Abstract:
A system for moving particles suspended in a first fluid, and for infusing them into the stream of a second fluid, includes a catheter with a multi-lumen distal separator. The separator is formed with a plurality of parallel lumens, wherein each lumen has a predetermined diameter. Importantly, the diameter of each lumen is dimensioned to sequentially receive particles therethrough, to prevent the particles from flocculating before they enter the stream of the second fluid. A recollection chamber in fluid communication with the separator allows for reconsolidation of the fluid after leaving the separator and for minimizing the damage caused to the vessel when the fluid exits the catheter. An inflatable balloon, affixed to the outside of the catheter, can be provided to regulate flow of the second fluid and thereby facilitate entry of the particles into the stream of the second fluid and increase retention of particles in targeted tissue.

Description:
[0001]    This application is a continuation-in-part of application Ser. No. 12/563,876, filed Sep. 21, 2009, which is currently pending. The contents of application Ser. No. 12/563,876 are incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention pertains generally to infusion systems for introducing particles into a fluid stream. More particularly, the present invention pertains to infusion systems for introducing (infusing) particles of biological matter (e.g. stem cells) into the vasculature of a patient without diminishing the therapeutic effectiveness of the biological matter. The present invention is particularly, but not exclusively useful as a system using a multi-lumen filter that allows particles to enter a lumen of the separator, either individually or in small groupings, for subsequent infusion into the vasculature of a patient. 
       BACKGROUND OF THE INVENTION 
       [0003]    An introduction of particles into the vasculature of a patient requires simultaneously satisfying several different concerns or considerations. Depending on the type of particles involved, a concern of significant importance involves preventing the particles from flocculating, i.e. clumping together, as they are being infused or introduced into the vasculature. This is of particular concern in the case of stem cells which can flocculate, but which are most effective in therapy if left to function either as individual cells or in small groups of cells. An additional benefit of preventing particles from flocculating is the prevention of heart attacks caused when clumps of cells are introduced into the coronary circulatory system. Also, it has been shown that the retention rate of stem cells in the heart, or other targeted tissue, increases when the stem cells are infused as individual cells or in small groups of cells. 
         [0004]    In all types of intravascular therapy (i.e. intracoronary, intra-arterial or intravenous), it is always an essential concern that the therapeutic agent (e.g. biologics or drugs) be infused or delivered in a predictably controlled manner. Furthermore, it is important that the therapeutic agent be effectively delivered to a proper destination in the vasculature. All of this involves dosage and delivery rate considerations. Moreover, it requires careful handling of the therapeutic agent to insure it (the therapeutic agent) is not damaged or otherwise compromised during an infusion. 
         [0005]    From a mechanical perspective, it is known that the diameter of a fluid passageway is a factor that will affect the rate of fluid flow through the passageway. For protocols where small groups of de-flocculated particles are to be infused into a vessel of a vasculature, the diameter of the passageway must obviously be large enough to individually accommodate the small groups of particles. On the other hand, it must also be small enough to separate and prevent larger groups of particles (cells) from clinging to each other. A consequence of this is that the rate at which particles can be carried through the passageway will be circumscribed by the dimensions of the passageway. A further consequence of this is that, as particles leave the passageway, they are then influenced by the flow of fluid (i.e. blood) in the vessel of the vasculature. Depending on the purpose of the protocol, this may mean that the downstream fluid flow in the vasculature will somehow also need to be regulated. 
         [0006]    In light of the above, it is an object of the present invention to provide an infusion system that can effectively introduce only small groups of particles into a fluid flow. Another object of the present invention is to provide an infusion system that coordinates the flow rate of a particle/fluid medium (i.e. a first fluid) with the flow rate of a fluid (i.e. a second fluid) into which the particle/fluid medium is being introduced. Still another object of the present invention is to provide an infusion system that produces a low flow rate to reduce the impact on a vessel wall caused when fluid exits a catheter and enters the vessel. Yet another object of the present invention is to provide an infusion system that is easy to use, is simple to manufacture and is comparatively cost effective. 
