Dual-stage syringe for independent delivery of two or more fluids

Abstract

In the present disclosure, embodiments of dual-stage syringes and delivery systems incorporating dual-stage syringes are disclosed. Embodiments of dual-stage syringes described herein include sleeve-type dual-stage syringes, fully enclosed dual-stage syringes, and dual-stage syringes including one or more one-way valves.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 673,632, filed on May 18, 2018, entitled “RADIOEMBOLIZATION DELIVERYDEVICE,” the disclosure of which is incorporated herein by reference; and claims the benefit of U.S. Provisional Patent Application No. 62 / 673,628, filed on May 18, 2018, entitled “DUAL-STAGE SYRINGES WITH LOCKING MECHANISM,” the disclosure of which is incorporated herein by reference. Technical Field

[0003] The present disclosure relates generally to syringes, and more particularly, to dual-stage syringes that independently deliver multiple fluids. Background Art

[0004] In cancer treatments involving radiation therapy, unintentional or excessive exposure to radiation from the radiotherapeutic agent can be harmful and put patients or medical personnel at risk of death. Therefore, medical devices used for radiation therapy must be constructed to confine the delivery of radioactive materials to specific areas of the patient's body while shielding other parts from unnecessary radiation.

[0005] Transarterial radioembolization is a transcatheter intra-arterial procedure performed by interventional radiology and is commonly used to treat malignant tumors. In this medical procedure, a microcatheter is navigated into the patient's liver, which is filled with a radioactive compound (such as yttrium-90( 90 Radioembolic microspheres containing Y or Y90) are delivered to the target tumor. The microspheres embolize the blood vessels supplying the tumor while also delivering radiation to kill tumor cells.

[0006] Typically, medical devices used to perform radioembolization procedures require multiple syringes, external tubing, vials containing radioactive compounds, and bulky shielding assemblies for containing and shielding the radioactive vials. Such devices typically involve time-consuming and labor-intensive setup procedures. Complex devices are typically fixed, thus limiting the physician's mobility in the operating room to within a certain proximity of the device.

[0007] Routine manipulation of product containers storing radioactive materials during radioembolization procedures typically requires a nuclear medicine technician who handles the material with forceps or tweezers. The process involves exposing other medical personnel to radiation and the additional possibility of contaminating the operating room. Syringes that manually administer radioactive compounds are prone to inconsistent flow rates and pressures. Inadequate injection rates can result in reduced bead dispersion, which can compromise treatment efficacy. Summary of the invention

[0008] Embodiments of the present disclosure will be used in any technical environment where it is necessary to deliver two separate and isolated media, such as during transarterial radioembolization for the treatment of malignant liver tumors. During a transarterial radioembolization procedure, a microcatheter is navigated into the liver and a therapeutic agent (e.g., a radiotherapeutic agent contained in microspheres) can be delivered to the target tumor. Throughout this process, different media can be used, including saline / D5W, contrast agent, and microspheres. As a result, a minimum of three different syringes are required, increasing setup and operating time. Another problem arises during a transarterial radioembolization procedure when using conventional types of syringes because two or more separate syringes are required during device activation. The first syringe can be an empty or pre-filled saline syringe for pumping. There is a risk of air entering the system during the replacement of two or more independent syringes.

[0009] The present disclosure describes a dual-stage syringe having two independent reservoirs connected in series via a single plunger for injecting or dispensing two separate media. In embodiments, the dual-stage syringe disclosed herein can be manually driven.

[0010] The dual-stage syringe of the present disclosure may include a single plunger mechanism for actuating two chambers and independently delivering the media in each chamber. The dual-stage syringe of the present disclosure may allow the inner or proximal chamber to be filled and purged multiple times without having to actuate the outer or distal chamber. In addition, some embodiments of the dual-stage syringe disclosed herein may include one or more locking mechanisms that can provide tactile and audible feedback and assurance for when to change various media.

[0011] Embodiments of the present disclosure may also address one or more of the following shortcomings of existing systems: difficulty in pushing the syringe to pressurize the liquid to flow through the microcatheter, numerous cumbersome steps (e.g., turning the stopcock, adjusting the needle height, adjusting the tubing set to dislodge trapped spheres, etc.) that delay the procedure and result in unnecessary radiation exposure, inability to control the flow rate, delivery volume, and delivery rate of beads, inability to easily analyze the contained Y90 activity as part of a quality assurance step, inability to easily split the therapeutic dose to allow treatment at different tumor sites, settling of particles or microspheres in the container or tube due to the inability to mix the particles or microspheres, and the bulky overall size of the device for transarterial radioembolization, which takes up valuable space and access channels in the operating room.

[0012] Example embodiments disclosed herein relate to a locking mechanism dual stage syringe.

[0013] These and other features, aspects and advantages of the present disclosure will become better understood with reference to the following description and appended claims.

[0014] Additional features and advantages of the embodiments described herein will be set forth in the following detailed description, and those skilled in the art will readily understand the invention in part from this description, or recognize these features and advantages by practicing the embodiments described herein (including the following detailed description, claims, and accompanying drawings).

[0015] It should be understood that both the foregoing general description and the following detailed description describe various embodiments and are intended to provide an overview or framework for understanding the nature and character of the claimed subject matter. The accompanying drawings are included to provide a further understanding of the various embodiments and are incorporated into and constitute a part of this specification. The accompanying drawings illustrate the various embodiments described herein and, together with the description, serve to explain the principles and operation of the claimed subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is a schematic diagram of a dual-stage injector according to an embodiment.

[0017] Figure 2 is a side view of an outer barrel of a dual-stage syringe according to an embodiment.

[0018] Figure 3 is a top perspective view of an outer barrel of a dual-stage syringe according to an embodiment.

[0019] Figure 4 is a bottom perspective view of an outer barrel of a dual-stage syringe according to an embodiment.

[0020] Figure 5 is a side perspective view of an outer barrel of a dual-stage syringe according to an embodiment.

[0021] Figure 6 is a side view of a main plunger of a dual-stage syringe according to an embodiment.

[0022] Figure 7 is a top perspective view of a main plunger of a dual stage syringe according to an embodiment.

[0023] Figure 8 is a side perspective view of a main plunger of a dual stage syringe according to an embodiment.

[0024] Fig. 9 is a side perspective view of a main plunger of a dual stage syringe including a sealing member on its distal end according to an embodiment.

[0025] Fig.10 is a side perspective view of a main plunger of a dual stage syringe including a sealing member on its distal end according to an embodiment.

[0026] Fig.11 is an exploded view of a sleeve-type dual-stage syringe according to an embodiment.

[0027] Fig.12 is a side perspective view of a locking sleeve according to an embodiment.

[0028] Fig.13 is a bottom perspective view of a locking sleeve according to an embodiment.

[0029] Fig.14 is a bottom view of a locking mechanism of a locking sleeve according to an embodiment.

[0030] Fig.15 is a top perspective view of a locking sleeve according to an embodiment.

[0031] Fig.16 is a side perspective view of an assembly including a locking mechanism and a main plunger having a sealing member on its distal end according to an embodiment.

[0032] Fig.17 is a front view of an assembly including a locking mechanism and a main plunger having a sealing member on its distal end according to an embodiment.

[0033] Fig.18 is a side view of a secondary plunger of a dual stage syringe according to an embodiment.

[0034] Fig.19 is a perspective view of a sleeve-locked dual-stage syringe according to an embodiment in a shipping configuration.

[0035] Fig. 20 Is in shipping configuration Fig.16 A perspective view of a sleeve-lock dual-stage syringe wherein the main plunger and locking mechanism are visible through the outer barrel.

[0036] Fig.21 Is in shipping configuration Fig.19 and Fig. 20 Longitudinal section of a sleeve-locked dual-stage syringe.

[0037] Fig. 22 is a perspective view of a sleeve-locked dual-stage syringe according to an embodiment in a flush configuration, with the main plunger and locking mechanism visible through the outer barrel.

[0038] Fig.23 Is in flushing configuration Fig. 22 Longitudinal section of a sleeve-locked dual-stage syringe.

[0039] Fig.24 is a perspective view of a sleeve-locked dual-stage syringe according to an embodiment in a piercing configuration, wherein the main plunger and locking mechanism are visible through the outer barrel.

[0040] Fig.25It is in the piercing configuration Fig.23 Longitudinal section of a sleeve-locked dual-stage syringe.

[0041] Fig.26 is a cross-sectional view of a sleeve-locked dual-stage syringe according to an embodiment in a primed configuration, with the main plunger and locking mechanism visible through the outer barrel.

[0042] Fig. 27 It is in the perfusion structure Fig.26 Longitudinal section of a sleeve-locked dual-stage syringe.

[0043] Fig.28 is a perspective view of a sleeve-locked dual-stage syringe according to an embodiment in a delivery configuration.

[0044] Fig.29 Is in the conveying structure Fig.28 Longitudinal section of a sleeve-locked dual-stage syringe.

[0045] Fig.30 is a side perspective view of an all-inclusive locking dual-stage syringe according to an embodiment.

[0046] Fig.31 yes Fig.30 A side perspective view of the secondary plunger and sealing member of the all-inclusive locking dual-stage syringe.

[0047] Fig.32 yes Fig.30 A side perspective view of an assembly of a primary plunger, secondary plunger and sealing member of an all-inclusive locking dual-stage syringe.

[0048] Fig.33 is a side cross-sectional view of an integrated one-way valve syringe according to an embodiment.

[0049] Fig.34A According to the embodiment, the first level Fig.33 Side cross-sectional view of a syringe with an integrated one-way valve.

[0050] Fig.34B is at the second level according to the embodiment Fig.33 Side cross-sectional view of a syringe with an integrated one-way valve.

[0051] Fig.34C According to the third level of the embodiment Fig.33 Side cross-sectional view of a syringe with an integrated one-way valve.

[0052] Fig.35 is a side cross-sectional view of an integrated one-way valve syringe according to an embodiment.

[0053] Fig.36A According to the embodiment, the first level Fig.35 Side cross-sectional view of a syringe with an integrated one-way valve.

[0054] Fig.36B is at the second level according to the embodiment Fig.35 Side cross-sectional view of a syringe with an integrated one-way valve.

[0055] Fig.36C is at the third level according to the embodiment Fig.35 Side cross-sectional view of a syringe with an integrated one-way valve.

