Abstract:
An applicator for dispensing a first and second component of a biological adhesive, such as fibrin glue. At least one of said components may contain a suspension of fibrin microbeads (FMB) or a suspension of cells. The present invention uses a single supply of pressurized gas to force the components from the applicator using positive fluid pressure and to atomize them into a convergent spray. Another embodiment of the present invention also provides for the endoscopic application of the biological adhesive directly to tissue defects. The application of positive pressure allows precise metering of the components and application of the adhesive, prevents internal coagulation of the fibrin or clogging by suspended particles and reduces waste and contamination of the components.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    I. Field of the Invention  
           [0002]    The invention relates generally to a device and method for dispensing two discrete, chemically reactive components, such as fibrinogen and thrombin as either a convergent spray or in droplet form. More specifically, the instant invention is directed to a spraying apparatus and method for dispensing fibrin sealant containing particles in either spray or droplet form, to tissues, organs, wound sites, or prosthetic devices.  
           [0003]    II. Description of Related Art  
           [0004]    Fibrinogen mixed with thrombin forms fibrin, a unique biomaterial. In circulating blood, fibrin is critical for establishing normal hemostasis. The clinical utility of virally inactivated fibrin glue from pooled blood plasma is based upon its ability to effectively induce hemostasis and tissue bonding, in addition to being biodegradable and generally non-immunogenic.  
           [0005]    Fibrin glue is formed by mixing two components, human fibrinogen (or a source of fibrinogen, such as freeze-dried plasma protein concentrate of fibrinogen/factor XIII) and an activating enzyme such as thrombin. Prior to use, the lyophilized protein concentrates are conventionally solubilized by adding water. Alternately, these components may be stored frozen and thawed prior to use. Thrombin-induced activation of fibrinogen results in the formation of fibrin. Factor XIII and calcium participate in the cross-linking and stabilization of fibrin to become a tight mesh of polymeric fibrin glue. Applied to tissue, the fibrin clot adheres to the site of application. The rate of coagulation and mechanical properties of the clot are dependent on the concentration of fibrinogen as well as thrombin. Traditional fibrin glue preparations are described in International Application No. WO93/05067 to Baxter International, Inc.; WO92/13495 to Fibratek, Inc.; and U.S. Pat. No. 5,607,694, (Marx, G., Biologic Bioadhesive Compositions Containing Fibrin Glue and Liposomes, Methods of Preparation and Use, Issued Jul. 29, 1997 which is hereby incorporated by reference).  
           [0006]    Fibrin can also be transformed into other potent tools for cell culturing and tissue engineering. For example, fibrin has been described as a permeable, visco-elastic matrix useful for organ cultures (Marx G, Methods for Tissue Embedding and Tissue Culturing, U.S. Pat. No. 5,411,885 issued May 2, 1995 which is hereby incorporated by reference). Based on fibrin&#39;s positive interactions with numerous cell types, fibrin microbeads (FMB) have been developed as a cell-culture matrix useful for culturing many types of mesenchymal cells to high density (Gorodetsky, R., et al. J. Lab. Clin. Med. 131: 269-280 (1998) and Marx G, et al., Fibrin Microbeads Prepared from Fibrinogen, Thrombin and Factor XMII, U.S. Pat. No. 6,150,505, issued Nov. 21, 2000, which is hereby incorporated by reference). When cells bound to FMB suspended in fibrinogen are applied to tissue, the result is like a “liquid tissue” which may be used for regenerating skin, bone, and other tissue in situ.  
           [0007]    However, because fibrinogen and thrombin are mutually reactive, have different viscosities, react efficiently with each other according to precise ratios, and are relatively precious commodities, complicated fibrin applicators have been developed that attempt, to varying degrees, and with limited success to address the need for an applicator that accommodates these characteristics.  
           [0008]    Furthermore, the delivery of FMB or particles suspended within fibrinogen has proven particularly difficult. Given the several potential uses of FMB including as drug delivery systems, as vehicles for growing and transplanting cultured cells, and to promote wound healing, the incorporation of FMB delivery with the convergent application of the two components of fibrin glue requires an applicator that can deliver particles in suspension with the same accuracy and reliability as fibrinogen or thrombin alone. Such fibrin applicators are still lacking.  
           [0009]    A few types of dual-channel applicators have been developed to deliver fibrin glue. Most designs have been based on a dual-syringe system wherein needles are used to extract the fibrinogen and thrombin solutions from vials. The vials and needles are discarded, and the loaded syringes are assembled into a unit docked onto a dual-cannula head. The twinned syringe plungers are then actuated with the thumb, and the twin streams of fibrinogen and thrombin are expelled as liquids which mix, either within the head or external to it. U.S. Pat. No. 4,354,049 to Redl et al., and U.S. Pat. No. 5,582,596 to Fukunaga et al. are examples of such applicators. Fukunaga et al. also teaches using an additional source of air to atomize the dual-liquid channels into a spray. Some variants of this utilize a dual-point head to form an atomized spray from thumb or trigger actuated syringes. U.S. Pat. No. 5,759,171 to Coelho et al. is an example of such an approach. Other applicators are operated by mechanically actuated atomizers such as those used in conventional spray pumps. U.S. Pat. No. 4,902,281 to Avoy uses such an approach wherein two pump-style atomizers are loaded with fibrinogen and thrombin and convergently aimed.  
