Therapeutic substance delivery device

Abstract

In some embodiments, a delivery device includes a device actuation member and a cannula portion through which a therapeutic substance is expelled. The cannula portion includes an outer shaft, a needle configured to move through the outer shaft, and a plunger configured to move through the needle, thereby forming a positive displacement configuration.

Description

[0001] Citation of relevant applications

[0002] This application claims the benefit of Provisional U.S. Patent Application No. 63 / 009,572, filed April 14, 2020. The entire disclosure of Provisional U.S. Patent Application No. 63 / 009,572 is incorporated herein by reference. Technical Field

[0003] The disclosed embodiments relate to a conveying device and related methods of use. Background Technology

[0004] Therapeutic substances can be delivered to patients through a variety of methods. There are multiple possible routes of administration, including: oral, inhalation, local, intravascular, intramuscular, subcutaneous, intraperitoneal, rectal / vaginal, transcavitary, and more tissue-specific routes (e.g., intrathecal, intraventricular, and intra-articular).

[0005] Cell-based therapies typically use conventional delivery devices for administration, such as needles and syringes or balloon dilation catheters. Injecting cell-based therapeutic agents through the skin or mucous membranes can help bypass some of the body's defenses and deliver the agents directly to specific sites. Summary of the Invention

[0006] 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. Actuation of the device actuator may cause the needle to pass through the needle lumen in a retraction direction and may cause the plunger to pass through the needle lumen in a deployment direction opposite to the deployment direction.

[0007] In some embodiments, a delivery device is provided. The delivery device may include a device actuator, an outer shaft having a shaft cavity, and a needle having a needle tip cavity. The needle tip may be configured to move through the outer shaft cavity. The delivery device may further include a plunger configured to move through the needle tip cavity. Actuation of the device actuator may cause the needle tip 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.

[0008] In some embodiments, a delivery device is provided. The delivery device may include a device housing, a device actuator rotatably mounted relative 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 can cause the plunger to move through the needle lumen.

[0009] In some embodiments, a method for delivering a substance via a delivery device is provided. The method may include rotating an actuator of the device at least 10 full revolutions to deliver a quantity of substance through the exit of a needle, wherein the quantity is between 1 microliter and 50 microliters, including 1 microliter and 50 microliters.

[0010] In some embodiments, a method for loading cells into a delivery device is provided. The method may include moving cells into the lumen of a needle through a delivery end of the needle, venting air from the lumen of the needle through a vent in the needle while the cells are being moved into the lumen, and sealing the fluid communication through the vent after the cells have been moved into the lumen.

[0011] In some 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 cavity extending through the shaft. The delivery device may also include a plunger configured to move through the needle cavity. The needle may also include a vent spaced from the delivery end in the shaft.

[0012] In some embodiments, a delivery device is provided. The delivery device may include a device actuator, an outer shaft having a shaft cavity, and a needle having a needle tip cavity. The diameter of the needle tip cavity may be 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 cavity. The delivery device may further include a plunger configured to move through the needle tip cavity, wherein the plunger has a travel distance of at least 100 mm relative to the outer shaft.

[0013] In some embodiments, a method for delivering cells via a delivery device is provided. The method may include moving a needle of the delivery device to a target site and occupying a volume of space at the target site with the needle. The method may further include actuating a device actuator to cause the needle to retract from the volume of space and to cause a plunger to move through the needle lumen into the volume of space, while simultaneously delivering cells into the volume of space containing the cells as the needle retracts.

[0014] In some 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 mark indicating the delivered dose. The indicator may be mechanically coupled to the device actuator, such that actuation of the device actuator causes the mark on the indicator to move physically without requiring electrical input.

[0015] In some 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 along 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.

[0016] It should be understood that the foregoing concepts, as well as other concepts discussed below, can be arranged in any suitable combination, as this disclosure is not limited in this respect. Furthermore, other advantages and novel features of this disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying drawings. Attached Figure Description

[0017] The accompanying drawings are not necessarily drawn to scale. In the drawings, each identical or nearly identical component shown in different figures may be indicated by similar reference numerals. For clarity, not every component is labeled in every drawing. In the drawings:

[0018] Figure 1 This is a schematic diagram of a delivery device that generates a return flow of the therapeutic substance during the injection of the therapeutic substance.

[0019] Figure 2 This is a schematic diagram of one embodiment of the conveying device described herein, wherein it is possible to reduce Figure 1 The potential backflow problem experienced by the conveying device;

[0020] Figure 3A This is a perspective view of one embodiment of the conveying device;

[0021] Figure 3B yes Figure 3A A partial sectional view of one embodiment of the conveying device, with a detailed view of the sleeve portion of the conveying device;

[0022] Figure 4A It is a perspective view of the needle of the delivery device, where the needle is shown in dashed lines to show the plunger of the delivery device;

[0023] Figure 4B It has a plunger seal. Figure 4A A schematic diagram of the plunger;

[0024] Figure 4C This is a perspective view of a needle in another embodiment of the delivery device, which is retractably arranged within the sleeve portion of the delivery device;

[0025] Figure 4D yes Figure 4C A cross-sectional view of the needle;

[0026] Figure 5This is a partial cross-sectional view of the needle translation screw in one embodiment of the delivery device when connected to the needle.

[0027] Figure 6 This is a partial cross-sectional view of a conveying device embodiment when the plunger translation screw is connected to the plunger;

[0028] Figure 7A yes Figure 3A A partial cross-sectional view of the conveying device in its pre-conveying state;

[0029] Figure 7B yes Figure 7A A view of the conveying device in its post-conveying state;

[0030] Figure 8 This is a perspective view of a planetary gear system according to one embodiment of the conveying device;

[0031] Figure 9 yes Figure 8 Another perspective view of the planetary gear system, with some components hidden and not visible;

[0032] Figure 10A This is a cross-sectional view of a conveying device undergoing a loading process according to one embodiment;

[0033] Figure 10B One example Figure 10A A cross-sectional view of the conveyor device during the rinsing process;

[0034] Figure 10C yes Figure 10B A cross-sectional view of the conveying device in the loading and pre-filling state;

[0035] Figure 11 This is a perspective view of an indicator component in one embodiment;

[0036] Figure 12 This is a view of a stereoscopic orientation frame used in conjunction with a conveying device according to one embodiment;

[0037] Figure 13 A flowchart of a method for preparing and pre-filling a delivery device for use, according to one embodiment; and

[0038] Figure 14 This is a flowchart of a method using a conveying device according to one embodiment. Detailed Implementation

[0039] For some conventional delivery devices, the device is inserted into the tissue to reach the target site, the therapeutic substance is ejected from the device and enters 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 undesirable backflow of the therapeutic substance from the target site during the injection of the therapeutic substance into the target site. The inventors have also recognized that, for some conventional cell delivery devices, cells supplied in a fluid solution held within the device experience a “cell sedimentation” effect, in which cells may clump together within the device, for example, due to gravity. Cell sedimentation may result in the delivery of inconsistent cell concentrations, which in turn may lead to variations in cell seeding density. The inventors have also recognized that some conventional delivery devices do not restrict the user from rapidly expelling the therapeutic substance. The inventors have recognized that high expulsion rates may have adverse effects on the therapeutic substance. For example, in cell delivery, high expulsion rates may reduce cell viability, for example, due to damage to cells caused by shear stress. The inventors have also recognized that high expulsion rates may lead to unwanted tissue damage. In some conventional delivery devices, therapeutic substances are loaded into the device from the rear. The inventors also recognized that rear loading may require the therapeutic substances to traverse a long path within the device before reaching the delivery end. Due to this long travel distance, some therapeutic substances may remain in the delivery path without being delivered, resulting in waste. Furthermore, in some conventional devices, the path may include changes in diameter and / or may include uneven transitions, both of which can adversely affect the therapeutic substances.

[0040] The inventors recognized the need for a conveying device that solves some or all of the aforementioned problems of conventional conveying devices.

[0041] Some embodiments described herein include delivery devices for delivering therapeutic substances via a volumetric configuration in which a plunger moves through the lumen of a needle to expel the therapeutic substance from the needle. In some embodiments, the therapeutic substance to be delivered is a cell or other microparticles having a certain diameter. However, it should be understood that the therapeutic substance is not limited to cells or microparticles. At any point in the discussion below, "cell" may be suitably replaced with any other therapeutic substance.

[0042] According to one aspect, the delivery device can be configured to reduce backflow of the therapeutic substance from the target site during injection of the therapeutic substance into the target site. In some embodiments, the needle can be arranged to retract as the plunger advances. The needle can create a cavity in the tissue for the therapeutic substance. As the therapeutic substance is ejected from the needle, the needle retracts, thereby providing a volume of space within the created cavity for retaining the therapeutic substance.

[0043] Figure 1 This reflux concept is illustrated by a delivery device 400 having an outer cannula 410 and a needle 500. The outer cannula 410 and the needle 500 of the delivery device have been inserted into tissue 210, and the needle 500 forms a cavity 211 in tissue 210. Therapeutic material 180 is delivered to target site 215. Since target site 215 is occupied by needle 500, therapeutic material 180 can be pushed upward 183 between tissue cavity 211 and delivery device 400 (instead of occupying target site 215).

[0044] In comparison, Figure 2 This is a schematic diagram of one embodiment of the delivery device described herein, which can reduce the potential backflow problem mentioned above. 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 to expel therapeutic material 180 from the needle 50 toward the target site 215, the needle 50 can simultaneously retract proximally from the cavity 211 202. Not wishing to be bound by theory, withdrawing the needle during the expulsion of the therapeutic material from the needle can create a space that will be occupied by the therapeutic material and can help reduce backflow of the therapeutic material from the target site 215.