       SUMMARY OF THE INVENTION 
       [0007]    In accordance with the present invention, an infusion system includes an elongated catheter which is formed with a central lumen that extends between the proximal and distal ends of the catheter. Preferably, the catheter is tubular shaped with a smooth, circular, outer surface and, for purposes of description, the catheter defines a longitudinal axis. A source of a fluid medium having particles suspended therein (i.e. a particle/fluid medium) is connected in fluid communication with the proximal end of the catheter, and a separator is connected at the distal end of the catheter. For purposes of the present invention, the separator is provided to prevent the particles from flocculating as they are infused or introduced into a vessel in the vasculature of a patient. As envisioned for the present invention, the particles can be either biologics (i.e. cell, gene or protein) or drugs. And, they can be introduced into the vasculature for intracoronary, intra-arterial, or intravenous therapy. 
         [0008]    Structurally, the separator is formed with a plurality of parallel lumens. Thus, with the separator affixed to the distal end of the catheter, each lumen of the separator is individually placed in fluid communication with the central lumen of the catheter. Importantly, each individual lumen is dimensioned to sequentially receive only small groups of particles (i.e. less than ten) therethrough. Specifically, although each lumen can receive several particles at a time, each lumen is sufficiently small to effectively separate particles from clinging to each other as they are received into the lumen. It follows that the system also includes a means for moving the particle/fluid medium through the lumen of the catheter, for further movement of the particles in alignment through individual lumens of the separator. For purposes of the present invention the means for moving this particle/fluid medium can be any such means well known in the pertinent art, such as an IV pole, a syringe, or a pump. 
         [0009]    In addition to the separator described above, the system of the present invention also includes a configurable (inflatable) valve, such as a balloon. Specifically, the configurable valve is positioned on the outer surface of the catheter to surround the catheter at a location that is proximal to the separator. Further, the valve is formed with a plurality of apertures that are arranged around the axis of the catheter. The purpose of these apertures is to control the axial movement of a fluid (e.g. blood) past the catheter in a distal direction substantially parallel to the axis of the catheter. This control is preferably provided by an inflator that selectively constricts the apertures of the valve to control the flow rate of fluid through the apertures. 
         [0010]    In a preferred embodiment of the present invention, the valve is formed as an annulus that is centered on the axis. With this structure, the annulus has an inner diameter that is affixed to the outer surface of the catheter. The valve also has a substantially non-compliant material positioned on the outer periphery of the annulus that maintains the outer diameter at a predetermined radial distance from the catheter when the valve is inflated into a base configuration. As mentioned previously, the valve can be a balloon as commonly used in the pertinent art, and the balloon can be of any material appropriate for this type of procedure. As examples, the balloon may be nylon, polyethylene, or polyethylene terephthalate (PET). Aside from the non-compliant material, the rest of the annulus is made of a compliant material. Importantly, this compliant material is responsive to the inflator to selectively constrict the apertures. Thus, in operation, an additional inflation of the valve beyond its base configuration substantially maintains the outer diameter at the predetermined radial position, while incrementally constricting the apertures. 
         [0011]    Additional features of the present invention include a provision for positioning the catheter in the vasculature over a monorail type guide wire. Also, a fluid flow controller can be provided to meter fluid flow from the source into the central lumen of the catheter at a selected fluid pressure. 
         [0012]    Within the context of the present invention, several structural variations are envisioned that will facilitate the infusion of biologics into the vasculature of a patient. These variations can also enhance the diffusion and retention rate of the stem cells, drugs, proteins, or particles by the heart. These include: 1) the creation of a recollection chamber at the distal end of the catheter for establishing a safe and effective fluid infusion velocity for the biologics; 2) the orientation of the proximal (upstream) surface of a separator that will promote separation of biologics from each other prior to their infusion; and 3) an inflatable balloon that will coordinate and control blood flow through the vasculature in cooperation with the infusion of biologics. One additional variation is the use of a butterfly catheter in place of the catheter disclosed previously. 
         [0013]    A recollection chamber used during an intravenous or an arterial infusion is provided at the distal end of the catheter and is created by positioning the separator in the central lumen of the catheter at a distance “d” from the distal end of the catheter. With this positioning, the recollection chamber will be substantially tubular, it will have a length “d”, and it will have a diameter the same as that of the central lumen. It should be noted that the valve, or balloon, does not extend to this location near the distal end of the catheter. 