           [0010]    These approaches tend to suffer from clogging or the inability to deliver suspended particles. Also, the applicators of the prior art suffer from inconvenient loading, leakage, and inadequate mechanical control of delivery volume.  
           [0011]    Still other designs utilize a positive gas and vacuum pressure to actuate or augment the delivery mechanism such as U.S. Pat. Nos. 6,007,515 and 6,063,055 to Epstein et al. Some designs rely upon a source of compressed gas to draw the fibrinogen and thrombin from separate reservoirs using the Bernoulli principle such as U.S. Pat. No. 6,059,749 to Marx. These designs also suffer from inconvenience of loading reservoirs and are highly complex from the standpoint of having many parts or circuitous fluid pathways that may not be appropriate for delivering very viscous solutions, or solutions containing suspended particles such as FMB.  
           [0012]    Therefore, what is needed is a mechanically simple applicator with unhindered liquid pathways for efficiently delivering precise ratios of fibrinogen and thrombin with suspended particles to form on surface or internal wounds, a fibrin matrix containing such particles.  
         SUMMARY OF THE INVENTION  
         [0013]    The present invention provides an applicator for delivering a homogeneous coating of a biological substance such as fibrin glue formed of two components, for example, fibrinogen and thrombin solutions carrying a suspension of FMB or cells. The applicator of the present invention provides: (a) a first hermetically scaled reservoir containing the first component; (b) a second hermetically sealed reservoir containing the second component; (c) a means for applying positive fluid pressure to each of the first and second reservoirs; (d) a first outlet conduit to carry the first component to an atomizer; and (e) a second outlet conduit to carry the second component to an atomizer; wherein pressure applied to the first and second reservoirs generates a convergent flow of the first and second components, resulting in a homogeneous coating applied to a surface.  
           [0014]    The present invention also provides a method for delivering a homogeneous spray coating of a biological substance such as fibrin glue formed of two components such as fibrinogen and thrombin onto a target surface, such as human tissue. The method of the present invention comprises: (a) pressurizing a first reservoir containing one of said two components thereby biasing the component to flow from a first outlet conduit; (b) pressurizing a second reservoir containing the other of said two components thereby biasing the component to flow from a second outlet conduit; (c) atomizing the flows of the first and second component and (d) orienting the first and second outlet conduit so that the atomized flows of the components intermix to form the biological substance during deposition thereof.  
           [0015]    The present invention further provides an applicator for delivering a biological substance such as fibrin glue formed of droplets of two components such as fibrinogen and thrombin solutions carrying a suspension of FMB or cells which mix immediately after exiting the applicator. The applicator of the present invention provides: (a) a first hermetically sealed reservoir containing the first component; (b) a second hermetically sealed reservoir containing the second component; (c) a means for applying positive fluid pressure to each of the first and second reservoirs; (d) a first outlet conduit to carry the first component to a first channel of a dual-cannula head; (e) a second outlet conduit to carry the second component to a second channel of a dual-cannula head; wherein pressure applied to the first and second reservoirs generates a convergent flow of the first and second components, resulting in a spray application of the biological substance.  
           [0016]    The present invention still further provides a method for delivering a biological substance such as fibrin glue formed of droplets of two components such as fibrinogen and thrombin solutions carrying a suspension of FMB or cells which mix immediately after exiting the applicator. The method of the present invention comprises: (a) pressurizing a first reservoir containing one of said two components thereby biasing the component to flow from a first out let conduit; (b) pressurizing a second reservoir containing the other of said two components thereby biasing the component to flow from a second outlet conduit; (c) directing said first and second component respectively into a first and second channel of a dual cannula head oriented to produce a convergent flow of the first and second components, resulting in a topical droplet application of the biological substance.  
           [0017]    Accordingly, it is an object of the present invention to provide an applicator that can reliably deliver two components of a biological adhesive at precise ratios whether or not the components carry a suspension of particles.  
           [0018]    It is a further object of the present invention to provide a method for applying fibrin glue whereby FMB or cells become incorporated into a fibrin matrix as the fibrinogen and thrombin are combined as a spray to coat a target.  
           [0019]    It is a further object of the present invention to provide a method for applying a fibrin matrix whereby FMB or cells become incorporated into a fibrin matrix formed as the fibrinogen and thrombin are combined as a mixed fluid applied topically (endoscopically) to a targeted wound area. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]    [0020]FIG. 1 is an isometric view of a preferred embodiment of the dual spray applicator of the present invention.  
         [0021]    [0021]FIG. 2 is a partially exploded view of the embodiment FIG. 1.  
         [0022]    [0022]FIG. 3 a  is a plan view of the atomizing carburetor of the present invention.  
         [0023]    [0023]FIG. 3 b  is a cross-section view of the outlet of the carburetor.  
         [0024]    [0024]FIG. 3 c  is a longitudinal cross section view of the carburetor.  