[0045] According to one aspect, the delivery device can be configured to help reduce cell or particle deposition in the needle lumen. In some embodiments, the diameter of the needle lumen is less than 1 mm. In some embodiments, the ratio of the diameter of the needle lumen to the diameter of the cell or particle is less than 100:1.

[0046] According to one aspect, the delivery device can be configured to help a user control the rate of expulsion of the therapeutic substance. For certain therapeutic substances, such as certain types of cells, a slower expulsion rate may help reduce shearing or other harmful effects on the cells, which may result in higher viability of the delivered cells. A slower expulsion rate can also reduce the risk of brain tissue damage. In some embodiments, the device actuator is a rotary actuator. In some embodiments, the rotary actuator needs to be rotated multiple times to deliver the total target amount.

[0047] According to one aspect, the delivery device can be configured to improve dosage assurance. In some embodiments, the therapeutic substance is contained within a small needle lumen with a constant diameter. In the case of cells, this configuration facilitates the coordinated movement of the cells with their fluid solution, which helps ensure the delivery of a larger fraction of the cells. In some embodiments, this configuration can help reduce cell deposition.

[0048] According to one aspect, the delivery device can be configured to help reduce waste of therapeutic material that may occur during loading of the therapeutic material into the delivery device. The inventors recognize that for some delivery devices in which material is loaded from the rear, some material may be lost due to the long travel distance from the loading end to the discharge end of the device. The inventors recognize that loading the delivery device from the front can help reduce waste of therapeutic material. Therefore, in some embodiments, the delivery device is configured to load the therapeutic material from the front. In some embodiments, the delivery device may include a venting configuration to allow front-side loading. In some embodiments, the delivery device may include a configuration for pre-injection after loading the therapeutic material to remove air from the delivery device before use, thereby preventing air from being injected into the target site.

[0049] According to one aspect, the conveying device may include an indicator comprising only mechanical components. Because there are no electrical components, this construction makes the conveying device more portable and easier to sterilize.

[0050] According to one aspect, the delivery device is used in conjunction with a stereotactic frame, for example, for neurosurgical applications. In some embodiments, the size and shape of the delivery device enable it to be compatible with existing stereotactic frames.

[0051] Please refer to the exemplary embodiments in the accompanying drawings. Figure 3A This is a perspective view of one embodiment of the conveying device 1, and... Figure 3B A partial cross-sectional view of the internal components of the conveying device is shown. The conveying device has a conduit portion 9 through which material is discharged, a housing 10, a handle 20, and a device actuator 30. Figure 3B As shown in the detailed drawing, the cannula portion 9 may include a plurality of components nested together. From the outermost component to the innermost component, the cannula portion 9 may include an outer shaft 40, a needle 50 within the outer shaft 40, and a plunger 60 within the needle 50.

[0052] The outer shaft 40 has an inner cavity 41 through which the needle 50 can move. The needle 50 has a needle cavity 51 through which the plunger 60 can move. Actuation of the device actuator 30 causes the plunger 60 to move distally 8 through the inner cavity 41. When a therapeutic substance is loaded into the needle cavity 51, the distal movement 8 of the plunger 60 through the needle cavity 51 displaces the therapeutic substance from the needle cavity 51, thereby delivering the therapeutic substance.

[0053] like Figure 3AAs shown, 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 of the outer shaft 40 toward 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 outer diameter range. Furthermore, another of the plurality of segments, adjacent to and arranged close to one of the segments, may have a second outer diameter or a second outer diameter range, wherein the second outer diameter is larger than the first outer diameter, and the second outer diameter range is larger than the first outer diameter range and does not overlap with the first outer diameter range. Additionally, the outer shaft 40 may include an end face that defines a step between one of the plurality of segments and another of the plurality of segments. The end face may project radially outward from the longitudinal axis 4 of the device. Alternatively, the end face may be formed as a chamfered surface that projects from the longitudinal axis 4 of the device at an angle of less than 90 degrees toward the proximal side of the device.

[0054] The outer shaft 40 may be formed of, for example, stainless steel. Other materials may also be used to form the outer shaft 40. For example, the outer shaft 40 may be formed of MRI-compatible materials, such as ceramics, glass, or rigid polymers. If such compatibility is not required during the use of the device and / or if other factors such as cost and reusability are preferred, the outer shaft 40 may also be formed of materials incompatible with MRI.

[0055] like Figure 4A As shown, the distal portions of the needle 50 and plunger 60 are illustrated. The needle 50 includes a needle tip 55 defining a needle opening 58 through which a therapeutic substance is dispensed. The needle tip 55 may be formed with a chamfered outer surface that connects to a plane including the needle opening 58 and the portion of the needle 50 along the longitudinal axis 4 of the device near the needle tip 55. The needle 50 may be formed of materials such as stainless steel, glass, ceramic, or rigid polymers.

[0056] Figure 4C This is a perspective view of the needle 50 in another embodiment. Figure 4D This is a cross-sectional view of the needle 50. The needle tip 55 of the needle 50 can be formed as a flat end face having a defining needle opening 58. This flat end face can be arranged on a plane orthogonal to the longitudinal axis 4 of the device. Although in Figure 4C and 4D Not shown, but the end face can be arranged on a plane that forms a non-orthogonal angle with the longitudinal axis 4 of the device. Alternatively, the needle tip 55 can be formed with, for example, Figure 4A The chamfered outer surface is shown.

[0057] like Figure 4DAs shown, the needle 50 may include a needle tube 53 defining a needle lumen 51. The needle tube 53 may be formed of materials such as stainless steel, glass, ceramic, or rigid polymers. More specifically, the needle tube 53 may be formed of materials such as polyimide-coated glass. The needle 50 may also include a clamp 54 attached to a portion of the needle tube 53. The clamp 54 may be attached to the portion of the needle tube 53 by adhesive or other means. The clamp 54 may be formed of a material selected to reinforce the portion of the needle tube 53 to which the clamp 54 is attached. For example, the clamp 54 may be formed of materials such as stainless steel. Figure 4D A clamp 54 is shown attached to a portion of the needle tube 53, extending along the longitudinal axis 4 from the distal end of the needle tube 53 to a proximal portion of the needle tube 53. The clamp 54 may also be attached to a portion of the needle tube 53 extending along the longitudinal axis 4 from a first portion near the distal end of the needle tube 53 to a second portion near that first portion. The length of the clamp 54 along the longitudinal axis 4 may be selected to be longer than the maximum length of a portion of the needle tube 53, and this portion may extend distally along the longitudinal axis 4 from the shaft cavity 41 and through an opening in the outer shaft 40 to reinforce that portion of the needle tube 53.

[0058] like Figure 4A and 4B As shown, the plunger 60 includes a plunger seal 68 that provides a seal to the needle cavity 51 while allowing the plunger 60 to move through the needle cavity 51. In some embodiments, the outer diameter of the plunger seal 68 is larger than the outer diameter of the rest of the plunger body 61. The length of the plunger seal 68 can be selected to ensure that therapeutic material loaded in the portion of the needle cavity 51 between the needle opening 58 and the distal end of the plunger seal 68 does not proximally pass through the plunger seal 68 into another portion of the needle cavity 51 near the plunger seal 68. Furthermore, the length of the plunger seal 68 can be selected such that when the plunger 60 advances to its furthest position within the needle cavity 51, the plunger seal 68 serves to close the vent 59 disposed in the wall 57 of the needle 50. The length of the plunger seal 68 is selected to ensure that the vent 59 is kept closed by the plunger seal 68 when the distal end of the plunger 60 passes through the vent 59, thereby preventing liquid from entering the needle cavity 51 through the vent 59 and passing through the plunger seal 68 into the distal portion of the needle cavity 51 of the plunger seal 68, and preventing liquid in the distal portion of the plunger seal 68 of the needle cavity 51 from flowing through the plunger seal 68 and into the proximal portion of the plunger seal 68 of the needle cavity 51.

[0059] In some embodiments, the distal portion of the plunger body 61 may be fitted within the plunger seal 68. The plunger seal 68 may be formed as a heat-shrink seal on the plunger body 61. The plunger seal 68 may also be formed as a polymer coating by deposition or coating techniques. In other embodiments, the plunger body 61 is not fitted within the plunger seal 68, but the two components are joined together. In other embodiments, the plunger body 61 and the plunger seal 68 are formed as a single unit.

[0060] According to one aspect, the needle can be arranged to retract as the therapeutic substance is ejected from the needle. In some embodiments, during use, the needle is inserted into tissue to reach a desired target site. The insertion of the needle creates a cavity in the tissue. As the therapeutic substance is ejected from the needle, the needle retracts simultaneously, thereby providing a volumetric space for the retention of the therapeutic substance. The inventors recognize that this configuration can help reduce the backflow of the therapeutic substance from the target site through channels formed in the tissue by the delivery device.

[0061] In embodiments where the delivery device uses a volumetric delivery configuration (e.g., 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 actuation of the device actuator. That is, actuation of the device actuator can cause the needle to retract proximally while the plunger advances distally.

[0062] As used herein, the "distal end" of a delivery device refers to the end through which the therapeutic substance is delivered. The "proximal end" of the delivery device is the end opposite to the distal end. As an example, Figure 3A The proximal end 2 and distal end 3 of the conveying device 1 are shown.

[0063] As used herein, "proximal direction" refers to the direction from the distal end to the proximal end of the conveying device. "Distal direction" refers to the direction from the proximal end to the distal end of the conveying device. As an example, Figure 3A The proximal direction 6 and the distal direction 8 are shown.

