WO2025212978A1

WO2025212978A1 - Delivery system for therapeutic substances

Info

Publication number: WO2025212978A1
Application number: PCT/US2025/023085
Authority: WO
Inventors: Matthew Gardner Maher; Stefanie POHLOD; Jonathan RUBIANTO
Original assignee: BlueRock Therapeutics LP
Current assignee: BlueRock Therapeutics LP
Priority date: 2024-04-05
Filing date: 2025-04-04
Publication date: 2025-10-09
Anticipated expiration: 2026-10-05

Abstract

A delivery system including: a device having a cannula and a wire stylet; and one or more holder assemblies. The cannula having a lumen extending from a distal end to a proximal end, and the wire stylet having a shaft configured to move through the cannula lumen. Movement of the wire stylet shaft within the cannula lumen infuses or ejects a substance out of the distal end of the cannula lumen. Each of the one or more holder assemblies includes: a holding member having a cavity and a channel; a sealing member having a passageway sized to permit at least one of the device group consisting of: the cannula, the wire stylet, and combinations thereof, the sealing member positioned within the cavity of the holding member; and a nut moveable on the holding member to compress the sealing member within the cavity of the holding member to adjust the size of the passageway of the sealing member.

Description

DELIVERY SYSTEM FOR THERAPEUTIC SUBSTANCES

FIELD

[0001] Disclosed embodiments are related to delivery systems and/or devices and related methods of use, including systems to deliver therapeutic substances or agents to a specific site in the body.

BACKGROUND

[0002] Therapeutic substances are administered to patients through a variety of methods.

Various routes of administration are possible, including: oral, inhalation, topical, intravascular, intramuscular, subcutaneous, intraperitoneal, rectal/vaginal, transluminal, and more tissuespecific routes (e.g., intracranial, intrathecal, intraventricular, and intra-articular).

[0003] Cell-based therapeutics are commonly administered using conventional delivery devices, such as a needle and syringe, or a balloon-dilating catheter. Injection of cell-based therapeutics through skin or mucosa or intracranially may help to bypass some of the body’s defense barriers, and may enable delivery of therapeutic substances, including cell-based therapeutics to a specific site.

SUMMARY

[0004] In one or more embodiments, a delivery system is provided. The delivery system includes a delivery device and one or more holder assemblies (also referred to as holding assemblies), e.g., at least a first holder assembly. The delivery device may include a cannula and a wire stylet insertable and moveable within the cannula to infuse and/or eject a substance, e.g., a therapeutic substance. The cannula has a lumen extending from a distal end to a proximal end, and the wire stylet has a shaft configured to move through the cannula lumen. Movement of the wire stylet shaft within the cannula lumen infuses (loads) or ejects a substance out of the distal end of the cannula lumen.

[0005] The at least first holder assembly of the delivery system includes in one or more embodiments: a first holding member having a first cavity and a first longitudinal channel; a first sealing member having a first passageway sized to permit at least one of a device group consisting of: the cannula, the wire stylet, and combinations thereof to move therethrough, the first sealing member positioned within the first cavity of the first holding member; and a first nut moveable relative to the first holding member to compress the first sealing member within the first cavity of the first holding member to adjust the size of the first passageway of the first sealing member. In an embodiment, the first nut has a threaded section to threadably attach to a mating thread on the first holding member, the first nut moveable relative to the first holding member by rotating the first nut on the first holding member.

[0006] In an embodiment the first holder assembly and/or first holding member is configured to be a secured to a stabilizing frame, e.g., a stereotactic frame, and in a further configuration a proximal end of the first holding member is securable to the stabilizing (e.g., stereotactic frame). In another embodiment the at least first holder assembly and/or the first holding member is configured to be associated with a depth stop on a stabilizing frame, e.g., a stereotactic frame, that controls how far the cannula goes into the frame, where in an embodiment the at least first holder assembly can be and/or act as the depth stop.

[0007] In one or more embodiments, the at least first holder assembly is configured so that movement of the first nut of the at least first holder assembly secures the at least first holder assembly to the device group. In one or more approaches, movement of the first nut of the at least first holder assembly adjustably compresses the first sealing member about the shaft of the wire stylet to provide adjustable friction to resist movement of the shaft of the wire stylet through the first sealing member. In an embodiment, the first nut is adjustable to compress the first sealing member about the shaft of the wire stylet to provide sufficient friction to both restrict and permit sliding movement of the wire stylet through the at least first holder assembly and/or first holding member. Movement of the first nut of the at least first holder assembly in one or more approaches compresses the first sealing member about the device group to prevent movement of the device group through the passageway of the first scaling member. In an arrangement, movement of the first nut of the at least first holder assembly compresses the first sealing member about the proximal end of the cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula. In an embodiment, the first sealing member is formed from silicone and in an arrangement, at least a portion of the first cavity is conically shaped.

[0008] The first holding member in an approach has an extension and a secondary channel wherein the secondary channel communicates with the first longitudinal channel in the first holding member. The first nut in a configuration has a through hole configured to permit the device group to pass therethrough and the first longitudinal channel of the first holding member in an arrangement is configured to permit the device group to pass therethrough. In one or more embodiments, the first holder member has a holder threaded section, the first nut has a nut threaded section such that the holder threaded section mates with the nut threaded section so that rotation of the first nut causes the first nut to move relative to the first holding member to compress the first passage ay and/or the first sealing member.

[0009] The delivery system in an embodiment further includes at least a second holder assembly, wherein the first holder assembly is configured to be attachable to the second holder assembly. In a configuration, the first holder assembly further includes a proximal extending portion configured to be attachable the second holder assembly. In an approach the second holder assembly optionally is further securable to the wire stylet in a manner that resists and permits sliding movement of the wire stylet through the second holder assembly. The second holder assembly in a configuration includes a casing extending proximally with graduations. In an arrangement the second holder assembly includes: a second holding member having a second cavity and a second longitudinal channel; a rigid stabilizing member having a passageway sized to permit the wire stylet to pass therethrough, the stabilizing member positioned within the cavity of the second holding member and configured to stabilize the wire stylet; and a second nut moveable relative to the holding member to contain the stabilizing member within the second cavity of the holding member. [0010] A holder assembly for stabilizing a delivery device is disclosed, where the delivery device in an embodiment includes a cannula and a wire stylet configured to move through a lumen of the cannula. The holder assembly according to an arrangement includes: a holding member having a cavity and a longitudinal channel; a sealing member having a passageway sized to permit at least one of a device group consisting of: a cannula, a wire stylet, and combinations thereof to pass therethrough, the sealing member positioned within the cavity of the holding member; and a nut moveable relative to the holding member to compress the sealing member within the cavity of the holding member to adjust the size of the passageway of the sealing member.