[0056] Fig.37 is a schematic diagram of a sleeve-locked dual-stage syringe with membrane technology according to an embodiment.

[0057] Fig.38 is a side view of a syringe with a ratcheting safety tab according to an embodiment.

[0058] Fig.39 is a side cross-sectional view of a syringe with a ratcheting safety tab according to an embodiment.

[0059] Fig.40A is a top view of a telemetered syringe plunger cap according to an embodiment.

[0060] Fig.40B is a cross-sectional view of a telemetered syringe plunger cap according to an embodiment.

[0061] Fig.40C is a cross-sectional view of a telemetric syringe plunger cap assembled on a syringe plunger according to an embodiment.

[0062] Fig.41 is a schematic diagram of a sleeve-lock dual-stage syringe according to an embodiment incorporated into an example of a radioembolic delivery system for delivering a radioembolic bead solution to a patient through a delivery catheter in fluid communication with the sleeve-lock dual-stage syringe. DETAILED DESCRIPTION

[0063] Reference will now be made in detail to embodiments of dual-stage syringes. In particular, embodiments of dual-stage syringes disclosed herein may relate to locking mechanism dual-stage syringes and dual-stage syringes with integrated one-way valves. As will be described in more detail subsequently, embodiments of locking mechanism dual-stage syringes may include sleeve-type dual-stage syringes. As will be described in more detail subsequently, other embodiments of locking mechanism dual-stage syringes may include all-inclusive dual-stage syringes. In other embodiments of dual-stage syringes described herein, dual-stage syringes with one or more integrated one-way valves will be described in more detail subsequently.

[0064] The dual-stage syringe can be incorporated into any system involving the delivery or mixing of multiple fluids, including medical procedures involving the delivery of multiple fluids, such as therapeutic agents, flushing solutions, excipient solutions, isotonic sterile solutions, contrast media, or combinations thereof. In some embodiments, the dual-stage syringe can be incorporated into a delivery system for cancer treatment, such as in a delivery system for a chemotherapeutic agent or a radiotherapeutic agent. In some embodiments, the dual-stage syringe can be incorporated into a delivery system for chemoembolization or radioembolization, such as for a fluid containing radioembolic beads mixed with one or more carrier fluids or contrast media, ready to be delivered to a patient in need of treatment. In some embodiments, the dual-stage syringe can be incorporated into a delivery system for transarterial radioembolization, for tumor treatment, such as liver tumor treatment.

[0065] As used herein with respect to the embodiments of the dual-stage syringe, the relative term "distal" refers to the direction toward which the plunger is inserted into the barrel of the dual-stage syringe and along which fluid is expelled from the dual-stage syringe during operation of the dual-stage syringe. Likewise, the relative term "proximal" refers to the direction opposite to the direction toward which the plunger is inserted into the barrel of the dual-stage syringe and along which fluid is expelled from the dual-stage syringe during operation of the dual-stage syringe. In general, it should be understood that the directional terms used herein (e.g., up, down, right, left, front, back, top, bottom, distal, and proximal) are made with reference only to the drawings as drawn and are not intended to imply an absolute orientation of any device, any device component, or any entire embodiment.

[0066] Locking mechanism dual stage syringe

[0067] Reference will now be made in detail to embodiments of a locking mechanism dual stage syringe. In embodiments, a locking mechanism dual stage syringe may include an outer barrel, a main plunger, and one or more locking mechanisms.

[0068] The one or more locking mechanisms may be configured to define a first boundary, a second boundary, and at least three stages. The second boundary may be distal to the first boundary. The at least three stages may include an initial stage, an intermediate stage, and a final stage. In the initial stage, the main plunger is inserted proximal to the first boundary and can move freely distally or proximally. In the intermediate stage, the main plunger is inserted distal to the first boundary and is prevented from moving proximally beyond the first boundary. In the final stage, the main plunger is inserted distal to the second boundary and is prevented from moving proximally beyond the second boundary.

[0069] In some embodiments, the one or more locking mechanisms may be incorporated into the outer barrel, the main plunger, one or more accessory components, or a combination thereof. In other embodiments, the one or more locking mechanisms may be included as features on the surface of the outer barrel, the main plunger, one or more additional components, or a combination thereof. Such features may be male features including one or more prongs, protrusions, projections, or a combination thereof. In an embodiment, such features may be female features including one or more grooves, tracks, indentations, depressions, other surface modifications, or a combination thereof. In some embodiments, the male features may have corresponding female features. In some embodiments, the one or more locking mechanisms may include a sleeve-type locking mechanism, an all-inclusive locking mechanism, or other locking mechanisms.

[0070] Reference Figure 1 According to an embodiment, a locking mechanism dual-stage syringe 100 is provided. Figure 1 In the illustrated embodiment, the locking mechanism dual-stage syringe 100 may include an outer barrel 10, a main plunger (piston) 50 accommodating a secondary plunger 70. Figure 1 , the locking mechanism dual stage syringe 100 is depicted as being aligned along a longitudinal axis 1 shared by the various components 10, 50, 70 and the locking mechanism dual stage syringe 100 itself when fully assembled. In an embodiment of the fully assembled locking mechanism dual stage syringe 100, the specific construction of which will be described in more detail subsequently, at least a portion of the main plunger 50 is housed within the outer barrel 10, and at least a portion of the secondary plunger may be housed within the main plunger 50. The aforementioned various components 10, 50, 70, the one or more locking mechanisms, and each of the various features thereof according to an embodiment of the locking mechanism dual stage syringe 100 will now be described in more detail.

[0071] The locking mechanism dual-stage syringe 100 may include an outer barrel 10. Referring now to Figure 1 −5. The outer barrel 10 may have a main chamber 90 defined through the outer barrel 10 from the proximal opening of the outer barrel 10 to the distal opening of the outer barrel 10 .

[0072] In an embodiment, the outer barrel 10 can be made of various materials, such as polymers, plastics or metals. Non-limiting example polymers for the outer barrel include polycarbonate (PC), polyethylene (PE), polyethylene terephthalate (PET). Non-limiting example plastics for the outer barrel 10 include poly (methyl methacrylate) (PMMA) and composite resins, such as polycarbonate loaded with tungsten. Non-limiting example metals and metal alloys for the outer barrel 10 include various alloys of stainless steel, titanium, copper, tungsten, aluminum, tin-lead alloy (pewter) and any of these. In some embodiments, the outer barrel 10 is made of radiation shielding materials, such as the plastics or metals listed above. The radiation shielding material can have a thickness sufficient to ensure that the radiation of the radioactive therapeutic material in the dual-stage syringe 100 with one or more locking mechanisms will not penetrate into the environment or cause safety issues for the personnel operating the locking mechanism dual-stage syringe 100. In an embodiment, suitable radiation shielding materials can shield the operator of the dual-stage syringe 100 with a sleeve-type locking mechanism from beta particle radiation, X-rays, or both.

[0073] Now refer to Figure 2 -4, an exemplary embodiment of the outer cylinder 10 is provided. Figure 2 In all exemplary embodiments provided in -4, the outer barrel 10 of the locking mechanism dual-stage syringe 100 may include an outer proximal opening 11, a proximal flared edge 13 surrounding the outer proximal opening 11, an outer distal opening 19 opposite to the outer proximal opening 11, and a main body portion 15 between the proximal flared edge 13 and the outer distal opening 19. Figure 2 The outer barrel 10 may include a neck 17 between the body portion 15 and the outer distal opening 19 .

[0074] Reference Figure 3 , the outer barrel 10 may optionally include a proximal recess 12, which may be configured to accommodate corresponding features of the main plunger 50, as described in more detail later. The outer proximal opening 11 of the outer barrel 10 may be wide enough to accommodate the main plunger 50 through the outer proximal opening 11. As will be described in more detail later, in an embodiment, the outer proximal opening 11 of the outer barrel 10 may be wide enough to accommodate a locking mechanism such as a sleeve-type locking mechanism through the outer proximal opening 11. Still referring to Figure 3 , the outer barrel 10 has a main chamber 90 defined therein. The main plunger 50 can be inserted into the main chamber 90. In some embodiments, a locking mechanism can be inserted into the main chamber 90.

[0075] Reference Figure 4 The outer barrel 10 may optionally include a gripping feature 14 on a distally facing surface of the proximal flared edge 13 .

[0076] As previously described, in some embodiments of the locking mechanism dual-stage syringe 100, the one or more locking mechanisms may be incorporated into the outer barrel 10. In such embodiments, the one or more locking mechanisms are incorporated into the outer barrel 10 as one or more features on the surface of the outer barrel 10, such as male features and / or female features. Male features may include, but are not limited to, protrusions, projections, or combinations thereof. Female features may include, but are not limited to, grooves, tracks, indentations, depressions, other surface modifications, and combinations thereof.

[0077] In an embodiment, the outer barrel 10 may include one or more male features on the surface of the outer barrel 10. In further embodiments, the one or more male features on the surface of the outer barrel 10 may have corresponding one or more female features on the main plunger 50, one or more additional components, or a combination thereof. In other embodiments, the outer barrel 10 may include one or more female features on the surface of the outer barrel 10. In further embodiments, the one or more female features on the surface of the outer barrel 10 may have corresponding one or more male features on the main plunger, one or more other components, or a combination thereof. In some embodiments, the outer barrel 10 may include a combination of male and female features on the surface of the outer barrel 10, which may have corresponding female and male features on the main plunger, one or more additional components, or a combination thereof, respectively.

[0078] Figure 5 An exemplary embodiment of a locking mechanism dual stage syringe 100 is shown having one or more locking mechanisms incorporated into the outer barrel 410. Referring now to Figure 5 , an embodiment of the outer barrel 410 may include an initial stage track 412, an intermediate stage track 414, and a final stage track 416 within the outer barrel 410. The initial stage track 412, the intermediate stage track 414, and the final stage track 416 are all negative features on the surface of the outer barrel 410. Figure 5 Indentation 418 is also a negative feature on the surface of outer barrel 410. In general, initial stage track 412, intermediate stage track 414, final stage track 416, and indentation 418 may be referred to as Figure 5 The female feature of the locking mechanism of the illustrated embodiment. As will be described in more detail later, Figure 5 The female feature of the locking mechanism of the embodiment shown in FIG. Figure 5 The corresponding male features on the main plunger of the embodiment shown. In general, Figure 5 The male and female features of the locking mechanism of the embodiment shown in FIG. 1 may be collectively referred to as Figure 5 The embodiment shown has a turn-key locking mechanism. Figure 5The embodiment shown in the figure may also be referred to as an all-inclusive embodiment of the locking mechanism dual-stage syringe 100. In other embodiments, the locking mechanism dual-stage syringe 100 may include an all-inclusive locking mechanism that includes only the initial stage track 412, the intermediate stage track 414, and the final stage track 416, but does not include the indentation 418. In other embodiments, the locking mechanism dual-stage syringe 100 may include an all-inclusive locking mechanism having the initial stage track 412, the intermediate stage track 414, the final stage track 416, the indentation 418, and one or more additional locking mechanisms.