         [0025]    [0025]FIG. 4 is an isometric view of another preferred embodiment of the spray applicator of the present invention.  
         [0026]    [0026]FIG. 5 is a partially exploded view of the embodiment of FIG. 4.  
         [0027]    [0027]FIG. 6 is a partial cross-section view of the spray head of FIG. 5.  
         [0028]    [0028]FIG. 7 is a partial cross-section view of an endoscopic delivery head attached to the body of the applicator.  
         [0029]    [0029]FIG. 8 is an example of methylene-blue stained FMB sprayed in fibrin by an applicator based on FIGS.  1  or  4  onto a flat surface.  
         [0030]    [0030]FIG. 9 is a cross-section side view of an alternate embodiment of the present invention incorporating an inverted reservoir mount.  
         [0031]    [0031]FIG. 10 is a partial cross-section view of the inverted reservoir mount of FIG. 9 showing both reservoirs.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0032]    Referring to FIG. 1, an applicator  100  according to one embodiment of the present invention is shown. The applicator  100  consists generally of main body  10 , having a spray head  20  attached at a distal end and a pressure inlet  30  attached at a proximal end thereof. Reservoirs  40   a  and  40   b  are shown attached to main body  10  at a lower surface thereof. Spray head  20  has faces  26   a  and  26   b  at a distal end thereof that receive atomizers  24   a  and  24   b  respectively. A bifurcated tap  14  and flow rate valves  17   a  and  17   b  on an upper surface of main body  10  are connected by feed lines  16   a  and  16   b.  Connection taps  18   a  and  18   b  are connected to atomizers  24   a  and  24   b  respectively by feed lines  19   a  and  19   b.  These components, described in greater detail below, are preferably made of medical grade material such as metal or plastic, however it is to be understood that other suitable materials may be used.  
         [0033]    As described below, a first series of interconnected conduits defining a first fluid passage extends from pressure inlet  30  through main body  10  to spray head  20 . With reference to FIG. 2, pressure inlet  30  is attached to main body  10  as by a threaded or press-fit connection (not shown) and has coaxial bore  32  disposed therein. Main body  10  has a main bore  12  therein that is in fluid communication with coaxial bore  32  and extends through main body  10  to its distal end.  
         [0034]    Spray head  20  is connected to main body  10  as by fasteners such as screws or may have interlocking components that may be press fit (not shown). Divergent bores  22   a  and  22   b  are in fluid communication with main bore  12  at a proximal end of spray head  20  and extend therethrough, terminating at atomizers  24   a  and  24   b  respectively thereby establishing a fluid passage between the atomizers and pressure inlet  30 .  
         [0035]    A second series of interconnected conduits defining a second fluid passage connects pressure inlet  30  to reservoirs  40   a  and  40   b  and therethrough individually to spray head  20 , the components associated with reservoir  40   b  shown in an exploded view. Specifically, bifurcated tap  14  located on a top surface of the main body  10  is in fluid communication with main bore  12 . Feed lines  16   a  and  16   b,  such as flexible hoses, establish fluid communication between bifurcated tap  14  and valves  17   a  and  17   b  respectively. Valve  17   b  in turn is in fluid communication with the interior of reservoir  40   b  via an inlet conduit  42  such as a hollow needle or luer connection. Likewise, valve  17   a  is in fluid communication with reservoir  40   a  via a similar inlet conduit (not shown). Valves  17   a  and  17   b  may be flow rate valves such as those well known in the art which selectively permit manual adjustment of fluid flow therethrough, or any other means appropriate to regulating fluid flow.  
         [0036]    Outlet conduit  44  extends from the interior of reservoir  40   b  where it is in fluid communication with the contents  46  of reservoir  40   b  which are preferably either fibrinogen or thrombin and may include FMB or cells. Outlet conduit  44  terminates at connection tap  18   b.  A similar outlet conduit (not shown) extends from the interior of reservoir  40   a  where it is in fluid communication with the contents thereof and terminates at connection tap  18   a.  The outlet conduits may be of a luer connection type such as that of the inlet conduit  42 , or a submersible tube or large-bore needle. Thus, the second fluid link incorporates the interior of reservoirs  40   a  and  40   b.    
         [0037]    Feed lines  19   a  and  19   b  extend the second fluid link from the connection taps  18   a  and  18   b  respectively to atomizers  24   a  and  24   b  respectively of spray head  20 . Atomizers  24   a  and  24   b  have a similar construction, FIG. 2 providing an exploded view of the components of atomizer  24   b.  Nozzle  50  is generally frusto-conical having tip  58  and annular base  52 . Aperture  56  is a bore which extends through tip  58  through frusto-conical nozzle  50 . Carburetor  60  is generally cylindrical and is provided with circular face  70  and annular shoulders  62  and  64  which receive o-rings  66  and  68 .  