[0064] In some embodiments, actuation of the device actuator 30 causes the plunger 60 to advance in a distal direction 8, while the needle 50 simultaneously retracts in a proximal direction 6. In some embodiments, the simultaneous movement of the plunger and the needle in opposite directions is achieved by a construction of a translation screw mounted in a threaded channel having oppositely oriented threads.

[0065] like Figure 3BAs shown, 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 channel 56, and the plunger translation screw 62 is mounted in a second threaded channel 66. The threads of the first threaded channel 56 are oriented in the opposite direction to the threads of the second threaded channel 66. For example, the first threaded channel 56 may have a right-hand thread, while the second threaded channel 66 may have a left-hand thread, or vice versa. Actuation of the device actuator 30 can transmit rotation to each of the first threaded channel 56 and the second threaded channel 66.

[0066] like Figure 3B As shown, 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 conveying device 1 along a direction parallel to the longitudinal axis 4 of the device and can be fixed relative to the housing 10. Figure 5 As shown, the needle translation screw 52 may include a guide rail cavity 152, through which guide rails 151 and 153 pass. The needle translation screw 52 can freely translate linearly along guide rails 151 and 153. Figure 6 As shown, the plunger translation screw 62 may include a guide rail cavity 162, through which guide rails 151 and 153 pass. The plunger translation screw 62 can freely translate linearly along the guide rails 151 and 153.

[0067] Guide rails 151 and 153 prevent the needle translation screw 52 from rotating with the first threaded channel 56 when the first threaded channel 56 rotates. As a result, due to the direction of the threads in the first threaded channel 56 and the presence of the guide rails passing through the needle translation screw 52, ​​rotation of the first threaded channel 56 causes the needle translation screw 52 to translate through the first threaded channel 56. Figure 3B In an exemplary embodiment, when the device actuator 30 is actuated, the needle translation screw 52 moves in the proximal direction 6. While the needle 50 is attached to the needle translation screw 52, ​​the proximal movement of the needle translation screw 52 moves the needle 50 in the proximal direction 6, thereby causing the needle to retract.

[0068] Similarly, guide rails 151 and 153 prevent the plunger translation screw 62 from rotating with the second threaded channel 66 when the second threaded channel 66 rotates. As a result, due to the thread direction in the second threaded channel 66 and the presence of the guide rails passing through the plunger translation screw 62, rotation of the second threaded channel 66 causes the plunger translation screw 62 to translate through the second threaded channel 66. Figure 3BIn an exemplary embodiment, when the device actuator 30 is actuated, the plunger translation screw 62 moves in a distal direction 8. 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 in a distal direction 8, thereby discharging the therapeutic substance from the needle opening.

[0069] like Figure 5 As shown in more detail, the needle 50 is connected to the needle translation screw 52. The needle 50 may extend at least partially into the screw cavity 53. The needle 50 may be attached to the needle translation screw 52 by any suitable construction, such as adhesive (e.g., epoxy or UV-resistant adhesive), mechanical interlocking, interference fit, welding the components together, or the needle 50 and the needle translation screw 52 may be integrally formed with each other.

[0070] As used in this article, components that are “integrated” with each other refer to components that are formed as a single part, such as being cast into a single piece simultaneously in die casting or injection molding, or cut from a single material in stamping or die cutting.

[0071] like Figure 6 As shown in more detail, plunger 60 is connected to plunger translation screw 62. Plunger 60 may extend at least partially into the screw cavity 63. Plunger 60 may be attached to plunger translation screw 62 by any suitable construction, as described above for needle 50 and needle translation screw 52.

[0072] 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 can be removed from the housing 10 and replaced with another needle and another needle translation screw and / or another plunger and another plunger translation screw attached to the other plunger. The other needle and the other needle translation screw can be arranged in the housing 10 to translate through a first threaded channel 56, and the other plunger and the other plunger translation screw can be arranged in the housing 10 to translate through a second threaded channel 66. The other needle can be a substitute for the needle 50 and has similar physical dimensions (e.g., the same size needle lumen) and similar functions (e.g., allowing the same amount of travel). Alternatively, the other needle can have different physical dimensions (e.g., a different size needle lumen) and different functions (e.g., allowing different amounts of movement) than the needle 50.

[0073] Figure 7A The conveying device is shown in its pre-conveying state. Figure 7BThe conveying device is shown in its post-conveying configuration. At the end of the conveying process, the needle translation screw 52 has been translated proximally 6 through the first threaded channel 56, thereby retracting the needle, and the plunger translation screw 62 has been translated distally 8 through the second threaded channel 66, thereby advancing the plunger in the deployment direction.

[0074] In some embodiments, after the therapeutic substance is delivered into a volume of space within the tissue created by the needle, the therapeutic substance occupies a portion of that volume of space. In some embodiments, the volume of the therapeutic substance occupied by the therapeutic substance is at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, or 60% of the volume of space. In some embodiments, the volume of the therapeutic substance occupied by the therapeutic substance is less than or equal to about 70%, 60%, 50%, 40%, 30%, 25%, 20%, 15%, 10%, or 5% of the volume of space. Combinations of the above ranges are also possible. In some embodiments, the volume of the therapeutic substance occupied by the therapeutic substance is about 5% to about 60%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, or about 5% to about 25% of the volume of space.

[0075] According to one aspect, the diameter of the needle lumen is compatible with the properties of the therapeutic substance. In some embodiments, the therapeutic substance comprises cells or other microparticles having a certain diameter. According to one aspect, the diameter of the needle lumen is close to the diameter of the cells or microparticles of the therapeutic substance. For example, in some embodiments, the ratio of the diameter of the needle lumen to the diameter of the cells or microparticles is less than 100:1. In some embodiments, this configuration can help reduce cell or microparticle deposition in the needle lumen. In some embodiments, this configuration can help cells move in tandem with their fluid solution, which can help ensure delivery of a larger fraction of cells. This configuration helps improve dosage assurance.

[0076] In some embodiments, the delivery device is configured to deliver nerve cells. In some embodiments, the cells are dopaminergic neurons, while in some embodiments, they may be dopaminergic neurons derived from iPSCs. However, it should be understood that the delivery device can be used to deliver other types of cells, such as 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, virus-reconstituted T cells, dendritic cells, regulatory T cells, macrophages), neural crest stem cells, neurons, glial cells, smooth muscle, cardiac tissue, chondrocytes, osteocytes, glial-restricted progenitor cells, astrocytes, oligodendrocytes, neuroblasts, megakaryocytes, megakaryocytes, monocytes, monocytes, macrophages, myeloid dendritic cells, proerythroblasts, erythroblasts, normal cells, and reticulocytes. Cells, coagulation cells, myeloid cells, progranulocytes, neutrophils, band neutrophils, neutrophils, eosinophils, band eosinophils, eosinophils, basophils, band eosinophils, basophils, directed lymphoid progenitors, proNK cells, NK lymphoblasts, NK cells, thymocytes, T lymphoblasts, T cells, plasmacytoid dendritic cells, proB cells, B lymphoblasts, B cells, plasma cells, osteoblasts, chondrocytes, myoblasts, myotube cells, fibroblasts, adipocytes, mesoderm, ectoderm, germ cells, sperm, oocytes, fixed endoderm, or any other suitable type of cell.

[0077] In some embodiments, the therapeutic substance comprises 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 comprises a cell concentration of less than or equal to about 500,000 cells / µL, less than or equal to about 400,000 cells / µL, less than or equal to about 300,000 cells / µL, less than or equal to about 200,000 cells / µL, less than or equal to about 100,000 cells / µL, or less than or equal to about 50,000 cells / µL. Combinations of the above ranges are also possible. For example, in some embodiments, the therapeutic substance comprises a cell concentration of approximately 50,000 cells / µL to approximately 500,000 cells / µL, or approximately 100,000 cells / µL to approximately 400,000 cells / µL, or approximately 200,000 cells / µL to approximately 300,000 cells / µL.

[0078] In some embodiments, the needle lumen may 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 may have a diameter less than or equal to about 1 mm, less than or equal to about 0.95 mm, less than or equal to about 0.9 mm, less than or equal to about 0.85 mm, less than or equal to about 0.8 mm, less than or equal to about 0.75 mm, less than or equal to about 0.7 mm, less than or equal to about 0.65 mm, less than or equal to about 0.6 mm, less than or equal to about 0.55 mm, less than or equal to about 0.5 mm, less than or equal to about 0.45 mm, less than or equal to about 0.4 mm, less than or equal to about 0.35 mm, less than or equal to about 0.3 mm, less than or equal to about 0.25 mm, less than or equal to about 0.2 mm, less than or equal to about 0.15 mm, or less than or equal to about 0.1 mm. Combinations of the above ranges are also possible. For example, in some embodiments, the needle lumen may 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.