[0079] Still refer to Figure 5 , the intersection of the initial stage track 412 and the intermediate stage track 414 corresponds to the initial stage of the main plunger. In the initial stage, the main plunger is inserted to the proximal side of the initial stage track 412 and can move freely distally or proximally. The intermediate stage track 414 corresponds to the intermediate stage of the main plunger. In the intermediate stage, the main plunger can traverse the intermediate stage track and be prevented from moving proximally beyond the intermediate stage track. The intersection of the final stage track 416 and the intermediate stage track 414 corresponds to the final stage of the main plunger. In the final stage, the main plunger is inserted to the distal side of the intermediate stage track and is prevented from moving proximally beyond the distal end of the final stage track. In other embodiments, the locking mechanism dual-stage syringe 100 may include an all-inclusive locking mechanism, which includes one or more additional tracks in the surface of the outer barrel 410, and the one or more additional tracks may define one or more additional stages.

[0080] Like the other embodiments of outer barrel 10, outer barrel 410 may include any of the polymers, plastics, metals, or alloys previously listed, or outer barrel 410 may include other materials, such as nylon.

[0081] Reference will now be made to an embodiment of the main plunger 50 of the locking mechanism dual stage syringe 100. Figure 1 , the main plunger 50 may have a secondary chamber defined through the main plunger 50 from the proximal opening of the main plunger 50 to the sealed distal end of the main plunger 50, the main plunger 50 being configured to receive the secondary plunger (piston) 70 through the proximal opening of the main plunger 50. In an embodiment, the main plunger 50 may be narrow enough to be accommodated by the outer barrel 10.

[0082] In embodiments, the main plunger 50 can be made of various materials, such as polymers, plastics, or metals. Non-limiting example polymers for the outer barrel include polycarbonate (PC), polyethylene (PE), polyethylene terephthalate (PET). Non-limiting example plastics for the main plunger 50 include poly (methyl methacrylate) (PMMA) and composite resins, such as polycarbonate loaded with tungsten. Non-limiting example metals and metal alloys for the main plunger 50 include stainless steel, lead, copper, tungsten, aluminum, tin-lead alloys, and various alloys of any of these. In some embodiments, the main plunger 50 is made of radiation shielding materials, such as the plastics or metals listed previously. The radiation shielding material can have a thickness sufficient to ensure that the radiation from the radioactive therapeutic material in the dual-stage syringe 100 with one or more locking mechanisms does not penetrate into the environment or cause safety issues for the personnel operating the locking mechanism dual-stage syringe 100. In embodiments, suitable radiation shielding materials can shield the operator of the dual-stage syringe 100 with a sleeve-type locking mechanism from beta particle radiation, X-rays, or both.

[0083] Now refer to Figure 6 -9, an exemplary embodiment of the main plunger 50 is provided. Figure 6 In -9, the main plunger 50 may include a proximal wing 51, a distal plunger opening 53, and a plunger body portion 55. The main plunger may include a secondary chamber 95 defined therein from the proximal wing 51 to the distal plunger opening 53. The main plunger 50 may optionally include a handle locking feature 52 on the proximal wing 51. The secondary chamber 95 may accommodate a secondary piston 70, which will be described in more detail later. The plunger body portion 55 may include one or more stop rings, such as a distal stop ring 56 and a proximal stop ring 58. In some embodiments, both the distal stop ring 56 and the proximal stop ring 58 may be configured to interact with an embodiment of a locking mechanism described in more detail later when the main plunger 50 moves.

[0084] Now refer to Figure 8 -9, in an embodiment, the main plunger 50 may include a sealing seat 59 for mounting a plunger seal 60. The plunger seal 60 may include a one-way valve, a valve flap, or a flow channel. Fig. 9 As shown, in an embodiment, the plunger seal 60 can be installed on the main plunger so that the plunger seal 60 covers the distal plunger opening 53 to prevent fluid from flowing through the distal plunger opening 53 until the appropriate stage in the operation of the locking mechanism dual-stage syringe 100, as will be described in more detail.

[0085] In some embodiments of the locking mechanism dual-stage syringe 100, one or more locking mechanisms may be incorporated into the main plunger. In such embodiments, the one or more locking mechanisms incorporated into the main plunger may include one or more features on the surface of the main plunger, such as male features and / or female features. Male features may include, but are not limited to, protrusions, projections, or combinations thereof. Female features may include, but are not limited to, grooves, tracks, indentations, depressions, other surface modifications, and combinations thereof.

[0086] In an embodiment, the main plunger 50 may include one or more male features on the surface of the main plunger 50. In other embodiments, the one or more male features on the surface of the main plunger 50 may have corresponding one or more female features on the outer barrel, one or more other components, or a combination thereof. In other embodiments, the main plunger 50 may include one or more female features on the surface of the main plunger 50. In further embodiments, the one or more female features on the surface of the main plunger 50 may have corresponding one or more male features on the outer barrel, one or more additional components, or a combination thereof. In some embodiments, the main plunger 50 may include a combination of male and female features on the surface of the main plunger 50, which may have corresponding female and male features, one or more additional components, or a combination thereof, respectively, on the outer barrel.

[0087] Fig.10 An exemplary embodiment of a dual-stage syringe having a locking mechanism incorporated into the main plunger is shown. Fig.10 , an embodiment of the main plunger 450 includes a male feature (tip) 465, the shape and size of which appropriately corresponds to the previously described Figure 5 In an embodiment, the shape and size of the male feature can be appropriately set to travel within the tracks 412, 414, 416 of the outer cylinder 410.

[0088] As previously described, the one or more locking mechanisms of the locking mechanism dual-stage syringe 100 can be configured to define a first boundary, a second boundary, and at least three levels. The second boundary can be distal to the first boundary. The at least three levels may include an initial level, an intermediate level, and a final level. In the initial level, the main plunger is inserted to the proximal side of the first boundary and can move freely distally or proximally. In the intermediate level, the main plunger is inserted to the distal side of the first boundary and is prevented from moving proximally beyond the first boundary. In the final level, the main plunger is inserted to the distal side of the second boundary and is prevented from moving proximally beyond the second boundary.

[0089] In some embodiments, the one or more locking mechanisms may be incorporated into a sleeve disposed within the main chamber 90. For example, the one or more locking mechanisms incorporated into a sleeve disposed within the main chamber 90 may include features, such as prongs, bumps, projections, grooves, tracks, indentations, or other surface modifications, disposed on a surface of the sleeve within the main chamber 90. Examples of locking mechanisms incorporated into a sleeve disposed within the main chamber 90 may include a sleeve-type locking mechanism, which will now be described in more detail.

[0090] Now refer to Figures 11 to 15 An embodiment of a dual-stage syringe having a sleeve-type locking mechanism is described. Fig.11 According to an embodiment, a dual-stage syringe 200 having a sleeve-type locking mechanism may include an outer barrel 210, a locking sleeve 230, and a main plunger 250 accommodating a secondary plunger 270. Fig.11 In the exploded view of FIG. 1 , when fully assembled, the components of the dual-stage syringe with a sleeve locking mechanism 300 are depicted as being aligned along a longitudinal axis 31 shared by the various components 210, 230, 250, 270 and the dual-stage syringe with a sleeve locking mechanism 200 itself. In the dual-stage syringe with a fully assembled sleeve locking mechanism 200 (the specific construction of which will be described in detail later), the locking sleeve 230 is housed within the outer barrel 210, at least a portion of the primary plunger 250 is housed in the locking sleeve 230 and the outer barrel 210, and at least a portion of the secondary plunger 270 may be housed within the primary plunger 250.

[0091] Refer again Fig.11 -15, an embodiment of a dual-stage syringe 200 with a sleeve-type locking mechanism may include a locking sleeve 230. Fig.11 -15, the locking mechanism 230 according to an embodiment may include a main body portion 235 having a shape that conforms to the contour of the outer barrel 10. The locking mechanism 230 may include one or more features that can be used for integrated assembly, such as a proximal ridge 232 configured to position the locking mechanism in the outer proximal opening 11 of the outer barrel 10. The locking mechanism 230 may include a distal capture member 240. The distal capture member 240 may have a variety of shapes and sizes suitable for performing the locking function, as will be described in more detail later. The distal capture member 240 may have sufficient elasticity to allow the main plunger 50 to pass through the locking mechanism in the distal direction, but deflect outward and prevent the main plunger 50 from moving proximally, as will be described.

[0092] exist Fig.11In the embodiment of -15, the distal capture member 240 is configured as a long capture piece 242 and a short capture piece 246 alternating around the circumference of the main body portion 235 at the distal end of the main body portion 235. The long capture piece 242 includes a long capture piece end 244, which is slightly inclined inwardly from the sleeve-type locking dual-stage syringe 200 (i.e., toward the longitudinal axis 1 (see Fig.11 )). The short catch piece 246 includes a short catch piece end 248, which is also slightly inclined inward. The length of the long catch piece 242 defines a distal stop height 243. Similarly, the length of the short catch piece 246 defines a proximal stop height 247. As will be described in more detail later, the distal stop height 243 and the proximal stop height 247 further define the following position: when the main plunger 50 is inserted into the outer barrel 10 and surrounded by the locking mechanism 30, the proximal movement of the main plunger 50 beyond the said position is prevented.