         [0038]    Carburetor  60  is shown in greater detail in FIGS. 3 a - 3   c.  In FIG. 3 a,  annular shoulders  64  and  62  are shown on either side of annular propellant channel  63  having a plurality of propellant bores  72  therein. Mounting step  65  is preferably a cylindrical ledge shown having a cross-section defining face  70  at one axial end thereof and terminating at a back stop  67  larger in diameter. Needle  75  is shown protruding from face  70 . FIG. 3 b  shows face  70  having a plurality of propellant bores  72  and discharge bore  74 . FIG. 3 c  is a cross-section view of carburetor  60  illustrating one of propellant bores  72  which extend axially from propellant channel  63  to face  70 . Discharge bore  74  extends axially through the carburetor  60  and comprises intermediate bore  76  and inlet bore  78 . Needle  75 , which ideally has a bore between  16  and  27  gauge, is shown press-fit into and extending along discharge bore  74  terminating at intermediate bore  76 . Due to the larger diameter of inlet bore  78  relative to intermediate bore  76 , the interface therebetween creates annular ridge  77 .  
         [0039]    As shown in FIG. 2, spray head  20  has bore  23  having a diameter sufficient to receive carburetor  60 . When assembled into spray head  20  as shown in FIG. 6, the carburetor  60  is inserted into bore  23  such that the o-rings  66  and  68 , which are preferably formed of resilient material such as viton, butyl rubber or similar medical-grade material, seal against the bore  23 . In place within bore  23 , rings  66  and  68  cooperate to form a sealed chamber linking propellant channel  63 , and propellant bores  72 , with bore  22   b.  Needle  75  has an axial bore ideally between  16  and  27  gauge and is press fit into discharge bore  74 . Nozzle  50  is attached to carburetor  60  as by a press fitting annular base  52  onto mounting step  65  up to back stop  67 . Thus, nozzle  50  forms aerosol chamber  59  when fitted over carburetor  60 . Union  80   b  is shown angled to be parallel with the centerline of the sprayer, facilitating removable mounting of head  20  onto the sprayer.  
         [0040]    As shown in FIG. 2, union  80   b  has axial bore  86  that communicates with feed line  19   b  which is attached at flange  88 . Union  80   b  also has flange  82  which is inserted into inlet bore  78  (FIG. 3 c ) and secured to carburetor  60  as by a press-fitting into inlet bore  78 . Seal  84 , such as a silicone washer, seals the union  80   b  to the carburetor  60 . Union  80   a  is similarly inserted into the carburetor (not shown) of atomizer  24   a.    
         [0041]    Atomizers  24   a  and  24   b  are understood to have similar constructions as described above from union  80   b  to nozzle  50  and are attached to faces  26   a  and  26   b  of spray head  20  respectively as shown in FIGS. 2 and 6. Faces  26   a  and  26   b  are angularly offset relative to each other at an angle shown in FIG. 1 as C such as 194° so that the axes of atomizers  24   a  and  24   b  intersect externally to applicator  11  at an angle, for example of 14°, that defines the focal point of the applicator during use as described in detail below. Thus, a second fluid passage is established between the atomizers  24   a  and  24   b  and pressure inlet  30 .  
         [0042]    Reservoirs  40   a  and  40   b  are hermetically sealed to the main body  10  by a docking mechanism such (not shown). The docking mechanism may be a threaded or bayonet-type connection sealed with medical grade neoprene or butyl rubber, or any other suitable means for establishing a hermetic seal to prevent the escape or contamination of the contents of the reservoirs  40   a  and  40   b.  The dock mechanisms should also be able to prevent leakage of fluid pressure from the interior of the reservoirs to the ambient atmosphere. One such dock mechanism is described in detail below.  
         [0043]    During operation, a source of fluid pressure, shown in FIG. 2 as P, preferably clean compressed gas, is supplied to pressure inlet  30 . Preferably, the pressure source is provided with a means for selectively interrupting the flow of gas into pressure inlet  30 , such as a trigger valve commonly known in the art to permit the pressure to be controlled by the user&#39;s finger or thumb. The source may also be self-contained, such as in the form of a small pressurized gas cannister also well known in the art.  
         [0044]    When the compressed gas enters the pressure inlet  30 , it flows simultaneously through the two fluid passages defined above. Specifically, after passing through coaxial bore  32 , to main bore  12  and through divergent bores  22   a  and  22   b  to the respective carburetors  60  of atomizers  24   a  and  24   b,  the gas is directed into propellant channel  63  by the seal created by w-rings  66  and  68  against bore  23  (FIG. 6). Thus, the compressed gas exits the carburetor via propellant bores  72  into aerosol chamber  59  and into the ambient environment through aperture  56  in nozzle  50  of both atomizers  24   a  and  24   b  simultaneously, according to the first fluid passage defined above.  
         [0045]    Ideally, the source of compressed gas is at a sufficiently high pressure, and the divergent bores  22   a  and  22   b  or other bores in the first fluid passage have a sufficiently small diameter that a significant positive back-pressure relative to the ambient environment is maintained in main bore  12 . The positive back-pressure drives a fraction of the compressed gas to flow from main bore  12  into bifurcated tap  14  and from there through feed lines  16   a  and  16   b  to valves  17   a  and  17   b  respectively. Valves  17   a  and  17   b  are preferably adjustable flow rate valves that, when open, permit a variable fraction of the pressurized gas to flow into reservoirs  40   a  and  40   b  through inlet conduits such as  42 . Because reservoirs  40   a  and  40   b  are hermetically sealed, the flow of compressed gas into the reservoirs pressurizes the individual contents  46  of the reservoirs  40   a  and  40   b  relative to the ambient environment.  