[0079] In some embodiments, the cells or particles of the therapeutic substance may have a diameter of at least about 400 nanometers, at least about 1 micrometer, at least about 2 micrometers, at least about 4 micrometers, at least about 6 micrometers, at least about 8 micrometers, at least about 9 micrometers, at least about 10 micrometers, at least about 11 micrometers, at least about 12 micrometers, at least about 13 micrometers, at least about 14 micrometers, at least about 15 micrometers, at least about 16 micrometers, at least about 17 micrometers, at least about 18 micrometers, at least about 19 micrometers, at least about 20 micrometers, at least about 25 micrometers, at least about 30 micrometers, at least about 40 micrometers, at least about 50 micrometers, at least about 70 micrometers, at least about 100 micrometers, at least about 200 micrometers, or at least about 500 micrometers. In some embodiments, the cells or particles may have a size of less than or equal to about 500 micrometers, less than or equal to about 300 micrometers, less than or equal to about 200 micrometers, less than or equal to about 150 micrometers, less than or equal to about 100 micrometers, less than or equal to about 90 micrometers, less than or equal to about 80 micrometers, less than or equal to about 70 micrometers, less than or equal to about 60 micrometers, less than or equal to about 50 micrometers, less than or equal to about 40 micrometers, less than or equal to about 30 micrometers, less than or equal to about 20 micrometers, less than or equal to about 19 micrometers, or less than or equal to [other sizes not specified in the original text]. Diameters of approximately 18 micrometers, less than or equal to approximately 17 micrometers, less than or equal to approximately 16 micrometers, less than or equal to approximately 15 micrometers, less than or equal to approximately 14 micrometers, less than or equal to approximately 13 micrometers, less than or equal to approximately 12 micrometers, less than or equal to approximately 11 micrometers, less than or equal to approximately 10 micrometers, less than or equal to approximately 9 micrometers, less than or equal to approximately 8 micrometers, less than or equal to approximately 7 micrometers, less than or equal to approximately 6 micrometers, less than or equal to approximately 5 micrometers, less than or equal to approximately 4 micrometers, less than or equal to approximately 2 micrometers, or less than or equal to approximately 1 micrometer. Combinations of the above ranges are also possible. For example, in some embodiments, the cells or particles may have a diameter of about 400 nanometers to about 500 micrometers, or about 1 micrometer to about 200 micrometers, or about 5 micrometers to about 150 micrometers, or about 8 micrometers to about 120 micrometers, or about 8 micrometers to about 100 micrometers, or about 8 micrometers to about 50 micrometers, or about 8 micrometers to about 40 micrometers, or about 8 micrometers to about 30 micrometers, or about 8 micrometers to about 20 micrometers, or about 10 micrometers to about 15 micrometers.

[0080] In some embodiments, the ratio of the diameter of the needle lumen to the diameter of the cell or particle 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 the diameter of the needle lumen to the diameter of the cell or particle is less than or equal to 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. Combinations of the above ranges are also possible. For example, in some embodiments, the ratio of the diameter of the needle lumen to the diameter of the cell or particle is approximately 10:1 to approximately 500:1, or approximately 50:1 to approximately 300:1, or approximately 60:1 to approximately 200:1, or approximately 70:1 to approximately 150:1, or approximately 80:1 to approximately 120:1, or approximately 90:1 to approximately 110:1.

[0081] In some embodiments, the entire amount 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, this configuration facilitates the coordinated movement of the cells with their fluid solution, which helps ensure the delivery of a larger fraction of the cells. This configuration helps improve dosage assurance. In some embodiments, this configuration can help reduce cell deposition.

[0082] In some embodiments, the density of the fluid solution containing cells and / or particles is selected to increase the buoyancy acting on the cells and / or particles. For example, the density of the fluid solution can be selected based on the known density of the cells and / or particles to be transported, to be close to that known density, thereby increasing the buoyancy acting on the cells and / or particles to achieve or approach neutral buoyancy. Furthermore, the density of the fluid solution can be selected based on the known density of the cells and / or particles to be transported, to be close to that known density, thereby increasing the buoyancy acting on the cells and / or particles, such that the concentration of cells and / or particles in the fluid solution discharged from the transport device is close to a predetermined concentration. In other embodiments, the viscosity of the fluid solution can be selected to reduce cell precipitation, such that the concentration of cells and / or particles in the fluid solution discharged from the transport device is close to a predetermined concentration. In other embodiments, both the density and viscosity of the fluid solution can be selected as described above. This configuration can further contribute to reducing cell precipitation.

[0083] According to one aspect, the volume of space through which the plunger moves in response to actuation of the device (and / or the volume of therapeutic material discharged by the delivery device) is close to or substantially equal to the volume of space through which the needle moves during needle retraction. In some embodiments, the volume of space through which the plunger moves (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% of the volume of space through which the needle moves. In some embodiments, the volume of space through which the plunger moves (and / or the volume of therapeutic material discharged by the delivery device) is less than or equal to 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% of the volume of space through which the needle moves. Combinations of the above ranges are also possible. In some embodiments, the volume of space through which the plunger moves (and / or the volume of therapeutic material discharged by the delivery device) is within the range of 1% to 50%, 1% to 40%, 1% to 30%, 1% to 25%, 1% to 20%, 1% to 15%, 1% to 10%, or 1% to 5% of the volume of space through which the needle moves.

[0084] The inventors recognized that, for volumetric configurations, the plunger travel distance can determine the delivery volume. However, in embodiments where the needle retracts as the plunger advances, the inventors recognized that, in all embodiments, the needle travel distance does not necessarily match the plunger travel distance. In some embodiments, the needle travel distance can be determined by the anatomical structure of the target site.

[0085] According to one aspect, the needle and plunger can travel different distances during delivery. This configuration allows the plunger to travel a certain distance to deliver the required amount of therapeutic material, while allowing the needle to travel a distance appropriate to the target anatomical structure.

[0086] In some embodiments, the different travel distances of the plunger and needle are achieved through the difference in the number of threads (e.g., threads per inch) of the threaded channel associated with the translation screw, or through a gear system, or in some embodiments through a combination of both.

[0087] exist Figure 3B In the exemplary embodiment shown, the first threaded channel 56 (i.e., the channel along which the needle translation screw 52 translates) has a first number of threads. The second threaded channel 66 (i.e., the channel along which the plunger translation screw 62 translates) has a second number of threads different from the first number of threads. In some embodiments, for example in Figure 3BIn the illustrated embodiment, the needle travels a shorter distance than the plunger. To achieve this difference in travel distance, the first threaded channel 56 has a larger number of threads (e.g., a higher number of threads per inch) than the second threaded channel 66. Therefore, with actuation of the device actuator 30, the plunger translation screw 62 translates a greater distance than the needle translation screw. Consequently, the plunger travels a greater distance than the needle.

[0088] In some embodiments, the ratio of the first number of threads to the second number of threads may be at least approximately 1.5:1, at least approximately 1.6:1, at least approximately 1.7:1, at least approximately 1.8:1, at least approximately 1.9:1, at least approximately 2:1, at least approximately 2.1:1, at least approximately 2.2:1, at least approximately 2.3:1, at least approximately 2.4:1, at least approximately 2.5:1, at least approximately 2.6:1, at least approximately 2.7:1, at least approximately 2.8:1, at least approximately 2.9:1, at least approximately 3:1, at least approximately 3.1:1, at least approximately 3.2:1, at least approximately 3.3:1, or at least approximately 3.4:1. At least 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 first number of threads to the second number of threads may be less than or equal to approximately 20:1, less than or equal to approximately 18:1, less than or equal to approximately 16:1, less than or equal to approximately 14:1, less than or equal to approximately 12:1, less than or equal to approximately 10:1, less than or equal to approximately 9:1, less than or equal to approximately 8:1, less than or equal to approximately 7:1, less than or equal to approximately 6:1, less than or equal to approximately 5:1, less than or equal to approximately 4.5:1, less than or equal to approximately 4:1, less than or equal to approximately 3.9:1, less than or equal to approximately 3.8:1, less than or equal to approximately 3.7:1, less than or equal to approximately 3.6:1, less than or equal to approximately 3.5:1, less than or equal to approximately 3... 4:1, less than or equal to approximately 3.3:1, less than or equal to approximately 3.2:1, less than or equal to approximately 3.1:1, less than or equal to approximately 3:1, less than or equal to approximately 2.9:1, less than or equal to approximately 2.8:1, less than or equal to approximately 2.7:1, less than or equal to approximately 2.6:1, less than or equal to approximately 2.5:1, less than or equal to approximately 2.4:1, less than or equal to approximately 2.3:1, less than or equal to approximately 2.2:1, less than or equal to approximately 2.1:1, less than or equal to approximately 2:1, less than or equal to approximately 1.9:1, less than or equal to approximately 1.8:1, less than or equal to approximately 1.7:1, less than or equal to approximately 1.6:1, or less than or equal to approximately 1.5:1. Combinations of the above ranges are also possible.For example, in some embodiments, the ratio of the first number of threads to the second number of threads may 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.

[0089] exist Figure 3B In an exemplary embodiment, a gear system is also employed to further reduce the needle travel distance relative to the plunger travel distance. For example... Figure 8 and Figure 9 As shown, the gear system is a planetary gear system 100 (also known as a planetary gear system). The planetary gear system 100 includes a sun gear 160, planetary gears 114, and a ring gear 110.

[0090] The sun gear 160 is connected to the device actuator 30 and the second threaded channel 66 (associated with the plunger translation screw). For example... Figure 3B As shown, the sun gear 160, the actuator 30, and the second threaded channel 66 are integrally formed as a single component. A full rotation of the actuator 30 also causes a full rotation of the sun gear 160 and a full rotation of the second threaded channel 66. The planetary gear 114 rotates around the sun gear 160 within the ring gear 110. Figure 9 As shown, planetary gear 114 is rotatably mounted on carrier 150, and carrier 150 is connected to first threaded channel 56 (associated with needle translation screw). A full rotation of carrier 150 results in a full rotation of first threaded channel. The relationship between sun gear 160 and planetary gear 114 creates a gear ratio in which multiple rotations of sun gear are required to achieve a single rotation of carrier. As a result, actuation of actuator 30 causes second threaded channel 66 to rotate more than first threaded channel 56, which in turn causes plunger translation screw 62 and plunger 60 to travel a greater distance than needle translation screw 52 and needle 50.