         [0014]    Insofar as structural variations of the separator are concerned, in an alternate embodiment of the separator disclosed above, the proximal (upstream) surface is slanted at an angle “α” relative to the axis of the catheter. Preferably, the angle “α” will be around 60°, with a consequence that the lumens established by the separator will have different lengths. In one version, the proximal (upstream) surface of the separator will be flat, with the entrance to each lumen angled at the angle “α” from the axis of the catheter. In another version, this surface will have a stepped configuration so that the entrance to each lumen will be perpendicular to the axis of the catheter. For both versions, the distal (downstream) surface of the catheter will be perpendicular to the axis of the catheter. 
         [0015]    In combination, the separator and the recollection chamber function to promote and maintain the separation of biologics as they are being safely infused. In particular, the recollection chamber slows the fluid velocity rate of the infusion fluid, after it has been accelerated through the separator. To further maintain safe fluid flow through the vasculature, an inflatable balloon can be attached to the outer surface of the catheter and it can be selectively inflated to coordinate the respective rates of blood flow and fluid infusion. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which: 
           [0017]      FIG. 1  is a schematic/perspective view of the system of the present invention shown with the system catheter positioned in an operational environment; 
           [0018]      FIG. 2  is a cross section view of the separator and distal portion of the system catheter as seen along the line  2 - 2  in  FIG. 1 ; 
           [0019]      FIG. 3  is a cross section view of an alternate embodiment of the infusion tip as seen along line  2 - 2  in  FIG. 1 ; 
           [0020]      FIG. 4  is a cross section view of an alternate embodiment of the infusion tip shown in  FIG. 3 ; 
           [0021]      FIG. 5A  is a plan view of the balloon of the present invention in a deflated configuration and shown with the catheter positioned in an operational environment; 
           [0022]      FIG. 5B  is a plan view of the balloon of the present invention in an inflated configuration and shown with the system catheter positioned in an operational environment; and 
           [0023]      FIG. 6  is a plan view of the butterfly catheter for the present invention. 
       
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0024]    Referring initially to  FIG. 1  a system for introducing (infusing) a fluid in accordance with the present invention is shown and is generally designated  10 . As shown, the system  10  includes a catheter  12  that can be advanced into a vessel  14  to position the catheter  10  at a predetermined location in the vasculature of a patient (not shown). For the purposes of the present invention, the vessel  14  is preferably an artery or a vein in the cardiovascular system of a patient, and the system  10  is used for an intra-arterial, intravenous or intracoronary protocol. 
         [0025]    In detail,  FIG. 1  shows that the system  10  includes a source  16  for holding a fluid medium  18 . As also shown in  FIG. 1 , a plurality of particles  20  are suspended in the fluid medium  18  to create a particle/fluid medium  22 . For the present invention, the particles  20  may be some form of a drug or, most likely, they will be some form of a biologics (i.e. cell, gene or protein). In any event, the particles  20  will be suspended in the particle/fluid medium  22  for transport from the source  16  through the system  10  and into the vessel  14 . As mentioned above for the system  10 , the source  16  can be a syringe of a type well known in the pertinent art.  FIG. 1  also shows that the system  10  includes a controller  24  that is in fluid communication with the source  16 . As envisioned for the present invention, the controller  24  can be any type device that is known in the pertinent art for moving a fluid (e.g. the particle/fluid medium  22 ) through a fluid flow system (e.g. system  10 ). In general, such a device may be an IV pump, an IV pole, a syringe, or some other fluid flow metering apparatus. For an embodiment of the system  10  wherein the source  16  is a syringe, however, there is no specific need for a controller  24 . 
         [0026]      FIG. 1  also shows that the system  10  includes an inflator  26  for a purpose to be discussed below. When both the controller  24  and the inflator  26  are used for the system  10 , they can be individually joined at a connector  28  to, respectively, establish separate fluid communication channels with the catheter  12 . Preferably, as shown, this connector  28  is connected in fluid communication with the proximal end  30  of the catheter  12 . 
         [0027]    Still referring to  FIG. 1 , it is seen that the system  10  includes a tip (filter)  32  (hereinafter sometimes also referred to as a separator  68 ) that is affixed to the distal end  34  of the catheter  12 . Further, it is seen that a valve  36  is mounted on the catheter  12  proximal the distal end  34 , and that the valve  36  is formed with a plurality of apertures, of which the apertures  38   a  and  38   b  are exemplary. The actual construction of the distal portion of the catheter  12 , and the cooperation of structure between the separator  68  and the valve  36  will perhaps be best appreciated with reference to  FIG. 2 . 
