SYSTEMS, DEVICES AND METHODS FOR DISPENSING BIOCOMPATIBLE REACTIVE FORMULATIONS AND CONTROLLING CROSS-LINKING OF THE REACTIVE COMPONENTS OF THE BIOCOMPATIBLE REACTIVE FORMULATIONS

A system for dispensing a biocompatible reactive formulation includes a first chamber containing a first fluid having a first reactive component, a second chamber containing a second fluid having a second reactive component, and a third chamber containing a third fluid. A spray tip assembly is configured for spraying a final mixture of the first, second and third fluids. The spray tip assembly has a spray tip housing, a mixing element disposed within the spray tip housing, a mixing chamber located between the mixing element and an inner surface of the spray tip housing. The mixing element has a proximal end adjacent the proximal end of the spray tip housing and a distal end adjacent the distal end of the spray tip housing, a third fluid inlet opening at the proximal end of the mixing element, and one or more third fluid exit openings formed in the outer surface of the mixing element that are in fluid communication with the third fluid inlet opening and that extend laterally to the outer surface of the mixing element for being in fluid communication with the mixing chamber. A fluid connector is secured to the proximal end of the spray tip housing and opposes the proximal end of the mixing element. The fluid connector has first and second fluid channels in fluid communication with the mixing chamber, and a third fluid channel in fluid communication with the third fluid inlet opening of the mixing element. A pump assembly is coupled with the first, second and third chambers for simultaneously forcing the first, second and third fluids to flow through the first, second and third fluid channels of the fluid connector and into the proximal end of the spray tip housing.

BACKGROUND OF THE INVENTION

Field of the Invention

The present patent application is generally related to biocompatible compositions used for sealing and hemostasis, and is more specifically related to systems, devices and methods for controlling the cross-linking of the reactive components of biocompatible reactive formulations.

Description of the Related Art

During a surgical procedure, incisions are created to access surgical sites. Once the surgical procedure has been completed, the incisions are closed for healing. In many instances, the incisions are closed with sutures or staples, however, tissue adhesives are also used for closing external incisions. In recent years, absorbable tissue adhesives have been developed for use in closing internal incisions.

Tissue adhesives and sealants include viscous gels that have little or no further curing after application, as well as compositions that solidify and/or cure once applied. Cyanoacrylates products such as Ethicon's Dermabond® and Covidien's Indermil® are examples of tissue adhesives that possess high strength and that cure in place. These materials polymerize to achieve the strength required, but do not offer the user any control over the time to curing. Without providing the ability to control of the degree of curing, they typically address only one clinical need, e.g., to close and hold incisions.

Other products such as Ethicon's synthetic Omnex™ and biological Evicel® and Cryolife's BioGlue® are examples of sealants that act to treat and prevent leakage. Once again, these materials typically address only one of the four clinical needs of acting as a sealant, acting as an adhesive, acting as a hemostatic agent, or acting as an adhesion preventing coating. The above-listed products do not offer the user the ability to change the performance characteristics to address different clinical needs.

Products such as Ethicon's Intercoat®, Genzyme's SepraGel®, Confluent's SprayGel®, and Covidien's SprayShield™, to name a few, are examples of adhesion barriers. These are either one of, or a combination of, hydrogels of PolyEthylene Glycol (PEG), Poly Vinyl Alcohol (PVA), CarboxyMethyl Cellulose (CMC), or HyaLuronic Acid (HLA). Once again, these materials typically only address one of the four clinical needs noted herein (e.g., to act as an adhesion prevention barrier), and do not provide users with the option to change the performance characteristics to address different clinical needs.

Although there may be some materials with properties mid-way between sealants and adhesion preventatives, their properties are not optimized for either application and they cannot be changed by the surgeon at the time of application during surgery. Many of the solutions that the art provides in the four areas of surgical adhesives, sealants, adhesion preventatives and hemostatic agents are based on cross-linkable systems. Initially, the product is flowable to allow application to a surgical site to be treated. After application, the product becomes non-flowable whereupon it stays in place to function properly.

The performance characteristics of the hydrogel products are intimately related to cross-link density. When cross-link density is high, mechanical strength is high and water swellability is low. High cross-link density hydrogels are often associated with products that function as adhesives. Sealants often require slightly less mechanical strength. As a result, hydrogel products in this category can have cross-link densities that are concomitantly slightly lower.

Finally, a class of surgical adhesion preventatives based on hydrogel technology is cross-linked at a much lower level than the other two product classes. Their lower cross-link density allows a greater amount of swellability leading to a very slippery behavior. This latter characteristic has been identified by some to contribute to the ability to prevent viscera from adhering to one another or the initiation of collagen deposition leading to adhesion formations. Likewise, clinically relevant properties of some hemostatic agents depend on the mixing ratios of components. For example, the mixing ratios of fibrinogen and thrombin alter the properties of the resulting matrix.