[0091] In some embodiments, the gear ratio of the sun gear 160 to the carrier 150 may be at least approximately 2:1, at least approximately 2.5:1, at least approximately 3:1, at least approximately 3.2:1, at least approximately 3.4:1, at least approximately 3.6:1, at least approximately 3.8:1, at least approximately 4:1, at least approximately 4.1:1, at least approximately 4.2:1, at least approximately 4.3:1, at least approximately 4.4:1, at least approximately 4.5:1, at least approximately 4.6:1, at least approximately 4.7:1, at least approximately 4.8:1, at least approximately 4.9:1, 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, or at least approximately 10:1. In some embodiments, the gear ratio of the sun gear to the carrier may be less than or equal to approximately 10:1, less than or equal to approximately 9:1, less than or equal to approximately 8:1, less than or equal to approximately 7:1, less than or equal to approximately 6:1, less than or equal to approximately 5:1, less than or equal to approximately 4.9:1, less than or equal to approximately 4.8:1, less than or equal to approximately 4.7:1, less than or equal to approximately 4.6:1, less than or equal to approximately 4.5:1, less than or equal to approximately 4.4:1, less than or equal to approximately 4.3:1, less than or equal to approximately 4.2:1, less than or equal to approximately 4.1:1, less than or equal to approximately 4:1, less than or equal to approximately 3.8:1, less than or equal to approximately 3.6:1, less than or equal to approximately 3.4:1, less than or equal to approximately 3.2:1, less than or equal to approximately 3:1, less than or equal to approximately 2.5:1, or less than or equal to approximately 2:1. Combinations of the above ranges are also possible. For example, in some embodiments, the gear ratio of the sun gear to the carrier may 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.

[0092] Although planetary gears are used in the conveying device shown in the attached figures, it should be understood that other types of gear systems may be used, such as spur gears, helical gears, racks and pinions, bevel gears, slant gears, worm gears, spiral gears, helical gears, hypoid gears, herringbone gears, internal gears, sawtooth gears, clock and pin gears, broken gears, cycloidal gear systems, intermittent gears, or any other suitable gear system, as this aspect is not limited thereto.

[0093] exist Figure 3BIn an exemplary embodiment, the delivery device 1 utilizes a combination of a gear system and a pair of threaded channels with different numbers of threads to enable the plunger and needle to travel different distances in response to actuation of the device actuator 30. This combination improves the travel distance ratio between the plunger and the needle. In other embodiments, the delivery device may utilize either a pair of threaded channels or a gear system without combining both.

[0094] In some embodiments, the stroke ratio between the plunger and the needle may be at least approximately 2:1, at least approximately 2.5:1, at least approximately 3:1, at least approximately 3.5:1, at least approximately 4:1, at least approximately 4.5:1, at least approximately 5:1, at least approximately 5.5:1, at least approximately 6:1, at least approximately 6.5:1, at least approximately 7:1, at least approximately 7.5:1, at least approximately 8:1, at least approximately 8.5:1, at least approximately 8.7:1, at least approximately 9:1, at least approximately 9.2:1, at least approximately 9.4:1, at least approximately 9.6:1, at least approximately 9.8:1, 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 17:1, at least approximately 18:1, at least approximately 19:1, or at least approximately 20:1. In some embodiments, the stroke ratio between the plunger and the needle may be less than or equal to approximately 20:1, less than or equal to approximately 18:1, less than or equal to approximately 16:1, less than or equal to approximately 14:1, less than or equal to approximately 12:1, less than or equal to approximately 11.8:1, less than or equal to approximately 11.6:1, less than or equal to approximately 11.4:1, less than or equal to approximately 11.2:1, less than or equal to approximately 11:1, less than or equal to approximately 10.9:1, less than or equal to approximately 10.8:1, less than or equal to approximately 10.7:1, less than or equal to approximately 10.6:1, less than or equal to approximately 10.5:1, less than or equal to approximately 10.4:1, less than or equal to approximately 10.3:1, less than or equal to... Approximately 10.2:1, less than or equal to approximately 10.1:1, less than or equal to approximately 10:1, less than or equal to approximately 9.9:1, less than or equal to approximately 9.8:1, less than or equal to approximately 9.7:1, less than or equal to approximately 9.6:1, less than or equal to approximately 9.5:1, less than or equal to approximately 9.4:1, less than or equal to approximately 9.3:1, less than or equal to approximately 9.2:1, less than or equal to approximately 9.1:1, less than or equal to approximately 9:1, less than or equal to approximately 8.7:1, less than or equal to approximately 8:1, less than or equal to approximately 7:1, less than or equal to approximately 6:1, less than or equal to approximately 5:1, less than or equal to approximately 4:1, less than or equal to approximately 3:1, or less than or equal to approximately 2:1. Combinations of the above ranges are also possible.For example, in some embodiments, the stroke ratio between the plunger and the needle may be 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 9.1:1 to approximately 10.9:1, or approximately 9.2:1 to approximately 10.8: 1. Or 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.

[0095] In some embodiments, the travel distance of the plunger can be at least approximately 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 less than or equal to approximately 300, 250, 200, 180, 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, or 10 mm. Combinations of the above ranges are also possible. For example, in some embodiments, the travel distance of the plunger may be approximately 10 to 300 mm, 20 to 250 mm, 30 to 200 mm, 40 to 180 mm, 50 to 160 mm, 60 to 140 mm, 70 to 140 mm, 100 to 140 mm, or 120 to 140 mm.

[0096] According to one aspect, the actuator of the delivery device may be a rotatable actuator. In some embodiments, the rotatable actuator can help slow the rate of expulsion of the therapeutic substance.

[0097] In some embodiments, such as Figure 3A As shown, the device actuator 30 is rotatably mounted relative to the housing 10. In some embodiments, such as in Figure 3A In an exemplary embodiment, the rotation axis of the device actuator is parallel to the longitudinal axis 4 of the conveying device 1. However, in other embodiments, the rotation axis of the device actuator may be perpendicular to the longitudinal axis of the conveying device. In some embodiments, the longitudinal axis of the conveying device is parallel to the outer shaft of the sleeve portion, the needle, and / or the plunger.

[0098] In some embodiments, the device actuator needs to be rotated multiple times to deliver the total target quantity. For example, in embodiments utilizing a delivery device with a volumetric configuration having a plunger that moves through a needle, to deliver the maximum quantity, the device actuator may need to be rotated multiple times to move the plunger from its pre-delivery position to its post-delivery position. In some embodiments, to deliver the maximum quantity, the distal end 65 of the plunger 60 (see...) Figure 3B The post-infusion position is located at or near needle opening 58 (see needle opening 58). Figure 4A ).

[0099] exist Figure 3B In the exemplary embodiment shown, the number of threads in the second threaded channel 66 determines how far the plunger translation screw 62 and plunger 60 move with each rotation of the device actuator 30.

[0100] In some embodiments, the number of threads in the second threaded channel may be at least about 1 thread per inch (TPI), at least about 4 TPI, at least about 4.4 TPI, at least about 4.6 TPI, at least about 4.8 TPI, at least about 5 TPI, at least about 5.1 TPI, at least about 5.2 TPI, at least about 5.3 TPI, at least about 5.4 TPI, at least about 5.5 TPI, at least about 5.6 TPI, at least about 5.7 TPI, at least about 5.8 TPI, at least about 5.9 TPI, at least about 6 TPI, at least about 6.1 TPI, at least about 6.2 TPI, at least about 6.3 TPI, at least about 6.4 TPI, at least about 6.5 TPI, at least about 7 TPI, at least about 8 TPI, at least about 9 TPI, at least about 10 TPI, at least about 12 TPI, at least about 14 TPI, at least about 20 TPI, at least about 40 TPI, at least about 60 TPI, or at least about 80 TPI. In some embodiments, the number of threads in the second threaded channel may be less than or equal to approximately 80 TPI, less than or equal to approximately 60 TPI, less than or equal to approximately 40 TPI, less than or equal to approximately 20 TPI, less than or equal to approximately 14 TPI, less than or equal to approximately 12 TPI, less than or equal to approximately 10 TPI, less than or equal to approximately 8 TPI, less than or equal to approximately 7 TPI, less than or equal to approximately 6.9 TPI, less than or equal to approximately 6.8 TPI, less than or equal to approximately 6.7 TPI, less than or equal to approximately 6.6 TPI, less than or equal to approximately 6.5 TPI, less than or equal to approximately 6.4 TPI, less than or equal to approximately 6.3 TPI, less than or equal to approximately 6.2 TPI, less than or equal to approximately 6.1 TPI, less than or equal to approximately 6 TPI, less than or equal to approximately 5.9 TPI, less than or equal to approximately 5.8 TPI, less than or equal to approximately 5.7 TPI, less than or equal to approximately 5.6 TPI, less than or equal to approximately 5.5 TPI, less than or equal to approximately 5.4 TPI, less than or equal to approximately 5.3 TPI, less than or equal to approximately 5.2 TPI, less than or equal to approximately 5.1 TPI, less than or equal to approximately 5 TPI, or less than or equal to approximately 4 TPI. Combinations of the above ranges are also possible.For example, in some embodiments, the number of threads in the second threaded channel may 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.

[0101] In some embodiments, to achieve maximum delivery, the actuator is rotated 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 revolutions. In some embodiments, to deliver maximum quantity, the actuator is rotated less than or equal to 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 full revolutions. Combinations of the above ranges are also possible. For example, in some embodiments, in order to deliver the maximum amount, the device actuator is rotated 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 full revolutions.

