9.9 to 1 or less, approximately 9.8 to 1 or less, approximately 9.7 to 1 or less, approximately 9.6 to 1 or less, approximately 9.5 to 1 or less, approximately 9.4 to 1 or less, approximately 9.3 to 1 or less, approximately 9.2 to 1 or less, approximately 9.1 to 1 or less, approximately 9 to 1 or less, approximately 8.7 to 1 or less, approximately 8 to 1 or less, approximately 7 to 1 or less, approximately 6 to 1 or less, approximately 5 to 1 or less, approximately 4 to 1 or less, approximately 3 to 1 or less, or approximately 2 to 1 or less. Combinations of the ranges referenced above are also possible.For example, in some embodiments, the ratio of travel distance between the plunger and the needle is approximately 2:1 to approximately 20:1, or approximately 3:1 to approximately 18:1, or approximately 4:1 to approximately 16:1, or approximately 5:1 to approximately 14:1, or approximately 6:1 to approximately 13:1, or approximately 7:1 to approximately 12:1, or approximately 8:1 to approximately 11:1, or approximately 9:1 to approximately 10:1, or approximately 9.1 to approximately 10.9:1, or approximately 9.2 to approximately 10.8: 1. It is possible to set the ratio to approximately 9.3:1 to approximately 10.7:1, or approximately 9.4:1 to approximately 10.6:1, or approximately 9.5:1 to approximately 10.5:1, or approximately 9.6:1 to approximately 10.4:1, or approximately 9.7:1 to approximately 10.3:1, or approximately 9.8:1 to approximately 10.2:1, or approximately 9.9:1 to approximately 10.1:1, or approximately 10:1 to approximately 10.1:1, or approximately 7:1 to approximately 10:1, or approximately 8:1 to approximately 9:1.

[0074] In some embodiments, the travel distance of the plunger can be at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 180, 200, 250, or 300 mm. In some embodiments, the travel distance of the plunger can be about 300, 250, 200, 180, 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, or 10 mm or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, the travel distance of the plunger can be approximately 10 mm to 300 mm, 20 mm to 250 mm, 30 mm to 200 mm, 40 mm to 180 mm, 50 mm to 160 mm, 60 mm to 140 mm, 70 mm to 140 mm, 100 mm to 140 mm, or 120 mm to 140 mm.

[0075] According to one embodiment, the device actuator of a delivery device can be a rotatable actuator. In some embodiments, the rotatable device actuator can help slow down the dispensing rate of the therapeutic substance.

[0076] In some embodiments, as seen in Figure 3A, the device actuator 30 is rotatably mounted on the housing 10. In some embodiments, such as the exemplary embodiment in Figure 3A, the rotation axis of the device actuator is parallel to the longitudinal axis 4 of the delivery device 1. However, in other embodiments, the rotation axis of the device actuator can be perpendicular to the longitudinal axis of the delivery device. In some embodiments, the longitudinal axis of the delivery device is parallel to the outer shaft, needle, and / or plunger of the cannula portion.

[0077] In some embodiments, multiple full turns of the device actuator are required to deliver the total target volume. For example, in embodiments of a delivery device utilizing a volumetric transfer configuration with a plunger moving through a needle, multiple full turns of the device actuator may be required to move the plunger from its pre-delivery position to its post-delivery position for the maximum volume to be delivered. In some embodiments, to deliver the maximum volume, the post-delivery position of the distal end 65 of the plunger 60 (see Figure 3B) is at or near the needle opening 58 (see Figure 4A).

[0078] In the exemplary embodiment shown in Figure 3B, the number of threads in the second threaded passage 66 can determine how far the plunger translation screw 62 (and thus the plunger 60) moves with each rotation of the device actuator 30.

