Patent Publication Number: US-2021162175-A1

Title: Agent delivery devices

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     This application claims the benefit of priority of U.S. Provisional Patent Application No. 62/942,887, filed Dec. 3, 2019, the entirety of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates generally to agent delivery devices. More particularly, the present disclosure relates to catheter devices for delivering one or more agents endoscopically. 
     BACKGROUND 
     Agents may be delivered during medical procedures, such as endoscopic procedures. During an endoscopic procedure, a user inserts a sheath of an endoscope into a body lumen of a patient. The user utilizes a handle of the endoscope to control the endoscope during the procedure. Tools are passed through a working channel of the endoscope via, e.g., a port in the handle, to deliver treatment at the procedure site, near a distal end of the endoscope. The procedure site is remote from the operator. 
     During an endoscopic procedure, agents may be delivered by a device inserted into the working channel of the endoscope. If an agent is introduced to the device at its proximal end, the port, some of the agent may be retained within portions of the device within the working channel and may not be delivered to the procedure site. However, a user may desire to deliver an entirety or near an entirety of an agent, without leaving leftover agent in the device. Therefore, a need exists for agent delivery devices. 
     SUMMARY 
     Examples of the present disclosure relate to, among other things, agent delivery devices. Each of the examples disclosed herein may include one or more of the features described in connection with the disclosed examples. 
     In an example, a medical device may comprise a handle and a flexible sheath extending from the handle. The sheath may include a first chamber configured to receive a first agent and a second chamber configured to receive a second agent. Each of the first chamber and the second chamber may be disposed in a distal portion of the sheath. The sheath may also include a first piston received within the first chamber and a second piston received within the second chamber and at least one actuation element configured to transmit a force from the handle to each of the first piston and the second piston. When the handle is in a first configuration, the first agent may be maintained within the first chamber and the second agent is maintained within the second chamber. When the handle is in a second configuration, the first agent may be released from the first chamber to mix with the second agent. 
     Any of the exemplary medical devices disclosed herein may include any of the following features. The second chamber may be defined by a tube disposed within the first chamber. A wall of the tube may include a plurality of holes. A distalmost end of the tube may be proximal of an opening in a distalmost end of the sheath. A central longitudinal axis of the tube may be approximately coaxial with a central longitudinal axis of the first chamber. The first piston may have an outer perimeter and an inner perimeter. The second piston may have an outer perimeter with a shape that is complementary to a shape of the inner perimeter of the first piston. The first actuation element may be a tube defining a lumen. The second actuation element may be a wire within the lumen. The at least one actuation element may include a first flexible actuation element having a proximal end operatively coupled to the handle and a distal end operatively coupled to the second piston, and a second flexible actuation element having a proximal end operatively coupled to the handle and a distal end operatively coupled to the second piston. The first actuation element may include a wire. The second actuation element may include a wire or a tube. The wire of the first actuation element may be disposed within a lumen of a tube of the second actuation element. The sheath may include at least one barrier preventing a release of the first agent from the first chamber. The at least one actuation element may include a pneumatic fluid. The first chamber may be pre-loaded with the first agent. The second chamber may be pre-loaded with the second agent. The distal portion of the sheath may be removably attached to a remainder of the sheath. 
     In another example, a medical device may comprise a handle including an actuator; and a sheath extending from the handle. A distal portion of the sheath may include: a first chamber configured to receive a first agent and a tube disposed within the first chamber. The tube may have an internal lumen defining a second chamber. A wall of the tube may include a plurality of holes. The distal portion of the sheath may also include at least one actuation element operatively to transmit a force from the actuator to each of a first piston received within the first chamber and a second piston received within the second chamber. Each of the plurality of holes may be configured to isolate the first agent from the second agent when the at least one actuation element receives no force and to release the second agent from the second chamber through the plurality of holes to mix with the first agent when the at least one actuation element receives the force. 
     Any of the exemplary medical devices disclosed herein may include any of the following features. The actuation element may include at least one of a wire, a tube, or a fluid. The at least one actuation element may be a first actuation element. The medical device may further comprise a second actuation element. The second actuation element may include at least one of a wire or a tube. 
     In another example, a medical device may comprise: a handle including an actuator and a sheath extending from the handle. The sheath may include: a first chamber configured to receive a first agent and a second chamber configured to receive a second agent, Each of the first chamber and the second chamber may be disposed in a distal portion of the sheath. The sheath may also include a first piston received within the first chamber and a second piston received within the second chamber; and a tube configured to transmit a force from the actuator to at least one of the first piston and the second piston. 