         [0046]    The pressure thus applied to the contents of reservoirs  40   a  and  40   b  biases them to flow from the reservoirs through outlet conduits  44  to connection taps  18   a  and  18   b.  The outlet conduits  44  must be oriented to be in fluid communication with the contents  46  of reservoirs  40   a  and  40   b  respectively during use to ensure that compressed gas is not lost through the outlet conduits. Preferably, the outlet conduits  44  are submerged below the hydrostatic level of the contents when the applicator  100  is oriented for use. Feed lines  19   a  and  19   b  carry the contents from connection taps  18   a  and  18   b  respectively to unions  80   a  and  80   b  respectively through which the contents flow into discharge bore  74  of carburetors  60 . The respective contents  46  are then forced through the corresponding needles  75  resulting in a mixing of the contents with the streams of compressed gas in the aerosol chamber  59  wherein the contents  46  are atomized, issuing from apertures  56  of atomizers  24   a  and  24   b  thus spraying the respective atomized contents convergently as component streams A and B shown in FIG. 1. An example of methylene blue-stained FMB sprayed in fibrin from a sprayer based on the above embodiment onto a flat surface is provided in FIG. 8.  
         [0047]    Thus, the fibrin applicator of the present invention functions to automatically deliver and atomize the components of fibrin upon application of a single supply of compressed gas P. Selective actuation of the compressed gas supply as by a trigger means (not shown) provides a controllable application of fibrin.  
         [0048]    Valves  17   a  and  17   b  can be configured to deliver different volumes of components  46  from the applicator  100 . For example, by opening valve  17   b,  the volume of compressed gas introduced into the interior of reservoir  40   b  is increased, thereby increasing the pressure on component  46  relative to the ambient environment. Therefore, the wider valve  17   b  is opened, the greater the flow of component  46  to atomizer  24   b.  Conversely, closing a valve tends to restrict the flow of a component from a reservoir. In this manner, the applicator  100  can easily be configured to deliver a precise ratio of components  46  in reservoirs  40   a  and  40   b  relative to each other from the applicator during use. Alternatively, the ratio can be set by the relative diameters of needles  75  in cases where the applicator does not require frequent tuning. Although the rate of fibrin delivery of the applicator  100  is proportional to the magnitude of pressure of compressed gas P, the ratio of components to each other remains constant. This reduces the waste of a component due to application of a sub-optimal ratio of components.  
         [0049]    Furthermore, the configuration of the outlet conduits  44  and needles  75  the discharge tips  28   a  and  28   b  can be modified to facilitate the specific characteristics of components  46 . For example, in the case of fibrinogen carrying a suspension of FMB or cells, an outlet conduit with a bore compatible with the diameter of the microbead particle would preferably be selected. Likewise, a needle could be selected having a bore that easily accommodates the delivery of microbeads from the applicator without clogging the second fluid passage. Similarly, the portion of the second passage between the reservoirs  40   a,    40   b  and atomizers  24   a,    24   b  preferably avoids lengthy or labyrinthine paths that may result in sedimentation of suspended particles.  
         [0050]    Additionally, pinch valves (not shown) may be provided in feed lines  19   a  and  19   b  between connection taps  18   a,    18   b  and atomizer  24   a,    24   b,  respectively. The pinch valves such as those commonly available selectively interrupt the flow of fluids through the feed line  19   a  and  19   b,  respectively and are actuated by a control means such as a trigger mechanism or an electrically operated solenoid.  
         [0051]    During operation, the fibrin applicator  100  using pinch values functions in most respects as disclosed with respect to FIG. 2 above. Specifically, a pressurized fluid “P” such as a clean compressed gas is provided at pressure inlet  30 . The compressed gas is then distributed between atomizers  24   a  and  24   b  following the first fluid pathway shown in detail in FIG. 2, and to valves  17   a  and  17   b  respectively via bifurcated tap  14 , following the second fluid pathway.  
         [0052]    The result upon application of compressed gas “P” is a tendency for the components contained within reservoirs  40   a  and  40   b  to be forced from said reservoir and toward atomizers  24   a  and  24   b  simultaneously with the stream of compressed gas that atomizes the components. In the embodiment of FIG. 1, for example, the addition of pinch valves permits intermittent application of fibrin without interrupting the flow of pressurized gas from the atomizers thus ensuring complete expulsion of the fibrin components delivered to the atomizer. When applying fibrin glue with the applicator of the present embodiment, such pinch valves serve to ensure that none of the relatively precious components that make up the fibrin are wasted.  
