Abstract:
A device and method for delivering an agent to the uterine cervix make use of a seal member that defines a chamber upon engagement with the cervix. An agent delivery port in fluid communication with the chamber is provided for delivery of the agent to the uterine cervix. A vacuum port in fluid communication with the chamber allows application and retention of vacuum pressure to the chamber. At least a portion of the seal member can be made deformable in response to contact with the outer surface of the uterine cervix and application of vacuum pressure. Upon deformation, the seal member substantially seals the chamber against leakage of the agent. The seal member may include a skirt-like member that promotes adhesion of the seal member to the cervix, and enhances the effectiveness of the seal. The device facilitates vacuum application, cervical fixation, and a resulting barrier against uterine fluid leakage, providing an atraumatic, temporary cervical plug that remains effective while the vacuum is applied. In this manner, the device is capable of improving diagnostic or therapeutic effectiveness while reducing waste and expense. The device and method also can be adapted for introduction of surgical or diagnostic instruments, such as ablation catheters or endoscopes.

Description:
TECHNICAL FIELD 
     The present invention relates generally to the delivery of agents for medical treatment or diagnosis and, more particularly, to the delivery of such agents to the female reproductive tract. 
     BACKGROUND 
     A variety of delivery devices has been developed for the delivery of anesthetics, drugs, irrigation fluids, imaging contrast agents, and other agents to the body. Delivery of such agents can be accomplished either systemically or locally. Systemic delivery generally refers to delivery of agents to the body as a whole. Agents delivered systemically tend to travel to many different areas of the body. Localized delivery generally refers to delivery of agents to a particular area of the body, i.e., on a more targeted basis. There are many methods and techniques for delivering agents to body tissue systemically or locally. Existing techniques include, for example, oral administration, direct injection into body tissue, topical or transcutaneous administration, and intravenous administration. 
     Systemic delivery has a number of disadvantages. When drugs are systemically administered at high levels, for example, healthy tissue can be harmed, causing serious side effects in some cases. Also, drugs and contrast agents can be expensive, making the delivery of limited dosages more desirable. Systemic delivery may require a higher dosage, however, to achieve a desired level of the agent at the intended site. As a result, a portion of the agent can be wasted, driving up the cost of the treatment or diagnostic procedure. The high cost of pharmaceuticals, contrast agents, and the like makes minimization of waste a significant concern. 
     The disadvantages of systemic delivery make localized delivery desirable for many applications. One technique for localized delivery is to inject the agent directly into target tissue. Unfortunately, injection requires penetration by a needle or similar device, which is intrusive, painful, and often inaccurate. Moreover, injection may not evenly distribute the agent throughout the target area. To aggravate this situation, several injections may be required for relatively large target areas. Also, injection can produce a high concentration of the agent at the site of the injection, creating a large concentration gradient. Large concentrations are more likely to introduce significant quantities of the agent into the patient&#39;s system, undermining the objective of localized delivery. 
     Transcutaneous delivery is another technique for localized delivery of agents to the body. Transcutaneous delivery systems generally are limited, however, to the application of an agent through the patient&#39;s skin or other surface tissue. As a result, transcutaneous delivery of an agent to a target area that is large or situated deep within the patient&#39;s body can be difficult. An example of a difficult target area for transcutaneous delivery is cervical and uterine tissue. Typically, a quantity of agent much larger than the amount required at the target site must be applied, resulting in waste and added expense. 
     SUMMARY 
     The present invention provides a device for localized delivery of an agent to cervical and/or uterine tissue. The delivery device may include a number of features that aid in reducing leakage of the agent, and thereby improve the efficiency of the device. With more efficient delivery, the device is capable of improving diagnostic or therapeutic effectiveness and reducing waste and expense. In addition, the delivery device can make use of features that facilitate positioning relative to the cervix and cervical fixation without the need for a tenaculum or other painful manipulation devices. 
     The device may include a seal member that is configured to engage an outer surface of the cervix. Upon engagement with the outer surface of the cervix, the seal member defines a chamber. The seal member further defines a vacuum port and an agent delivery port, both of which are in fluid communication with the chamber. 
     The seal member can be mounted about an elongated member. The elongated member may take the form of a cannula having a distal end mounted at the agent delivery port. The cannula includes an inner lumen for introduction of an agent delivery catheter through the agent delivery port and into the cervical canal. As an alternative to use of a mounted cannula, a catheter may be introduced directly into the agent delivery port, e.g., via a catheter fitting such as a grommet. The catheter can be guided to the os of the cervical canal for delivery of the agent to the uterus. 