[0011] The holder assembly is configured so that movement of the nut secures the holder assembly to the device group. In an arrangement, the holding assembly is configured so that movement of the nut compresses the sealing member about a shaft of the wire stylet to provide friction to resist and permit sliding movement of the shaft of the wire stylet through the passageway of the sealing member. The holding assembly according to another embodiment is configured so that movement of the nut compresses the sealing member about the device group to prevent movement of the device group through the passageway of the sealing member. The holding assembly according to a further embodiment is configured so that movement of the nut compresses the sealing member about the proximal end of the cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula. The sealing member in one or more embodiments formed of silicone. In a further optional arrangement, at least a portion of the cavity of the holding member is conically shaped.

[0012] The nut in a configuration has a through hole configured to permit the device group therethrough and the channel of the holding member is also configured to permit the device group to pass therethrough. The holder assembly in a further arrangement further includes a casing with graduations. In a further embodiment, the holding member has a secondary channel in communication with the longitudinal channel of the holding member for flushing at least the cannula. In yet an optional further embodiment, the holder member has an extension, the extension having a passageway in communication with the secondary channel. A distal end of the holding member according to an arraignment is configured to be secured to a stabilizing frame.

[0013] Also disclosed is a manner of operating the delivery system including assembling one or more holder assemblies on the delivery device, and using the one or more holding assemblies to front load the substance, e.g., the therapeutic substance, into the distal end of the cannula by withdrawing the wire stylet within the cannula lumen away from the proximal end of the cannula and to eject or deliver the substance out of the distal end of the cannula by sliding the wire stylet proximally within the cannula lumen.

[0014] It should be appreciated that the foregoing concepts, and additional concepts discussed below, may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying figures.

BRIEF DESCRIPTION OF DRAWINGS

[0015] The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:

[0016] FIG. 1 is a perspective view of one example embodiment of a delivery system;

[0017] FIG. 2 is a cross-sectional view of the example delivery system of FIG. 1;

[0018] FIG. 3 is a perspective view of the wire stylet of the example delivery system of FIG. 1; [0019] FIG. 4 is a stereotactic frame for use with the delivery system, according to one embodiment;

[0020] FIG. 5 is a perspective view of another example embodiment of a delivery system;

[0021] FIG. 6 is a cross-sectional view of the example delivery system of FIG. 5; and

[0022] FIG. 7 is a perspective view of the wire stylet of the example delivery system of FIG. 5.

DETAILED DESCRIPTION

[0023] With some conventional delivery devices, the delivery device is inserted into tissue to reach a target site, a therapeutic substance is ejected out of the delivery device and into the target site, and then the delivery device is withdrawn from the target site. As discussed in more detail below, the inventors have appreciated that some of these conventional delivery devices experience undesirable instability of the delivery device for delivering the therapeutic substance. The inventors have also appreciated that, with some conventional cell delivery devices, handling, and delivery of the therapeutic substance out of the distal end of the delivery device to the target site can be difficult and cumbersome. The inventors also appreciate that, with some conventional cell delivery devices, infusing the cells in a fluid solution into the delivery device presents challenges. With some conventional delivery devices, therapeutic substances are back-loaded into the device. The inventors have also appreciated that back-loading may require the therapeutic substance to traverse a long pathway through the device before reaching the delivery end of the device. Due to the long travel distance, some of the therapeutic substance may remain trapped within the pathway of the delivery device instead of being delivered, resulting in wastage of the therapeutic substance. Furthermore, in some conventional devices, loading and handling of the delivery device can result in loss of the substance so that less than the entire dosage is delivered to the target site. [0024] The inventors have recognized the need for delivery systems, including delivery devices, that address some or all of the above-described problems of conventional delivery devices.

[0025] In one or more embodiments a delivery system is described that delivers a therapeutic substance via a positive displacement arrangement in which a wire stylet and/or plunger moves through a lumen of a cannula to eject the therapeutic substance out of the distal or front end of the cannula. In one or more embodiments, the therapeutic substance is loaded and/or infused into the distal and/or front end of the cannula. In one or more embodiments, the therapeutic substance to be delivered are cells, or other particles having a certain diameter. It should be appreciated, however, that the therapeutic substance is not limited to cells or particles. Wherever discussed hereinafter, “cells” may be substituted with any other therapeutic substance, as appropriate.

[0026] According to one aspect, the delivery system, including the delivery device, is used with a stereotactic frame, e.g., for neurosurgery applications. In some embodiments, the delivery system may be sized and shaped to be compatible with existing stereotactic frames, for example, a Leksell Frame.

[0027] According to one aspect, the delivery system includes one or more holder assemblies to secure the delivery device to a stereotactic frame to prevent or substantially limit movement of the delivery device in its use setting, e.g., for neurosurgery applications. In one or more embodiments, the delivery system is configured to be fixed or secured in a stereotactic frame, for example, the frame shown in FIG. 4.

[0028] The delivery system and/or delivery device of the present disclosure may be formed of medical or non-medical grade plastics, polyvinyl chloride (PVC), polyethylene, polypropylene, polytetrafluoroethylene, polyvinylchloride, and polyurethane thermoplastics, injection molded, blow-molded, extruded, compression molded, rotational molded, thermoformed, vacuum casted or computer printed. The delivery device (e.g., the holder assembly) may alternatively be constructed from stainless steel, aluminum or any suitable alloyed metal (e.g., cobalt-chromium). The delivery system and/or delivery devices may be designed for one-time usage or multiple uses following conventional sterilization following a medical procedure.

[0029] Turning to the illustrative embodiments, FIGS. 1-3 show an example embodiment of a delivery system 1 that includes a delivery device 2 and one or more holder assemblies 20. FIG. 1 is a perspective view of an embodiment of delivery system 1 that includes a delivery device 2 and one or more holder assemblies 20, FIG. 2 is a perspective view of a portion of delivery device 2 with a cross sectional view of holder assemblies 20, and FIG. 3 is a perspective view of a proximal end of delivery device 2 including wire stylet 10 and a perspective view of proximal end of second holder assembly 20b. The delivery device 2 has a cannula 5 having a lumen 6 through which a wire stylet 10 translates and/or slides. While FIGS. 1-2 shows delivery system 1 having two holder assemblies 20, it can be appreciated that a single holder assembly can be used as well as more than two holder assemblies.

[0030] Turning first to the delivery device 2 of the delivery system 1, the wire stylet 10 of the delivery device 2 has a distal end 11 and a proximal end 14 that is optionally attached to an end handle 15. In a preferred embodiment the wire stylet 10 is fixedly attached to the optional end handle 15, although in one or more embodiments the wire stylet can slide (rotate and/or translate) relative to the optional end handle 15. The end handle 15 assists with manipulating the wire stylet 10 to translate and/or slide within the cannula lumen 6. In one or more embodiments the wire stylet 10 can both translate and rotate within the cannula lumen 6, however, the cannula 5 and wire stylet 10 can be configured so that the wire stylet 10 can only slide and/or translate in the cannula lumen 6 and cannot rotate.