         [0053]    [0053]FIG. 4 shows an alternate embodiment  200  of the fibrin applicator of the present invention. The applicator  200  consists generally of a main body  110  having a spray head  120  attached at a distal end and a pressure inlet  130  attached at a proximal end thereof. Reservoirs  140   a  and  140   b  are attached to main body  110  at a lower surface thereof. Spray head  120  has faces  126   a  and  126   b  at a distal end thereof that receives atomizers  124   a  and  124   b  respectively. Flow rate valves  115   a  and  115   b  on an upper surface of main body  110  are connected by feed lines  119   a  and  119   b  to atomizers  124   a  and  124   b  respectively. Pressure regulators  192  and  194  are formed in a side surface in main body  110  and spray head  120  respectively. As in the previous embodiments, these components are preferably made of medical grade material such as metal or plastic, however, other suitable material may be used.  
         [0054]    As shown in FIG. 5, a series of interconnected conduits defining a first fluid passage extend from pressure inlet  130  through main body  110  to spray head  120 . Pressure inlet  130  is attached to main body  110  as by a threaded or press-fit connection (not shown) and has co-axial bore  132  disposed therein. Main body  110  has a main bore  112  therein that is in fluid communication with co-axial bore  132  and extends through main body  110  to its distal end. Spray head  120  is connected to main body  110  as by fastener or press fit connection (not shown). Divergent bores  122   a  and  122   b  are in fluid communication with main bore  112  within spray head  120  and extends therethrough terminating at atomizers  124   a  and  124   b  respectively, thereby establishing a fluid passage between the atomizers and pressure inlet  130 .  
         [0055]    A second series of interconnected conduits defining a second fluid passage connects pressure inlet  130  to reservoirs  140   a  and  140   b  and therethrough individually to spray head  120 , the components associated with reservoir  140   b  shown in the exploded view in FIG. 5. Specifically, divergent bores  191   a  and  191   b  intercept at main bore  112  establishing fluid communication therewith within main body  110 . Bore  191   b  extends from main bore  112  and terminates at pressure regulator  192 . Bore  191   b  is also in fluid communication with the interior of reservoir  140   b  via an inlet conduit  142  such as hollow needle or luer connection. Likewise, bore  191   a  extends from main bore  112 , terminating at an inlet conduit in fluid communication with the interior of reservoir  140   a  (not shown). Thus, divergent bores  191   a  and  191   b  provide a direct connection between main bore  112  and the respective interiors of reservoirs  140   a  and  140   b.    
         [0056]    Outlet conduit  144  extends from the interior of reservoirs  140   b  where it is in fluid communication with the contents of  146  of reservoir  140   b  which are preferably either fibrinogen or thrombin and may include FMB or cells. The outlet conduit  144  is also preferably a hollow needle or luer connection. Outlet conduit  144  terminates at flow rate valve  115   b.  A similar outlet conduit (not shown) extends from the interior of reservoir  140   a  where it is in fluid communication with the contents thereof and terminates at flow rate valve  115   a.  The outlet conduits may be of a luer connection type similar to that of the inlet conduit  142  or a submersible tube or large bore needle. Flow rate valves  115   a  and  115   b  may be flow rate valves such as those well known in the art for permitting manual adjustment of fluid flow therethrough, or any other means appropriate to regulating fluid flow.  
         [0057]    Feed lines  119   a  and  119   b  extend the second fluid link from flow rate valve  115   a  and  115   b  respectively to atomizers  124   a  and  124   b  at spray head  120 . Atomizers  124   a  and  124   b  have a similar construction to that of the embodiment shown in FIG. 2, FIG. 5 providing an exploded view of the components of atomizer  124   b.  Specifically, nozzle  150  has tip  158  and base  152 . Aperture  156  extends through tip  158  and through nozzle  150 . Carburetor  160  is shown having a face  170  and shoulders  162  and  164  which receives o-rings  166  and  168 .  
         [0058]    As shown in FIG. 5, spray head  120  has bore  123  having a diameter sufficient to receive carburetor  160 . When assembled into spray head  120 , the carburetor  160  is inserted into bore  123  such that o-rings  166  and  168  seal against bore  123 . Thus, a sealed chamber is formed linking carburetor  160  with divergent bore  122   b.  The same structure comprises atomizer  124   a.    
         [0059]    Union  180   b  has bore  186  that communicates with feed line  119   b  which is attached at flange  188 . Union  180   b  also has flange  182  which is inserted into and sealed with carburetor  160 . Union  180   a  is similarly inserted into the carburetor (not shown) of atomizer  124   a.  Thus, a second fluid passage is established between the atomizer  124   a  and  124   b  and pressure inlet  130 .  
         [0060]    During operation, a source of fluid pressure, shown in FIG. 5 as P, preferably clean compressed gas having a means for selectively interrupting the flow of said gas is supplied to pressure inlet  130 . When the compressed gas enters pressure inlet  130 , it flows simultaneously through the two fluid passages defined above. Specifically, after passing through co-axial bore  132  to main bore  112  and through divergent bores  122   a  and  122   b  to the respective carburetors  160  of atomizers  124   a  and  124   b,  the gas is directed into and out of nozzle  150  from carburetor  160  through aperture  156 .  
         [0061]    Ideally, the source of compressed gas is at a sufficiently high pressure that a significant positive back pressure relative to the ambient environment is maintained in main bore  112 . The positive back pressure drives a fraction of the compressed gas to flow from main bore  112  into divergent bores  191   a  and  191   b  thereby pressurizing the interior of reservoir  140   a  and  140   b  respectively.  