[0093] Reference Fig.16 -17, the main plunger 250 can be inserted into the locking sleeve 230. When the main plunger 250 is inserted in the distal direction through the locking sleeve 230, the distal stop ring 256 and the subsequent proximal stop ring 258 pass distally through the distal capture member 340 (e.g., the long capture piece 342 and the short capture piece 346). The distal capture member 340 is then deflected inwardly, thereby locking the main plunger 350 in a manner that prevents the main plunger 350 from retracting proximally beyond the point 340 (i.e., beyond the long capture piece end 44) ​​at which the proximal stop ring 358 passes back through the distal capture member in the proximal direction. In other embodiments, the distal capture member 240 can be a capture piece of varying length around the circumference of the main body portion 235 at the distal end of the main body portion 235. In other embodiments, the elongated capture member 242 includes an elongated capture member end 244 that can be angled slightly outwardly (ie, away from the longitudinal axis 1 (see FIG. Fig.11 )). In other embodiments, the short capture member 246 includes a short capture member end 248 that may be slightly inclined outward.

[0094] Reference Fig.18 , the secondary plunger 70 may include an elongated portion 74, a handle portion 75, and a secondary seal 80. The elongated portion 74 of the secondary plunger 70 may include a ribbed member 76 perpendicular to the elongated portion 74 to provide stability to the elongated portion 74 and facilitate insertion of the secondary plunger 70 into the secondary chamber 95 of the primary plunger 50. The secondary plunger 70 may include an insertion stop 72 that limits the maximum extent to which the secondary plunger 70 can be inserted into the secondary chamber 95 of the primary plunger 50. It should be understood that the insertion stop 72, the elongated portion 74, the handle portion 75, and the ribbed member 76 (if any) may have various shapes, sizes, or configurations and are not limited to Fig.18Specific embodiments of the present invention.

[0095] The major components of the dual-stage syringe with sleeve locking mechanism 200, and the general operating principle of the locking sleeve 230 have been described. The major components and general operating principle lead to at least five stages of operation of the dual-stage syringe with sleeve locking mechanism 200, which will now be referred to. Fig.19 -29 describes each of the five phases. In particular, the operations phase includes shipping construction ( Fig.19 ﹣21) Flushing structure ( Fig. 22 ﹣23) Piercing structure ( Fig.24 ﹣25) Infusion structure ( Fig.26 ﹣27) and conveying structure ( Fig.28 -29). It should be understood that the description of these operation stages is intended to illustrate one way of operating the sleeve-locked dual-stage syringe 200, and by illustrating one way of operating the sleeve-locked dual-stage syringe 200, to further clarify the functions and synergy of the main components of the sleeve-locked dual-stage syringe 200.

[0096] In an embodiment, the sleeve-lock dual-stage syringe 200 Fig.19 The shipping configuration of -21 is one in which the sleeve-locked dual-stage syringe 200 can be received by a qualified physician who intends to incorporate the sleeve-locked dual-stage syringe 200 into a delivery system for use in, for example, radioembolization procedures. In the shipping configuration, the locking mechanism 230, the primary plunger 250, and the secondary plunger 270 are all inserted into the outer barrel 210 to varying degrees. In particular, the locking mechanism 230 is fully inserted into the outer barrel 210 such that the proximal ridge 232 is located in the exterior proximal opening 211 of the outer barrel 210. The primary plunger 250 is only partially inserted into the outer barrel 210 such that a certain amount of the plunger body portion 255 remains outside the outer barrel 210. Moreover, the primary plunger 250 is only inserted far enough through the locking mechanism such that the distal stop ring 256 has not yet distally exceeded the long catch piece end 244 of the long catch piece 242 of the locking mechanism 230.

[0097] In the shipping configuration of the sleeve-lock dual-stage syringe 200, the portion of the main chamber 290 that is not filled by the main plunger 250 initially contains a fluid such as saline, which is intended to flush air in the system at the beginning of a radioembolization procedure. For illustrative purposes only, the delivery needle 150 is shown as protruding into the main chamber 290. In some embodiments, the delivery needle 150 can be attached to the sleeve-lock dual-stage syringe 200 in the shipping configuration. In other embodiments, the delivery needle 150 can be a component of the delivery system. Some embodiments may include a distal fixing device 5. In some embodiments, the distal feature 5 can be a gasket that seals the outer distal opening 217 of the outer barrel 210 to prevent fluid communication between the main chamber 290 and the outside of the outer barrel 210, except through the delivery needle 150. In other embodiments, the distal feature 5 can be a Luer connector that can be used to connect the locking dual-stage syringe 200 to a delivery device. In other embodiments, the Luer connector can be a male Luer connector that has a corresponding female Luer connector on the delivery device. In other embodiments, distal feature 5 may be another connection feature, such as a slip fit, a needleless connection port, or any other connection suitable for attachment to a delivery device.

[0098] In the shipping configuration of the sleeve-lock dual-stage syringe 200, the secondary plunger 270 is inserted into the secondary chamber 295 to such an extent that the insertion stop 272 abuts the proximal wing 251 of the primary plunger 250. The portion of the secondary chamber 295 not occupied by the secondary plunger 270 is filled with radioembolic beads (not shown). The radioembolic beads are sealed within the secondary chamber by the plunger seal 260. There is no fluid communication between the primary chamber 290 and the secondary chamber 295.

[0099] In an embodiment, upon receiving the sleeve-lock dual-stage syringe 200 in the shipping configuration and optionally attaching the sleeve-lock dual-stage syringe 200 to an appropriate delivery system including a reservoir (not shown) fluidly connected to the delivery needle 150, the physician can pull the secondary plunger 270 proximally to move both the primary plunger 250 and the secondary plunger 70 proximally, thereby expanding the primary chamber 290 and drawing the fluid in the reservoir into the primary chamber 290 by suction. The physician can then push the secondary plunger distally to push the fluid in the primary chamber 290 back into the reservoir and place the sleeve-lock dual-stage syringe 200 in the flushing configuration.

[0100] In an embodiment, in the sleeve-lock dual-stage syringe 200 Fig. 22In the flush configuration of -23, the proximal stop ring 258 has passed through the short catch end 248 and is substantially flush with the long catch end 244 but has not passed through the long catch end 244 in the distal direction. When the proximal stop ring 258 passes through the short catch end, the short catch end 248 can snap inwardly with an audible click to notify the physician that the flush configuration has been reached. Once the audible click is heard, the main plunger cannot move proximally beyond the position where the short catch end 48 abuts the proximal stop ring 258. In the flush configuration of the sleeve-lock dual-stage syringe 200, the delivery needle 150 has not pierced the plunger seal 260 of the main plunger 250. However, through the continued movement of the main plunger 250 in the distal direction, the sleeve-lock dual-stage syringe 200 reaches the piercing configuration so that the radioembolic beads within the secondary chamber 295 of the main plunger 250 can begin to mix with the fluid in the reservoir that is forced into the delivery system.

[0101] In an embodiment, in the sleeve-lock dual-stage syringe 200 Fig.24 In the piercing configuration of -25, the main plunger 250 has been inserted into the outer barrel 210 to the maximum extent, so that the delivery needle 150 pierces the plunger seal 260, and the piercing end 155 of the delivery needle 150 is placed in the secondary chamber 295 containing the radioembolic beads. In addition, when the piercing configuration is reached, the proximal stop ring 258 passes through the long catch end 244 of the locking mechanism 230. In turn, the long catch end 244 deflects inwardly due to its elasticity, resulting in a second audible click to notify the physician that the piercing configuration has been reached and the secondary chamber 295 is in fluid communication with the reservoir of the delivery system outside the sleeve-locked dual-stage syringe 100. Therefore, the main plunger 250 is locked for the second time, and the main piston 250 is completely prevented from moving proximally.

[0102] Once the piercing configuration is achieved during the procedure, the physician can unlock the secondary plunger 270, for example, by rotating the secondary plunger 270. The physician can then pull the secondary plunger 270 in a proximal direction to expand the secondary chamber 295 and draw fluid from the reservoir of the delivery system into the secondary chamber 295 for intimate mixing with the radioembolic beads in the secondary chamber 295. When the secondary plunger 270 is pulled proximally to the maximum extent without removing the secondary plunger 270 from the secondary chamber 295, the sleeve-lock dual-stage syringe 200 is in the priming configuration.

[0103] In some embodiments, in the sleeve-lock dual-stage syringe 200 Fig.26 In the perfusion configuration of -27, the secondary chamber 295 has its maximum volume and contains: a treatment mixture, such as a mixture of radioembolic beads; and a suitable carrier fluid (such as saline). This mixture is a delivery mixture, which is ready for infusion into the patient.

[0104] In an embodiment, in the sleeve-lock dual-stage syringe 200 Fig.28 In the delivery configuration of -29, the physician pushes the secondary plunger 270 in the distal direction to expel the delivery mixture produced when the sleeve-locked dual-stage syringe 200 is placed in the aforementioned priming configuration distally through the delivery needle 150 and into the delivery system for injection into the patient. The physician is signaled that the secondary plunger 270 has been fully depressed and the dose of the delivery mixture has been completed by abutting the insertion stop 272 of the secondary plunger 270 against the proximal wing 251 of the main plunger 250. Alternatively, the physician may pump the secondary plunger 270 multiple times to complete multiple cycles of replenishing the secondary chamber 295 with fluid and expelling the contents of the secondary chamber 295 to ensure that the entire dose of the radioembolic beads has been sent to the delivery system.

[0105] Having described in detail an embodiment of the sleeve-locked dual-stage syringe 200, reference will now be made to Fig.30 ﹣ Fig.32 An embodiment of an all-inclusive locking dual stage syringe 400 is described. The various components of an embodiment of an all-inclusive locking dual stage syringe 400, including the outer barrel 410 and the main plunger 450, have been previously described.

[0106] like Fig.30 As shown, an exemplary embodiment of a fully assembled all-inclusive locking dual-stage syringe 400 includes an outer barrel 410 , a primary plunger 450 (housed within the outer barrel 410 ), and a secondary plunger 470 .