[0031] The wire stylet 10 preferably does not extend beyond the distal end 7 of the cannula 5, however, the wire stylet 10 can be configured to extend, and be manipulated and moved so that the distal end 11 of the wire stylet 10 extends beyond the distal end 7 of the cannula 5. The wire stylet 10 preferably has a plurality of graduations 12 to indicate the amount of therapeutic substance being loaded (aspirated) into cannula 5 and the amount of therapeutic substance being dispensed (infused) from cannula 5. The wire stylet 10 is sized and configured so that its linear translation a given and/or predetermined length within and through the cannula lumen 6 dispenses a known volume and/or amount of therapeutic substance out the distal end 7 of the cannula 5. The wire stylet 10 is further sized and configured so that its linear retraction (translation) a given and/or predetermined length within and through the cannula lumen loads a known volume and/or known amount of therapeutic substance within the cannula lumen 6.

[0032] It can be appreciated that the outer diameter of the wire stylet 10 is configured and sized to be close fitting within the cannula lumen 6 to inject and eject the therapeutic substance, more particularly all the therapeutic substance contained within the cannula 5. That is, as the distal end 11 of the wire stylet 10 moves in a proximal direction 24 within the cannula lumen 6, the distal end 11 pushes out all the therapeutic substance without any or a miniscule amount of the therapeutic substance passing around and between the shaft 17 of the wire stylet and the cannula lumen 6 so no or only minuscule amounts of the therapeutic substance are retained in the cannula 5. While the wire stylet 10 is preferably made of stainless steel, aluminum, or any suitable alloyed metal (e.g., cobalt-chromium), other materials can be used to form wire stylet 10. In an embodiment, the wire stylet 10 can include a plunger portion at distal end 11 that can be formed of a different material than the wire stylet shaft 17, including, for example, silicone and/or other materials that are deformable, resilient, and/or flexible to provide a seal with cannula 5 to facilitate dispensing all the therapeutic substance from the cannula, and/or to provide a seal that facilitates loading and infusing therapeutic substance into and within the cannula 5 by creating an effective seal to provide a vacuum when retracting the wire stylet 10 within the cannula lumen 6.

[0033] The cannula 5 has a distal end 7 from which therapeutic material is loaded (aspirated) into and expelled (deployed) out of the cannula 5 and a proximal or back end 8 through which the wire stylet 10 extends out the back end 8 of the cannula 5. The outer shaft 9 of the cannula 5 can include a step 4 of reduced diameter, although the outer shaft 9 can be of uniform diameter throughout its length. More or less steps 4 can be formed in the outer shaft 9 of cannula 5. The lumen 6 of cannula 5 preferably has a uniform inner diameter 3. The cannula 5 can be configured and sized to provide and/or contain different amounts of therapeutic substance. In one or more embodiments cannula 5 can have different sized inner diameters 3 to contain different amounts of therapeutic substance. Other dimensions of the cannula 5 can be configured to provide a desired amount and/or volume of therapeutic substance. The cannula 5 can be configured to contain, for example, microliters and/or milliliters of therapeutic substance, although other amounts of therapeutic substance can be contained within and/or dispensed from cannula 5. The cannula 5 is preferably rigid and can be formed of a material such as stainless steel. Other materials may be used to form cannula 5. For example, the cannula 5 may be formed of an MRI- compatible material such as ceramic, glass and/or polymers, preferably rigid polymers. The cannula 5 may also be formed of material that is not MRI-compatible if such compatibility is not needed during use of the device and/or if other factors such as cost and reusability are prioritized.

[0034] According to one aspect, as shown in FIG. 2, the wire stylet 10 is arranged to retract, preferably using the end handle 15, to ingest, infuse, and/or load therapeutic substance into the front or distal end 7 of the cannula 5, preferably using the graduations 12 on the shaft 17 of the wire stylet 10 to determine the amount of therapeutic substance loaded into the cannula 5. According to another aspect, the wire stylet 10 is arranged to be moved within the cannula 5, preferably by applying a force to the end handle 15, to move the distal end 11 of the wire stylet toward the distal end 7 of the cannula 5 to eject, deploy and/or expel the therapeutic substance from the front end 7 of the cannula, preferably using the graduations 12 on the shaft 17 of the wire stylet 10 to determine the amount of therapeutic substance ejected from the cannula 5. In one or more embodiments, the wire stylet 10 is loaded into the cannula 5 by inserting the distal end 11 of the wire stylet into the cannula lumen 6 at the proximal end 8 of the cannula 5. During use the cannula 5 is inserted into tissue so that the distal end 7 reaches a desired target location. One can appreciate that manipulating the cannula 5 to reach the desired location and/or manipulating the wire stylet can be cumbersome. Movement of the wire stylet 10 within the cannula 5 can prove difficult while retaining the cannula at the target site. To facilitate manipulation of the cannula 5 and/or wire stylet 10, e.g., the delivery device 2, the delivery system 1 includes one or more holder assemblies 20.

[0035] As shown in FIGS. 1-2, holder assembly 20 includes a holding member 30, a nut 50, and a sealing member 60. It can be appreciated that holder assembly 20a is the same as or substantially the same as holder assembly 20b, and that the two holder assemblies 20 may be referred to herein as first holder assembly 20a and second holder assembly 20b. In light of the similarity in structure and operation of holder assemblies 20a, 20b, the structure, configuration and operation of holder assembly 20a, 20b will be described with reference to holder assembly 20. Differences between first holder assembly 20a and second holder assembly 20b will be noted.

[0036] Sealing member 60 in holder assembly 20 is preferably formed of a flexible, deformable, elastic, and/or resilient material, for example silicone, although other materials beside silicone can be used. Movement of nut 50 compresses sealing member 60 about cannula 5 and/or wire stylet 10, preferably to hold and stabilize the cannula 5 and/or wire stylet 10, while also preferably permitting the wire stylet 10 to move through the holder assembly 20, including through the passage 65 created in sealing member 60. By adjusting the nut 50 on holding member 30 the amount of compression provided by sealing member 60 on the cannula 5 and/or wire stylet 10 can be adjusted and/or varied. In this manner, the compression and holding force applied to the cannula 5 and/or wire stylet 10 can be adjusted to, for example, fixedly hold the cannula 5 and/or wire stylet 10 to the holder assembly 20 in a stationary manner and/or permit movement of the cannula 5 and/or wire stylet 10 through the holding member 30, including through the passage 65 created in the sealing member 60.