     Any of the medical devices disclosed herein may include any of the following features. The second chamber may be defined by a tube disposed within the first chamber. A radial wall of the tube may include a plurality of holes. 
     It may be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. As used herein, the terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term “exemplary” is used in the sense of “example,” rather than “ideal.” The term “distal” refers to a direction away from an operator, and the term “proximal” refers to a direction toward an operator. The term “approximately,” or like terms (e.g., “substantially”), includes values+/−10% of a stated value. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate examples of the present disclosure and together with the description, serve to explain the principles of the disclosure. 
         FIG. 1  shows an exemplary agent delivery device. 
         FIGS. 2A-4B  show exemplary distal ends of the agent delivery device of  FIG. 1 . 
         FIGS. 5A-5B  show another exemplary agent delivery device. 
         FIGS. 6A-6J  show other exemplary agent delivery devices. 
     
    
    
     DETAILED DESCRIPTION 
     An agent delivery device may be configured to house an agent at a distal end of the delivery device so that, after the agent is deployed to a treatment site, an amount of agent remaining within the delivery device is minimal and waste of the agent is avoided. The delivery device may be configured to house single component agents or multi-component agents. In the case of multi-component agents, the delivery device may be configured to allow for mixing of the components, prior to delivery from the device. Various mechanisms may be utilized in order to actuate the delivery device to deliver the agent. These mechanisms may include pneumatics, wires, tubes, or any suitable combination thereof. 
       FIG. 1  depicts an exemplary delivery device  10 . Delivery device  10  may include a handle  12  (which may be an operation portion) and a sheath  14  (which may be an insertion portion). Sheath  14  may include a catheter  15  or other suitable component. Sheath  14 , or at least components of sheath  14  (such as catheter  15 ), may be flexible so that sheath  14  may be advanced through a working channel of an endoscope in a body lumen, which may be tortuous. A cross-sectional diameter of sheath  14  may be such that sheath  14  can be advanced through a working channel of an endoscope. A lumen  20  (see  FIGS. 2A-4B ) may extend from a proximal portion of catheter  15  to a distal end of catheter  15 . 
     Sheath  14  may also include a distal portion  16 . Distal portion  16  may be a separate component from catheter  15  or may be a single, unitary structure with catheter  15 . Distal portion  16  may be rigid or flexible and may be sized so as to permit advancement of distal portion  16  through a working channel of an endoscope. Distal portion  16  may be fixedly or removably attached to a distal end of catheter  15 . Distal portion  16  may be configured to house an agent in, for example, a compartment. Distal portion  16  may have various configurations, as discussed herein with respect to  FIGS. 2A-4B . 
       FIGS. 2A-4B  show cross-sectional views of exemplary distal portions  16 ,  116 ,  216  of delivery device  10 . The features of distal portions  16 ,  116 ,  216  may be combined with one another in any suitable combination. Where possible, like reference numbers are used to indicate corresponding structures. 
       FIGS. 2A and 2B  show an example distal portion  16 . Distal portion  16  may include a chamber  30  for housing an agent  32 . Chamber  30  may be defined by the same surface(s) that define(s) lumen  20 . For example, inner surfaces of catheter  15  may define lumen  20  and chamber  30  in configurations where distal portion  16  is a single, unitary structure with catheter  15 . Alternatively, chamber  30  may be defined by other surface(s). Although chamber  30  is shown as occupying an entire cross-sectional width of a lumen defined by distal portion  16 , chamber  30  may be a subset of distal portion  16 . For example, a tube or similar structure may be disposed within distal portion  16 , and chamber  30  may be located within the tube or other structure. Opening  18  may be in fluid communication with chamber  30  so that agent  32  may pass through opening  18  when desired by a user, as described below. 
     A piston  52  may be slidably housed within at least one of chamber  30  and lumen  20 . Piston  52  may be fitted with a seal to prevent agent  32  from moving proximally past piston  52 . Piston  52  may be configured to move proximally and/or distally within chamber  30 . An actuator  50  of handle  12  ( FIG. 1 ) may be used to move piston  52 . Actuator  50  may include a plunger, as shown in  FIG. 1 , or alternative structures, such as those discussed below. For example, actuator  50  may include a knob, a button, a switch, a lever, a slider, or another structure. Exemplary mechanisms for operatively connecting actuator  50  to piston  52  are discussed in further detail with respect to  FIGS. 5A-6J , below. 