[0079] In some embodiments, the number of threads in the second threaded passage is at least about one thread per inch (TPI). It is possible that the TPI is at least approximately 4 TPI, at least approximately 4.4 TPI, at least approximately 4.6 TPI, at least approximately 4.8 TPI, at least approximately 5 TPI, at least approximately 5.1 TPI, at least approximately 5.2 TPI, at least approximately 5.3 TPI, at least approximately 5.4 TPI, at least approximately 5.5 TPI, at least approximately 5.6 TPI, at least approximately 5.7 TPI, at least approximately 5.8 TPI, at least approximately 5.9 TPI, at least approximately 6 TPI, at least approximately 6.1 TPI, at least approximately 6.2 TPI, at least approximately 6.3 TPI, at least approximately 6.4 TPI, at least approximately 6.5 TPI, at least approximately 7 TPI, at least approximately 8 TPI, at least approximately 9 TPI, at least approximately 10 TPI, at least approximately 12 TPI, at least approximately 14 TPI, at least approximately 20 TPI, at least approximately 40 TPI, at least approximately 60 TPI, or at least approximately 80 TPI. In some embodiments, the number of threads in the second threaded passage can be approximately 80 TPI or less, approximately 60 TPI or less, approximately 40 TPI or less, approximately 20 TPI or less, approximately 14 TPI or less, approximately 12 TPI or less, approximately 10 TPI or less, approximately 8 TPI or less, approximately 7 TPI or less, approximately 6.9 TPI ​​or less, approximately 6.8 TPI or less, approximately 6.7 TPI or less, approximately 6.6 TPI or less, approximately 6.5 TPI or less, approximately 6.4 TPI or less, approximately 6.3 TPI or less, approximately 6.2 TPI or less, approximately 6.1 TPI or less, approximately 6 TPI or less, approximately 6 TPI or less, approximately 5.9 TPI ​​or less, approximately 5.8 TPI or less, approximately 5.7 TPI or less, approximately 5.6 TPI or less, approximately 5.5 TPI or less, approximately 5.4 TPI or less, approximately 5.3 TPI or less, approximately 5.2 TPI or less, approximately 5.1 TPI or less, approximately 5 TPI or less, or approximately 4 TPI or less. Combinations of the ranges referenced above are also possible.For example, in some embodiments, the number of threads in the second threaded passage can be approximately 1 TPI to approximately 80 TPI, or approximately 4 TPI to approximately 14 TPI, or approximately 4.2 TPI to approximately 12 TPI, or approximately 4.4 TPI to approximately 10 TPI, or approximately 4.6 TPI to approximately 9 TPI, or approximately 4.8 TPI to approximately 8.6 TPI, or approximately 5 TPI to approximately 7 TPI, or approximately 5.2 TPI to approximately 6.8 TPI, or approximately 5.4 TPI to approximately 6.6 TPI, or approximately 5.6 TPI to approximately 6.4 TPI, or approximately 5.8 TPI to approximately 6.2 TPI, or approximately 5.9 TPI ​​to approximately 6.1 TPI, or approximately 6 TPI to approximately 6.1 TPI.

[0080] In some embodiments, to achieve the maximum delivery volume, the device actuator is rotated by at least 5, 10, 12, 14, 16, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 44, 46, 48, 50, 55, or 60 full rotations. In some embodiments, to deliver the maximum volume, the device actuator is rotated by 60, 50, 48, 46, 44, 42, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 22.5, 21, 20, 18, 16, 14, 12, 10, or 5 or fewer full rotations. Combinations of the ranges referenced above are also possible. For example, in some embodiments, to deliver the maximum volume, the device actuator is rotated only a total of 5 to 60, or 10 to 50, or 20 to 40, or 22 to 38, or 24 to 36, or 25 to 35, or 26 to 34, or 27 to 33, or 28 to 32, or 29 to 31, or 30 to 31, or 15 to 30 revolutions.

[0081] In other embodiments, the device actuator may be rotated only one full turn or less to deliver the maximum delivery volume. In some embodiments, to deliver the maximum delivery volume, the device actuator is rotated only about 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, or 360 degrees. In some embodiments, to achieve the maximum delivery volume, the device actuator is rotated only about 360, 340, 320, 300, 280, 260, 240, 220, 200, 180, 160, 140, 120, or 100 degrees or less. Combinations of the ranges referenced above are also possible. For example, in some embodiments, to deliver the maximum delivery volume, the device actuator is rotated only by about 100 degrees to about 360 degrees, or about 120 degrees to about 340 degrees, or about 160 degrees to about 300 degrees, or about 200 degrees to about 260 degrees.