[0037] Holding member 30 includes a channel 32 sized and configured to permit the cannula 5 and/or wire stylet 10 to be inserted therethrough. Holding member 30 also has a cavity 35 for receiving and holding sealing member 60. Cavity 35 may be cylindrical and/or conically shaped, and in an embodiment includes a conically shaped portion to facilitate compression of the sealing member 60 contained within the cavity 35. Channel 32 communicates with cavity 35 and cannula 5 and/or wire stylet 10 can be inserted through both the channel 32 and cavity 35 so that the cannula 5 and/or wire stylet 10 extends through holding member 30. In an embodiment, the holding member is permanently fixed to cannula shaft 9, for example, by using adhesive, an over-molding process, and/or a press fit operation. Holding member 30 is preferably formed of a rigid material and may be formed of medical or non-medical grade plastics, polyvinyl chloride (PVC), polyethylene, polypropylene, polytetrafluoroethylene, polyvinylchloride, and polyurethane thermoplastics, injection molded, blow-molded, extruded, compression molded, rotational molded, thermoformed, vacuum castcd or computer printed. The holding member 30 may alternatively be constructed from stainless steel, aluminum or any suitable alloyed metal (e.g., cobalt-chromium). The holding member 30 (and/or holding assembly 20) may be designed for one-time usage or multiple uses following conventional sterilization following a medical procedure.

[0038] Nut 50 has a through hole 55 extending from front end 52 to proximal end 58 to permit cannula 5 and/or wire stylet to fit therethrough. Nut 50 is sized and configured to compress the sealing member 60 within cavity 35 to provide an adjustable force about the cannula 5 and/or wire stylet 10. In an approach, movement of nut 50 moves and/or compresses sealing member 60 in cavity 35 thereby compressing and/or reducing the passage 65 through which cannula 5 and/or wire stylet 10 is contained and/or passes through. More specifically, in an approach, nut 50 translates so that a front (distal) potion 52 of nut 50 abuts and compresses sealing member 60 within cavity 35 to compress against the cannula and/or wire stylet that extends through the sealing member 60 and/or holding member 30. Compression of sealing member 60 acts to restrict movement of the cannula 5 and/or wire stylet 10. Nut 50 is preferably formed of a rigid material and may be formed of medical or non-medical grade plastics, polyvinyl chloride (PVC), polyethylene, polypropylene, polytetrafluoroethylene, polyvinylchloride, and polyurethane thermoplastics, injection molded, blow-molded, extruded, compression molded, rotational molded, thermoformed, vacuum casted or computer printed. The nut 50 may alternatively be constructed from stainless steel, aluminum, or any suitable alloyed metal (e.g., cobaltchromium). The nut 50 (and/or holding assembly 20) may be designed for one-time usage or multiple uses following conventional sterilization following a medical procedure.

[0039] In one or more embodiments, holding member 30 includes a proximal or real’ portion 36 having a threaded section 37 that cooperates and/or mates with a threaded section 54 on nut 50 so that nut 50 rotates and translates with respect to holding member 30. A user can rotate nut 50 with respect to holding member 30 to compress sealing member 60 about the cannula 5 and/or wire stylet 10. By adjusting the amount nut 50 is rotated on holding member 30, a user can adjust the compression force exerted by the sealing member 60 about the cannula 5 and/or wire stylet 10. In an approach, the nut 50 can be adjusted (positioned) relative to the holding member 30 to provide a compression force on the cannula 5 and/or wire stylet 10 to prevent movement of the holding assembly 20 relative to cannula 5 and/or stylet 10. Alternatively, and/or in addition, the nut 50 can be adjusted (positioned) relative to the holding member 30 to provide a compression force that both resists, inhibits, and yet permits movement of the cannula 5 and/or wire stylet 10 with respect to the holding assembly 20. In this manner, the holding assembly 20 can provide a holding function and provide stability to the cannula 5 and/or wire stylet 10 so that delivery device 2 can be more stable and can be more easily manipulated by a user.

[0040] In one or more embodiments the front or distal end 31 of holding member 30, and in an arrangement first holding member 30a, can be configured to interface with a frame 300, for example, a Leksell Frame, as shown in FIG. 4. It should be appreciated that the delivery device may be compatible with other stereotactic frames, as this aspect is not so limited. In this manner one or more holding assemblies 20 and/or delivery devices can be stabilized and held stationary in the frame 300 by one or more interfaces 302 while the one or more holding assemblies 20 can hold and stabilize the cannula 5 and/or wire stylet 10 (e.g., the delivery device 2). The front or distal end 31 of the holding member 30, and in an arrangement first holding member 30a, can be configured with a connecting mechanism and/or interface to connect and/or interface with the frame 300.

[0041] As used herein, the distal or front end of the delivery device 1 and/or cannula 5 is the end 7 through which the therapeutic substance is delivered. The proximal or rear end of the delivery device 1, the cannula 5, and/or wire stylet 10 is the end of the device that is opposite to the distal end of the delivery device 2, the cannula 5, and/or wire stylet 10. As an illustrative example, FIGS. 1 and 2 depicts a proximal end 14 of the wire stylet 10 and a distal end 7 of the cannula 5. As used herein, the proximal direction is a direction that points from the distal end of the delivery device, cannula, and/or wire stylet toward the proximal end. The distal direction is a direction that points from the proximal end of the delivery device, cannula, and/or stylet toward the distal end. As an illustrative example, FIG. 3 depicts a proximal direction 22 and a distal direction 24.

[0042] Additionally, and/or alternatively, the distal end 31 of the holding member 30 can be configured to attach to the proximal end 58 of the nut 50. For example, first holding assembly 20a can be connected to second holding assembly 20b by connecting the first nut 50a of the first holding assembly 20a to the second holding member 30b and more specifically by connecting the proximal end 58 of the first nut 50a to the distal end 31b of the second holding member 30b. A connection mechanism, for example a bayonet connection mechanism, can be used to connect first holding assembly 20a to second holding assembly 20b. In an embodiment, one or more radial lugs or pins 59 on the proximal end 58 of the first nut 50a is received within an opening in the distal end 31b of the second holding member 30b and held by a ledge within the opening of the distal end 31b of the second holding member 30b. Other connection mechanisms are contemplated for attaching first holding assembly 20a to second holding assembly 20b, for example a threaded connection.

[0043] In one or more embodiments, the end handle 15 of the wire stylet 10 can be configured to attach to the holding assembly 20, for example to second holding assembly 20b. In an example, the proximal end 58 of the nut 50, e.g., second nut 50b, can be attached to the end handle 15 to hold, stabilize, and/or steady the wire stylet 10 in position. The end handle 15 in an embodiment is attached to the nut 50, e.g., second nut 50b, of the holding assembly 20 e.g., second holding assembly 20b, when the wire stylet 10 is inserted fully into the cannula 5.

[0044] In use, in one or more embodiments, the delivery device 2 loaded with therapeutic substance is deployed into tissue by advancing the delivery device 2 distally. If the delivery device 2 is attached to a stereotactic frame, the frame may assist in guiding distal movement of the delivery device 2. In some embodiments, one or more holding assemblies 20, e.g., first holding assembly 20a and/or second holding assembly 20b, may further assist in guiding movement of the delivery device 2, including the cannula 5 and wire stylet 10, to the target location. Then, to deliver the therapeutic substance, the operator may actuate and/or move the wire stylet 10 distally through the cannula 5 to eject and deliver the therapeutic substance to the target location. One of skill in the art can appreciate that one or more of holding assemblies 20, c.g., first holding assembly 20a and/or second holding assembly 20b, can hold and stabilize the cannula 5 and/or wire stylet 10 making manipulation of the delivery device 2 and delivery of the therapeutic substance easier for the operator.