         [0028]    Referring to  FIG. 2 , and with specific reference to the separator  68 , it will be seen that the separator  68  is formed with a plurality of lumens, of which the lumens  40   a,    40   b,  and  40   c  are exemplary. More specifically, the lumens extend axially through the separator  68  and are substantially parallel to each other. They are also substantially parallel to the axis  42  that is generally defined by the catheter  12 . Importantly, each lumen is established with a diameter  44  that is specifically dimensioned to receive only individual or small groups of particles  20 . Although each lumen can receive several de-flocculated particles  20  at a time, the individual particles  20  or small groups of particles remain separated while they transit the lumen (e.g. see lumen  40   a ). Further, the separator  68  can be formed with a monorail lumen  46  that will interact with a guide wire  48 , in a manner well known by the skilled artisan, for the purpose of positioning the catheter  12  within the vessel  14 . 
         [0029]    With the structure of the separator  68  in mind, as described above, it is an important aspect of the present invention that the diameter  44  of each lumen be dimensioned to prevent the entry of large groups of flocculated particles  20  into the lumen from the central lumen  50  of the catheter  12 . In particular, for different therapeutic protocols, it may be very necessary that the particles  20  be dispersed as they enter the vessel  14 , to thereby minimize the possibility of subsequent flocculation in the vessel  14 , which may lead to heart attack or stroke if the cells are infused into the coronary circulatory system. 
         [0030]    Recall, the valve  36  is formed with a plurality of apertures. Further, with cross reference to  FIG. 1  and  FIG. 2 , it will also be appreciated that, when inflated, the valve  36  is generally shaped as an annulus and is formed with an inflation chamber  52 . As shown, the inflation chamber  52  is connected in fluid communication with the inflator  26  via an inflation line  54 . Within this structure, the inflation line  54  can be integrated into the catheter  12 . For operational purposes, the valve  36  includes a valve body  56  that is made of a compliant, inflatable material. The valve  36  also includes a rim  58  made of a substantially non-compliant material that is located on the periphery of the annulus shaped valve  36 . For the system  10 , the valve  36  is located proximal to the separator  68 , and it is affixed to the outer surface  60  of the catheter  12  by any means known in the pertinent art, such as by gluing or bonding. 
         [0031]    Operationally, the valve  36  (balloon) starts from a deflated configuration, and it is then inflated by the inflator  26  into a base configuration (see  FIGS. 1 and 2 ) wherein the valve  36  is constrained by the rim  58 . In this base configuration, the valve  36  will extend from the surface  60  of catheter  12  through a radial distance  62  and, in the base configuration, it will most likely make contact with the vessel  14 . Also, in the base configuration, each aperture (e.g. aperture  38   a ) will have a diameter  64 . With an additional inflation of the valve  36  by the inflator  26 , however, two different structural consequences occur. For one, the rim  58  does not expand from the base configuration. Thus, the radial distance  62  remains substantially constant. For another, the valve body  56  will expand in response to the inflator  26  such that the apertures are incrementally constricted. Stated differently, and with specific reference to the aperture  38   a,  the diameter  64  will be diminished. In an alternate embodiment for the present invention, there may be no need for the valve  36 . 
         [0032]    For an operation of the system  10  in an intra-arterial, intravenous or intracoronary protocol, a guide wire  48  is first prepositioned in the vasculature of a patient. The guide wire  48  is then received into the monorail lumen  46  of the catheter  12 , and the catheter  12  is advanced over the guide wire  48  and into position in the vasculature of the patient. Once the catheter  12  has been properly positioned, the valve  36  is inflated into its base configuration, or beyond. The exact extent of inflation for valve  36  will depend on the desired flow rate for fluid through the apertures in the vessel  14 . With the valve  36  inflated, the controller  24  is then activated to cause a flow of particle/fluid medium  22  from the source  16  and through the central lumen  50  of the catheter  12 . As particles  20  in the particle/fluid medium  22  arrive at the separator  68 , the respective diameters  44  of individual lumens in the separator  68  allow only individual particles  20  or small groups of particles  20  to enter the lumen. Thus, the flocculation of particles  20  in the central lumen  50  is disrupted, and flocculation of the particles  20  after they have passed through the separator  68  is minimized. Although the above discussion has focused on applications of the system  10  within the cardiovascular system of a patient, the system  10  is appropriate for any use wherein particles  20  may be suspended in a particle/fluid medium  22  for subsequent release as individual particle  20  into a fluid flow (e.g. blood flow through a vessel  14 ). 