         [0062]    Thus, the pressure applied to the contents of reservoirs  140   a  and  140   b  biases them to flow through outlet conduit  44  to flow rate valve  115   a  and  115   b.  When the valves are open, the respective contents flow from the reservoirs through feed lines  119   a  and  119   b  to unions  180   a  and  180   b  respectively, through which the contents flow into atomizers  124   a  and  124   b  resulting in a mixing of the contents with the compressed air flowing from carburetor  160  thus atomizing the respective contents convergently as component streams A and B having a focal point defined by angle C of faces  126   a  and  126   b  as shown in FIG. 4.  
         [0063]    Thus, the fibrin applicator  200  of the present embodiment functions automatically to deliver and atomize the components of fibrin upon application of a single supply of compressed gas P. In this embodiment however, the result is achieved with fewer parts, as divergent bores  191   a  and  191   b  eliminate the need for a bifurcated tap and the additional connection taps required in the embodiment of FIG. 1. Additionally, fibrin applicator  200  provides pressure regulator  192  at divergent bore  191   b  and pressure regulator  194  at divergent bore  122   b  which can be adjusted to ensure delivery of proper gas pressure to the first and second fluid paths respectively.  
         [0064]    Valves  115   a  and  115   b  can be configured to deliver different volumes of individual components  146  from the applicator  200 . For example, by opening valve  115   b,  the volume of the liquid expelled from reservoir  140   b  can be regulated relative to the flow of components through valve  115   a.  In this manner, the applicator  200  can be configured to deliver precise ratios of components  146 , thus reducing waste due sub-optimal delivery of components. As in he embodiment of FIG. 1, the component ratios can be set by varying the bore of needles  175  in case frequent tuning of the ratios is not required.  
         [0065]    The docking mechanism of the present invention is shown in detail in FIG. 5. Specifically, reservoir  140   b  is shown containing component  146  such as a suspension of FMB in fibrinogen, attached to main body  110 . Inlet conduit  142  and outlet conduit  144  are shown as hollow bores such as needles wherein outlet conduit  144  is shown submerged below the hydrostatic level of contents  146 , and inlet conduit  142  is shown above the hydrostatic level within void  147 .  
         [0066]    As discussed above, gas entering from divergent bore  191   b  into bore  147  through inlet conduit  142  displaces component  146 , forcing it out through outlet conduit  144 . The docking connection  148  between reservoir  140   b  and main body  110  must allow for both inlet conduit  142  and outlet  144  to pass into said reservoir  140   b  during insertion thereof onto main body  110 . At the same time, it is essential that a fluid-tight seal is maintained between the conduits, main body and reservoir to prevent compressed gas from escaping void  147  and exiting directly into the ambient atmosphere. Such a leak would result in an unpredictable amount of each component discharged during operation of the applicator, altering the ratio of components to each other and wasting component material. Although the structure of applicator  200  of FIGS. 4 and 5 has distinct advantages over applicator  100  of FIGS. 1 and 2 insofar as flow rate valve  115   a  and  115   b  are downstream from any leak of gas from reservoir  140   a  and  140   b,  thereby minimizing the effect of a minor pressure leak, a sufficient leak of gas from either reservoir through its docking connection  148  could result in insufficient pressure within reservoirs  140   a  and  140   b  to propel contents  146  through outlet conduit  144 .  
         [0067]    Docking connection  148  ideally comprises a union having a threaded connection such as that shown in FIG. 5. In the alternative, a resilient gasket material such as medical-grade rubber or silicon may be disposed between the main body  110  and reservoirs  140   a  and  140   b.  Further, reservoirs  140   a  and  140   b  may comprise a vial having at one end a self-sealing septum capable of removably receiving the inlet conduit  142  and outlet conduit  144  without breaking the seal between the interior of reservoirs  140   a  and  140   b  and the ambient environment. In such a configuration, inlet conduit  142  and outlet conduit  144  ideally share a single needle having two bores (not shown). In such a configuration the docking connection  148  could be disposed for example on the top surface of main body  110  allowing for inverted loading of the reservoirs.  
         [0068]    An example of such an inverted loading arrangement is shown in FIGS. 9 and 10. In FIG. 9, a single reservoir  440  of a dual reservoir system is shown as a vial having self-sealing septum  450  which removably receives an inlet conduit  442  and outlet conduit  444  which are shown in a dual needle configuration. In FIG. 9 body  410  is shown having frame  510  attached at an upper surface thereof for guiding reservoir  440  onto inlet/outlet conduits  442 / 444 . Pressure inlet  430  disposed at the rear of body  410  is in fluid communication with air passage  432  and extends to atomizer  424  via bore  412 .  
         [0069]    Inlet conduit  442  is a hollow needle having openings  443  and  445  at opposite ends thereof. Opening  443  is in fluid communication with air passage  432 . Likewise, opening  445  is in fluid communication with the interior  447  of reservoir  440 . Outlet conduit  444  is a hollow needle having opening  449  at one end thereof which is in fluid communication with the contents  446  of the reservoir  440 . Outlet conduit  444  extends from opening  447  through body  410  and terminates at a discharge orifice  475  within the air chamber defined by atomizer  424 .  