[0045] FIGS. 5-7 illustrate another embodiment of a delivery system 1 that includes a delivery device 2 and one or more holding assemblies 20. FIG. 5 is a perspective view of an embodiment of delivery system 1 that includes a delivery device 2 and one or more holder assemblies 20, e.g., 20c, 20d; FIG. 6 is a perspective view of a portion of delivery device 2 with a cross sectional view of holding assemblies 20, e.g., 20c, 20(1; and FIG. 7 is a perspective view of a proximal end of delivery device 2 including wire stylet 10 and a perspective view of proximal end of second holder assembly 20d. The delivery device 2 has a cannula 5 having a lumen 6 through which a wire stylet 10 translates and/or slides. While FIGS. 5-7 shows delivery system 1 having two holder assemblies 20, e.g., third holder assembly 20c and fourth holder assembly 20d, it can be appreciated that a single holder assembly can be used as well as more than two holder assemblies. It can be appreciated that many of the features and structures of holder assemblies 20c, 20d of the embodiment of FIGS. 5-7 are the same as holder assemblies 20a, 20b of the embodiment of FIGS. 1-3 and will not be further repeated in the description of the embodiment of FIGS. 5-7.

[0046] Third holder assembly 20c is substantially the same as and works in substantially the same manner as first holder assembly 20a of the embodiment of FIGS. 1-3, and which was described with reference to holder assembly 20. In a configuration, third holder assembly 20c is a variation of first holder assembly 20a and includes a third holding member 30c, a third nut 50c, and a third sealing member 60c. Third holding member 30c has a secondary channel 67 configured as a flush line that can be used to flush the delivery device 2 with a fluid to prime the delivery device 2. Flush line 67 is located on the distal end 31 of third holding member 30c so that it is below the sealing member 60 (e.g., sealing member 60c). Flush line 67 is part of an extension 66 on third holding member 30c. In an arrangement, extension 66 includes a port to connect extension 66 to a flushing fluid supply. [0047] Extension 66 in an embodiment includes a closing mechanism 69 to close channel 68 which is in communication with secondary channel 67. Closing mechanism 69 preferably is an actuatable valve, for example a two-way valve. Other closing mechanisms 69 are contemplated, for example, a clamp can be used. Third holding member 30c further has a conical shape to cavity 35c to facilitate insertion of the wire stylet 10 into cannula 5 if the wire stylet 10 is removed to facilitate priming through the flush line 67.

[0048] In an embodiment, as shown in FIGS. 5-7, delivery system 1 has a casing 71 extending from the proximal end of fourth holding assembly 20d. The casing 71 is preferably transparent and has an inner channel 72 that preferably stabilizes the wire stylet 10. Casing 71 has graduations 73. The graduations 73 on the casing 71 and an indicator, e.g., a marker 13, on the wire stylet 10 indicate the volume and/or amount of substance being aspirated (loaded) or dispensed (expelled) from the delivery device 2. That is, the marker 13 is visible through the casing 71 and the position of the marker 13 relative to the graduations 73 on the casing 71 indicates the amount of substance aspirated into and/or dispensed from the delivery device 2.

[0049] Casing 71 in one or more arrangements is secured on and/or connected to fourth holding assembly 20d, for example connected to fourth nut 50d. In an example embodiment, casing 71 is fitted into a conical channel 57 on the backend of nut 50d of the fourth holding assembly 20d. For example, nut 50d has no proximal extension 58 and is configured as an endcap with channel 57 at its proximal end. Channel 57 can have a taper to assist with securing casing 71. Casing 71 can be further secured in one or more embodiments by adhesively glueing the casing 71 in channel 57. In an arrangement, casing 71 is inserted into channel 57, e.g., tapered channel 57, until it hits a stopping depth and is then glued in position. It can be appreciated that the connection between casing 71 and fourth nut 50d and/or fourth holding assembly 20d can be changed so that casing 71 is connected proximally to holding assembly 20d in a variety of ways, including for example, threading casing 71 into fourth holding assembly 20d and/or fourth nut 50d. [0050] Fourth sealing member 60d in holding member 30d can be configured as sealing member 60b used in holding member 30b. That is fourth scaling member 60d, also referred to as a cavity member, can be configured to compress passageway 65d in the sealing member 60d and perform a sealing function, prevent movement of wire stylet 10, and/or resist and permit movement of wire stylet 10 therethrough. In an alternative embodiment, sealing member 60d does not have to act as a sealing member and can perform a stabilizing function. Sealing member 60d (e.g., cavity member 60d) can also be referred to as a stabilizing member 60d. Since a sealing function is already performed by sealing member 60c in third holding assembly 20c, where sealing member 60c is configured similar to or the same as sealing member 60a, cavity/stabilizing member 60d in a configuration of delivery system 1 may not perform a sealing function. Stabilizing member 60d in an embodiment can be configured to support the wire stylet 10 but not compress about wire stylet 10 and/or provide any significant amount of further friction to the movement of wire stylet 10 through fourth holding assembly 20d. In an arrangement, stabilizing member 60d can be a rigid material, for example a plastic, and is not compressible around wire stylet 10 and does not provide a further sealing function, and preferably does not prevent or significantly inhibit or resist movement of wire stylet 10 through the passageway 65 in stabilizing member 60d. Stabilizing member 60d can be a plastic, a metal, a composite, rubber, silicone, and/or combinations thereof. Other materials are contemplated for sealing member 60d. Stabilizing member 60d in the alternative embodiment can provide enough support to ensure that the wire stylet 10 is concentric within the cannula 5.

[0051] In a further embodiment, sealing member 60 can be removed from holding assembly 20b, 20d and/or from holding member 30b, 30d. Alternatively, holding assembly 20b/20d can be removed or holding member 30b, 30d can be removed from delivery system 1.

[0052] Also disclosed is a kit that includes at least a first holder assembly and a second holder assembly. The first holder assembly in the kit includes: a first holding member having a first cavity and a first longitudinal channel; a first sealing member having a first passageway sized to permit at least one of a device group consisting of: a first or second cannula, a first or second wire stylet, and combinations thereof to pass therethrough, the first sealing member positioned within the first cavity of the first holding member; and a first nut moveable relative to the first holding member to compress the first scaling member within the first cavity of the first holding member to adjust the size of the first passageway of the first sealing member. The second holder assembly in the kit includes: a second holding member having a second cavity and a second longitudinal channel; a second cavity member having a second passageway sized to permit at least one of the device group to pass therethrough, the second cavity member positioned within the second cavity of the second holding member; and a first nut moveable relative to the first holding member to contain the second cavity member within the second cavity of the second holding member.