     Agent  32  may be any suitable type of agent in any suitable form. Agent  32  may be a gel, liquid, powder, etc. For example, agent  32  may include a hemostatic agent, a clotting agent, a drug or other medicament, etc. Agent  32  may come preloaded in distal portion  16 . Where agent  32  is preloaded, delivery device  10  or portions of delivery device  10  may be single-use. Alternatively, a user may load agent  32  into distal portion  16 . For example, agent  32  may be loaded into distal portion  16  by withdrawing actuator  50  to move piston  52  proximally. Distal portion  16  may include markings or other indicators of how much of agent  32  has been loaded into or dispensed from distal portion  16 . Distal portion  16  may be removably attached to catheter  15  (e.g., via threads, snap-fit, or other mechanisms) such that a distal portion  16  pre-loaded with agent  32  in compartment  30  may be attached to a re-usable (or disposable) catheter  15  prior to use. After agent  32  has been dispensed from opening  18 , as described below, distal portion  16  may be replaced with a new, preloaded distal portion  16 . 
     Agent  32  may be retained within chamber  30  by various mechanisms. For example, a force of air pressure on agent  32  may retain agent  32  within chamber  30 . A force of gravity may not overcome the air pressure on agent  32 , causing agent  32  to be retained within chamber  30 . Alternatively, or additionally, a removable barrier  90  may be disposed at or near opening  18 . Barrier  90  may be punctured or otherwise removed when, as discussed below, agent  32  is advanced out of opening  18 . Additionally or alternatively, a viscosity of agent  32  may be sufficiently high that agent  32  does not pass through opening  18  until actuator  50  is manipulated, as described below. 
     In  FIG. 2A , distal portion  16  is shown in a first configuration. For example, the configuration of  FIG. 2A  may be a configuration of distal portion  16  prior to administering any of agent  32  to a site of a procedure. Agent  32  may be housed in chamber  30 , distal to piston  52 . In  FIG. 2B , distal portion  16  is shown in a second configuration, in which piston  52  has been moved distally of the position shown in FIG.  2 A. In the second configuration, at least some of agent  32  may have been administered at a desired site, by the mechanisms described below. In order to transition piston  52  from the first configuration to the second configuration, actuator  50  may be manipulated. For example, a plunger may be depressed or another mechanism may be activated to cause piston  52  to move distally, as described in further detail below (see  FIGS. 5A-6J ). As piston  52  moves distally toward opening  18 , piston  52  may push agent  32  out of opening  18 . Piston  52  and/or chamber  30  may be configured so that all or approximately all of agent  32  may be delivered to a procedure site or to another chamber via opening  18  when piston  52  is fully distally advanced. Only an amount of agent  32  that is desired to be delivered to a procedure site may be loaded into chamber  30  so as to avoid waste of agent  32 . As agent  32  is pushed out of opening  18 , the force of agent  32  (transmitted from piston  52 ) may break or otherwise puncture any barrier  90  over opening  18 . 
       FIGS. 3A and 3B  show an alternative distal portion  116 , which may have any of the properties of distal portion  16  and which may be used in conjunction with as part of delivery device  10 . Distal portion  116  may facilitate mixing of multi-component agents and delivery of a mixed agent to a procedure site. Distal portion  116  may include a chamber  130 , which may have any of the properties of chamber  30 . A tube  132  may be housed within chamber  130 . Tube  132  may have an internal lumen that defines a chamber for receiving an agent, as described below. Tube  132  and chamber  130  may be coaxial/concentric or may have parallel longitudinal axes. Alternatively, longitudinal axes of tube  132  and  130  may be transverse to one another. Tube  132  may have a round cross-sectional shape or an alternative shape (e.g., square, rectangular, polygonal, oval, etc.). Tube  132  may be fenestrated such that at least a radially outer wall of tube  132  includes a plurality of holes  134 . Holes  134  may have any suitable shape (e.g., a round shape). Further details of holes  134  are provided below. Tube  132  may also optionally include a distal opening (not shown), or a distally-facing wall with or without holes  134 . A first component agent  136  may be housed within chamber  130 , and a second component agent  138  may be housed within a lumen of tube  132 . 
     A first piston  154  may be slidably disposed within chamber  130  (or lumen  120 ). First piston  154  may have a washer shape, with a central opening, so that tube  132  fits within the central opening. First piston  154  may movably slide around an outer surface of tube  132 . A second piston  156  may be disposed within the central opening of, and slidably disposed within, tube  132 . Second piston  156  may have a shape and size that mates with a central opening of first piston  154 . First piston  154  may form a seal with outer walls of tube  132  and inner walls of chamber  130  to prevent passage of first component agent  136  proximally past first piston  154 . Second piston  156  may form a seal with inner walls of tube  132  such that second component agent  138  may not move distally past second piston  156 . An outer perimeter of first piston  154  may have a complementary shape to walls of tube  132 , and an inner perimeter of first piston  154  may have a complementary shape to an outer surface of tube  132  and an outer perimeter of second piston  156 . 