[0107] By comparing with the embodiment of the dual-stage syringe having a sleeve-type locking mechanism, the all-inclusive locking dual-stage syringe 400 includes an all-inclusive locking mechanism instead of the locking sleeve 230 of the aforementioned sleeve-type locking dual-stage syringe 200. Figure 30 to Figure 32 In the embodiment illustrated in FIG. 1 , the all-inclusive locking mechanism may include an initial stage track 412, an intermediate stage track 414, and a final stage track 416 within the outer barrel 410. In other embodiments, the all-inclusive locking dual-stage syringe 400 may include one or more additional tracks. Like the previously described sleeve-locked dual-stage syringe 200, the all-inclusive locking dual-stage syringe 400 may include any of the polymers, plastics, metals, or alloys listed above, or it may include other materials such as nylon. Referring now to FIG. Fig.10 , an embodiment of the main plunger 450 includes a male feature 465, the shape and size of which appropriately corresponds to the previously described Figure 5 In an embodiment, the shape and size of the male feature 465 can be appropriately set to travel within the tracks 412, 414, 416 of the outer cylinder 410.

[0108] The intersection of the initial stage track 412 and the intermediate stage track 414 corresponds to the initial stage of the main plunger. The intersection of the initial stage track 412 and the intermediate stage track 414 corresponds to the position of the main plunger 450 similar to the flushing structure of the sleeve-type locking dual-stage syringe 200 described previously. In the initial stage, the main plunger is inserted to the proximal side of the initial stage track 412 and can move freely distally or proximally. The intermediate stage track 414 corresponds to the intermediate stage of the main plunger. In the intermediate stage, the main plunger can traverse the intermediate stage track and is prevented from moving proximally beyond the intermediate stage track. The physician rotates the secondary plunger 470 to transfer the male feature 465 through the intermediate stage track 414 and prepare to make the all-inclusive locking dual-stage syringe 400 enter the delivery structure. The intersection of the final stage track 416 and the intermediate stage track 414 corresponds to the final stage of the main plunger. The final push of the secondary plunger 470 in the distal direction causes the male feature 465 to slide down the final stage track 416 far enough to allow the delivery needle to pierce the secondary seal 80 of the main plunger 450. In the final stage, the main plunger is inserted distal to the intermediate stage track and is prevented from moving proximally beyond the distal end of the final stage track. In other embodiments, the all-inclusive locking dual-stage syringe 400 can include an all-inclusive locking mechanism that includes one or more additional tracks in the surface of the outer barrel 410, which can define one or more additional stages.

[0109] Dual-stage injectors with one or more integrated non-return valves

[0110] In some embodiments, the dual-stage syringe described herein comprises an integrated one-way valve dual-stage syringe. In some embodiments, the integrated one-way valve dual-stage syringe can be a dual-stage syringe with an integrated one-way valve and a needle. In some embodiments, the integrated one-way valve dual-stage syringe can be a dual-stage syringe with two integrated one-way valves. Embodiments of the integrated one-way valve dual-stage syringe can be used in any technical environment where it is necessary to deliver two separate and isolated media, such as during transarterial radioembolization to treat malignant liver tumors.

[0111] Reference now Fig.33 -36C, provides an embodiment of an integrated one-way valve dual-stage syringe 600. In some embodiments, the integrated one-way valve dual-stage syringe 600 may include a main plunger 650, which may be configured to independently deliver at least two media.

[0112] Reference Fig.33 and Fig.35 According to an embodiment, a dual-stage syringe 600 with an integrated one-way valve is provided. Fig.33In the embodiment illustrated in FIG. 1 , the integrated one-way valve dual-stage syringe 600 may include an outer barrel 610 housing a main plunger 650. The outer barrel 610 may have a main chamber 690 defined through the outer barrel 610 from a proximal opening of the outer barrel 610 to a distal opening 619 of the outer barrel 610. In an embodiment, a floating diaphragm plunger 674 may be disposed in the main chamber 690 of the outer barrel 610. In an embodiment, a partition 672 may be disposed in the main chamber 690 of the outer barrel 610, the partition separating the secondary chamber 606 from the main chamber 690.

[0113] In an embodiment, the outer barrel 610 can be made of various materials, such as polymers, plastics or metals. Non-limiting example polymers for the outer barrel include polycarbonate (PC), polyethylene (PE), polyethylene terephthalate (PET). Non-limiting example plastics for the outer barrel 610 include poly (methyl methacrylate) (PMMA) and composite resins, such as polycarbonate loaded with tungsten. Non-limiting example metals and metal alloys for the outer barrel 610 include stainless steel, lead, copper, tungsten, aluminum, tin-lead alloys, and various alloys of any one thereof. In some embodiments, the outer barrel 610 is made of radiation shielding materials, such as plastics or metals listed previously. The radiation shielding material can have a thickness sufficient to ensure that the radiation from the radioactive therapeutic material in the integrated one-way valve dual-stage syringe 600 will not penetrate into the environment or will not cause safety issues for the personnel operating the integrated one-way valve dual-stage syringe 600. In an embodiment, suitable radiation shielding materials can shield the operator of the integrated one-way valve dual-stage syringe 600 from beta particle radiation, x-rays, or both.

[0114] Still referring to Fig.33 and Fig.35 The outer barrel 610 may include an outer proximal opening 611 , an outer distal opening 619 opposite to the outer proximal opening 611 , and a main body portion 615 between the outer proximal opening 611 and the outer distal opening 619 .

[0115] Some embodiments of the integrated one-way valve dual-stage syringe 600 may include one or more locking mechanisms, such as those previously described. For example, the integrated one-way valve dual-stage syringe 600 may include a locking sleeve. Fig.33An example of an integrated one-way valve dual-stage syringe 600 including a locking sleeve 630 is provided in and FIG. 36 . The locking sleeve 630 can be similar to the locking sleeve 230. Thus, like the locking sleeve 230, the locking sleeve 630, which can include a distal capture member, is constructed as a long capture piece and a short capture piece that alternately surround the circumference of the body portion at the distal end of the locking sleeve 630. In another embodiment, the one or more locking mechanisms 630 can allow for greater delivery control and can provide tactile and audible feedback to ensure when the media is changed. In an embodiment, the locking mechanism of the integrated one-way valve dual-stage syringe 600 can be temporary or permanent.

[0116] Still referring to Fig.33 and Fig.35 , the integrated one-way valve dual-stage syringe 600 may include a main plunger 650 of the locking mechanism dual-stage syringe 100. The main plunger 650 may have a sealed distal end 604 defining a secondary chamber 606. In an embodiment, the main plunger 650 may be narrow enough to be accommodated by the outer barrel 610. The main plunger 650 may engage the secondary chamber 606 and cause the secondary chamber 606 to act as a plunger for the outer barrel 610. This can ensure that during actuation of the outer barrel 610, little pressure can be applied to the medium in the secondary chamber 606.

[0117] In an embodiment, the main plunger 650 can be made of various materials, such as polymers, plastics, or metals. Non-limiting example polymers for the outer barrel include polycarbonate (PC), polyethylene (PE), polyethylene terephthalate (PET). Non-limiting example plastics for the main plunger 650 include poly (methyl methacrylate) (PMMA) and composite resins, such as polycarbonate loaded with tungsten. Non-limiting example metals and metal alloys for the main plunger 650 include various alloys of stainless steel, lead, copper, tungsten, aluminum, tin-lead alloys, and any of these. In some embodiments, the main plunger 650 is made of radiation shielding materials, such as plastics or metals listed previously. The radiation shielding material can have a thickness sufficient to ensure that the radiation from the radioactive therapeutic material in the integrated one-way valve dual-stage syringe 600 does not penetrate into the environment or does not cause safety issues for the personnel operating the integrated one-way valve dual-stage syringe 600. In an embodiment, suitable radiation shielding materials can shield the operator of the integrated one-way valve dual-stage syringe 600 from beta particle radiation, x-rays, or both.

[0118] An embodiment of the integrated one-way valve dual-stage syringe 600 may include a one-way valve 682 configured to allow flow in only one direction, which may be from the secondary chamber 606 to the main chamber 690. The one-way valve 682 may allow the medium in the secondary chamber 606 to mix with the fluid from the main chamber 690. In other embodiments, the integrated one-way valve dual-stage syringe 600 may allow the medium in the secondary chamber 606 to mix with the fluid from the main chamber 690 multiple times and allow the main chamber 690 to be cleaned multiple times. In particular, the integrated one-way valve dual-stage syringe 600 may include one or more additional one-way valves, each of which is configured to allow flow in only one direction. In particular, the one-way valve may allow such a flow path that mixes the medium contained in the main chamber 690 with the medium in the secondary chamber 606 while eliminating the need for secondary or external connections such as secondary or external connections to one or more additional syringes. In embodiments, the number and size of chambers may vary.

[0119] Now refer to Fig.33 In some embodiments, the integrated one-way valve dual-stage syringe 600 may include a needle 150 that passes through a floating diaphragm plunger 674 and enters a main chamber 690. This embodiment may include a one-way valve 681 at the distal end of the needle 150. Fig.33 In some embodiments, the partition 672 may include a port 673. In some embodiments, the port 673 may be aligned with the needle 150. In other embodiments, the main plunger 650, the outer barrel 610, or other components may be rotated in order to align the port 673 with the needle 150.

[0120] Fig.34A , 34B and 34C example Fig.33 Operation of an embodiment of an integrated one-way valve dual-stage injector 600. Fig.34A In the embodiment of the present invention, the main plunger 650 is advanced distally, which advances the secondary chamber 606 and the sealing distal end 604 distally. Fig.34B In the embodiment of the present invention, the first lock of the locking sleeve 630 can be engaged, and the barrel can be rotated to engage the second lock of the locking sleeve 630 and align the needle 150 and the sealing port 673. Fig.34C In the embodiment of the present invention, the second lock of the locking sleeve 630 can be engaged and the needle 150 can pierce the port 673. Fig.34C In the embodiment of the present invention, the medium from the main chamber 690 can flow from the main chamber 690 through the one-way valve 682 into the secondary chamber 606 to be mixed with the fluid from the main chamber 690. The mixed fluid can then flow through the port 673, through the hollow needle 150, through the one-way valve 681, and out of the external distal opening 619.

[0121] Now refer to Fig.35In some embodiments, the integrated one-way valve dual-stage syringe 600 may include a one-way valve 683 on one side of the outer barrel 610 that may allow flow from the secondary chamber 606 to a channel 627 disposed within a sidewall 629 of the outer barrel 610 .