[0053] In a configuration, the first holder assembly in the kit is configured so that movement of the first nut secures the holder assembly to the device group. In an embodiment, the first holding assembly is configured so that movement of the first nut compresses the first sealing member about a shaft of at least one of the first or second wire stylet to provide friction to resist and permit sliding movement of the shaft of the first or second wire stylet through the first passageway of the first sealing member. The first holding assembly can also be configured so that movement of the first nut compresses the first sealing member about the device group to prevent movement of the device group through the first passageway of the first sealing member. Alternatively, and/or additionally, the first holding assembly can be configured so that movement of the first nut compresses the first sealing member about a proximal end of the first or second cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula. The first sealing member is formed of silicone, and in an arrangement, at least a portion of the first cavity of the first holding member is conically shaped. The first holding member in an embodiment has a secondary channel in communication with the first longitudinal channel of the first holding member for flushing at least the first or second cannula, and optionally, the first holding member has an extension, the extension having an extension passageway in communication with the secondary channel.

[0054] The second holder assembly in the kit is configured to be attachable to the first holder assembly. The second holder assembly optionally includes a casing with graduations. The cavity member in an arrangement is a rigid stabilizing member configured to stabilize the first or second stylet. In yet another embodiment, the second holder assembly is configured so that movement of the second nut secures the second holder assembly to the first or second stylet. In a further embodiment, the second holder assembly is configured so that movement of the second nut compresses the second sealing member about a shaft of at least one of the first or second wire stylet to provide friction to resist and permit sliding movement of the shaft of the first or second wire stylet through the first passageway of the second sealing member. In a further optional embodiment, the second holding assembly is configured so that movement of the second nut compresses the second sealing member about the first or second stylet to prevent movement of the first or second stylet through the second passageway of the second sealing member.

[0055] Operation and use of delivery system 1 comprising delivery device 2 (cannula 5 and wire stylet 10) and one or more holder assemblies 20 will be described. While the operation and use of delivery system 1 will be described as comprising a series and/or number of steps, it is to be understood that the process does not need to be performed as a series of steps and/or the steps do not have to be performed in the order described, but the use and operation of delivery device system 1 can be integrated and/or one or more steps may be performed together, simultaneously, or the steps can be performed in the order disclosed or in an alternative order. Moreover, it should be appreciated that the delivery device 2 can be different than described and illustrated.

[0056] While the operation and use of delivery system 1 with holding assemblies will be described by reference to holding assemblies 20, and in instances with reference to first and second holding assemblies 20a, 20b as illustrated and described by reference to FIGS. 1-3, it can be appreciated that the one or more holding assemblies 20 can be other holding assemblies, for example, one or more of third and fourth holder assemblies 20c, 20d described and illustrated in FIGS. 5-7. It should be further appreciated that additional holding assemblies can be used; that first and second holding assemblies 20a, 20b can be the same, or there can be differences between first holding assembly 20a and second holding assembly 20b; and/or third and fourth holding assemblies 20c, 20d can be the same, or there can be differences between third holding assembly 20c and fourth holding assembly 20d. That is, while the operation and use of delivery system 1 is discussed in terms of using first and second holding assemblies 20a, 20b, it will be appreciated that holding assemblies can have other configurations, designs and can operate differently. In addition, delivery system 1 (e.g., one or more holding assemblies 20) can be provided as a single component or a kit without delivery devices, with multiple different sized and/or multiple of the same sized delivery devices, and/or one or more of the same and/or different sized or configured holder assemblies.

[0057] In an example approach, wire stylet 10 can be loaded into cannula 5 by inserting the distal end 11 of the wire stylet 10 into the lumen 6 at the proximal end 8 of the cannula 5 and moving the shaft 17 of the wire stylet 10 through the cannula lumen 6. In an arrangement, the wire stylet 10 is advanced in a distal direction 24 until the end handle 15 is at or close to the proximal end 8 of the cannula 5. The assemblies 20 (e.g., first and second holder assemblies 20a, 20b) are then loaded onto the delivery device 1 (e.g., the combined wire stylet 10 inserted into the cannula 5). In an example approach, with the nut 50b in a loosened position to fit over the cannula shaft 9, the second holding assembly 20b is slid first over the front end 7 of the cannula 5 and moved over the cannula shaft 9 and beyond the proximal end 8 of the cannula 5 to be positioned over the shaft 17 of the wire stylet 10. Then, with the nut 50a in a loosened or open position to permit the first holder assembly 20a to fit over the cannula shaft 9, the first holder assembly 20a is slid over the front end 7 of the cannula 5 and moved over the cannula shaft 9 so that the first holder assembly 20a is positioned about the proximal end 8 of the cannula 5 where the wire stylet 10 is inserted into the cannula lumen 6. During placement of the first and second holder assemblies 20a, 20b on the delivery device 2, the wire stylet 10 can be positioned so that there is enough clearance between the end handle 15 and the proximal end 8 of the cannula 8 so that the second holder assembly 20b is positioned on the shaft 17 of the wire stylet 10 and away from the proximal end 8 of the cannula 5 so that the first holder assembly 20a can be positioned about the proximal end 8 of the cannula 5.

[0058] The first holder assembly 20a is positioned on the cannula 5 so that the first sealing member 60a will be positioned at the proximal end 8 of the cannula 5 where the wire stylet shaft 17 exits the cannula lumen and the first nut 50a is tightened preferably to fix the first holder assembly 20a on the cannula 5 and seal the proximal end 8 of the cannula 5 where the wire stylet shaft 17 exits the lumen 6 of the cannula 5. More specifically, in an approach, with the first holder assembly 20a in position the first nut 50a is tightened so that the first sealing member 60a is compressed in cavity 35 so that the passageway 65 in the sealing member 60a is compressed about cannula 5 so that it grips the cannula 5 in a manner that first holding member 20a will remain stationary with the cannula 5 during manipulation of the wire stylet 10. Preferably, the first holder assembly 20a is positioned such that tightening the first nut 50a not only secures the first holding assembly 20a to the cannula 5 but additionally provides a seal, e.g., a liquid tight seal that does not permit fluid to pass, about the proximal end 8 of the cannula 5 where the wire stylet shaft 17 exits the cannula lumen 6. Forming a seal, e.g., a water/liquid tight seal, about the proximal end 8 of the cannula 5 where the shaft 17 of the wire stylet 10 exits the cannula 5 that does not allow fluid to pass facilitates and helps to ensure volume assurance.