     In a first configuration, as shown in  FIG. 3A , tube  132  (including holes  134 ) and pistons  154 ,  156  may be configured such that first component agent  136  may be retained within chamber  130  (and external to tube  132 ) and second component agent  138  may be retained within tube  132 . For example, a force of air pressure on component agents  136 ,  138  may retain component agents  136 ,  138  within component  130  and tube  132 , respectively. Air pressure may retain component agents  136 ,  138  because such air pressure may have a force that exceeds that of gravity. Holes  134  may be sized such that surface tension of agent  138  or other forces retain second component agent  138  within tube  132  without undesired leaking through holes  134 . For example, holes  134  may have a sufficiently small diameter and have a sufficient length through a wall of tube  132  such that component agents  136 ,  138  do not pass through holes  134  until a force is exerted by piston  156 . Additionally or alternatively, a viscosity of component agents  136 ,  138  may be such that they do not pass through holes  134  until a force is exerted by piston  156 . Holes  134  may also be covered by a movable/removable barrier, which may have any of the features of barrier  90 . Chamber  130  may also include a barrier  190  at or proximal to opening  118 , which may have any of the features of barrier  90 . Holes  134  may be approximately 0.1 microns to 2 millimeters in width (e.g., diameter). Holes  134  may be uniform or may vary (e.g., different sizes and/or shapes of holes  134  may deliver second component agent  138  at varying rates). Holes  134  may be circular or may have an alternative shape (e.g., oval, polygon, slit, etc.). As described above with respect to distal portion  16 , distal portion  116  may be pre-loaded with component agents  136 ,  138 . Alternatively, a user may load component agents  136 ,  138  within chamber  130  and tube  132 , respectively. 
       FIG. 3B  shows a second configuration of distal portion  116 , in which pistons  154 ,  156  have been advanced distally through chamber  130  and tube  132 , respectively. Pistons  154 ,  156  may be configured to move together or independently to facilitate intended mixing of first component agent  136  and second component agent  138 . As piston  156  is advanced distally through tube  152 , second component agent  138  may pass through holes  134  into chamber  130 . First component agent  136  may also move distally within tube  152  as a result of distal movement of piston  154 . First component agent  136  and second component agent  138  may mix together to form a combined agent  140  within chamber  130 . Mixing may be facilitated by presence of an empty portion of chamber  130  that is distal to a distal end of tube  132 . For example, a distal end of tube  132  may be proximal to opening  118 . Alternatively, mixing may occur in a portion of chamber  130  that includes tube  132  passing therethrough (e.g., in a portion of chamber  130  that is empty of first component agent  136  prior to activation of actuator  150 ). For example, mixing may occur in an area of chamber  130  distal to barrier  190 . Distal movement of piston  154  and/or piston  156  may cause combined agent  140  to pass through distal opening  118  and to be delivered to a procedure site. As with distal portion  16  of  FIGS. 2A-2B , distal portion  116  may facilitate dispensing of all or substantially all of first component agent  136  and second component agent  138 , combined into combined agent  140 . Thus, distal portion  116  may avoid waste of first component agent  136  and second component agent  138 . 
     Although  FIGS. 3A and 3B  show one tube  132  and one chamber  130 , it will be appreciated that more than one tube  132  or chamber  130  may be used (for example, should a mixture of three or more components be desired). An appropriate number of corresponding pistons (e.g., pistons  152 ,  154 ) may be used. 
       FIGS. 4A and 4B  show another alternative distal portion  216 , which may have any of the properties of distal portions  16 ,  116 , described above. Distal portion  216  may include a chamber  230  having multiple sub-chambers  230   a ,  230   b . Sub-chambers  230   a ,  230   b  may be defined by tubes contained within chamber  230 . Alternatively, sub-chambers  230   a ,  230   b  may be formed by a divider extending longitudinally between sub-chambers  230   a ,  230   b , so that sub-chambers  230   a ,  230   b  are defined by inner walls of chamber  230  and by the divider. While  FIGS. 4A and 4B  show two sub-chambers  230   a ,  230   b , it will be appreciated that any number of suitable sub-chambers  230   a ,  230   b  may be used. Sub-chambers  230   a ,  230   b  may be parallel to one another or may be transverse to one another. Each of sub-chambers  230   a ,  230   b  may include an opening at its distal end. A first component agent  236  may be housed in a first sub-chamber  230   a , and a second component agent  238  may be housed in a second sub-chamber  230   b . As shown in  FIGS. 4A and 4B , sub-chambers  230   a  and  230   b  may be approximately the same size, or sub-chambers  230   a  and  230   b  may be different sized. For example, where more of first component agent  236  than second component agent  238  is desired to be used, sub-chamber  230   a  may be larger than chamber  230   b . Sub-chambers  230   a ,  230   b  may have uniform cross-sections or may have variable cross-sections designed to effect a desired mixing ratio of first component agent  236  and second component agent  238 . 