         [0033]    Referring to  FIG. 3 , an infusion tip for biologics is shown and generally is designated  66 . In this embodiment, a separator  68 ′ is located in the central lumen  50  of the catheter  12  at a distance “d” from the distal end  34  of the catheter  12 . As so located, the separator  68 ′ creates a recollection chamber  70  having a length “d” at the distal end  34  of the catheter  12 . Specifically, the recollection chamber  70  is a tubular section formed onto the distal end  34  of the catheter  12 . If necessary, the recollection chamber  70  may be established by a stand-alone piece of tubing that can be attached to the distal end  34  of the catheter  12 . 
         [0034]    Still referring to  FIG. 3 , it is seen that the separator  68 ′ has a proximal (upstream) surface  72  and a distal (downstream) surface  74 . In detail, the proximal surface  72  of the separator  68 ′ is oriented at a slant angle “α” relative to the axis  42  of the catheter  12 . The distal surface  74  of the separator  68 ′, however, is perpendicular to the axis  42 , and it is substantially flat. Keeping in mind the structure disclosed above, a consequence of the slanted proximal surface  72  is that the proximal end of each lumen  76   a - c  will also be slanted at angle “α” relative to the axis  42  of catheter  12 . Consequently, when fluid flows through the catheter  12  and encounters the slanted proximal surface  72  of the catheter  12 , it is redirected to flow through the lumens  76   a - c  of the separator  68 ′. In operation, this redirection helps prevent particles  20  in the fluid from flocculating prior to entering the vasculature of the patient. Upon exiting the lumens  76   a - c  of the separator  68 ′, the fluid enters the recollection chamber  70  where it is allowed to slow down before entering the vasculature of the patient. 
         [0035]    For embodiments shown in  FIGS. 3 and 4 , the guide wire exit lumen  78  is formed onto the catheter  12  at a location approximately 25-30 millimeters proximal the separator  68 ′ and  68 ″. 
         [0036]    Referring now to  FIG. 4 , a variation of the infusion tip  66 ′ is shown wherein the proximal surface  72  of the separator  68 ″ is formed with a step configuration. Due to the step configuration, the proximal end of each lumen  80   a - c  remains substantially perpendicular to the axis  42  of the catheter  12 . Thus, in all important respects, the infusion tips  66 ,  66 ′ shown in  FIGS. 3 and 4 , respectively, are the same with the exception that the proximal surfaces differ. It should be noted that the proximal surface  72  of the separator  68  can also take the shape shown in  FIG. 2  for the separator  32 / 68 . 
         [0037]    Referring now to  FIG. 5A  and  FIG. 5B , a selectively inflatable balloon  82  is shown attached to the catheter  12  at a location proximal the separator  68 . When inflated as shown in  FIG. 5B , the balloon  82 ′ controls the flow rate of blood around the catheter  12  by expanding radially away from the catheter  12  towards the vessel wall  84 . As envisioned for the present invention, the flow rate of the blood outside the catheter  12  should be compatible with the flow rate of fluid inside the catheter  12  in order to minimize turbulence at the distal end  34  of the catheter  12 . In any event, the overall objective for the recollection chamber  70  and the inflatable balloon  82  is to decrease the probability of damage or injury to the vasculature of the patient during an infusion by decreasing the flow rate of blood to allow particles additional time to diffuse and to travel through blood vessels and into the tissue to be treated. 
         [0038]    Referring now to  FIG. 6 , it is to be appreciated that an infusion tip  66  in accordance with the present invention can be employed in a butterfly catheter  86  of a type that is well-known in the pertinent art. If a butterfly catheter  86  is used, the infusion tip  66  will be essentially the same as disclosed above for other embodiments. The advantage here is that, in appropriate situations, the butterfly catheter  86  may be secured to the patient prior to the release of fluid from the fluid source  16 . For example, the wings  90   a - b  are secured to the patient prior to the release of fluid  18  from the fluid source  16 . In all other important respects, the operation of the butterfly catheter  86  with the infusion tip  66  of the present invention is identical to the operation disclosed previously. 
         [0039]    While the particular Infusion Catheter Tip for Biologics as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.