     The seal member, or a portion thereof, can be made from a compliant material that permits substantial deformation. For example, the seal member can be equipped with a compliant skirt-like member that contacts the outer surface of the cervix. Upon application of vacuum pressure via the vacuum port, at least a portion of the seal member, e.g., the skirt-like member, deforms and substantially seals the outer surface of the cervix against leakage of the agent. In this manner, fluid delivered to the cervix via the agent delivery catheter is substantially retained within the chamber, and more effectively transmitted to the cervix. 
     The use of vacuum pressure in combination with compliant characteristics of the seal member also facilitate positioning of the device relative to the cervix. In particular, the device permits a firm grasp of the cervix without significant trauma or discomfort. Thus, manipulation of the cervix can be less painful relative to other techniques such as the use of a tenaculum. At the same time, the device can facilitate catheter alignment and insertion for delivery of the desired agent or agents. 
     The seal member may include inner and outer walls that subdivide the chamber into an outer, annular chamber and an inner, central chamber, which are substantially concentric with one another. In this case, the vacuum port is in fluid communication with the annular chamber, whereas the agent delivery port is in fluid communication with the central chamber. Upon application of vacuum pressure, the inner and outer walls engage the outer surface of the cervix, and serve to separate the annular and central chambers from one another. 
     In this manner, fluid communication between the vacuum port and the central chamber is substantially avoided, preventing aspiration of the agent delivered via the central chamber by the vacuum port. A plug member that protrudes into the chamber can be further incorporated in the seal member. A catheter can be guided through the plug member. The plug member can be oriented for introduction into the os of the cervical canal, providing an added seal against leakage of agent delivered by the catheter. 
     Examples of agents that can be delivered using a device in accordance with the present invention include pharmaceutical agents, biological agents, cytotoxic agents, chemotherapeutic agents, hormones, radiotherapeutic agents, anesthetic agents, dyes such as methylene blue, imaging contrast agents, and irrigation fluids. Delivery of such agents using a device constructed as described herein reduces leakage and the resulting costs associated with waste. By preventing significant leakage, the device permits delivery of more precise amounts of an agent in a targeted manner. Moreover, the device can increase and expedite the effectiveness of the agent. 
     Although the present invention will be described primarily in the context of the delivery of agents in the form of drugs, contrast agents, and the like, the delivery device can be used for the introduction of imaging or surgical devices into the female reproductive tract, i.e., the uterine cervix and uterus. For example, the seal member can be configured to permit introduction of a variety of rigid or flexible devices such as hysteroscopes for endoscopy or ablation procedures within the uterus or cervix. In this case, the agent delivery port can be referred to as an instrument introduction port. Again, the structure of the seal member in combination with the application of vacuum pressure can facilitate the positioning of such devices. Moreover, the delivery device can substantially prevent leakage of distension fluids or other agents used in the course of such procedures. 
     The present invention provides, in one embodiment, a device for delivery of an agent to the uterine cervix, the device comprising a seal member that defines a chamber upon engagement with the cervix, an agent delivery port in fluid communication with the chamber, and a vacuum port in fluid communication with the chamber, wherein at least a portion of the seal member is deformable in response to application of vacuum pressure via the vacuum port to thereby substantially seal the chamber against leakage of the agent. 
     In another embodiment, the present invention provides a method for delivering an agent to the uterine cavity, the method comprising inserting a catheter through the cervical canal and into the uterine cavity, engaging a seal member with an outer surface of the cervix to define a chamber, at least a portion of the seal member being compliant, wherein the catheter passes through the seal member, applying vacuum pressure to a vacuum port associated with the chamber such that at least a portion of the seal member deforms to substantially seal the chamber against leakage, and delivering the agent to the uterine cavity via the catheter. 
     In a further embodiment, the present invention provides a device for delivery of an agent to the uterine cervix, the device comprising a seal member that, upon engagement with the cervix, includes an outer wall and an inner wall that together define an annular chamber and a central chamber substantially concentric within the annular chamber, a vacuum port in fluid communication with the annular chamber, and an agent delivery port in fluid communication with the central chamber, the seal member substantially sealing the central chamber against leakage of the agent upon application of vacuum pressure via the vacuum port. 