     A first piston  252   a  may be slidably disposed within first sub-chamber  230   a . A second piston  252   b  may be slidably disposed within second sub-chamber  230   a . First piston  252   a  may form a seal with inner surface(s) of first sub-chamber  230   a , and second piston  252   b  may form a seal with inner surface(s) of second sub-chamber  230   b . First piston  252   a  may be jointly or independently movable with second piston  252   b . As first piston  252   a  and/or second piston  252   b  are advanced distally, first component agent  236  and/or second component agent  238 , respectively, may be advanced distally. First component agent  236  and second component agent  238  may mix to form a combined agent  240  in a portion of chamber  230  that is distal to distal openings of sub-chambers  230   a ,  230   b . Combined agent  240  may be pushed out of distal opening  218  as pistons  252   a ,  252   b  advance distally. As with distal portions  16 ,  116  of  FIGS. 2A-3B , distal portion  216  may facilitate dispensing of all or substantially all of first component agent  236  and second component agent  238 , combined into combined agent  240 . Thus, distal portion  216  may avoid waste of first component agent  236  and second component agent  238 . 
     Prior to advancing pistons  252   a ,  252   b , first component agent  236  and second component agent  238  may be retained within sub-chambers  230   a ,  230   b , respectively, due to forces of air pressure or a viscosity of component agents  236 ,  238 , as discussed above with respect to  FIGS. 2A-3B . Additionally or alternatively, membranes  290   a ,  290   b  may be disposed at or near distal ends of sub-chambers  230   a ,  230   b . Membrane  290  may have any of the properties of membrane  90 . A membrane (not shown) may also be disposed at or near opening  218  and may have any of the features of membrane  90 . 
     Although  FIGS. 4A and 4B  show two sub-chambers  230   a ,  230   b , it will be appreciated that any number of sub-chambers may be used, along with an appropriate number of corresponding pistons. 
       FIGS. 5A-6J  show exemplary mechanisms for actuating the pistons of the distal portions pictured in  FIGS. 2A-4B . Alternatively, features of  FIGS. 5A-6J  may be used independently of the distal portions of  FIGS. 2A-4B . Similarly, the distal portions of  FIGS. 2A-4B  may be used with mechanisms other than those described below with respect to  FIGS. 5A-6J . Although certain of the actuation mechanisms below may be described as having suitability for certain of the distal portions described above, it will be appreciated that these compatibilities are not limiting and that various combinations of aspects of distal portions and actuation mechanisms may be used. When possible, corresponding reference numbers are used to denote corresponding structures. 
       FIGS. 5A and 5B  show a cross-section of an example delivery device  300 , which may have any of the features of delivery device  10 . Delivery device  300  may have a handle  312  (e.g., an operation portion) and a sheath  314  (e.g., an insertion portion). Sheath  314  may include a catheter  315  or other suitable component. A lumen  320  may extend from a proximal portion of catheter  315  to a distal end of catheter  315 . 
     Sheath  314  may also include a distal portion  316 . Distal portion  316  may be a separate component from catheter  315  or may be a single, unitary structure with catheter  315 . Distal portion  316  may be fixedly or removably attached to a distal end of catheter  315 . Distal portion  316  may be configured to house an agent  332 . Distal portion  316  may have any of the properties of distal portions  16 ,  116 ,  216 , described above. Although distal portion  316  is shown as having one chamber  330 , it will be appreciated that multiple chambers may be utilized, as shown, for example, in  FIGS. 3A-4B . Chamber  330  may terminate in a distal opening  318 . An agent  332  may be contained in chamber  330 . A piston  352  may be slidable within chamber  330  and may have any of the properties of any of the pistons described above, with respect to  FIGS. 2A-4B . 
     The example of  FIGS. 5A-5B  may utilize pneumatic actuation mechanisms for causing piston  352  to slidably move within chamber  330 . It will be appreciated that the actuation mechanisms of  FIGS. 5A-5B  may be used in combination with the actuation mechanisms of  FIGS. 6A-6J , discussed below. The actuation mechanisms of  FIGS. 5A-5B  may also be used with device  10 , including any of distal ends  16 ,  116 ,  216 . 