The above-identified products provide pre-determined properties to address unique clinical needs, however, the products provide physicians with no flexibility or choice to alter or dial in the properties for other clinical needs at the time of application during surgery.

There have been some attempts to overcome the above-noted deficiencies. For example, US 2015/0250463, assigned to Ethicon, Inc. of Somerville, N.J., the disclosure of which is hereby incorporated by reference herein, teaches a method of applying a coating onto tissue. The coating has at least two physiologically distinct layers that are delivered from a single device by delivery of a multi-part biomedical composition in different blended or mixing ratios. Disclosed methods include connecting at least two syringe barrels that contain inter-reacting components of the multi-part biomedical composition. Each syringe barrel has a piston that is internally slidable for expression of the components. The first syringe has a first retention compartment and a second retention compartment that are spaced axially therein, with a gasket positioned in the first retention compartment. The method includes advancing the pistons through each syringe to express onto a surface the reactive components of the multi-part biomedical composition in a first blended or mixing ratio, and continuing to advance the pistons to disengage a gasket from the piston of a first syringe at a point between the first retention compartment and the second retention compartment, and still further advancing the pistons through each syringe to express the reactive components of the multi-part biomedical composition in a second blended or mixing ratio to form a biomedical coating having physiologically distinct layers.

U.S. Pat. No. 6,830,756 to Hnojewyj discloses systems, methods, and compositions for achieving closure of vascular puncture sites. The systems and methods form a vascular closure composition by mixing together a first component, a second component, and a buffer material. The first component includes an electrophilic polymer material having a functionality of at least three. The second component includes a nucleophilic material that, when mixed with the first component within a reaction pH range of between 7 to 9, cross-links with the first component to form a non-liquid, three-dimensional barrier. The buffer material has a pH within the reaction pH range. The systems and methods apply the composition to seal a vascular puncture site.

Commonly assigned U.S. patent application Ser. No. 16/593,783, filed on Oct. 4, 2019, the disclosure of which is hereby by incorporated by reference herein, discloses a device with a spray tip for dispensing fluids that react together. The device includes a first lumen for a first fluid, a second lumen for a second fluid, and a dispensing cap located at distal ends of the respective first and second lumens that defines a distal end of the spray tip. The dispensing cap includes a distal end wall defining a closed end of the dispensing cap. A first spray opening is formed in the distal end wall that is in fluid communication with the first lumen, a second spray opening is formed in the distal end wall that is in fluid communication with the second lumen, and an external dividing wall projects distally from the distal end wall of the dispensing cap and extends between the first and second spray openings for forming a barrier between the first and second spray openings.

Commonly assigned U.S. patent application Ser. No. 16/593,799, filed on Oct. 4, 2019, the disclosure of which is hereby by incorporated by reference herein, discloses a spray device including a first spray tip having a first fluid pathway defining a first flow area, and a second spray tip including a second fluid pathway that defines a second flow area that is larger than the first flow area of the first spray tip. The first and second spray tips are side-by-side and spaced from one another at a distal end of the spray device. When a first fluid having a volumetric flow rate is introduced into the first spray tip and a second fluid having the same volumetric flow rate is introduced into the second spray tip, the first fluid will flow through the first fluid pathway at a greater velocity than the second fluid will flow through the second fluid pathway.

Commonly assigned U.S. Provisional Application Ser. No. 63/127,308, filed on Dec. 18, 2020, the disclosure of which is hereby by incorporated by reference herein, discloses a method of making a biocompatible composition for sealing tissue includes mixing a first fluid having a first reactive component (e.g., an electrophile) and a second fluid having a second reactive component (e.g., a nucleophile) to form a mixture and expressing the mixture. During expression, a pH modifying fluid (e.g., NaOH) is added to the mixture at a rate that changes. In one embodiment, a higher ratio of the pH modifying fluid is added to the mixture during a first expressing stage and a lower ratio of the pH modifying fluid is added to the mixture during a second expressing stage. During the first expressing stage, a mixing ratio of the pH modifying fluid, the first fluid and the second fluid is 0.7-1.4:1:1. During the second expressing stage, the mixing ratio of the pH modifying fluid, the first fluid and the second fluid is 0.12-0.24:1:1.

In spite of the above-identified advances, there remains a need for improved systems, devices and methods for controlling cross-linking of the reactive components of biocompatible reactive formulations for effectively sealing tissue and hemostasis.

SUMMARY OF THE INVENTION

In one embodiment, an applicator instrument for mixing and expressing biocompatible reactive formulations, such as tissue adhesives and sealants, preferably has a proximal end and a distal end including a spray tip assembly located at the distal end. In one embodiment, the applicator instrument is preferably configured for mixing together two or more fluid components (e.g., three components) to form a final mixture of a biocompatible reactive formulation (e.g., a tissue adhesive). In one embodiment, the final mixture of the biocompatible reactive formulation is preferably expressed from the spray tip assembly.