         [0070]    The dual reservoir arrangement of the present invention is more clearly shown in FIG. 10 where reservoirs  440   a  and  440   b  are shown prior to insertion onto dual inlet/outlet conduit needles  442   a/   444   a  and  442   b / 444   b  respectively. Each of reservoirs  440   a  and  440   b  may have a separate air passage associated with it, which feed gas individually to atomizers  424   a  and  424   b.  Frame  510  is shown attached to an upper surface of body  410  and spray head  420  is shown having atomizers  424   a  and  424   b.  A grip  520  may be attached a to a lower portion of body  410  for use in holding the body by hand.  
         [0071]    During operation, a source of fluid pressure, shown in FIG. 9 as P, preferably clean compressed gas having a means for selectively interrupting the flow of said gas, is supplied to pressure inlet  430 . When the compressed gas enters fluid passage  432 , it flows simultaneously through bore  412  and through inlet conduit  442  via opening  443 .  
         [0072]    Thus, as shown in FIG. 9, pressure is applied to the contents  446  of reservoir  440  via the introduction of gas into the interior  447  thereof. The contents  446  are thus biased to flow from reservoir  440  via outlet conduit  444  into atomizer  424 , where it mixes with compressed gas exiting from bore  412  dispersing contents  446  upon exit from atomizer  424 .  
         [0073]    The advantages of the docking system disclosed in FIGS. 9 and 10 include the ability to quickly load and exchange vials, the self-sealing design of which is commonly known in the medical arts. Similarly to the previous embodiments, the ratios of components  446   a  to  446   b  may be controlled by varying the diameters of inlet and outlet conduits  442  and  444  for each of reservoirs  440   a  and  440   b.  Additionally, bore  412  may be selectively narrowed to increase back pressure in air chamber  432  resulting in an increase flow of contents  446  from reservoir  440 . A separate adjustable valve at bores  412  associated with each of reservoirs  440   a  and  440   b  can also effectively adjust and achieve any desired component ratios.  
         [0074]    Depending on the configuration of the head, the device  200  of FIGS. 4 and 5 could deliver the fibrin either as a spray as described above or as a topically mixed liquid which coagulates upon mixing of the fibrinogen with the thrombin solution. FIG. 7 shows a detail of a dual-cannula endoscopic appliance mounted on spray head  120  wherein carburetor  160  having needle  175  is shown inserted within bore  123  of spray head  120 . To provide for endoscopic application of fibrin, nozzles  150  of atomizers  124   a  and  124   b  (FIG. 5) are shown replaced by endoscopic appliance  300 . Therefore, the fibrin applicators, for example, of FIGS. 1 and 4 can easily be converted for endoscopic use by removing the nozzles and installing endoscopic delivery appliance  300  as described below and shown in FIG. 7 with respect to the spray head embodiment of FIGS. 4 and 5.  
         [0075]    As shown with respect to carburetor  160 , endoscopic appliance  300  has bore  320  which receives mounting flange  165  of carburetor  160 , securing the endoscopic appliance  300  to spray head  120 . Annular gasket  330  is formed of a compressible, resilient material that seals propellant bores  172 . Bore  310   b  is in fluid communication with needle  175 . Bore  310   a  is similarly in fluid communication with the needle associated with atomizer  124   a  (FIG. 5), endoscopic appliance  300  engaging said needle and carburetor in a similar manner to that shown with respect to carburetor  160 , but blocking the atomizing gas discharge from orifice  172 , resulting in a bilateral structure terminating at endoscopic tip  340 .  
         [0076]    During operation, the fibrin applicator having endoscopic appliance  300  installed functions in a manner similar to that of the embodiment shown in FIGS. 4 and 5 insofar as the contents of each of the two reservoirs are delivered individually to head  120  by the force of a pressurized gas. Thus, the contents are expelled from head  120  (FIG. 7), and are propelled through bores  310   a  and  310   b.  In cases when fibrin glue is to be delivered directly to a tissue defect, an applicator head equipped with endoscopic appliance  300  permits a more precisely directed topical application of fibrin glue via tip portion  340 . In this configuration, the fibrin applicator delivers two discrete flows of fibrinogen and thrombin as droplets respectively from bores  310   a  and  310   b.  The fibrinogen and thrombin mix immediately after exiting their respective bores.  
         [0077]    When the fibrin applicator is used with endoscopic appliance  300 , (FIG. 7) compressed gas flowing through the first fluid passage defined by main bore  112  and the divergent bores  122   a  and  122   b  is prevented from escaping from propellent bore  172  such as that shown in carburetor  160  by annular gasket  330 , the carburetor being sealed with respect to divergent bore  122   b  by O-rings  166  and  168 . Thus, compressed gas is prevented from entering bores  310   a  and  310   b.    
         [0078]    Although this invention has been described in terms of certain preferred embodiments, other embodiments that are apparent to those of ordinary skill in the art are also intended to be within the scope of this invention. Accordingly, the scope of the present invention is intended to be limited only to the claims appended hereto.