     Handle  312  may include a plunger  350 . Plunger  350  may be operatively connected to a piston  354  via a stem  356 . Although piston  354  is described as being disposed within handle  312 , it will be appreciated that piston  354  may also be disposed within sheath  314 . Handle  312  may include a lumen  322  in which piston  354  is slidably disposed. Piston  354  may form a seal with surfaces of lumen  322 . Lumen  322  may have a larger cross-sectional diameter than lumen  320 , as shown in  FIG. 5A . Alternatively, lumen  322  may have the same cross-sectional diameter to lumen  320  or a smaller cross-sectional diameter than lumen  320 . A larger cross-section of lumen  322  may enable device  300  to have a shorter stem  356 . 
     A fluid  370  may be disposed within lumen  322 , distal to piston  354  and proximal of piston  352 . Pistons  352 ,  354  may include sealing features that retain fluid  370  between piston  352  and piston  354 .  FIG. 5A  shows delivery device  300  in a first configuration, in which plunger  350  has not been depressed and agent  332  has not been dispensed via opening  318 .  FIG. 5B  shows delivery device  300  in a second configuration, in which plunger  350  has been at least partially depressed so that at least some of agent  332  has been dispensed via opening  318 . As plunger  350  is depressed/advanced distally, piston  354  may advance by a corresponding (e.g., an equivalent) amount. Plunger  350  may exert a force on fluid  370  to advance fluid  370  distally. Fluid  370  may exert a force on piston  352 , which, in turn, advances agent  332  through opening  318 , as described above, with respect to  FIGS. 1-4B . 
     Fluid  370  may be incompressible or may be compressible. For example, if fluid  370  is incompressible, as plunger  350  is depressed, agent  332  may immediately or approximately immediately be dispensed from opening  318 . If fluid  370  is compressible, there may be a delay between depression of plunger  350  and dispensing of agent  332  from opening  318 , as fluid  370  is compressed. Fluid  370  may include any suitable fluid. For example, fluid  370  may be bio-compatible and may include saline. 
     The use of fluid  370  as an actuation mechanism may allow sheath  314  to be flexible such that sheath  314  may be passed through a working channel of an endoscope and through torturous body lumens of a subject. This flexibility of sheath  314  facilitates positioning of agent  332  in distal portion  316 , so that agent  332  is not wasted. 
       FIGS. 6A-6J  show alternative actuation mechanisms.  FIG. 6A  shows a delivery device  400 , which may have any of the properties of delivery devices  10 ,  300 . Delivery device  400  may have a handle  412  (e.g., an operation portion) and a sheath  414  (e.g., an insertion portion). Sheath  414  may include a catheter  415  or other suitable component. A lumen  420  may extend from a proximal portion of catheter  415  to a distal end of catheter  415  (see, e.g.,  FIGS. 6A-6B ). 
     Sheath  414  may also include a distal portion  416 . Distal portion  416  may be a separate component from catheter  415  or may be a single, unitary structure with catheter  415 . Distal portion  416  may be fixedly or removably attached to a distal end of catheter  415 . Distal portion  416  may be configured to house an agent. Distal portion  416  may have any of the properties of distal portions  16 ,  116 ,  216 ,  316 , described above.  FIGS. 6C, 6E, 6F, 6H, and 6J  below show exemplary distal portions  464 ,  466 ,  468 ,  470 ,  472 , that may be used in place of distal portion  416 . Features of distal portions  464 ,  466 ,  468 ,  470 ,  472  may be used in combination with any features of distal portions  16 ,  116 ,  216 ,  316 , and corresponding structures are identified with like reference numbers. 
     Handle  412  may include a plunger  450 , which may be operatively connected to finger loops  462 . Plunger  450  may have a component that is within lumen  420 . Handle  412  may also include a proximal thumb loop  464 . Advancing finger loops  462  distally over a body  465  of handle  412  may cause plunger  450  to be advanced distally. The features of handle  412  may also be used with handles  12 ,  312 , described above. Plunger  450  may be operatively connected (e.g., mechanically coupled) to the actuation mechanisms described herein, with respect to  FIGS. 6B-6J . Features of handle  464 , including finger loops  462  and thumb loop  464 , also may be used with devices  10 ,  300 , described above. 