     In an added embodiment, the present invention provides a method for delivery of an agent to the uterine cervix, the method comprising engaging a deformable seal member with the cervix to define a chamber, applying vacuum pressure to the chamber to substantially seal the chamber against leakage, and delivering the agent to the chamber via a port defined in the seal member. 
     In a further embodiment, the present invention provides a device for introduction of an instrument to a position proximate to the female reproductive tract, the device comprising a seal member that defines a chamber upon engagement with the uterine cervix, an introduction port in communication with the chamber, the introduction port defining an aperture for introduction of an instrument, and a vacuum port in communication with the chamber, wherein at least a portion of the seal member is deformable in response to application of vacuum pressure via the vacuum port to thereby substantially seal the chamber. 
     In another embodiment, the present invention provides a method for introduction of an instrument to a position proximate to the female reproductive tract, the method comprising engaging a seal member with an outer surface of the uterine cervix to define a chamber, at least a portion of the seal member being compliant, the seal member defining an aperture, inserting an instrument through the aperture defined by the seal member, applying vacuum pressure to a vacuum port associated with the chamber such that at least a portion of the seal member deforms to substantially seal the chamber against leakage, and positioning a distal end of the instrument proximate to the female reproductive tract. 
     In an additional embodiment, the present invention provides a device for introduction of an instrument to a position proximate a portion of the female reproductive tract, the device comprising a seal member that, upon engagement with the uterine cervix, includes an outer wall and an inner wall that together define an annular chamber and a central chamber substantially concentric within the annular chamber, a vacuum port in fluid communication with the annular chamber, and an instrument introduction port in communication with the central chamber, the seal member substantially sealing the central chamber against the uterine cervix upon application of vacuum pressure via the vacuum port. 
     In yet another embodiment, the present invention provides a method for introduction of an instrument to a position proximate the female reproductive tract, the method comprising engaging a seal member with the uterine cervix to define a chamber, at least a portion of the seal member being deformable, wherein the seal member defines an aperture, applying vacuum pressure to the chamber to cause deformation of at least the portion of the seal member and substantially seal the chamber against the uterine cervix, introducing an instrument through the aperture defined by the seal member, and positioning a distal end of the instrument proximate to the female reproductive tract. 
    
    
     The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
     DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is an exploded cross-sectional view of an agent delivery device; 
     FIG. 2A is a cross-sectional view of an agent delivery device as shown in FIG. 1 in use; 
     FIG. 2B is a cross-sectional view of an agent delivery device as shown in FIG. 1 illustrating application of vacuum pressure; 
     FIG. 3A is a cross-sectional view of a seal member for use with a device as shown in FIG. 1; 
     FIG. 3B is a cross-sectional view of another seal member for use with a device as shown in FIG. 1; 
     FIG. 4 is an exploded cross-sectional view of another agent delivery device; 
     FIG. 5 is a side view of an elongated member for use with an agent delivery device as shown in FIG. 4; 
     FIG. 6 is a cross-sectional view of an agent delivery device having a seal member with an integrated plug member; 
     FIG. 7 is a cross-sectional view of a plug member for use with a device as shown in FIG. 6; 
     FIG. 8A is a cross-sectional view of an agent delivery device as shown in FIG. 6 in use; 
     FIG. 8B is a cross-sectional view of an agent delivery device as shown in FIG. 6 illustrating application of vacuum pressure; 
     FIG. 9 is a cross-sectional view of a device having an alternative plug arrangement; 
     FIG. 10A is a cross-sectional view of another agent delivery device having an integrated plug member; and 
     FIG. 10B is a cross-sectional view of a device as shown in FIG. 10A with an integrated plug member having an alternative depth; 
     FIG. 10C is an exterior view of an agent delivery device as shown in FIG. 10B; 
     FIG. 11 is another view of an agent delivery device as shown in FIGS. 10A,  10 B, and  10 C coupled to a cannula and vacuum line; and 
     FIG. 12 is a view of the agent delivery device of FIG. 11 illustrating introduction of a catheter. 
    
    
     Like reference numbers and designations in the various drawings indicate like elements. 
     DETAILED DESCRIPTION 
     FIG. 1 is an exploded cross-sectional view of an agent delivery device  100 . As shown in FIG. 1, device  100  may include a seal member having a cup-like member in the form of a vacuum cup  102 . Vacuum cup  102  is sized for engagement with an outer surface of the uterine cervix. Upon engagement with the cervix, vacuum cup  102  defines a chamber  103  for delivery of an agent to the female reproductive tract, i.e., the cervix and/or uterus. Cup  102  incorporates a base portion  104  that defines an agent delivery port  106 . Agent delivery port  106  provides an aperture for introduction of a cannula or catheter. An outer wall  108  extends from base portion  104  and terminates at an outer rim or outer contact ring  110 . An inner wall  112  also extends from base portion  104 , circumscribes port  106 , and terminates at an inner rim or inner contact ring  114 . 