[0102] In other embodiments, to deliver the maximum conveying capacity, the device actuator may be rotated one full revolution or less than one full revolution. In some embodiments, to deliver the maximum conveying capacity, the device actuator is rotated at least about 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, or 360 degrees. In some embodiments, to achieve the maximum conveying capacity, the device actuator is rotated less than or equal to about 360, 340, 320, 300, 280, 260, 240, 220, 200, 180, 160, 140, 120, or 100 degrees. Combinations of the above ranges are also possible. For example, in some embodiments, to deliver the maximum conveying capacity, the device actuator is rotated about 100 to about 360 degrees, or about 120 to about 340 degrees, or about 160 to about 300 degrees, or about 200 to about 260 degrees.

[0103] In some embodiments, the maximum delivery capacity may be at least approximately 1 μL, at least approximately 2 μL, at least approximately 3 μL, at least approximately 4 μL, at least approximately 5 μL, at least approximately 6 μL, at least approximately 7 μL, at least approximately 7.2 μL, at least approximately 7.4 μL, at least approximately 7.6 μL, at least approximately 7.8 μL, at least approximately 8 μL, at least approximately 8.1 μL, at least approximately 8.2 μL, at least approximately 8.3 μL, at least approximately 8.4 μL, at least approximately 8.5 μL, at least approximately 8.6 μL. Liters, 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 milliliter, at least about 10 milliliters, at least about 100 milliliters, at least about 500 milliliters, or at least about 800 milliliters. In some embodiments, the maximum delivery volume may be less than or equal to about 1000 ml, less than or equal to about 800 ml, less than or equal to about 500 ml, less than or equal to about 100 ml, less than or equal to about 10 ml, less than or equal to about 1 ml, less than or equal to about 100 μL, or less than or equal to about 90 μL, or less than or equal to about 80 μL, or less than or equal to about 70 μL, or less than or equal to about 60 μL, or less than or equal to about 50 μL, or less than or equal to about 40 μL, or less than or equal to about 30 μL, or less than or equal to about 20 μL, or less than or equal to about 15 μL, or less than or equal to about 12 microliters, or less than or equal to about 10 microliters, or less than or equal to about 9.9 microliters, or less than or equal to about 9.8 microliters, or less than or equal to about 9.7 microliters, or less than or equal to about 9.6 microliters, or less than or equal to about 9.5 microliters, or less than or equal to about 9.4 microliters, or less than or equal to about 9.3 microliters, or less than or equal to about 9.2 microliters, or less than or equal to about 9.1 microliters, or less than or equal to about 9 microliters, or less than or equal to about 8.8 microliters, or less than or equal to about 8.2 microliters, or less than or equal to about 8 microliters, or less than or equal to about 7 microliters, or less than or equal to about 6 microliters, or less than or equal to about 5 microliters. Combinations of the above ranges are also possible.For example, in some embodiments, the maximum delivery volume is 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 μL to about 100 μL, or about 2 μL to about 60 μL, or about 3 μL to about 30 μL, or about 4 μL to about 20 μL, or about 5 μL to about 18 μL, or about 6 μL to about 16 μL, or about 7 μL to about 14 μL, or about 8 μL to about 10 μL, or about 8.5 μL to about 9.5 μL, or about 8.9 μL to about 9.1 μL, or about 9 μL to about 9.1 μL.

[0104] While at least some of the exemplary embodiments discussed herein may be purely mechanical, it should be understood that in other embodiments, the delivery device may be electrically powered. For example, in some embodiments, the delivery device may include an electric motor that can be actuated by a user to advance the plunger and / or retract the needle. In some embodiments, the delivery device may be remotely controlled using wireless communication. The delivery device may have a portable power supply and / or be adapted to receive power from a power outlet. In some embodiments, the delivery device may be connected to an external electric motor via a flexible torque cable.

[0105] According to one aspect, the therapeutic substance is loaded into the delivery device from the front via a dispensing end of the apparatus. This configuration helps reduce waste or loss of the therapeutic substance (e.g., by avoiding transfer of the substance through multiple components).

[0106] In some embodiments, the delivery device may include a venting configuration to allow front-side loading. In some embodiments, during loading of the delivery device, drawing therapeutic material into the needle lumen expels air from the needle lumen. In some embodiments, a vent is provided to allow displaced air to escape from the needle lumen. In some embodiments, such a venting configuration can help avoid or reduce pressurization of the therapeutic material and / or the needle lumen. In some embodiments, such a venting configuration can help prevent air and therapeutic material from competing for volume space. In some embodiments, such a venting configuration can help reduce the introduction of air bubbles into the therapeutic material.

[0107] exist Figure 3B In the exemplary embodiment shown, the needle 50 includes a vent 59 in the form of a through-hole opening penetrating the wall 57 of the needle 50. The vent 59 is opened or closed based on the position of the plunger 60. When the distal end 65 of the plunger 60 is away from the vent 59, as... Figure 3B As shown, vent 59 is closed. Vent 59 opens when the distal end 65 of plunger 60 approaches vent 59.

[0108] exist Figures 10A-10CThe diagram illustrates some embodiments of the front loading sequence. When the vent 59 is in the open state, as... Figure 10A As shown, the therapeutic substance 180 is moved into the needle lumen 51 through the needle opening 58 in the proximal loading direction 181. As the therapeutic substance 180 is moved into the needle lumen 51, the air previously occupying the needle lumen 51 is discharged through the open vent 59 and enters the shaft lumen 41.

[0109] In some embodiments, the delivery device is passively loaded with the therapeutic substance; for example, the delivery device itself is not actuated during loading. An active loading device, such as a pump, can be used to move the therapeutic substance into the needle lumen. The pump can be an infusion pump or any other suitable pump. In some embodiments, the therapeutic substance is transferred from a retainer into the needle lumen.

[0110] Next, as Figure 10B As shown, the vent 59 is closed. In some embodiments, the user closes the vent 59 by actuating the device actuator 30 to push the plunger 60 distally until the distal end 65 of the plunger is distal to the vent 59.

[0111] In some embodiments, a flushing step is performed to remove air from the inner cavity of the space between the outer shaft and the needle. For example... Figure 10B As shown, the delivery device includes a flushing port 90. Flushing fluid 184, such as a transplantation medium, can be injected through the flushing port 90 in the flushing direction 185, and allowed to pass through valve 92, channel 93, and opening 49 in the outer shaft 40. The transplantation medium can pass through the space between the outer shaft 40 and the needle 50, as indicated by arrow 182. The user can observe the flushing fluid flowing out from the distal end 45 of the outer shaft 40, indicating to the user that the device has been pre-injected and is ready for delivery into the tissue. Figure 10C The device is shown as a pre-injected device ready for delivery, wherein therapeutic substance 180 is loaded into the needle lumen, plunger 60 covers vent 59, and air is expelled from cannula portion 9.

[0112] The inventors recognized that after the therapeutic substance is expelled from the needle into a space of a certain volume created at the target site 215 by withdrawing the needle, a suction effect occurs when the cannula portion 9 is withdrawn from the tissue into which it was inserted. This suction effect may pull a portion of the therapeutic substance away from the target site 215, thereby reducing the dose of the therapeutic substance delivered to the target site 215.

[0113] The delivery device can be configured to mitigate the suction effect experienced during withdrawal of the cannula portion 9 from the tissue. For example, the valve 92 of the flushing port 90 can be configured to be in the open position to expose the interior of the cannula portion 9 (particularly the space between the outer shaft 40 and the needle 50) to atmospheric pressure, thereby draining flushing fluid 184 into the tissue as the cannula portion 9 is withdrawn. The valve 92 can be configured to receive a device, such as an open needle, to expose the space between the outer shaft 40 and the needle 50 to atmospheric pressure, thereby draining flushing fluid 184 into the tissue as the cannula portion 9 is withdrawn. The discharge of flushing fluid 184 to the target site 215 can counteract the suction effect, thereby mitigating the dose reduction of the therapeutic substance delivered to the target site 215 as the cannula portion 9 is withdrawn from the tissue.

[0114] According to one aspect, the conveying device may include an indicator comprising only mechanical components. Because there are no electrical components, such a construction makes the conveying device more portable and / or easier to sterilize.

[0115] In some embodiments, a transmission system may be used to transmit the actuating force applied to the device actuator to a component having a marker reflecting the amount delivered and / or a marker reflecting the status of the device (e.g., ready to load therapeutic substances), so as to move it. Figure 11 An exemplary embodiment of a mechanical indicator is shown in the figure. Figure 11 The indicator device uses an intermittent gear system 200. The intermittent gear system 200 includes a first drive wheel 230 that can rotate at 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 that interacts with and drives a driven wheel portion 252 of an indicator gear 250. The indicator gear 250 also includes a marking portion 254. Figure 1 and Figure 2 As shown, the markings on the marking portion 254 can be seen through the indicator window 255 of the conveying device. When the device actuator 30 is actuated, the marking portion 254 rotates, reflecting the amount that has been conveyed.

[0116] Although Figure 11 In the exemplary embodiments, an intermittent gear system is used to connect the device actuator 30 to the marking portion 254; however, it should be understood that any other suitable gear system or force transmission system may be used. In some embodiments, the conveying device uses a digital display to indicate the conveying quantity and / or convey any other suitable information.

[0117] In some embodiments, any of the delivery devices described herein can be used in conjunction with a stereotactic frame, for example, for neurosurgical applications. Figure 12 An exemplary example of a stereoscopic frame is shown. The stereoscopic frame 300 includes an arm 302 for receiving a conveying device. In some embodiments, the conveying device is sized to be physically compatible with the stereoscopic frame. Figure 3A In the exemplary embodiment shown, the conveying device 1 includes a mounting connector 80 sized to mate with an arm of a stereoscopic frame. The mounting connector of the conveying device can be held by the stereoscopic frame. In some embodiments, the conveying device is compatible with LEKSELL stereoscopic frames. However, it should be understood that the conveying device can be compatible with other stereoscopic frames, as this aspect is not limited thereto.