       FIG. 6B  shows a first exemplary actuation mechanism  481  in cross-section along line A-A, shown in  FIG. 6A , and  FIG. 6C  shows an exemplary cross-section of distal portion  464  that may be used in conjunction with the actuation mechanism of  FIG. 6B . As shown in  FIG. 6B , an actuation mechanism may include a wire  482 , which may be located within lumen  420  of sheath  414 . A proximal portion of wire  482  may be operatively coupled to plunger  450  via, e.g., crimping, soldering, gluing, or other fixing mechanisms. Wire  482  and plunger  450  may alternatively be formed of a single, unitary material. A distal portion of wire  482  may be operatively connected (e.g., mechanically connected) to a piston  452 , which may slidably movable within a chamber  430 . Wire  482  may be crimped, soldered, glued, or otherwise fixed to piston  452 . Alternatively, wire  482  and piston  452  may be formed of a single, unitary material. Wire  482  may be made from a flexible material, such as nitinol, stainless steel, flexible plastic, polymer, a braided coil, Nylon-12, or any other suitable material. Wire  482  may be sufficiently rigid so as to transmit a force from movement of plunger  450  to piston  452 . However, wire  482  may be sufficiently flexible so as to not inhibit or may not substantially inhibit a flexibility of sheath  414 . Although the term “wire” is used, it will be appreciated that wire  482  may encompass structures made of materials such as plastic. 
     When plunger  450  is advanced distally, wire  482  may transmit the force and/or motion to piston  452 , which causes piston  452  to advance, and which may result in dispensing of an agent, as described above, (e.g., with respect to  FIGS. 2A-2B ). 
       FIG. 6D  shows another exemplary actuation mechanism  483  in cross-section along line A-A, shown in  FIG. 6A .  FIGS. 6E and 6F  show exemplary distal portions  466 ,  468 , which may be used in conjunction with the actuation mechanism of  FIG. 6D . As shown in  FIG. 6D  an actuation mechanism may include a tube  484 , which may be located within a lumen  420  of sheath  414 . A proximal portion of tube  484  may be operatively coupled to plunger  450  via, e.g., crimping, soldering, gluing, or other fixing mechanisms. Tube  484  and plunger  450  may alternatively be formed of a single, unitary material. Tube  484  may have a central lumen or opening extending longitudinally therethrough. 
     As shown in  FIG. 6E , actuation mechanism  483  may be used in conjunction with a distal portion  466  that is similar to distal portion  16  of  FIGS. 2A-2B  and may have any of the properties of distal portion  16 . Distal portion  466  may include one chamber  430 , and a piston  452  may be slidably disposed within chamber  430 . A distal portion of tube  484  may be operatively connected (e.g., mechanically connected) to piston  452 . Tube  484  may be crimped, soldered, glued, or otherwise fixed to piston  452 . Alternatively, tube  484  and piston  452  may be formed of a single, unitary material. Tube  484  may be made from a flexible material, such as a plastic material, nitinol, flexible polymer, braided coil, or other suitable material. Tube  484  may be sufficiently rigid so as to transmit a force from movement of plunger  450  to piston  452 . However, tube  484  may be sufficiently flexible to not inhibit or may not substantially inhibit a flexibility of sheath  414 . Although tube  484  is shown as having a hollow center core, it will be appreciated that tube  484  may also have a solid cross-section, a latticed cross-section, etc. 
     When plunger  450  is advanced distally, tube  484  may transmit the force from plunger  450  to piston  452 , which causes piston  452  to advance, which may result in dispensing of an agent, as described above (e.g., with respect to  FIGS. 2A-2B ). 
     As shown in  FIG. 6F , actuation mechanism may  483  may alternatively be used in conjunction with a distal portion  468 , which may be similar to distal portion  216  of  FIGS. 4A-4B  and may have any of the features thereof. Distal portion  468  may include a first chamber  430   a  and a second chamber  430   b . A first piston  452   a  may be slidably disposed within first chamber  430   a , and a second piston  452   b  may be slidably disposed within second chamber  430   b . A distal portion of tube  484  may be operatively connected (e.g., mechanically connected) to first piston  452   a  and second piston  452   b . Tube  484  may be crimped, soldered, glued, or otherwise fixed to first piston  452   a  and second piston  452   b . Alternatively, tube  484  and pistons  452   a ,  452   b  may be formed of a single, unitary material. Tube  482  may include slots or other features (not shown) to accommodate wall(s) of first chamber  430   a  and second chamber  430   b  between first chamber  430   a  and second chamber  430   b.    
     When plunger  450  is advanced distally, tube  484  may transmit the force from plunger  450  to both of pistons  452   a ,  452   b , which causes pistons  452   a ,  452   b  to advance, which may result in dispensing of an agent, as described above (e.g., with respect to  FIGS. 4A-4B ). 
       FIG. 6G  shows another exemplary actuation mechanism  486  in cross-section along line A-A, shown in  FIG. 6A .  FIG. 6H  shows an exemplary cross-section of distal portion  470  that may be used in conjunction with the actuation mechanism of  FIG. 6G . Distal portion  470  may include a first chamber  430   a  and a second chamber  430   b . A first piston  452   a  may be slidably disposed within first chamber  430   a , and a second piston  452   b  may be slidably disposed within second chamber  430   b.    