     The height of inner wall  112  may be approximately half the height of outer wall  108  in the example of FIG.  1 . In other embodiments, however, inner wall  112  may have a height that is substantially less than half the height of outer wall  108 . Additionally, outer and inner walls  108  and  112  may be generally circular and concentric to one another. Inner wall  112  defines an inner, central chamber  111  for fluid communication with agent delivery port  106  and the source of the agent to be delivered. An outer, annular chamber  116  is defined between inner and outer walls  108  and  112  for fluid communication with a vacuum port  117  and a source of vacuum pressure. 
     Cup  102  can be formed with a biologically compatible material such as polyethylene, polyurethane, polycarbonate, acetyl butadeine styrene (ABS), or silicone. Thus, in various embodiments, cup  102  can be made from a substantially rigid material or more compliant materials. In some embodiments, however, at least a portion of cup  102  is made from a compliant material. A compliant material may allow outer contact ring  110  to more easily conform to variations in the outer surface of the patient&#39;s cervix, and to partially deform upon application of vacuum pressure via vacuum port  117 . This feature may contribute to a more robust seal between cup  102  and the outer surface of the uterine cervix. 
     Device  100  may be suitable for delivery of a variety of agents. An agent can include any type of composition suitable for therapy or diagnosis. Examples include drugs, compositions useful for diagnostic purposes such as dyes or fixatives, genetic material such as DNA, RNA, genes, antisense oligonucleotides, and other antisense material, local anesthetics such as lidocaine, therapeutic agents such as cytotoxic, chemotherapeutic, photosensitive agents, and antiviral agents, adjuvant, penetration enhancers, hormones, and other substances that have medical therapeutic or diagnostic applications. Additionally, the term “agent” can mean an agent in the form of a solution, gel, liquid, or liposome. Although the term is often used in a singular form, it can connote either a single agent or a combination of agents. 
     With further reference to FIG. 1, a cylindrical flange  118  extends around agent delivery port  106  and extends from base portion  104  in a direction opposite to inner and outer walls  112  and  108 . Cylindrical flange  118  has an inner surface  120 . Vacuum port  117  extends from outer wall  108  and interconnects with a nozzle of a vacuum line  122 . Vacuum port  117  is in fluid communication with annular chamber  116  defined between inner and outer walls  112  and  108 . A radially-oriented flange  124  extends between the outer surface of outer wall  108  and the outer surface of cylindrical flange  118 . Radially-oriented flange  124  provides a convenient place for a caregiver to grip cup  102  for vaginal introduction into the patient. 
     Device  100  further may include an elongated member  127  having a proximal end  129  and a distal end  131 . A fluid fitting  133  can be mounted at proximal end  129  for introduction of the agent into catheter  127 , e.g., using a syringe. For use, cup  102  can be mounted adjacent distal end  131  of elongated member  127 . In particular, cup  102  may slidably engage elongated member  127 . In this manner, cup  102  can be selectively repositionable along the length of elongated member  127 , allowing the care giver to adapt device  100  to particular conditions. In the example of FIG. 1, elongated member  127  takes the form of a catheter. The catheter defines an inner lumen for delivery of an agent. A catheter grommet  126  is mounted at distal end  131  of elongated member  127 . Catheter grommet  126  may have a generally conical shape, a proximal end  128 , and a distal end  130 . The diameter of distal end  130  is greater than the diameter of proximal end  128 . A rim  132  is formed around the circumference of distal end  130 . At least a portion of the edge of rim  132  has a rib or arcuate profile  134  that extends around the entire circumference of the rim. Distal end  130  of catheter grommet  126  is sized to be inserted into cylindrical flange  118  of vacuum cup  102  such that profile  134  of rim  132  engages inner surface  120  of the cylindrical flange and creates a compression seal therebetween. 