[0059] More specifically, in an approach, with the first holder assembly 20a in position the first nut 50a is tightened so that the first sealing member 60a is compressed in cavity 35 so that the passageway 65 of the first sealing member 60a is compressed about the proximal end 8 of the cannula 5 and compressed about the shaft 17 of the wire stylet 10 to form a seal about the shaft 17 of the wire stylet 10. While the first nut 50a is tightened to form a seal at the proximal end 8 of the cannula 5 about the shaft 17 of the wire stylet 10, the wire stylet 10 is permitted to move by a user through the passageway 65 in the first sealing member 60a. The seal created by the first sealing member 60a about the proximal end 8 of the cannula 5 preferably inhibits, resists, and/or prevents therapeutic substance from being expelled or ejected out the proximal end 8 of the cannula 5 and also preferably inhibits, resists, and/or prevent air from passing into or out of the delivery device 2 at the proximal end 8 of the cannula 5, which as discussed below provides improved operation of the delivery device 2.

[0060] With the first holding assembly 20a in position and secured to the cannula 5, the second holding assembly 20b can be connected to the first holding assembly 20a. That is, the first nut 50a of the first holding assembly 20a can be connected to the second holding member 30b of the second holding assembly 20b. With the second holding assembly 20b connected to the first holding assembly 20a, the second holding assembly 20b can be secured to the shaft 17 of the wire stylet 10. More specifically, in an example approach, second nut 50b is tightened to compress the second sealing member 60b so that the passageway 65b through the second sealing member 60b is compressed about the shaft 17 of the wire stylet 10 to secure the second holding assembly 20b to the wire stylet 10. Movement (e.g., rotation) of second nut 50b can provide an adjustable compressive force about the shaft 17 of the wire stylet 10 so that an operator of delivery device 2 can adjust the compression of the second sealing member 60b about the shaft 17 of the wire stylet 10. The second nut 50b can be adjusted to vary the compressive force applied by the second sealing member 60b to permit the second holding assembly 20’ to easily move over the shaft 17 of the wire stylet 10, to prevent movement of the second holding assembly 20b over the shaft 17 of the wire stylet 10, and/or to resist or inhibit movement but still permit sliding of the shaft 17 of the wire stylet 10 through the second holding assembly 20b. For example, while the second nut 50b is tightened to secure the second holding assembly 20b to the wire stylet 10, the second nut 50b preferably is not tightened to an extent that prevents movement of the wire stylet 10 through the second holding member 20b. That is, the second holding assembly 20b is arranged and positioned so that the wire stylet 10 is permitted to slide through the second holding assembly 20b more specifically the second sealing member 60b is not compressed about the wire stylet 10 to an extent that unduly inhibits or prevents movement of the wire stylet 10 within the second holding assembly 20b.

[0061] Preferably with the first and second holding assemblies 20a, 20b in position on the delivery device 2, the therapeutic substance can be front loaded into cannula 5 by retracting wire stylet 10 by moving end handle 15 away from the proximal end 8 of the cannula 5. That is, the second holder assembly 20b is configured so that the wire stylet 10 can be moved through the second holding assembly 20b and in a proximal direction 22 to draw a therapeutic substance into the front end 7 of the cannula 5. The graduations 12 on the shaft 17 of the wire stylet 10 (and/or the marker 13 on the shaft 17 of the wire stylet in combinations with the graduations 73 on casing 71) can be used to provide (contain) the proper dosage of therapeutic substance within the cannula 5. The second holding assembly 20b provides stability to the wire stylet 10 as it is retracted from the lumen 6 of the cannula 5 while the first holding assembly 20a provides a seal about the distal end 8 of the cannula 5 while the wire stylet 10 is being moved proximally to provide a better vacuum (more suction) to permit the therapeutic substance to be more easily loaded (drawn) into the cannula 5.

[0062] With the delivery device 2 loaded with therapeutic substance, the second nut 50b on the second holding assembly 20b optionally can be tightened to prevent and/or further inhibit movement of the stylet 10 within the cannula lumen 6. In this manner, the delivery device 2 loaded with therapeutic substance can be more easily manipulated without losing any of the therapeutic substance dosage. The first holding assembly 20a providing a seal about the proximal end 8 of the cannula also helps to retain the therapeutic substance within the cannula 5 as it is being moved about and manipulated to the target site so that the dosage delivered by the delivery device 2 will be correct.

[0063] With the delivery device 2 loaded with therapeutic substance, the delivery system 1 can be mounted in a delivery frame, e.g., a stereotactic frame 300, for example, the Leksell Frame of FIG. 4. More specifically the proximal end 32 of the first holding assembly 20a can interface and be mounted in a delivery frame. With the delivery system 1 mounted in the delivery frame, and the cannula 5 positioned at the target location, the therapeutic substance can be delivered to the target. More specifically, the end handle 15 of the wire stylet can be moved by an operator in a proximal direction 24 to eject the therapeutic substance out the distal end 7 of the cannula 5 and into the target location. The graduations 12 on the shaft 17 of the wire stylet 10 (and/or the marker 13 on the shaft 17 of the wire stylet in combinations with the graduations 73 on casing 71) can be used while delivering the therapeutic substance, for example, for timing purposes.

During delivery of the therapeutic substance, the second nut 50b on the second holding assembly 20b can be tightened as desired to prevent movement of the wire stylet 10. Upon completion, e.g., after delivering the therapeutic substance, the end handle 15 can be attached to the second nut 50b of the second holding assembly 20b to keep the wire stylet 10 in position and inserted in the cannula 5. [0064] While the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments or examples. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. Accordingly, the foregoing description and drawings are by way of example only.

Claims

1. A delivery system, comprising: a device comprising: a cannula having a lumen extending from a distal end to a proximal end; and a wire stylet having a shaft configured to move through the cannula lumen, wherein movement of the wire stylet shaft within the cannula lumen loads or ejects a substance out of the distal end of the cannula lumen; and at least a first holder assembly, wherein the at least first holder assembly comprises: a first holding member having a first cavity and a first longitudinal channel; a first sealing member having a first passageway sized to permit at least one of a device group consisting of: the cannula, the wire stylet, and combinations thereof to pass therethrough, the first sealing member positioned within the first cavity of the first holding member; and a first nut moveable relative to the first holding member to compress the first sealing member within the first cavity of the first holding member to adjust the size of the first passageway of the first sealing member.

2. The delivery system of claim 1, wherein the at least first holder assembly is configured to be secured to a stabilizing frame.

3. The delivery system of claim 2, wherein a distal end of the first holder member of the at least first holding assembly is configured to secure to the stabilizing frame.

4. The delivery system of claim 1, wherein the at least first holder assembly is configured so that movement of the first nut of the at least first holder assembly secures the at least first holder assembly to the device group.

5. The delivery system of claim 4, wherein the first holder assembly is configured so that movement of the first nut compresses the first sealing member about the shaft of the wire stylet to provide friction to resist and permit sliding movement of the shaft of the wire stylet through the first passageway of the first scaling member.

6. The delivery system of claim 4, wherein movement of the first nut of the at least first holder assembly compresses the first sealing member about the device group to prevent movement of the device group through the first passageway of the first sealing member.

7. The delivery system of claim 4, wherein movement of the first nut of the at least first holder assembly compresses the first sealing member about the proximal end of the cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula.