     As shown in  FIG. 6G , actuation mechanism  486  may include wires  482   a  and  482   b , which may be located within a lumen  420  of sheath  414 . Although  FIG. 6G  shows two wires  482   a  and  482   b , any suitable number of wires may be used. A proximal portion of each of wires  482   a ,  482   b  may be operatively coupled to plunger  450  via, e.g., crimping, soldering, gluing, or other fixing mechanisms. Wires  482   a ,  482   b  and plunger  450  may alternatively be formed of a single, unitary material. Alternatively, wires  482   a  and  482   b  may be independently movable via, for example, multiple plungers (not shown). 
     A distal portion of wire  482   a  may be operatively connected (e.g., mechanically connected) to first piston  452   a . Wire  482   a  may be crimped, soldered, glued, or otherwise fixed to first piston  452   a . Alternatively, wire  482   a  and first piston  452   a  may be formed of a single, unitary material. A distal portion of wire  482   b  may be operatively connected (e.g., mechanically connected) to second piston  452   b . Wire  482   b  may be crimped, soldered, glued, or otherwise fixed to second piston  452   b . Alternatively, wire  482   b  and second piston  452   b  may be formed of a single, unitary material. 
     Wires  482   a ,  482   b  may have any of the properties of wire  482 , described above. When plunger  450  is advanced distally, wire  482   a  may transmit the force and/or motion to first piston  452   a , which causes piston  452   a  to advance. Simultaneously (unless wires  482   a  and  482   b  are separately controlled), wire  482   b  may transmit the force and/or motion of plunger  450  to second piston  452   b . Advancing plunger  450  distally may result in in dispensing of an agent, as described above (e.g., with respect to  FIGS. 4A-4B ). 
       FIG. 6I  shows another exemplary actuation mechanism  488  in cross-section along line A-A, shown in  FIG. 6A , and  FIG. 6J  shows an exemplary cross-section of distal portion  472  that may be used in conjunction with actuation mechanism  488 . Distal portion  472  may have any of the properties of distal portion  116 , described above with respect to  FIGS. 3A-3B . Distal portion  472  may include a chamber  430  and a tube  432 . A first piston  454  may be slidably disposed within chamber  430 , and a second piston  456  may be slidably disposed within tube  432 . 
     As shown in  FIG. 6I , actuation mechanism  488  may include wire  482 , which may be located within lumen  420  of sheath  414 , and may have any of the properties described above, with respect to  FIG. 6B . A proximal portion of wire  482  may be operatively coupled to plunger  450  via, e.g., crimping, soldering, gluing, or other fixing mechanisms. Wire  482  and plunger  450  may alternatively be formed of a single, unitary material. Actuation mechanism  488  may also include a tube  484 , which may also be located within lumen  420  of sheath  414 , and which may have any of the properties described above with respect to  FIGS. 6D-6F . A proximal portion of tube  484  may be operatively coupled to plunger  450  via, e.g., crimping, soldering, gluing, or other fixing mechanisms. Tube  484  and plunger  450  may alternatively be formed of a single, unitary material. Alternatively, wire  482  and tube  484  may be separately movable. Wire  482  may be located within a tube  484 . For example, wire  482  may be coaxial with a central longitudinal axis of tube  484 , or may be parallel to the central longitudinal axis of tube  484 . 
     A distal portion of wire  482  may be operatively connected (e.g., mechanically connected) to first piston  456 . Wire  482  may be crimped, soldered, glued, or otherwise fixed to first piston  456 . Alternatively, wire  482  and first piston  456  may be formed of a single, unitary material. A distal portion of tube  484  may be operatively connected (e.g., mechanically connected) to second piston  454 . Tube  484  may be crimped, soldered, glued, or otherwise fixed to second piston  454 . Alternatively, tube  484  and piston  454  may be formed of a single, unitary material. 
     When plunger  450  is advanced, wire  482  may transmit the force from plunger  450  to piston  456 , and tube  484  may transmit the force from plunger  450  to piston  454 . Advancing plunger  450  distally may result in in dispensing of an agent, as described above (e.g., with respect to  FIGS. 3A-3B ). 
     While principles of the present disclosure are described herein with reference to illustrative examples for particular applications, it should be understood that the disclosure is not limited thereto. Those having ordinary skill in the art and access to the teachings provided herein will recognize additional modifications, applications, and substitution of equivalents all fall within the scope of the examples described herein. Accordingly, the invention is not to be considered as limited by the foregoing description.