     Catheter grommet  126  has an inner surface that defines a passage  136  extending between distal and proximal ends  128  and  130 . Distal end  130  of passage  136  opposes port  106  in base  104  of cup  102 . Two parallel ribs or arcuate profiles  138  and  140  are formed in the inner surface of catheter grommet  126  and extend around the circumference of passage  136 . Profiles  138 ,  140  are axially displaced from one another along the length of passage  136 . In the example of FIG. 1, catheter  127  slidably engages catheter grommet  126  and extends through passage  136  and into cup  102 . Profiles  138  and  140  engage catheter  127  and create a compression seal between the inner surface of catheter grommet  126  and the catheter. Catheter grommet  126  can be made from a compliant material to permit deformation for insertion into the aperture defined by inner surface  120 . 
     FIG. 2A is a cross-sectional view of an agent delivery device  100  in use. As shown in FIG. 2A, a caregiver estimates the length of the patient&#39;s cervical canal and uterine cavity. The caregiver then adjusts the distance between distal end  131  of catheter  127  and distal end  130  of catheter grommet  126  so that the distal end of the catheter will not penetrate into the top portion of the uterine wall when cup  102  engages the patient&#39;s cervix. The caregiver then inserts distal end  131  of catheter  127  through the cervical canal until contact ring  110  of outer wall  108  engages the patient&#39;s cervix. Air is then withdrawn through vacuum port  117  to create a vacuum in cup  102 . 
     FIG. 2B is a cross-sectional view of agent delivery device  100  illustrating application of vacuum pressure. As shown in FIG. 2B, evacuation of chamber  103  causes the tissue of the patient&#39;s cervix to be drawn into cup  102  and thereby engage contact ring  114  of inner wall  112 . This vacuum also serves to seat cup  102  against the cervix and creates a seal between the cervix and inner and outer contact rings  114  and  110 . In particular, the vacuum substantially seals chamber  103  against leakage. In various embodiments, the amount of vacuum pressure that is drawn in cup  102  may be in the range of about −25 to about −600 cm H 2 O. The amount of vacuum pressure may vary, however, with the diameter, depth, and resulting volume of cup  102 , and could be greater. Also, the rate at which the vacuum pressure is applied may be selected to minimize trauma to the cervical tissue, or pain or discomfort to the patient. 
     In some embodiments, in response to the vacuum pressure, at least a portion of vacuum cup  102  may partially deform to better match the shape and contour of the cervix. After the vacuum is created and inner and outer contact rings  114  and  110  are sealed against the surface of the patient&#39;s cervix, the caregiver infuses an agent through catheter  127  and into the uterine cavity. Notably, upon engagement of contact ring  114  with the outer surface of the cervix, chamber  103  provides two separate chambers. Specifically, central chamber  111  and annular chamber  116  are separated from one another by wall  112 . Vacuum pressure is applied to annular chamber  116  to provide a seal, whereas central chamber  111  accommodates catheter  127 . In this manner, the fluid delivery chamber, i.e., central chamber  111 , is separated from the vacuum chamber, i.e., annular chamber  116 . Backflow of agent from the uterus is thereby confined to central chamber  111 , preventing aspiration of the agent by vacuum port  117 . 
     In some embodiments, the entire uterine cavity can be filled with agent, which permits uniform delivery throughout the uterine wall. The agent then can be passively absorbed into the uterine wall. In other embodiments, an electrode can be positioned on the distal end of the catheter while another electrode is positioned in electrical communication with the patient&#39;s body at a point outside the uterine cavity. An electrical current is then conducted between the electrodes to actively transport the agent into the uterine wall. The catheter can include other structures for actively delivering the agent such as ultrasonic transducers, which deliver the agent using principles of phonophoresis. Yet another embodiment may incorporate a heating element at the distal end of the catheter, e.g., for thermal activation of certain agents. 
     FIGS. 3A and 3B are cross-sectional views of vacuum cup  102  with different inner wall heights. As shown in FIGS. 3A and 3B, the height of inner wall  112  can be varied to accommodate different cervical sizes and shapes. For example, in the embodiment shown in FIG. 3A, the height of inner wall  112  is substantially more than half of the height of outer wall  108 . In a more specific example, the height of inner wall  112  may be as high as 0.15 inches. This embodiment may be useful for patients that tend to have a flatter cervix. 
     In another embodiment, as shown in FIG. 3B, the height of inner wall  112  is substantially less than half the height of outer wall  108 . In a more specific example, the height of inner wall  112  is between about 0.15 inches and about 0.50 inches. This embodiment may be useful for patients that have a deeper and more conically-shaped cervix. Yet other embodiments may have different proportions between the height of the inner and outer walls  112  and  108 , and different diameters for inner and outer contact rings  114  and  110 . Furthermore, the overall profile for cup  102  itself can vary. For example, cup  102  could have more of a conical shape or more of a spherical shape. 