[0082] In some embodiments, the maximum delivery volume is at least about 1 microliter, at least about 2 microliters, at least about 3 microliters, at least about 4 microliters, at least about 5 microliters, at least about 6 microliters, at least about 7 microliters, at least about 7.2 microliters, at least about 7.4 microliters, at least about 7.6 microliters, at least about 7.8 microliters, at least about 8 microliters, at least about 8.1 microliters, at least about 8.2 microliters, at least about 8.3 microliters, at least about 8.4 microliters, at least about 8.5 microliters, and at least about 8.6 microliters. It can be a microliter, at least about 8.7 microliters, at least about 8.8 microliters, at least about 8.9 microliters, at least about 9 microliters, at least about 9.5 microliters, at least about 10 microliters, at least about 11 microliters, at least about 12 microliters, at least about 13 microliters, at least about 14 microliters, at least about 15 microliters, at least about 20 microliters, at least about 30 microliters, at least about 100 microliters, at least about 1 mL, at least about 10 mL, at least about 100 mL, at least about 500 mL, or at least about 800 mL.In some embodiments, the maximum delivery volume is approximately 1000 mL or less, approximately 800 mL or less, approximately 500 mL or less, approximately 100 mL or less, approximately 10 mL or less, approximately 1 mL or less, approximately 100 microliters or less, or approximately 100 microliters or less, or approximately 90 microliters or less, or approximately 80 microliters or less, or approximately 70 microliters or less, or approximately 60 microliters or less, or approximately 50 microliters or less, or approximately 40 microliters or less, or approximately 30 microliters or less, or approximately 20 microliters or less, or approximately 15 microliters or less, or approximately 12 microliters or less, or approximately 10 microliters. It is possible for the volume to be less than or equal to approximately 9.9 microliters, or less than or equal to approximately 9.8 microliters, or less than or equal to approximately 9.7 microliters, or less than or equal to approximately 9.6 microliters, or less than or equal to approximately 9.5 microliters, or less than or equal to approximately 9.4 microliters, or less than or equal to approximately 9.3 microliters, or less than or equal to approximately 9.2 microliters, or less than or equal to approximately 9.1 microliters, or less than or equal to approximately 9 microliters, or less than or equal to approximately 8.8 microliters, or less than or equal to approximately 8.2 microliters, or less than or equal to approximately 8 microliters, or less than or equal to approximately 7 microliters, or less than or equal to approximately 6 microliters, or less than or equal to approximately 5 microliters. Combinations of the ranges referenced above are also possible.For example, in some embodiments, the maximum delivery volume can be 1 mL to about 1000 mL, or about 10 mL to about 800 mL, or about 100 mL to about 500 mL, or about 1 microliter to about 100 microliters, or about 2 microliters to about 60 microliters, or about 3 microliters to about 30 microliters, or about 4 microliters to about 20 microliters, or about 5 microliters to about 18 microliters, or about 6 microliters to about 16 microliters, or about 7 microliters to about 14 microliters, or about 8 microliters to about 10 microliters, or about 8.5 microliters to about 9.5 microliters, or about 8.9 microliters to about 9.1 microliters, or about 9 microliters to about 9.1 microliters.

[0083] While at least some of the exemplary embodiments discussed herein can be purely mechanical, it should be recognized that in other embodiments, the delivery device may be motorized. For example, in some embodiments, the delivery device may include a motor that is operated by a user to advance a plunger and / or retract a needle. In some embodiments, the delivery device may be controlled remotely using wireless communication. The delivery device may have a portable power supply and / or be adapted to receive power from an electrical outlet. In some embodiments, the delivery device may be connected to an external motor via a flexible torque cable.

[0084] In one embodiment, the therapeutic substance is front-loaded into the delivery device through the device's dispensing end. Such an arrangement can help reduce waste or loss of the therapeutic substance (for example, by avoiding the transfer of the substance through multiple components).

[0085] In some embodiments, the delivery device may include an air vent configuration to allow front loading. In some embodiments, drawing the therapeutic material into the needle lumen during loading of the delivery device displaces air from the needle lumen. In some embodiments, a vent is provided to allow the displaced air to be vented out of the needle lumen. In some embodiments, this vent configuration may help avoid or reduce pressurization of the therapeutic material and / or the needle lumen. In some embodiments, this vent configuration may help avoid competition between air and therapeutic material for volumetric space. In some embodiments, this vent configuration may help reduce the introduction of air bubbles into the therapeutic material.