[0122] Fig.36A , 36B and 36C exemplify Fig.35 Operation of an embodiment of an integrated one-way valve dual-stage injector 600. Fig.35 In A, the main plunger 650 is advanced distally, which advances the secondary chamber 606 and the sealing distal end 604 distally. Fig.34B , the first lock of the locking sleeve 630 can be engaged, and the barrel can be rotated to engage the second lock of the locking sleeve 630 and open the opening 677 (see Fig.35 ) is aligned with the one-way valve 683. Fig.34C In the embodiment of the present invention, the second lock of the locking sleeve 630 can be engaged and the one-way valve 683 can be aligned so that the secondary chamber 606 is in fluid communication with the channel 627 disposed in the side wall 629 of the outer sleeve 610. Fig.34C 6, the medium from the main chamber 690 can flow from the main chamber 690 through the one-way valve 682 into the secondary chamber 606 to be mixed with the fluid from the main chamber 690. The mixed fluid can then flow through the one-way valve 627, through the channel 627, through the one-way valve 681, and out of the external distal opening 619.

[0123] In an embodiment, the integrated one-way valve dual-stage syringe 600 includes any biocompatible material, such as metals, metal alloys, and polymers. In some embodiments, the integrated one-way valve dual-stage syringe 600 may include polymers such as polycarbonate, polyethylene, and polyethylene terephthalate. In some embodiments, the integrated one-way valve dual-stage syringe 600 may include a seal made of any suitable material, such as a thermoplastic elastomer, a thermoplastic vulcanizate, or a silicone. In some embodiments, the integrated one-way valve dual-stage syringe 600 may include a metal, such as lead, stainless steel, and copper. In other embodiments, the integrated one-way valve dual-stage syringe 600 may be overmolded by a material such as a thermoplastic elastomer, a thermoplastic vulcanizate, or a silicone.

[0124] In the embodiments of the dual-stage syringe described herein, which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve, the one or more safety features may include a distal feature 5 (see Fig.21), such as a gasket, a Luer connector, a slip-fit, a needle-free connection port, or any other connection suitable for attachment to a delivery device. For example, embodiments of the dual-stage syringe described herein (which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve) may include a Fig.21 The outer barrel has a gasket similar to the distal feature 5, which seals the outer distal opening of the outer barrel to prevent fluid communication between the main chamber and the outside of the outer barrel, except through the delivery needle. Other embodiments of the dual-stage syringe described herein (which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve) may include a Luer connector similar to the distal feature 5 (see Fig.21 ), the Luer connector can be used to connect to a delivery device. In other embodiments, the Luer connector can be a male Luer connector with a corresponding female Luer connector on the delivery device. In other embodiments, the distal feature 5 can be another connection feature, such as a slip-fit, a needle-free connection port, or any other connection suitable for attachment to a delivery device.

[0125] In the embodiments of the dual-stage syringe described herein, which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve, the dual-stage syringe may include one or more safety features that may help make the embodiments of the dual-stage syringe described herein suitable for the safe and effective delivery of hazardous therapeutic substances. As will be described in more detail subsequently, the safety features that may optionally be incorporated into the embodiments of the dual-stage syringe described herein may include membrane technology, safety tabs, telemetered syringe plunger caps, needle features, magnetic walls, and combinations thereof. Referring now to Figure 4 In some embodiments, distal end 19 may be sealed with a removable or pierceable material. Similarly, distal end 419 (see Figure 5 ) and the remote end 610 (see Fig.33 , 35 ) may be sealed with a removable or pierceable material.

[0126] In the embodiments of the dual-stage syringe described herein (which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve), the one or more safety features may include a pressure relief valve or a pressure relief vent, for example, which may function to relieve pressure within the syringe when the main plunger is advanced distally. In some embodiments, the pressure relief valve or the pressure relief vent 3 may be integrated into the distal end of the outer barrel, such as Fig.21 shown.

[0127] Now refer to Fig.37In the embodiments of the dual-stage syringe described herein (which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve), the dual-stage syringe may optionally include membrane technology 800 to facilitate venting air from the system. Fig.37 As shown, an exemplary embodiment includes a sleeve-lock dual-stage syringe 200 in a piercing configuration in fluid communication with a membrane technology 800. In some embodiments, the membrane technology 800 may include components that work together to form a dry, leak-proof connection, a gas-tight expansion chamber that reduces surface contamination and prevents microbial intrusion. In other embodiments, the components of the membrane technology may be adapted to a standard that is compatible with all standard sizes of hazardous drug vials and intravenous connections and tubing.

[0128] Now refer to Fig.38 -39. In the embodiments of the dual-stage syringe described herein (which may include a locking mechanism dual-stage syringe and a dual-stage syringe with an integrated one-way valve), the dual-stage syringe may optionally include a ratchet safety tab 900 to help mix or suspend the drug and particles in a determined volume of solution.

[0129] In the case of radioembolization, radioactive particles (e.g., microspheres) can be transported to a medical facility in a pre-filled syringe (e.g., an embodiment of a dual-stage syringe described herein). During this time, the radioactive particles can settle to the bottom of the syringe. Therefore, the medical professional needs to draw a certain amount of saline into the syringe to help resuspend the particles so that the therapeutic fluid containing the particles has the appropriate concentration for effective delivery. Without such resuspension, there may be a risk of delivering the particles to the patient in a large dose and / or there is a risk that the large dose will clog the administration tubing set, which may lead to incorrect administration.

[0130] Thus, the ratchet safety tab 900 may be incorporated into the embodiments of the dual-stage syringe described herein to aid in mixing or suspending the drug and particles in a defined volume of solution. Fig.38 An embodiment of the ratchet safety tab 900 may include a safety tab 910 connected to the main plunger 50 at one end of the safety tab 910 via a plunger attachment portion 940, wherein the plunger attachment portion 940 may include one or more bevel teeth 920 at the distal end 930 of the ratchet safety tab 900.

[0131] Fig.39 A side cross-sectional view of a ratchet safety tab 900 constructed in an embodiment of a dual-stage syringe as described herein is shown. In an embodiment, the one or more beveled teeth 920 may engage one or more retaining clips attached to the main plunger 50. In other embodiments, various mating mechanisms (e.g., pins and slots) may be used that may engage one or more retaining clips attached to the main plunger 50.

[0132] Reference Fig.39 , when the main plunger 50 is pulled proximally, one or more beveled teeth 920 on the tab 910 slide over the retaining clip 11. In addition, as the beveled teeth 920 on the ratchet safety tab 900 slide proximally over the retaining clip 11, a hard stop is generated when attempting to advance the main plunger 50 distally. In an embodiment, the main plunger 50 can be pulled proximally until each of the one or more beveled teeth 920 on the safety tab 910 slides over the retaining clip 11. In other embodiments, the geometry can have any configuration so that the main plunger 50 must be pulled a predetermined distance before the safety tab 910 is removed. Once the safety tab 910 is removed, the main plunger 50 can then be depressed and the drug administration treatment can be performed. In other embodiments, it may not be necessary to remove the safety tab 910 from the main plunger 50 in order to administer the drug administration treatment. Once the main plunger 50 is pulled beyond the predetermined distance, the user can rotate the safety tab 910 to the "unlocked" or "delivery" position. Once the safety tab 910 is unlocked, the main plunger 50 can then be depressed and the drug administration treatment can be performed. When the safety tab 910 is locked, the main plunger 50 cannot be depressed and the drug administration treatment cannot be performed.

[0133] In embodiments, the ratchet safety tab 900 may include any biocompatible material, such as metals, metal alloys, and polymers. In some embodiments, the ratchet safety tab 900 may include polymers such as polycarbonate, polyethylene, polypropylene, and polyethylene terephthalate. In some embodiments, the ratchet safety tab 900 may include a seal made of any suitable material, such as a thermoplastic elastomer, a thermoplastic vulcanizate, or silicone. In some embodiments, the ratchet safety tab 900 may include a metal, such as lead, aluminum, stainless steel, and copper.

[0134] Now refer to Fig.40A , 40B and 40C, in some embodiments, the dual-stage syringe described herein may include a telemetered syringe plunger cap 1000.

[0135] During transarterial radioembolization procedures, changes in injection pressure and flow rate can impact the safety, efficacy, and patient comfort of medical devices and systems. As previously mentioned, for example, liver cancer can be treated with embolic beads in combination with chemotherapy. In this setting, the vasculature has been structurally awakened from the chemotherapy. Therefore, there may be a limit to the injection pressure that the physician can safely use. However, the efficacy and dispersion of the embolic beads are associated with increases in injection pressure and flow rate.

[0136] Thus, in some embodiments, the dual-stage syringe described herein may include a telemetered syringe plunger cap 1000 that can monitor and record the injection pressure and flow rate of the embolic beads delivered from the dual-stage syringe and allow the desired dispersion to be achieved without damaging the vasculature. In embodiments, the telemetered syringe plunger cap can provide real-time feedback to medical professionals, and the resulting data can be correlated with patient outcomes for quantified training and providing input to automated systems and ergonomic devices. In some embodiments, one or more of the pressure sensors and / or displacement sensors of the telemetered syringe plunger cap can sense the corresponding movement of the syringe plunger as the sensed plunger movement; when the syringe plunger moves in a translational direction, the movement in the translational direction toward one of the proximal or distal directions advances the syringe plunger. In embodiments, this then generates one or more output signals based on the sensed plunger movement via one or more of the pressure sensors and displacement sensors of the telemetered syringe plunger cap. This then generates, via the processor, at least one of a flow rate of the administered fluid, a flow rate of the administered fluid, a pressure of the administered fluid, a pressure applied to a syringe plunger, or a translational direction of movement of the syringe plunger relative to the syringe based on the one or more output signals. In some embodiments, at least one of the flow rate of the administered fluid, the flow rate of the administered fluid, the pressure of the administered fluid, or the translational direction of movement of the syringe plunger relative to the syringe can be displayed on a display communicatively coupled to the syringe.

[0137] Fig.40A A top view of a telemetric syringe plunger cap 1000 is shown. In an embodiment, the telemetric syringe plunger cap 1000 may include a wireless transmitter 1008, a pressure sensor 1005, and a displacement sensor 1001 housed within a cap that is attached to the proximal end of the plunger or syringe 100. Fig.40B Shown along Fig.40A The cross-sectional view taken along line A-A is shown. Fig.40C The telemetry syringe plunger cap 1000 is shown attached to the proximal end of the plunger or syringe 100. In other embodiments, the mechanism for engagement between the telemetry syringe plunger cap 1000 and the syringe 100 can be, for example, mechanical, chemical, or magnetic. In some embodiments, the wireless transmitter 1008 can be a Bluetooth transmitter. In some embodiments, the displacement sensor 1001 can include an accelerometer. In some embodiments, the cap can be made of polyethylene.