     FIG. 4 is an exploded cross-sectional view of another agent delivery device  146 . Like device  100  of FIG. 1, device  146  includes a seal member incorporating a vacuum cup  102 . Again, cup  102  includes a base portion  104  defining agent delivery port  106 , inner and outer walls  112  and  108 , a cylindrical flange  118 , and a vacuum port  117 . In contrast to device  100 , however, device  146  includes a cannula  148  and cannula grommet  150  instead of catheter grommet  126 . Cannula  148  defines an inner lumen  170  sized to accommodate an agent delivery catheter, as will be described. A distal end  169  of cannula  148  may incorporate a fluid fitting  171  for delivery of agents directly within cannula  148 . Alternatively, a catheter can be introduced via cannula  148 . 
     As shown in FIG. 4, cannula grommet  150  includes a first cylindrical portion  152  at a proximal end  154 , a second cylindrical portion  156  at a distal end  158 , and a conical portion  160  extending between first and second cylindrical portions  152  and  156 . A neck  162  extends from the proximal end of first cylindrical portion  152 . First and second cylindrical portions  152  and  156 , conical portion  160 , and neck  162  are axially aligned to one another and define a lumen  164  that extends along the axis. A rim  166  extends around the circumference of first cylindrical portion  152 , and is positioned adjacent proximal end  154 . An o-ring  168  is mounted on rim  166 . Rim  166  and o-ring  168  are sized to engage inner surface  120  of cylindrical flange  118  of cup  102  and form a seal therebetween. The diameter of first cylindrical portion  152  of cannula grommet  150  is sized to pass through port  106  of base portion  104  of cup  102 . 
     Cannula  148  defines a lumen  170  and has a distal end  172  opposing neck  162  of cannula grommet  150 . O-ring  174  is positioned between distal end  172  of cannula  148  and neck  162 . A collar  178  extends around neck  162  of cannula grommet  150 , o-ring  174 , and distal end  172  of cannula  148 . Lumen  170  of the cannula is aligned with lumen  164  of cannula grommet  150 . Collar  178  fastens cannula  148  to neck  162  of cannula grommet  150 . In one embodiment, the length of cannula  148  is between about four inches and about ten inches. Cannula  148  may be substantially straight. In another embodiment shown in FIG. 5, however, cannula  148  is bent at a position proximal to collar  178 . Cannula  148  can be bent at an angle of about 30°, for example, making it easier for the caregiver to handle and position cup  102  relative to the cervix. 
     The embodiments of device  146  shown in FIGS. 4 and 5 can be used in a manner similar to the embodiment shown in FIG.  1 . However, the caregiver can more readily grip cannula  148  to position cup  102  against the patient&#39;s cervix. The caregiver then inserts a catheter through the cannula  148  to a delivery position and draws a vacuum in cup  102 . In an alternative embodiment, the catheter can be positioned through cannula  148  before cup  102  is positioned against the cervix. In either case, cannula  148  facilitates both manipulation of device  146  and introduction of the agent delivery catheter relative to the cervix. Alternatively, cannula  148  or some other introduction device, e.g., a syringe, could be used with device  146  to simply deliver an agent to the cervix via agent delivery port  106  without the need for catheterization. 
     FIG. 6 is a cross-sectional view of an agent delivery device  180  having a cup  102  with a plug member  182 . Device  180  is substantially similar to the embodiment shown in FIGS. 3 and 4, and includes cup  102  having a base portion  104 , inner and outer walls  112  and  108 , and a cylindrical flange  118 . Additionally, however, plug member  182  is positioned within inner wall  112 . Plug member  182  has a base portion  184  that extends from inner surface  186  of inner wall  112 , a tip portion  188  that extends beyond outer contact ring  110 , an inner surface  190 , and an opening  192  defined in tip portion  188 . 
     Tip portion  188  can be oriented to center a catheter introduced through a cannula  148  within central chamber  111  defined by inner walls  112 . Plug member  182  is oriented to engage the cervix proximate to the external os of the cervical canal upon engagement of cup  102  with the cervix. In particular, tip portion  188  engages the os of the cervical canal, providing an added seal against leakage of agent introduced into the uterus. Thus, plug member  182  protrudes from cup  102  and into chamber  103 . Agent delivery port  106  extends through plug member  182 . 