[0086] In the exemplary embodiment shown in Figure 3B, the needle 50 includes a vent 59 in the form of a through-hole opening extending through the wall portion 57 of the needle 50. The vent 59 is open or closed based on the position of the plunger 60. As shown in Figure 3B, when the distal end 65 of the plunger 60 is distal to the vent 59, the vent 59 is closed. When the distal end 65 of the plunger 60 is proximal to the vent 59, the vent 59 is open.

[0087] Several front-loading sequences according to different embodiments are shown in Figures 10A to 10C. As shown in Figure 10A, with the vent 59 open, the therapeutic material 180 is moved into the needle lumen 51 through the needle opening 58 in the proximal loading direction 181. As the therapeutic material 180 moves into the needle lumen 51, the air that previously occupied the needle lumen 51 is vented into the shaft lumen 41 through the opened vent 59.

[0088] In some embodiments, the delivery device passively loads the therapeutic substance, and for example, the delivery device itself is not activated during loading. An active loading device (e.g., a pump) may be used to move the therapeutic substance into the needle lumen. The pump can be a syringe pump or any other suitable pump. In some embodiments, the therapeutic substance is transferred from the holder into the needle lumen.

[0089] Next, the vent 59 is closed, as shown in Figure 10B. In some embodiments, the user closes the vent 59 by operating the device actuator 30 to advance the plunger 60 distally until the distal end 65 of the plunger is distal to the vent 59.

[0090] In some embodiments, a flushing step is performed to remove air from the outer lumen in the space between the outer shaft and the needle. As shown in Figure 10B, the delivery device includes a flushing port 90. A flushing fluid 184 (e.g., implantation medium) is injected through the flushing port 90 in the flushing direction 185, and can also be injected through a valve 92, a channel 93, and an opening 49 in the outer shaft 40. The implantation medium can travel through the space between the outer shaft 40 and the needle 50, as indicated by arrow 182. The user can observe the flushing fluid exiting from the distal end 45 of the outer shaft 40, which indicates to the user that the device has been primed and is ready for delivery into the tissue. Figure 10C shows a primed device ready for delivery with the therapeutic material 180 loaded into the needle lumen, the plunger 60 covering the vent 59, and air flushed out of the cannula portion 9.

[0091] The inventors have recognized that an aspiration effect is generated when the cannula portion 9 is withdrawn from the tissue (the cannula portion 9 is inserted into the tissue) after the therapeutic substance has been discharged from the needle into the volume of space at the target site 215 created by the withdrawal of the needle. The aspiration effect can pull a portion of the therapeutic substance out of the target site 215, thereby reducing the amount of therapeutic substance delivered to the target site 215.

[0092] The delivery device may be configured to mitigate the aspiration effect experienced during the withdrawal of the cannula portion 9 from the tissue. For example, the valve 92 of the flushing port 90 may be configured to be set in the open position, exposing the inside of the cannula portion 9 and, in particular, the space between the outer shaft 40 and the needle 50 to atmospheric pressure, allowing the flushing fluid 184 to drain into the tissue when the cannula portion 9 is withdrawn from the tissue. The valve 92 may be configured to accept a device (e.g., an open needle), exposing the space between the outer shaft 40 and the needle 50 to atmospheric pressure, allowing the flushing fluid 184 to drain into the tissue when the cannula portion 9 is withdrawn from the tissue. Draining the flushing fluid 184 toward the target site 215 can counteract the aspiration effect and thereby mitigate the reduction in the dose of therapeutic substance delivered to the target site 215 when the cannula portion 9 is withdrawn from the tissue.

[0093] According to one embodiment, the delivery device may include an indicator comprising only mechanical components. Such an arrangement can make the delivery device more portable and / or easier to sterilize due to the absence of electrical components.