[0138] In an exemplary embodiment, a telemetered syringe plunger cap 1000 can be attached to the proximal end of a plunger or syringe 100 containing a radioactive substance (e.g., microspheres). When the physician applies pressure to the top of the syringe, the telemetered syringe plunger cap 1000 will deflect, and the pressure will be measured by an internal pressure sensor 1005. As the syringe 100 translates forward, the displacement sensor 1001 will record the movement. Information from both the pressure sensor 1005 and the displacement sensor 1001 can be wirelessly transmitted to a computer or smart device in real time, and the information can be viewed and stored on the computer and smart device. Once the process is completed, the telemetered syringe plunger cap 1000 can be discarded or recycled for sterilization and reuse. In certain embodiments, the telemetered syringe plunger cap 1000 can communicate with other devices by various communication methods including Bluetooth, WiFi, and wired connections.

[0139] In other embodiments, the telemetered syringe plunger cap 1000 may include any number of various types of sensors, such as capacitive sensors, resistive sensors, laser sensors, and optical sensors, which may produce the same outputs as described above. In other embodiments, the telemetered syringe plunger cap 1000 may include any number of various types of sensors, such as RFID tags and temperature sensors, which may produce additional outputs or tags. In some embodiments, additional sensors may be added to monitor withdrawal force, pressure, or rate.

[0140] The telemetered syringe plunger cap 1000 may include different display formats, such as LED, projection, and tactile display formats. In other embodiments, the telemetered syringe plunger cap 1000 may include an alert feature, such as a flashing light, sound, vibration.

[0141] In embodiments, the telemetered syringe plunger cap 1000 may include any biocompatible material, such as metals, metal alloys, and polymers. In some embodiments, the telemetered syringe plunger cap 1000 may include polymers, such as polycarbonate, polyethylene, polypropylene, and polyethylene terephthalate. In some embodiments, the telemetered syringe plunger cap 1000 may include a seal made of any suitable material, such as a thermoplastic elastomer, a thermoplastic vulcanizate, a silicone. In some embodiments, the telemetered syringe plunger cap 1000 may include polyoxymethylene and acrylonitrile butadiene styrene. In some embodiments, the telemetered syringe plunger cap 1000 may include metals, such as lead, aluminum, stainless steel, and copper.

[0142] In some embodiments, the outer barrel 10 of the dual-stage syringe embodiments described herein may include one or more needles that may be attached to or mounted on the outer barrel near the outer distal opening 19 of the outer barrel 10 .

[0143] In some embodiments, the magnetic component can be incorporated into one or more individual components of the dual-stage syringe such that the magnetic component and the individual component can generate one or more magnetic fields. For example, in some embodiments, the main plunger can include one or more magnetic components. Return to Reference Figure 7 , the main plunger 50 may have a secondary chamber defined through the main plunger 50 from the proximal opening of the main plunger 50 to the sealed distal end of the main plunger 50. The main plunger 50 may include one or more magnetic components in the plunger body portion 55, so that the magnetic components included in the plunger body portion 55 can generate a magnetic field. As described in more detail subsequently, the one or more magnetic components can generate a magnetic field that repels the diamagnetic material of the plurality of microspheres. This repulsion between the one or more magnetic components and the diamagnetic material of the plurality of microspheres can cause the plurality of microspheres to be suspended in an embodiment of the dual-stage syringe. As a result, the magnetic components incorporated into the embodiments of the dual-stage syringe described herein can reduce the interaction or binding of the radiotherapeutic microspheres with the dual-stage syringe, which can prevent browning and / or embrittlement of the materials used to form the embodiments of the dual-stage syringe described herein. In addition, in some embodiments, the magnetic components incorporated into the components of the dual-stage syringe described herein can, for example, generate an inhomogeneous magnetic field along the plunger body portion 55 of the main plunger 50, which can promote mixing of the radiotherapeutic microspheres in a suspension medium such as saline.

[0144] In an embodiment, the dual-stage syringe may include any suitable gamma-compatible material. The gamma-compatible material may be any radiation-stable medical-grade polymer material. The radiation stability of the gamma-compatible material may depend on the tolerance of the specific type of medical-grade polymer material. Once the radiation dose absorbed by the container material exceeds the tolerance of the container material, browning or embrittlement of the dual-stage syringe may occur. Exemplary gamma-compatible materials include, but are not limited to: thermoplastics including acrylonitrile / butadiene / styrene, aromatic polyesters, cellulose, fluoropolymers, polyacetals, polyacrylates, polyamides, polyethylene polyimides, polymethylpentenes, polyphenylene sulfides, polypropylene, polystyrene, polysulfones, polyurethanes, polyvinyl butyral, polyvinyl chloride, polyvinylidene chloride, styrene / acrylonitrile; thermosetting materials including allyl carbonate, epoxy resins, phenolic resins, polyesters, polyurethanes; elastomers including butyl, ethylene-propylene diene monomers, fluoroelastomers, natural rubber, nitrile, polyacrylates, polychloroprene, silicones, styrene-butadiene and polyurethane resins. The resistance of the elastomer may be affected by the base polymer and the curing system used. In some embodiments, the dual-stage syringe can be made of a gamma-compatible material having a resistance of about 5 kGy to about 100,000 kGy, about 5 kGy to about 10,000 kGy, about 5 kGy to about 5,000 kGy, about 5 kGy to about 1,000 kGy, about 5 kGy to about 500 kGy, about 5 kGy to about 100 kGy, about 100 kGy to about 100,000 kGy, about 100 kGy to about 10,000 kGy, about 100 kGy to about 5,000 kGy, about 100 kGy to about 1,000 kGy, about 100 kGy to about 5 kGy, about 500 kGy to about 100,000 kGy, about 500 kGy to about 10,000 kGy, about 500 kGy to about 5,000 kGy, about 500 kGy to about 1,000 kGy, about 1,000 kGy to about 100,000 kGy, about 1000 kGy to about 10,000 kGy, about 1,000 kGy to about 5,000 kGy, about 5,000 kGy to about 100,000 kGy, about 5,000 kGy to about 10,000 kGy, or from about 10,000 kGy to about 100,000 kGy.

[0145] In an embodiment, the dual-stage syringe may include one or more magnetic fields. The one or more magnetic fields of the dual-stage syringe may interact with the plurality of microspheres in a manner that prevents the plurality of microspheres from directly contacting the dual-stage syringe. In some embodiments, the one or more magnetic fields of the dual-stage syringe may interact with the plurality of microspheres in a manner that promotes mixing of the plurality of microspheres. The shape of the dual-stage syringe may at least partially promote mixing. In an embodiment, the strength, position, and pattern of the one or more magnetic fields of the dual-stage syringe may vary. The size of the magnetic field may be sufficient to cause the plurality of microspheres on the surface of the dual-stage syringe to float or be repelled. The size may depend on various factors, including the tolerance of the material contained in the dual-stage syringe; the amount of therapeutic agent in the microspheres, more specifically, the amount of radiotherapeutic substance in the microspheres; the type of therapeutic agent in the microspheres, more specifically, the amount of radiotherapeutic material in the microspheres; the amount (mass) of microsphere material, the type of microsphere material, the amount (mass) of diamagnetic material in the microspheres, the type of diamagnetic material in the microspheres, and a combination of these factors. The size of the magnetic field may be sufficient to cause the plurality of microspheres to float or be repelled at a height sufficient to prevent browning or embrittlement of the dual-stage syringe. Not being bound by theory, since the dose is 1 / R 2 Reduced, so relatively small changes in distance can have a significant effect on the dose absorbed by the dual-stage syringe.

[0146] In some embodiments, due to the magnetic components incorporated into the features of the dual-stage syringe, multiple magnetic fields can exist within the dual-stage syringe. The multiple magnetic fields can have varying strengths. For example, at least a portion of the magnetic field of the dual-stage syringe can have a smaller strength, and at least a portion of the magnetic field of the dual-stage syringe can have a larger strength. The varying strengths of the magnetic field of the dual-stage syringe can promote mixing of the multiple microspheres within the dual-stage syringe.

[0147] In an embodiment, the magnetic field of a dual-stage syringe can be generated by incorporating one or more magnetic components into the walls of individual components of the dual-stage syringe. In other embodiments, the magnetic field of a dual-stage syringe can be generated by surrounding the dual-stage syringe with one or more magnetic components. When the wall of the container described herein includes one or more magnetic components, the wall may include any number of single magnetic components (e.g., one, two, three, four, five, six, seven, or eight or more, etc.). Each magnetic component can be fixed in or on the dual-stage syringe by any suitable method. For example, in some variations, one or more magnetic components can be embedded, adhered or friction-fitted in the dual-stage syringe by any suitable manufacturing method, and the suitable manufacturing method includes coating, overmolding, printing, or gluing the one or more more magnetic components to the dual-stage syringe. In an embodiment in which one or more magnetic components surround the dual-stage syringe, each magnetic component may not be fixed in or on the dual-stage syringe, so the magnetic field generated by the magnetic component may be movable. In other embodiments in which one or more magnetic components surround the dual-stage syringe, each magnetic component may be embedded, adhered or friction-fitted in a housing, a cover or other external component surrounding at least a portion of the dual-stage syringe.

[0148] In an embodiment, the magnetic component may include a permanent magnet. The magnet may be made of any suitable material capable of generating a magnetic field. In some embodiments, the magnetic component may be a permanent magnet made of a ferromagnetic material. For example, in some variations, the magnetic component may include: one or more rare earth magnets, cobalt, gadolinium, iron, nickel, alloys of these metals with other metals (e.g., aluminum nickel cobalt alloys) or alloys without other metals, compounds (e.g., ferrites), or any combination of these metals or their alloys. In other embodiments, the rare earth magnet may include a samarium cobalt magnet or a neodymium magnet.