     Plug member  182  can have a variety of different shapes. In one example, plug member  182  has a conical shape with a substantially straight surface  194 . In another example, as shown in FIG. 7, surface  194  of plug member  182  is slightly curved to give it an acorn-shaped profile. Plug member  182  preferably is integrally formed with cup  102 , e.g., by injection molding. Alternatively, plug member  182  could be bonded to cup  102 , e.g., by adhesive, thermal, or ultrasonic bonding techniques. 
     Although plug member  182  is illustrated with a cup  102  having central chamber  111  and outer chamber  116 , it could be used with a single-chamber cup. In this case, plug member  182  could be engaged within the cervical os to augment the seal provided by cup  102  and chamber  103 . In some applications, the use of a single chamber cup  102  with plug member  182  may be effective. However, incorporation of inner and outer chambers  111 ,  116  is generally preferred. 
     Delivery device  180  further includes an annular skirt  189 . Together, cup  102  and skirt  189  form the seal member. Annular skirt  189  has a base portion  191  that is attached to outer contact ring  110 . Annular skirt  189  extends out to a rim  193  that can be made thinner than base portion  191 . Annular skirt  189  is formed from a compliant material and will substantially conform to the outer surface of the patient&#39;s cervix, improving the seal achieved by cup  102 . In a preferred embodiment, skirt  189  is insert molded over ring  110  of cup  102 , thereby coupling the skirt to the cup to provide a generally integral construction. Skirt  189  can be bonded to cup  102  using other techniques, however, such as adhesive, thermal, or ultrasonic bonding techniques. 
     In one embodiment, the material forming the annular skirt  189  has enough compliance so that rim  193  will fan out and at least a portion of inner surface  195  of annular skirt  189  will lay against the surface of the patient&#39;s cervix. Examples of materials that can be used to form annular skirt  189  include a variety of biocompatible silicone gel materials or low durometer silicone. A suitable silicone material may have a hardness, for example, in the range of 5 to 30 Shore A. An example of one suitable silicone gel material is MED 6340, commercially available from NUSIL Silicone Technologies, of Carpinteria, Calif. The MED 6340 silicone gel is tacky and exhibits a hardness characteristic such that a 19.5 gram shaft with a 6.35 mm diameter has been observed to penetrate the gel approximately 5 mm in approximately 5 seconds. This hardness characteristic is not a requirement, but merely representative of that exhibited by the commercially available MED 6340 material. 
     Device  180  also may include a cannula grommet  196  similar to cannula grommet  150  shown in FIGS. 4 and 5, but generally conical in shape. Cannula grommet  196  can be sized to pass through port  106  in base portion  104  and generally conform to inner surface  190  of plug member  182 . A rim  198  extends from a proximal portion  200  of cannula grommet  196  and is sized to engage inner surface  120  of cylindrical flange  118  on cup  102 . A neck  162  extends from the proximal portion of cannula grommet  196 . Cannula grommet  196  has an inner surface that defines a lumen  164 . The inner surface has a radial portion  197 . An o-ring  174  can be seated against radial portion  197  of the inner surface. A distal end  172  of cannula  148  is inserted into lumen  164  of cannula grommet  196  and adjacent o-ring  174 . Lumen  170  of cannula  148  is aligned with and in fluid communication with lumen  164  of cannula grommet  196 . Lumens  164 ,  170  may accommodate an agent delivery catheter. 
     In use, cup  102  of device  180  is positioned against the cervix in a manner similar to the embodiment shown in FIGS. 2A and 2B. However, tip portion  188  of plug member  182  is inserted into or to a point proximate to the os of the cervical canal, which adds an additional seal directly at the os and cervical canal. As shown in FIG. 8A, for example, annular skirt  189  is positioned in contact with the outer surface of the cervix. A catheter  127  is translated through cannula  148  and into the os of the cervix. Upon application of vacuum pressure, as shown in FIG. 8B, plug member  182  is drawn into the os of the cervical canal. At the same time, inner wall  112  is drawn into contact with the outer surface of the cervix. The compliant skirt  189  compresses and deforms upon application of the vacuum pressure, to permit inner wall  112  to engage the outer surface of the cervix, and enhance the resulting seal. 