[0094] In some embodiments, a gearing system may be used to transmit an actuation force applied to a device actuator to move a component having an indicator that reflects the volume delivered and / or an indicator that reflects the state of the device (e.g., ready to be loaded with therapeutic material). One exemplary embodiment of a mechanical indicator is shown in Figure 11. The indicator configuration in Figure 11 uses a Geneva gear system 200. The Geneva gear system 200 includes a first drive wheel 230, which is capable of rotating in a 1:1 ratio with the device actuator 30. The first drive wheel 230 interacts with and drives a driven wheel portion 242 of a gear assembly 240. The gear assembly 240 also includes a drive wheel portion 244, which interacts with and drives a driven wheel portion 252 of an indicator gear 250. The indicator gear 250 also includes an indicator portion 254. As shown in Figures 3A and 3B, the indicator of the indicator portion 254 can be seen through the indicator window 255 of the delivery device. When the device actuator 30 is activated, the indicator portion 254 rotates to reflect the delivered volume.

[0095] In the exemplary embodiment shown in Figure 11, a Geneva gear system is used to link the device actuator 30 to the indicator portion 254, but it should be recognized that any other suitable gear system or force transmission system may be used. In some embodiments, the delivery device uses a digital display to indicate the delivery volume and / or convey any other suitable information.

[0096] In some embodiments, any one of the delivery devices described herein may be used with a stereotactic frame (for example, for neurosurgical applications). An exemplary example of a stereotactic frame is shown in Figure 12. The stereotactic frame 300 includes an arm 302 for receiving the delivery device. In some embodiments, the delivery device may be sized to physically fit with the stereotactic frame. In the exemplary embodiment shown in Figure 3A, the delivery device 1 includes a seating connector 80, which is sized to fit with the arm of the stereotactic frame. The seating connector of the delivery device may be held by the stereotactic frame. In some embodiments, the delivery device fits with a stereotactic frame from LEKSELL. However, it should be recognized that the embodiments are not so limited, and the delivery device may also fit with other stereotactic frames.

[0097] In some embodiments, the delivery device is compatible with a frameless positioning system. For example, the subject's head (including the targeted tissue) may be secured by a clamp (e.g., a standard Mayfield clamp). Furthermore, the delivery device may include a portion of a tracking system for tracking the position and angle of the delivery device. The tracking system may include one or more optical-based tracking systems and electromagnetic tracking systems. An optical-based tracking system may include one or more optical cameras, which are configured to track one or more identifiable structures incorporated into or provided with the delivery device, or to track one or more intrinsic optical wavelengths emitted from emitters incorporated into or provided with the delivery device. An optical-based tracking system may calculate the position and angle of the delivery device relative to the subject's head by utilizing techniques such as distance measurement using the principle of parallax, object recognition, and other image processing techniques. An electromagnetic tracking system may include one or more electromagnetic field emitters and one or more electromagnetic field detectors. One or more electromagnetic field emitters and one or more electromagnetic field detectors may be incorporated into or provided with the delivery device, or the other of the one or more electromagnetic field emitters and one or more electromagnetic field detectors may be positioned near the delivery device. An electromagnetic tracking system can calculate the position and angle of the delivery device relative to the subject's head based on known values ​​of the electromagnetic fields emitted by one or more electromagnetic field emitters and the electromagnetic fields detected by one or more electromagnetic field detectors. The position and angle of the delivery device calculated by the tracking system may be output as a visual guide to guide the insertion of the delivery device.Furthermore, the position and angle of the delivery device calculated by the tracking system may be output to a robotic system, which controls one or more actuators to guide the insertion of the delivery device. Additionally, the position and angle of the delivery device calculated by the tracking system may be superimposed on images acquired through an imaging system (e.g., computed tomography, magnetic resonance imaging, and positron emission tomography) to assist in the insertion of the delivery device. It should be recognized that the embodiment is not limited thereto, and the delivery device can be adapted to other frameless positioning systems.

[0098] During use, in some embodiments, the needle is deployed into the tissue by advancing the entire delivery device distally. If the delivery device is mounted on a stereotactic frame, the frame can assist in guiding the distal movement of the delivery device. The operator can then activate the device actuator to deliver the therapeutic substance.

[0099] It should be recognized that in some embodiments, the needle may be actuated to move in the deployment direction relative to the outer shaft and / or the housing of the delivery device. In some embodiments, a single device actuator may be used for both moving the needle in the deployment direction and dispensing the therapeutic substance. In other embodiments, a first actuator is used to move the needle in the deployment direction, and a second actuator is used to dispensing the therapeutic substance.