[0149] In an embodiment, the magnetic component may include an electromagnet. When the magnetic component includes an electromagnet, the electromagnet may be selectively activated to generate a magnetic field. For example, when an embodiment of a dual-stage syringe includes one or more electromagnets, the electromagnet may be activated before the plurality of microspheres are loaded into the dual-stage syringe; during storage of the plurality of microspheres, the electromagnet may remain activated to gently float the plurality of microspheres and prevent them from settling in the dual-stage syringe; and then the electromagnet may be deactivated after the plurality of microspheres are removed from the dual-stage syringe or after the radioembolization procedure is completed. When the dual-stage syringe includes multiple electromagnets, these magnetic components may be activated independently or may be activated as a group. In an embodiment, the one or more electromagnets may be selectively activated by electronic interaction, such as by a battery and a switch or other suitable activation device. In some embodiments, the one or more electromagnets may be selectively activated in a manner that generates one or more pulsating magnetic fields. In other embodiments, multiple electromagnets may be selectively activated in a manner that generates multiple pulsating magnetic fields with varying amplitudes.

[0150] In an embodiment, the dual-stage syringe may include a plurality of magnetic components. In other embodiments, the plurality of magnetic components may be any combination of permanent magnets, ferromagnetic components, or electromagnets. In an exemplary embodiment, only the sidewall of the dual-stage syringe may include permanent magnets. In these variations, the bottom wall may include only permanent magnets, only ferromagnetic components, only electromagnets, or a mixture of some or all of these elements. A permanent magnet may be included in the sidewall of the dual-stage syringe, and the bottom wall or cover may include only an electromagnet that may be activated after the plurality of microspheres have been loaded into the dual-stage syringe.

[0151] In an embodiment, each magnetic component may have any suitable size and shape. For example, each magnetic component may be cylindrical, semi-cylindrical, tubular, box-shaped, flat, spherical, etc. Typically, the size of the magnetic component may be limited by the size of the dual-stage syringe carrying the magnetic component, which in turn may be limited by the radioembolization procedure itself. For example, the radioembolization procedure may require a specific dose or delivery device, in which case the size of the dual-stage syringe may be specifically designed to accommodate the dose or fit within the delivery device. Each magnetic component may have any suitable length. In some embodiments, each magnetic component may have a length of approximately 5 mm, approximately 10 mm, approximately 15 mm, approximately 20 mm, or each magnetic component may extend along the entire length of one wall of the dual-stage syringe.

[0152] Fig.4140 is a schematic diagram of an exemplary delivery system 2000, in which a sleeve-locked dual-stage syringe 200 may be incorporated. Other exemplary delivery systems are included in U.S. Patent Application No. [Agent Docket No. P-18891] entitled "RADIOEMBOLIZATIONDELIVERY DEVICE" filed concurrently with the present disclosure, the entire contents of which are incorporated herein by reference. In the exemplary delivery system 2000, the sleeve-locked dual-stage syringe 200 and additional components may be housed in a system housing, as schematically represented by dashed lines around the components of the exemplary delivery system 2000 in FIG. 40. In some embodiments, the sleeve-locked dual-stage syringe 200 may include a geometric (directional) feature that makes the sleeve-locked dual-stage syringe 200 suitable for receiving in the exemplary delivery system 2000. Non-limiting examples of geometric features may include a feature that orients the sleeve-locked dual-stage syringe 200 in the exemplary delivery system 2000 or a feature that locks the sleeve-locked dual-stage syringe 200 in an appropriate position in the exemplary delivery system 2000.

[0153] In the exemplary delivery system 2000, the sleeve-lock dual-stage syringe 200 is shown in a piercing configuration in which the delivery needle 150 held in place by the needle hub 2100 provides fluid communication between the system reservoir 2200 and the secondary chamber 95 of the sleeve-lock dual-stage syringe 200. One or more additional fluid reservoirs 2300 (for illustration purposes, not shown in FIG. 2 ) may be included in the exemplary delivery system 2000. Fig.41 The system reservoir 2200 and the additional fluid reservoir 2300 may be fluidly coupled to the mixing valve 2500 via coupling lines 2250, 2400. The mixing valve, in turn, may be fluidly coupled to the delivery valve 2700 via an outlet line 2600. The delivery valve 2700 may be fluidly coupled to a delivery device 2800, such as a catheter or microcatheter, which is fluidly coupled intravenously to a patient receiving treatment.

[0154] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present disclosure belongs. The terms used in the description herein are only used to describe specific embodiments and are not intended to be limiting. As used in the specification and the appended claims, the singular forms "a", "an", and "the" are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0155] As used herein, the terms "horizontal" and "vertical" are relative terms only, indicating only a general relative orientation, and not necessarily indicating verticality. For convenience, these terms may also be used to refer to the orientations used in the accompanying drawings, which are only for conventional purposes and are not intended to be features of the devices shown. The present disclosure and embodiments thereof to be described herein may be used in any desired orientation. Moreover, horizontal and vertical walls generally only need to be intersecting walls and do not have to be perpendicular.

[0156] For purposes of describing and defining the present disclosure, it is noted that the term "substantially" is used herein to represent the inherent degree of uncertainty attributable to any quantitative comparison, value, measurement, or other representation. The term "substantially" is also used herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. As such, it is used to represent the inherent degree of uncertainty attributable to any quantitative comparison, value, measurement, or other representation, meaning that an arrangement of elements or features that would theoretically be expected to exhibit an exact correspondence or behavior may, in practice, exhibit some imperfections of exact precision.

[0157] Although specific embodiments have been illustrated and described herein, it should be understood that various other changes and modifications may be made without departing from the spirit and scope of the claimed subject matter. Moreover, although various aspects of the claimed subject matter have been described herein, these aspects need not be used in combination. Therefore, it is intended that the appended claims cover all such changes and modifications within the scope of the claimed subject matter.

Claims

1. A sleeve-type two-stage syringe, the sleeve-type two-stage syringe comprising: an outer barrel having a main chamber defined through the outer barrel from a proximal opening of the outer barrel to a distal opening of the outer barrel; a primary piston having a secondary chamber defined through the primary piston from a proximal opening of the primary piston to a sealed distal end of the primary piston, the primary piston being configured to receive a secondary piston through the proximal opening of the primary piston; and a locking sleeve disposed within the main chamber, in: The master piston and the locking sleeve include a locking mechanism configured to define a first boundary, a second boundary distal to the first boundary, and at least three stages, the at least three stages including: an initial stage in which the main piston is inserted proximally of the first boundary and is freely movable distally or proximally; an intermediate stage in which the master piston is inserted distally of the first boundary and is prevented from moving proximally beyond the first boundary; and a final stage in which the main piston is inserted distally of the second boundary and is prevented from moving proximally beyond the second boundary; Wherein, the locking mechanism comprises: a main body portion, the shape of the main body portion conforms to the contour of the outer tube; and a distal capture member, the distal capture member comprises a long capture piece and a short capture piece around the circumference of the main body portion at the distal end of the main body portion, the short capture piece end of the short capture piece defines the first boundary and the long capture piece end of the long capture piece defines the second boundary; Wherein, the main piston includes a piston body part, and the piston body part includes at least a proximal stop ring; and wherein, when the proximal stop ring passes through the end of the short capture piece, the short capture piece end prevents the main piston from moving proximally beyond the first boundary; and when the proximal stop ring passes through the end of the long capture piece, the long capture piece end prevents the main piston from moving proximally beyond the second boundary.

2. The sleeve-type dual-stage syringe according to claim 1, wherein: The locking mechanism includes one or more features for integral assembly.

3. The sleeve-type dual-stage syringe according to claim 2, wherein: The locking mechanism includes a proximal ridge configured to seat the locking mechanism in an outer proximal opening of the outer barrel.

4. The telescopic dual-stage syringe according to claim 1, wherein: The long capture members and the short capture members alternate around the circumference of the body portion at the distal end of the body portion.

5. The telescopic dual-stage syringe according to claim 4, wherein: The long catch piece end of the long catch piece, the short catch piece end of the short catch piece, or both are angled inwardly from the sleeve locking dual stage syringe.

6. The telescopic dual-stage syringe according to claim 4, wherein: The long catch piece end of the long catch piece, the short catch piece end of the short catch piece, or both are angled outwardly from the telescopic locking dual stage syringe.

7. The telescopic dual-stage syringe according to claim 1, wherein: The telescopic dual-stage syringe also includes one or more sensors.

8. The telescopic dual-stage syringe according to claim 1, wherein: The outer cylinder further includes a shielding member.

9. A delivery system, comprising: System housing; as well as A dual-stage syringe housed within the system housing, the dual-stage syringe comprising: an outer barrel having a main chamber defined through the outer barrel from a proximal opening of the outer barrel to a distal opening of the outer barrel; a primary piston having a secondary chamber defined through the primary piston from a proximal opening of the primary piston to a sealed distal end of the primary piston, the primary piston being configured to receive a secondary piston through the proximal opening of the primary piston; and a locking sleeve disposed within the main chamber, in: The master piston and the locking sleeve include a locking feature configured to define a first boundary, a second boundary distal to the first boundary, and at least three stages, the at least three stages including: an initial stage in which the main piston is inserted proximally of the first boundary and is freely movable distally or proximally; an intermediate stage in which the master piston is inserted distally of the first boundary and is prevented from moving proximally beyond the first boundary; and a final stage in which the main piston is inserted distally of the second boundary and is prevented from moving proximally beyond the second boundary; wherein the locking feature comprises: a main body portion, the shape of the main body portion conforming to the contour of the outer barrel; and a distal capture member, the distal capture member comprising a long capture piece and a short capture piece around the circumference of the main body portion at the distal end of the main body portion, the short capture piece end of the short capture piece defining the first boundary and the long capture piece end of the long capture piece defining the second boundary; Wherein, the main piston includes a piston body part, and the piston body part includes at least a proximal stop ring; and wherein, when the proximal stop ring passes through the end of the short capture piece, the short capture piece end prevents the main piston from moving proximally beyond the first boundary; and when the proximal stop ring passes through the end of the long capture piece, the long capture piece end prevents the main piston from moving proximally beyond the second boundary.

10. The delivery system according to claim 9, wherein: The delivery system also includes an orientation feature configured to orient the dual-stage syringe within the system housing.

11. The delivery system according to claim 9, wherein: The delivery system also includes a locking feature configured to lock the dual-stage syringe in place within the system housing.

12. The delivery system according to claim 9, wherein: The delivery system also includes membrane technology.

13. The delivery system according to claim 9, wherein: The delivery system also includes one or more sensors.

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