8. The delivery device of claim 1, wherein the first sealing member is formed of silicone.

9. The delivery device of claim 1, wherein the first nut has a first through hole configured to permit the device group to pass therethrough and the first longitudinal channel of the first holding member is configured to permit the device group to pass therethrough.

10. The delivery device of claim 1, wherein the first holder member has a first holder threaded section, the first nut has a first nut threaded section such that the first holder threaded section mates with the first nut threaded section so that rotation of the first nut causes the first nut to move relative to the first holding member to compress the first sealing member.

11. The delivery system of claim 1, further comprising at least a second holder assembly, wherein the first holder assembly is configured to be attachable to the second holder assembly.

12. The delivery device of claim 11, wherein the first holder assembly is securable to the proximal end of the cannula to fixedly attach the first holder assembly to the cannula and seal the proximal end of the cannula where the wire stylet exits the proximal end of the cannula, and the second holder assembly is securable to the wire stylet in a manner that resists and permits sliding movement of the wire stylet through the second holder assembly.

13. The delivery system of claim 1, further comprising at least a second holder assembly, wherein the first holder assembly further comprises a proximal extending portion configured to be attachable the second holder assembly.

14. The delivery system of claim 1, further comprising at least a second holder assembly, wherein the second holder assembly comprises a casing extending proximally with graduations.

15. The delivery system of claim 1, comprising at least a second holder assembly, wherein the second holder assembly comprises: a second holding member having a second cavity and a second longitudinal channel; a rigid stabilizing member having a passageway sized to permit the wire stylet to pass therethrough, the stabilizing member positioned within the cavity of the second holding member and configured to stabilize the wire stylet; and a second nut moveable relative to the holding member to contain the stabilizing member within the second cavity of the holding member.

16. The delivery system of claim 1, wherein the first holding member has an extension and a secondary channel wherein the secondary channel communicates with the first longitudinal channel in the first holding member.

17. The delivery system of claim 1, wherein at least a portion of the first cavity of the first holding member is conically shaped.

18. A holder assembly for stabilizing a delivery device comprising a cannula and a wire stylet configured to more through a lumen of the cannula, the holder assembly comprising: a holding member having a cavity and a longitudinal channel; a sealing member having a passageway sized to permit at least one of a device group consisting of: a cannula, a wire stylet, and combinations thereof to pass therethrough, the sealing member positioned within the cavity of the holding member; and a nut moveable relative to the holding member to compress the sealing member within the cavity of the holding member to adjust the size of the passageway of the scaling member.

19. The holder assembly of claim 18, wherein the holder assembly is configured so that movement of the nut secures the holder assembly to the device group.

20. The holder assembly of claim 19, wherein the holding assembly is configured so that movement of the nut compresses the sealing member about a shaft of the wire stylet to provide friction to resist and permit sliding movement of the shaft of the wire stylet through the passageway of the sealing member.

21. The holder assembly of claim 19, wherein the holding assembly is configured so that movement of the nut compresses the sealing member about the device group to prevent movement of the device group through the passageway of the sealing member.

22. The holder assembly of claim 19, wherein the holding assembly is configured so that movement of the nut compresses the sealing member about the proximal end of the cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula.

23. The holder assembly of claim 18, wherein the sealing member is formed of silicone.

24. The holder assembly of claim 18, wherein the nut has a through hole configured to permit the device therethrough and the channel of the holding member is also configured to permit the device group to pass therethrough.

25. The holder assembly of claim 18, wherein the holder assembly further comprises a casing with graduations.

26. The holder assembly of claim 18, wherein the holding member has a secondary channel in communication with the longitudinal channel of the holding member for flushing at least the cannula.

27. The holder assembly of claim 26, wherein the holding member has an extension, the extension having a passageway in communication with the secondary channel.

28. The holder assembly of claim 18, wherein the holding member has a distal end configured to be secured to a stabilizing frame.

29. The holder assembly of claim 18, wherein at least a portion of the first cavity of the first holding member is conically shaped.

30. A kit comprising at least a first holder assembly and a second holder assembly, wherein the first holder assembly comprises: a first holding member having a first cavity and a first longitudinal channel; a first sealing member having a first passageway sized to permit at least one of a device group consisting of: a first or second cannula, a first or second wire stylet, and combinations thereof to pass therethrough, the first sealing member positioned within the first cavity of the first holding member; and a first nut moveable relative to the first holding member to compress the first sealing member within the first cavity of the first holding member to adjust the size of the first passageway of the first sealing member, wherein, the second holder assembly comprises: a second holding member having a second cavity and a second longitudinal channel; a second cavity member having a second passageway sized to permit at least one of the device group to pass therethrough, the second cavity member positioned within the second cavity of the second holding member; and a first nut moveable relative to the first holding member to contain the second cavity member within the second cavity of the second holding member.

31. The kit of claim 30, wherein the first holder assembly is configured so that movement of the first nut secures the holder assembly to the device group.

32. The kit of claim 30, wherein the first holding assembly is configured so that movement of the first nut compresses the first sealing member about a shaft of at least one of the first or second wire stylet to provide friction to resist and permit sliding movement of the shaft of the first or second wire stylet through the first passageway of the first sealing member.

33. The kit of claim 30, wherein the first holding assembly is configured so that movement of the first nut compresses the first sealing member about the device group to prevent movement of the device group through the first passageway of the first sealing member.

34. The kit of claim 33, wherein the first holding assembly is configured so that movement of the first nut compresses the first sealing member about a proximal end of the first or second cannula to create a seal at the proximal end of the cannula where the wire stylet exits the cannula.

35. The kit of claim 30, wherein the first sealing member is formed of silicone.

36. The kit of claim 30, wherein at least a portion of the first cavity of the first holding member is conically shaped.

37. The kit of claim 30, wherein the second holder assembly is attachable to the first holder assembly.

38. The kit of claim 30, wherein the second holder assembly further comprises a casing with graduations.

39. The kit of claim 30, wherein the first holding member has a secondary channel in communication with the first longitudinal channel of the first holding member for flushing at least the first or second cannula.

40. The kit of claim 39, wherein the first holding member has an extension, the extension having an extension passageway in communication with the secondary channel.

41. The kit of claim 30, wherein the cavity member is a rigid stabilizing member configured to stabilize the first or second stylet.

42. The kit of claim 30, wherein the second holder assembly is configured so that movement of the second nut secures the second holder assembly to the first or second stylet.

43. The kit of claim 30, wherein the second holder assembly is configured so that movement of the second nut compresses the second sealing member about a shaft of at least one of the first or second wire stylet to provide friction to resist and permit sliding movement of the shaft of the first or second wire stylet through the first passageway of the second sealing member.

44. The kit of claim 30, wherein the second holding assembly is configured so that movement of the second nut compresses the second sealing member about the first or second stylet to prevent movement of the first or second stylet through the second passageway of the second sealing member.