[0100] Next, a method for preparing and priming the delivery device for use will be described with reference to Figure 13. The method may include step S1302. Step S1302 may include positioning one or more of the needle 50, the needle translation screw 52 attached to the needle 50, the plunger 60, and the plunger translation screw 62 attached to the plunger 60 within the housing 10 and outer shaft 40 of the delivery device. For example, the needle translation screw 52 may be positioned to engage with a first threaded passage 56, and the plunger translation screw 62 may be positioned to engage with a second threaded passage 66 within the housing 10. Furthermore, the plunger 60 may be positioned within the needle lumen 51 of the needle 50, and the needle 50 (having the plunger 60 positioned within it) may be positioned within the shaft lumen 41 of the outer shaft 40. Step S1302 may allow the needle 50 and plunger 60 to be replaced with needles and plungers of the same type. Furthermore, step S1302 can allow different types of needles 50 (for example, needles 50 having needle lumens 51 with different volumes) and corresponding plungers 60 to be selected and placed inside the housing 10 of the delivery device.

[0101] Step S1304 may be performed after step S1302. Step S1304 may include the step of operating the device actuator 30 to cause relative movement of the needle 50 and the plunger 60, positioning the needle opening 58 distal to the opening 45 of the outer shaft 40 on the longitudinal axis 4 and positioning the distal end 65 of the plunger 60 proximal to the vent 59 of the needle 50, as illustrated in Figure 10A.

[0102] Step S1306 may be performed after step S1304. Step S1306 may include the step of passively front-loading the therapeutic substance 180 into the needle lumen 51 of the needle 50, as illustrated in Figure 10A. For example, an active loading device (e.g., a pump) may be used to move the therapeutic substance 180 into the needle lumen 51 in the proximal loading direction 181 through the needle opening 58. In step S1304, the distal end 65 of the plunger 60 is moved proximal to the vent 59 of the needle 50, so that as the therapeutic substance 180 is moved into the needle lumen 51, the air previously occupied by the needle lumen 51 is vented into the shaft lumen 41 through the opened vent 59.

[0103] Step S1308 may be performed after step S1306. Step S1308 may include operating the device actuator 30 to advance the distal end of the plunger 60 to the distal position of the vent 59, as illustrated in Figure 10B, thereby closing the vent 59 of the needle 50. Alternatively, step S1308 may include operating the device actuator 30 to move one or more of the needle 50 and plunger 60, simultaneously driving the indicator configuration to a position where the indicator reflects that the entire dose (of the target volume) of the therapeutic substance 180 has been loaded into the needle lumen 51.

[0104] Step S1310 may be performed after step S1308. Step S1310 may include injecting flushing fluid 184 into the space between the outer shaft 40 and the needle 50 in the flushing direction 185 through the flushing port 90 of the delivery device and through the opening 49 of the outer shaft 40, as illustrated in Figure 10B, thereby removing air from the space between the outer shaft 40 and the needle 50. The injection of flushing fluid 184 may be performed until it is observed that the flushing fluid 184 has exited from the distal end 45 of the outer shaft 40. At this point, the delivery device may be considered to be in a primed state, as illustrated in Figure 10C.

[0105] It should be noted that a method for preparing and priming a delivery device may include some of the steps described above, while omitting one or more of the steps described above. In situations where the delivery device is intended for single use, step S1302, which involves placing the needle 50, needle translation screw 52, ​​plunger 60, and plunger translation screw 62 into the housing 10, may be omitted. Alternatively, in situations where the housing 10 is configured to accommodate different types of needles and plungers, step S1302 may be included in the method.

[0106] Next, a method for using the delivery device will be described with reference to Figure 14. This method may include step S1402. Step 1402 may include deploying the needle 50 and outer shaft 40 into the tissue. The step of deploying the needle 50 and outer shaft 40 into the tissue may include advancing the entire delivery device distally and positioning the needle tip 55 at the target site 215. The step of advancing the entire delivery device may be performed manually. Alternatively, the step of advancing the entire delivery device may include guiding the delivery device with a stereotactic frame or frameless stereotactic system to guide the delivery device and positioning the needle tip 55 at the target site 215.