[0118] In some embodiments, the delivery device is compatible with frameless stereotactic systems. For example, the subject's head (including target tissue) can be secured with clamps, such as standard Mayfield clamps. Furthermore, the delivery device may include part of a tracking system for tracking the position and angle of the delivery device. This tracking system may include one or more optical tracking systems and electromagnetic tracking systems. The optical tracking system may include one or more optical cameras configured to track one or more identifiable structures built into or disposed on the delivery device, or to track one or more unique optical wavelengths emitted from transmitters built into or disposed on the delivery device. The optical tracking system may employ techniques such as distance measurement utilizing parallax principles, object recognition, and other image processing techniques to calculate the position and angle of the delivery device relative to the subject's head. The electromagnetic tracking system may include one or more electromagnetic field transmitters and one or more electromagnetic field detectors. One of the one or more electromagnetic field transmitters and the one or more electromagnetic field detectors may be built into or disposed on the delivery device, while another of the one or more electromagnetic field transmitters and the one or more electromagnetic field detectors may be arranged near the delivery device. The electromagnetic tracking system can calculate the position and angle of the delivery device relative to the subject's head based on known values ​​of electromagnetic fields emitted by the one or more electromagnetic field emitters and electromagnetic fields detected by the one or more electromagnetic field detectors. The position and angle of the delivery device calculated by the tracking system can be used as a visual guidance output to guide the insertion of the delivery device. The position and angle of the delivery device calculated by the tracking system can also be output to a robotic system that controls one or more actuators to guide the insertion of the delivery device. The position and angle of the delivery device calculated by the tracking system can also be superimposed on images obtained by imaging systems such as computed tomography, magnetic resonance imaging, and positron emission tomography to aid in the insertion of the delivery device. It should be understood that the delivery device is compatible with other frameless stereotactic systems, as it is not limited thereto.

[0119] In some embodiments, the needle is deployed into the tissue by advancing the entire delivery device distally. If the delivery device is connected to a stereotactic frame, the frame can help guide the delivery device distally. The operator can then actuate the device actuators to deliver the therapeutic substance.

[0120] It should be understood that in some embodiments, the needle can be actuated to move in a deployment direction relative to the outer shaft and / or relative to the housing of the delivery device. In some embodiments, a single actuator can be used to move the needle in the deployment direction and dispense 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 dispense the therapeutic substance.

[0121] Next, we will refer to Figure 13 This describes a method for preparing and pre-filling a delivery device for use. The method may include step S1302. Step S1302 may include arranging one or more of a needle 50, a needle translation screw 52 attached to the needle 50, a plunger 60, and a plunger translation screw 62 attached to the plunger 60 in the housing 10 and outer shaft 40 of the delivery device. For example, the needle translation screw 52 may be arranged to engage a first threaded channel 56, and the plunger translation screw 62 may be arranged to engage a second threaded channel 66 within the housing 10. Furthermore, the plunger 60 may be arranged within the needle cavity 51 of the needle 50, and the needle 50 with the plunger 60 arranged therein may be arranged within the shaft cavity 41 of the outer shaft 40. Step S1302 may allow the needle 50 and plunger 60 to be replaced with the same type of needle and plunger. Furthermore, step S1302 allows for the selection of different types of needles 50 (e.g., needles 50 with different capacities of needle cavities 51) and corresponding plungers 60, and their arrangement within the housing 10 of the delivery device.

[0122] After step S1302, step S1304 can be performed. Step S1304 may include operating the actuator 30 to cause relative movement between the needle 50 and the plunger 60, thereby arranging the needle opening 58 distal to the opening 45 of the outer shaft 40 in the direction of the longitudinal axis 4, and arranging the distal end 65 of the plunger 60 proximal to the vent 59 of the needle 50, as shown. Figure 10A As shown.

[0123] After step S1304, step S1306 can be performed. Step S1306 may include passively loading the therapeutic substance 180 from the front into the needle lumen 51 of the needle 50, such as... Figure 10A As shown. For example, an active loading device such as a pump can be used to move the therapeutic substance 180 into the needle cavity 51 through the needle opening 58 in a proximal loading direction 181. As the distal end 65 of the plunger 60 moves proximal to the vent 59 of the needle 50 in step S1304, air previously occupying the needle cavity 51 is discharged into the shaft cavity 41 through the open vent 59 as the therapeutic substance 180 moves into the needle cavity 51.

[0124] After step S1306, step S1308 can be performed. Step S1308 may include operating the actuator 30 to advance the distal end of the plunger 60 to a position distal to the exhaust port 59, such as... Figure 10B As shown, the vent 59 of the needle 50 is closed. Step S1308 may also include operating the device actuator 30 to move one or more of the needle 50 and the plunger 60, and simultaneously driving the indicator device to a position where a mark reflecting the full dose (target amount) of the therapeutic substance 180 is loaded into the needle lumen 51.

[0125] After step S1308, step S1310 can be performed. Step S1310 may include directing the flushing fluid 184 through the flushing port 90 of the conveying device and the opening 49 of the outer shaft 40 into the... Figure 10B The flushing fluid 184 is injected into the space between the outer shaft 40 and the needle 50 in the indicated flushing direction 185 to eliminate air from the space between the outer shaft 40 and the needle 50. The injection of flushing fluid 184 can continue until flushing fluid 184 is observed to flow out from the distal end 45 of the outer shaft 40. At this point, the delivery device can be considered to be in a position similar to... Figure 10C The pre-injection status is shown.

[0126] It should be noted that the method for preparing and pre-injecting the delivery device may include a portion of the steps described above, while omitting one or more of the steps. When the delivery device is for single-use, step S1302, which involves arranging the needle 50, needle translation screw 52, ​​plunger 60, and plunger translation screw 62 within the housing 10, may be omitted. Alternatively, when the housing 10 is configured to accommodate different types of needles and plungers, step S1302 may be included in the method.

[0127] Next, we will refer to Figure 14 A method for using a delivery device is described. This method may include step S1402. Step S1402 may include deploying the needle 50 and outer shaft 40 into the tissue. Deploying the needle 50 and outer shaft 40 into the tissue may include advancing the entire delivery device distally to position the needle tip 55 at the target site 215. Advancing the entire delivery device may be done manually. Alternatively, advancing the entire delivery device may include guiding the delivery device using a stereotactic frame or a frameless stereotactic system to guide the delivery device to position the needle tip 55 at the target site 215.

[0128] Following step S1402, step S1404 may be performed. Step S1404 may include operating the device actuator 30 to discharge the therapeutic substance 180 at the target site 215. Discharging 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 discharge the therapeutic substance 180. Specifically, discharging the therapeutic substance 180 may include retracting the needle 50 to create a volumetric space for the therapeutic substance 180 discharged from the delivery device to suppress, thereby reducing, backflow of the therapeutic substance 180 outside the target site 215.

[0129] Following step S1404, step S1406 may be performed. Step S1406 may include discharging the flushing fluid 184 occupying the space between the outer shaft 40 and the needle 50 toward the target site 215. Discharging the flushing fluid 184 may include setting the valve 92 of the flushing port 90 to the open position to expose the space between the outer shaft 40 and the needle 50 to atmospheric pressure, thereby discharging the flushing fluid 184 into the tissue. For example, a device such as an open needle may be inserted into the valve 92 to set the valve 92 to the open position.

[0130] After step S1406, step S1408 may be performed. Step S1408 may also be performed together with step S1406. Step S1408 may include withdrawing the needle 50 and outer shaft 40 from the tissue. Withdrawing the needle 50 and outer shaft 40 from the tissue may include retracting the entire delivery device proximally to separate the needle tip 55 and outer shaft 40 from the tissue. Retraction of the entire delivery device may be performed manually. Alternatively, retraction of the entire delivery device may include guiding the delivery device through a stereotactic frame or frameless stereotactic system to separate the needle tip 55 and outer shaft 40 from the tissue.

[0131] It should be noted that the method of using the delivery device may include a portion of the steps described above, while omitting one or more of the steps. For example, if the risk of aspiration effect caused by withdrawing the needle 50 from the tissue is considered to be minimal, then step S1406 of draining the flushing fluid 184 may be omitted.

[0132] While this teaching is illustrated in conjunction with various embodiments and examples, it is not intended to limit this teaching to these embodiments or examples. Rather, those skilled in the art will understand that this teaching encompasses various alternatives, modifications, and equivalents. Therefore, the foregoing description and figures are merely exemplary.

Claims

1. A conveying device, comprising: Device actuator; A needle with an internal lumen; as well as A first translational screw attached to the needle tip and located within a first threaded channel; A plunger configured to move through the inner cavity of a needle; and The second translation screw is attached to the plunger and located within the second threaded channel. The actuation of the actuator causes rotation of the first and second threaded channels, which in turn causes the first translation screw to translate through the first threaded channel and the second translation screw to translate through the second threaded channel. This, in turn, causes the needle to move in the retraction direction and the plunger to move through the needle cavity in the deployment direction, the retraction direction being opposite to the deployment direction. The movement of the needle occurs simultaneously with the movement of the plunger.

2. The delivery device of claim 1, further comprising an outer shaft having an inner cavity, the needle being configured to move through the inner cavity.

3. The delivery device of claim 2, wherein actuation of the device actuator causes the needle to move a first distance relative to the outer shaft and causes the plunger to move a second distance relative to the outer shaft, the first distance being different from the second distance.