     FIG. 9 is a cross-sectional view of an agent delivery device, generally shown as  201 , having an alternative plug arrangement. Device  201  is substantially similar to the embodiment shown in FIG.  6 . Cup  102  includes, for example, inner and outer walls  112  and  108 , a base portion  104 , a cylindrical flange  118 , and a plug member  182 . Additionally, inner surface  190  of plug member  182  defines a radially-oriented surface  202 , and two o-rings  204  and  206 , which are seated against radially-oriented surface  202 . O-rings  204  and  206  are held in place by an annular member  208 . This embodiment is used in a manner similar to the embodiment shown in FIG.  1 . However, the catheter can be passed directly through agent delivery port  106  in base portion  104 , through o-rings  204  and  206 , and out opening  192  at the tip of plug member  182 . O-rings  204  and  206  seal any gaps between cup  102  and the catheter. Hence, a grommet is generally unnecessary in the embodiment of FIG. 9, but could be incorporated along with a cannula if desired. 
     FIG. 10A is a cross-sectional view of another agent delivery device  210  having a cup  102  with a plug member  182 . Device  210  conforms substantially to device  180  of FIG.  6 . For example, agent delivery device  210  includes a seal member formed by cup  102 , skirt  189 , agent delivery port  106 , and vacuum port  117 . In contrast to device  180 , however, device  210  makes use of a one-piece construction in which both plug member  182  and a cannula receptacle  212  are integrally formed with cup  102 , e.g., by injection molding. FIG. 10A further illustrates the connection of a vacuum line  122  between vacuum port  117  and a four-way stopcock  211  that can be connected to vacuum pump. Stopcock  211  is coupled to vacuum line  122  via a connector  213 . In particular, a first inlet  221  engages connector  213 . Outlet  217  communicates with a remote vacuum pump and first inlet  221 . A second inlet  219  permits inflow of air to release the vacuum applied to chamber  103 . 
     As shown in FIG. 10A, cannula receptacle  212  defines a cylindrical first bore  214 , formed by wall  216 . In the example of FIG. 10A, first bore  214  is sized to receive a cannula  148 , and can be bonded to the cannula. First bore  214  also may incorporate one or more o-rings  215  for receipt of a catheter, either directly or via cannula  148 . In either case, bore  214  terminates at a proximal portion of plug member  182 , at which point the plug member defines a second bore  218 . Second bore  218  has a diameter sized to accommodate a catheter for introduction into the cervical canal. Together, bores  214 ,  218  and o-ring  215  define agent delivery port  106  for accommodation of an agent delivery catheter. 
     FIG. 10B is a cross-sectional view of an agent delivery device  220  that conforms substantially to that shown in FIG. 10A, but which incorporates an integrated plug member  182  having an alternative height. In the embodiment of FIG. 10A, for example, plug member  182  has a height, extending from a proximal portion of skirt  189 , that is substantially more than half of the height of the skirt. In the example of FIG. 10B, the height of plug member  182  is substantially less than half of the height of skirt  191 . In particular, in the example of FIG. 10A, the height of plug member  182  is between about 5.4 and about 6.4 mm. In the example of FIG. 10B, the height of plug member  182  is between about 2.8 and about 3.8 mm. 
     The embodiment of FIG. 10B may be more suitable for a patient with a flatter cervix, whereas the embodiment of FIG. 10A may be more suitable for a patient with a deeper and more conically-shaped cervix. In operation, device  210 ,  220  as shown in FIG. 10A or  10 B can be used substantially in the manner shown in FIGS. 8A and 8B. In particular, vacuum pressure can be applied to cup  102  to form a first seal, while plug member  182  is engaged with the os of the cervical canal to form a second seal. FIG. 10C is an exterior view of an agent delivery device as shown in FIG.  10 B. 
     FIG. 11 is another view of an agent delivery device  220  as shown in FIGS. 10A,  10 B, and  10 C coupled to a cannula  148  and vacuum line  122 . Cannula  148  may include a introduction port  224  for receipt of agent delivery catheters, surgical catheters, diagnostic catheters and the like. For example, cannula  148  may accommodate a hysteroscope providing a laser or thermal ablation catheter for surgery or an endoscope for imaging. Such catheters may include multiple lumens, e.g., for agent delivery, imaging, and surgery. Incorporation of other surgical or diagnostic instruments are conceivable. 
     FIG. 12 is a view of the agent delivery device  220  of FIG. 11 illustrating introduction of a catheter  127 . As shown in FIG. 12, catheter  127  is introduced via an inner lumen defined by cannula  148  and through cup  102 . A proximal end of catheter  127  can be fitted with a luer lock injection port  228  by which a caregiver may inject an agent into the catheter. 
     A number of embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.