[0107] Step 1404 may be performed after step S1402. Step S1404 may include operating the device actuator 30 to dispense the therapeutic substance 180 to the target site 215. The step of dispensing the therapeutic substance 180 may include moving the plunger 60 relative to the needle 50 by moving one or both of the plunger 60 and the needle 50 to dispense the therapeutic substance 180. Specifically, the step of dispensing the therapeutic substance 180 may include retracting the needle 50 to create a space of a certain volume for the therapeutic substance 180 dispensed from the delivery device to reside in, thereby reducing the backflow of the therapeutic substance 180 out of the target site 215.

[0108] Step S1406 may be performed after step S1404. Step S1406 may include draining the flushing fluid 184 occupying the space between the outer shaft 40 and the needle 50 toward the target site 215. The step of draining the flushing fluid 184 may include setting the valve 92 of the flushing port 90 to the open position, exposing the space between the outer shaft 40 and the needle 50 to atmospheric pressure, and draining the flushing fluid 184 into the tissue. For example, a device (e.g., an open needle) may be inserted into the valve 92 to set the valve 92 to the open position.

[0109] Step S1408 may be performed after step S1406. Alternatively, step S1408 may be performed together with step S1406. Step S1408 may include withdrawing the needle 50 and outer shaft 40 from the tissue. The step of withdrawing the needle 50 and outer shaft 40 from the tissue may include retracting the entire delivery device proximal to separate the needle tip 55 and outer shaft 40 from the tissue. The step of retracting the entire delivery device may be performed manually. Alternatively, the step of retracting the entire delivery device may include guiding the delivery device by a stereotactic frame or frameless stereotactic system to separate the needle tip 55 and outer shaft 40 from the tissue.

[0110] It should be noted that the method for using the delivery device may include some of the steps described above, while omitting one or more of the steps described above. For example, if the risk of aspiration caused by withdrawing the needle 50 from the tissue is considered small, step S1406 of draining the flushing fluid 184 may be omitted.

[0111] While this instruction has been described in relation to various embodiments and examples, it is not intended to be limited to such embodiments or examples. Rather, this instruction encompasses various alternatives, modifications, and equivalents, as will be recognized by those skilled in the art. Accordingly, the foregoing description and drawings are for illustrative purposes only. [Explanation of symbols]

[0112] 1 Delivery device 2. Proximal end 3. Distal end 4. Longitudinal axis 6. Proximal direction 8. Distal direction 9. Cannula portion 10 Housing 20 handles 30 Device Actuators 40 Outer shaft 41 shaft lumens 45 Opening 49 Opening 50 needles 51 needle lumens 52 Needle Translation Screw 53 Needle Tube 54 ferrules 55 Needle tip 56 First threaded passage 57 Wall 58 Needle opening 59 Bent 60 plungers 61 Plunger body 62 Plunger Translation Screw 63 screw lumens 65 Distal end 66 Second threaded passage 68 Plunger Seal 80 Seating Connectors 90 Flushing Ports 92 valves 93 channels 100 Planetary Gear System 110 Ring Gear 114 Planetary Gear 150 carriers 151 Guide Rail 152 guide rail lumens 153 Guide rail 160 Sun Gear 162 guide rail lumens 180 Therapeutic Substances 181 Proximal loading direction 182 Arrow 183 Upward 184 Flushing fluid 185 Flushing direction 200 Geneva Gear System 201 forward 202 Retreat 210 Organization 211 Tissue Cavity 215 Target Site 230 First drive wheel 240 Gear Assembly 242 Driven wheel section 244 Drive wheel section 250 Indicator Gear 252 Driven wheel portion 254 Indicator part 255 Indicator Window 300 positional frames 302 Arm 400 delivery devices 410 External cannula 500 needles

Claims

1. A device for delivering substances, A needle having a needle lumen, A first translational screw, which is attached to the needle and positioned in a first threaded passage, A plunger configured to move through the needle lumen, A second translational screw, which is attached to the plunger and positioned within a second threaded passage, Equipped with, A device in which the operation of a device actuator causes rotation of the first threaded passage and the second threaded passage, thereby causing the first translational screw to translate through the first threaded passage to move the needle, and the second translational screw to translate through the second threaded passage to move the plunger through the needle lumen.