4. The conveying device as claimed in claim 3, wherein the first distance is less than the second distance.

5. The conveying device of claim 3, wherein the ratio of the second distance to the first distance is 2:1 to 20:

1.

6. The conveying device as claimed in claim 5, wherein the ratio is 10:

1.

7. The conveying device as claimed in claim 1, wherein the rotation of the first threaded channel occurs in a first rotational direction, and the rotation of the second threaded channel occurs in a second rotational direction opposite to the first rotational direction.

8. The conveying device of claim 7, wherein the first threaded channel includes a first thread having a first number of threads, and the second threaded channel includes a second thread having a second number of threads, the first number of threads being different from the second number of threads.

9. The conveying device as claimed in claim 8, wherein the first number of threads is greater than the second number of threads.

10. The conveying device of claim 7, wherein the first threaded channel includes a first thread having a first thread orientation, and the second threaded channel includes a second thread having a second thread orientation, the first thread orientation and the second thread orientation being opposite to each other.

11. The conveying device of claim 10, wherein the first thread orientation is a right-hand thread and the second thread orientation is a left-hand thread.

12. The conveying device of claim 7, further comprising a gear system for connecting the device actuator to the first threaded channel.

13. The conveying device of claim 12, wherein the gear system comprises a planetary gear system including a sun gear and a plurality of planetary gears rotatably mounted on a bracket, and wherein the sun gear is coupled to a device actuator and a second threaded channel, and wherein the bracket is coupled to a first threaded channel.

14. The conveying device of claim 1, further comprising a gear system connecting the device actuator to the plunger and the needle.

15. The conveying device of claim 14, wherein the gear system comprises a planetary gear system having a sun gear and a plurality of planetary gears rotatably mounted on a carrier, wherein the sun gear is attached to a device actuator and coupled to a plunger, and wherein the carrier is coupled to a needle.

16. The delivery device of claim 1, wherein the needle cavity has a constant diameter over the entire length of the needle.

17. The delivery device of claim 1, wherein the volume of space through which the plunger passes in response to device actuation is within 1% to 20% of the volume of space through which the needle passes.

18. The conveying device as claimed in claim 1, comprising: An outer shaft with an inner cavity, through which the needle is configured to move. The actuation of the actuator in the device causes the needle to move a first distance relative to the outer shaft, and causes the plunger to move a second distance relative to the outer shaft, the first distance being different from the second distance. The first distance is less than the second distance.

19. The conveying device of claim 18, wherein the ratio of the second distance to the first distance is 2:1 to 20:

1.

20. The conveying device of claim 19, wherein the ratio is from 7:1 to 10:

1.

21. The conveying device of claim 18, wherein the first distance is 0.1 inches to 1 inch.

22. The conveying device of claim 21, wherein the first distance is 0.3 inches to 0.7 inches.

23. The conveying device of claim 18, wherein the second distance is 3 inches to 7 inches.

24. The conveying device of claim 23, wherein the second distance is 4 inches to 5 inches.

25. The delivery device of claim 18, wherein actuation of the device actuator causes the needle to move in a retraction direction through the shaft cavity and causes the plunger to move in a deployment direction through the needle cavity, the retraction direction being opposite to the deployment direction.

26. The conveying device of claim 1, wherein the first threaded channel includes a first thread having a first number of threads, and the second threaded channel includes a second thread having a second number of threads, the first number of threads being different from the second number of threads.

27. The conveying device of claim 26, wherein the first number of threads is less than the second number of threads.

28. The conveying device of claim 1, wherein the first threaded channel includes a first thread having a first thread orientation, and the second threaded channel includes a second thread having a second thread orientation, the first thread orientation and the second thread orientation being opposite to each other.

29. The conveying device of claim 28, wherein the first thread orientation is a left-hand thread and the second thread orientation is a right-hand thread.

30. The conveying device of claim 1, further comprising a gear system connecting the device actuator to the first threaded channel and the second threaded channel.

31. The conveying device of claim 30, wherein the gear system comprises a planetary gear system having a sun gear and a plurality of planetary gears rotatably mounted on a bracket, and wherein the sun gear is attached to a device actuator and a second threaded channel, and wherein the bracket is attached to a first threaded channel.

32. The conveying device as claimed in claim 1, comprising: Device housing; as well as A device actuator that is rotatably mounted relative to the device housing. The rotation of the actuator in the device causes the plunger to move through the inner cavity of the needle.

33. The conveying device of claim 32, wherein the device actuator has a rotation axis parallel to the extension direction of the plunger.

34. The conveying device of claim 32, wherein the actuator of the device needs to be rotated multiple full revolutions to achieve the maximum conveying capacity.

35. The conveying device of claim 34, wherein the plurality of full rotations comprises 5 to 40 rotations.

36. The conveying device of claim 34, wherein the maximum conveying capacity comprises 5 to 15 microliters.

37. The delivery device of claim 32, wherein actuation of the actuator causes the needle to move through the inner cavity of the outer shaft and simultaneously causes the plunger to move through the inner cavity of the needle in a deployment direction, the retraction direction being opposite to the deployment direction.

38. The conveying device of claim 32, further comprising a gear system connecting the device actuator to the plunger and the needle.

39. The conveying device of claim 38, wherein the gear system comprises a planetary gear system having a sun gear and a plurality of planetary gears rotatably mounted on a bracket, wherein the sun gear is attached to a device actuator and coupled to a plunger, and wherein the bracket is coupled to a needle.

40. The conveying device of claim 39, wherein the sun gear and the device actuator are integrally formed as a single component.

41. A method of loading material into a delivery device, the delivery device comprising a needle having a needle lumen and a plunger configured to move through the needle lumen, wherein actuation of a device actuator in a first direction causes the needle to move in a retraction direction and simultaneously causes the plunger to move through the needle lumen in a deployment direction, the retraction direction being opposite to the deployment direction, the method comprising: Cells are transferred into the inner lumen of the needle through the delivery end of the needle; As the cells are transferred into the needle lumen, air is expelled from the needle lumen through the vent in the needle; and After the cells are transferred into the needle lumen, the fluid connection through the vent is shut off.

42. The method of claim 41, further comprising loading the substance into the delivery device by moving the substance into the needle lumen of the needle.

43. The method of claim 41, further comprising loading the substance into the needle such that the substance is completely contained within the lumen of the needle, wherein, The vent is configured to be in an open position during front loading to allow air to escape from the needle lumen during the loading of the material into the delivery device.

44. The method of claim 41, wherein the step of shutting off fluid communication through the vent includes moving a plunger in the needle cavity along a deployment direction to cover the vent, the vent comprising an opening in the wall of the needle.

45. The method of claim 41, further comprising flushing the outer axis surrounding the needle with a flushing fluid.

46. ​​The conveying device as claimed in claim 1, comprising: Device housing; as well as The needle has a delivery end, a shaft, and a needle cavity extending through the shaft. The needle also includes a vent located in the shaft, which is spaced apart from the delivery end.

47. The conveying device of claim 46, wherein the plunger has a first position and a second position, wherein in the first position, fluid communication through the vent is opened, and in the second position, fluid communication through the vent is closed.

48. The conveying device of claim 46, further comprising a device actuator, wherein the actuation of the device actuator moves the plunger in the deployment direction and shuts off the fluid communication through the vent.

49. The conveying device of claim 46, wherein the vent is a through hole penetrating the wall of the shaft.

50. The conveying device as claimed in claim 46, further comprising: Flushing port; The outer axis surrounding the needle tip has an opening; as well as A valve that controls the fluid communication between the flushing port and the opening of the outer shaft.

51. The delivery device of claim 46, further comprising a therapeutic substance loaded into the delivery device, wherein the therapeutic substance is completely contained within the needle lumen.

52. The delivery device of claim 51, wherein the needle cavity has a constant diameter over its entire length.

53. The conveying device as claimed in claim 1, comprising: An outer shaft with an internal cavity, The diameter of the inner cavity of the needle is between 0.1 mm and 0.7 mm, including 0.1 mm and 0.7 mm, and the needle is configured to move through the inner cavity of the shaft; The plunger has a travel distance of at least 100 mm relative to the outer shaft. The actuation of the actuator of the device causes the needle to move a first distance relative to the outer shaft and causes the plunger to move a second distance relative to the outer shaft, the first distance being different from the second distance.

54. The delivery device of claim 53, wherein actuation of the device actuator causes the plunger to move through the needle cavity while the needle moves through the shaft cavity.

55. The delivery device of claim 54, wherein the device actuator is rotatably mounted relative to the device housing, wherein rotation of the device actuator causes the plunger to move through the needle cavity.

56. The conveying device of claim 55, wherein the device actuator has a rotation axis parallel to the extension direction of the plunger.

57. The conveying device of claim 56, wherein the actuator of the device needs to be rotated multiple full revolutions to achieve the maximum conveying capacity.

58. The conveying device as claimed in claim 1, comprising: An indicator with a mark indicating the delivered dose is mechanically coupled to a device actuator, such that actuation of the device actuator causes the mark on the indicator to move physically without requiring an electrical input.

59. The conveying device of claim 58, further comprising a gear system mechanically connecting the indicator to the device actuator.

60. The conveying device of claim 59, wherein the gear system comprises an intermittent gear system.

61. The conveying device as claimed in claim 1, comprising: Therapeutic substances completely contained within the needle lumen. The inner diameter of the needle lumen is constant along the entire length of the needle. The actuator of the device is configured to move a plunger through the needle lumen to expel the therapeutic substance from the delivery end of the needle.

Images