2. The device according to claim 1, wherein the operation of the device actuator causes the needle to move in a retracting direction and the plunger to move through the needle lumen in an unfolding direction, the unfolding direction being opposite to the retracting direction.

3. The device according to claim 1 or 2, wherein the movement of the needle occurs simultaneously with the movement of the plunger.

4. The device according to any one of claims 1 to 3, wherein the operation of the device actuator causes the needle to move a first distance relative to the delivery device housing and the plunger to move a second distance relative to the delivery device housing, the first distance being different from the second distance.

5. The device according to claim 4, wherein the first distance is smaller than the second distance.

6. The device according to any one of claims 1 to 5, wherein the rotation of the first threaded passage occurs in a first rotational direction, and the rotation of the second threaded passage occurs in a second rotational direction opposite to the first rotational direction.

7. The device according to any one of claims 1 to 6, wherein the first threaded passage has a first thread having a first number of threads, and the second threaded passage has a second thread having a second number of threads, and the number of threads is different from the number of threads of the first and second threads.

8. The device according to any one of claims 1 to 7, wherein the first threaded passage has a first thread having the orientation of the first thread, and the second threaded passage has a second thread having the orientation of the second thread, the orientation of the first thread being opposite to the orientation of the second thread.

9. The device according to any one of claims 1 to 8, further comprising a gear system that connects the device actuator to the first threaded passage and optionally to the second threaded passage.

10. The gear system includes a planetary gear system comprising a solar gear and a plurality of planetary gears, the planetary gears being rotatably mounted on a carrier. The device according to claim 9, wherein the sun gear is coupled to the device actuator and the second threaded passage, and the carrier is coupled to the first threaded passage.

11. The device according to any one of claims 1 to 10, further comprising a gear system connecting the device actuator to the plunger and the needle.

12. The gear system includes a planetary gear system having a solar gear and a plurality of planetary gears, the planetary gears being rotatably mounted on a carrier. The device according to claim 11, wherein the sun gear is attached to the device actuator and coupled to the plunger, and the carrier is coupled to the needle.

13. The device according to any one of claims 1 to 12, wherein the device actuator is rotatably mounted on the device housing, and the rotation of the device actuator causes the plunger to move through the needle lumen.

14. The device actuator has a rotation axis parallel to the extending direction of the plunger, according to any one of claims 1 to 13.

15. The device according to any one of claims 1 to 14, wherein multiple complete rotations of the device actuator are required to achieve the maximum delivery volume.

16. The device according to claim 10 or 12, wherein the sun gear and the device actuator are integrally formed as a single component.

17. The device according to any one of claims 1 to 16, further comprising an indicator having an index indicating the amount of a substance delivered, wherein the indicator is mechanically coupled to the device actuator, so that the operation of the device actuator causes the index of the indicator to move physically without electrical input.

18. The device according to claim 17, further comprising a gear system that mechanically couples the indicator to the device actuator.

19. The device according to any one of claims 1 to 18, wherein the first translational screw and the second translational screw are mounted on a guide rail.

20. The device according to claim 19, wherein the guide rail extends in a direction parallel to the longitudinal axis of the device and is fixed to the housing.

21. The device according to claim 19 or 20, wherein the first translational screw has a guide rail lumen through which the guide rail passes, and the second translational screw has a guide rail lumen through which the guide rail passes.

22. The device according to any one of claims 1 to 21, further comprising an outer shaft having a shaft lumen, wherein the needle is configured to move through the shaft lumen.

23. The needle has a delivery end, a shaft, and a needle lumen extending through the shaft. The device according to any one of claims 1 to 22, wherein the needle further includes a vent in the shaft, the vent being spaced apart from the delivery end.

24. The device according to claim 23, wherein the vent is a through-hole extending through the wall of the shaft of the needle, the plunger is configured to be positioned in a first position where fluid communication through the vent is open and in a second position where fluid communication through the vent is closed, and the device actuator is configured to move the plunger in the deployment direction and close the fluid communication through the vent.

25. The device according to any one of claims 1 to 24, further comprising a therapeutic substance to be loaded into the delivery device, wherein the substance is completely contained within the needle lumen.

Images