In one embodiment, the applicator instrument preferably includes a first syringe barrel that is adapted to contain a first reactive fluid of a multiple component reactive formulation (e.g., a tissue adhesive; a sealant). In one embodiment, the first syringe barrel is adapted to receive a first syringe plunger, which may be used for forcing the first reactive fluid from the distal end of the first syringe barrel.

In one embodiment, the applicator instrument preferably includes a second syringe barrel that is adapted to contain a second reactive fluid of the multiple component biocompatible reactive formulation. In one embodiment, the second syringe barrel is adapted to receive a second syringe plunger, which may be used for forcing the second reactive fluid from the distal end of the second syringe barrel. The first and second reactive fluids may be mixed together to form a first mixture. In one embodiment, the first and second reactive fluids may be adapted for chemically reacting with one another to form a biocompatible reactive formulation, such as an adhesive or a sealant. An adhesive may be used for bonding with a surface or between two surfaces, such as tissue to tissue bonding and tissue to biomaterial bonding. A sealant may be used to bond to tissue surrounding an opening such as a wound or incision to halt the ingress or egress of liquids and/or gases.

In one embodiment, the applicator instrument desirably includes the third syringe barrel, which is adapted to receive a third syringe plunger. In one embodiment, the third syringe barrel is adapted to contain a third fluid component (e.g., a neutralizing buffer; a diluent, such as H2O). In one embodiment, the third syringe plunger may be depressed for forcing the third fluid component from the distal end of the third syringe barrel, whereupon the third fluid may be added into and/or mixed with the first mixture of the first and second reactive fluids.

In one embodiment, proximal ends of the syringe plungers are preferably secured to a plunger head, which may be depressed for simultaneously moving the syringe plungers in a distal direction to simultaneously dispense the first, second and third fluids from the distal ends of the respective first, second and third syringe barrels.

In one embodiment, the applicator instrument preferably includes a fluid manifold that is located downstream from the distal ends of the first, second and third syringe barrels. In one embodiment, the fluid manifold preferably includes a first connector adapted to receive a distal end of the first syringe barrel, a second connector adapted to receive a distal end of the second syringe barrel, and a third connector adapted to receive a distal end of the third syringe barrel.

In one embodiment, the first connector of the fluid manifold is preferably in fluid communication with the first syringe barrel. In one embodiment, a first component of a multiple component biocompatible reactive formulation that is pre-loaded into the first syringe barrel may be forced to flow into the first connector of the fluid manifold, such as by depressing the first syringe plunger.

In one embodiment, the second connector of the fluid manifold is preferably in fluid communication with the second syringe barrel. In one embodiment, a second component of a multiple component biocompatible reactive formulation that is pre-loaded into the second syringe barrel may be forced to flow into the second connector of the fluid manifold, such as by depressing the second syringe plunger.

In one embodiment, the third connector of the fluid manifold is preferably in fluid communication with the third syringe barrel. In one embodiment, a third component of a multiple component biocompatible reactive formulation that is pre-loaded into the third syringe barrel may be forced to flow into the third connector of the fluid manifold, such as by depressing the third syringe plunger.

In one embodiment, the applicator instrument preferably includes a syringe barrel support frame that is adapted to receive and hold the first, second and third syringe barrels. The syringe barrel support frame desirably holds the syringe barrels together for stabilizing the syringe barrels and enhancing the structural integrity and consistent performance of the applicator instrument.

In one embodiment, the syringe barrel support frame preferably has a distal end with a distal projection having threads, which are adapted to mesh with threads of a connecting nut for securing the distal end of the syringe barrel support frame to the connecting nut. In one embodiment, the connecting nut may also be utilized for securing both the distal projection of the syringe barrel support frame and the distal end of the third syringe barrel to the second connector of the fluid manifold.

In one embodiment, the distal end of the first syringe barrel is inserted into the first fluid inlet opening of the first connector of the fluid manifold. A first O-ring retainer and a first O-ring may be utilized to form a fluid-tight coupling between the distal end of the first syringe barrel and the first connector of the fluid manifold.

In one embodiment, the distal end of the second syringe barrel is inserted into the second fluid inlet opening of the second connector of the fluid dispensing manifold. A second O-ring retainer and a second O-ring may be utilized for forming a fluid-tight coupling between the distal end of the second syringe barrel and the second connector of the fluid manifold.

In one embodiment, the distal end of the third syringe barrel is inserted into the third fluid inlet opening of the third connector of the fluid dispensing manifold. A third O-ring retainer and a third O-ring may be utilized for forming a water-tight coupling between the distal end of the third syringe barrel and the third connector of the fluid manifold.

In one embodiment, a first fluid dispensing opening located at the distal end of the first syringe barrel is preferably in fluid communication with a first fluid tube for directing the first fluid of a mixture from the first syringe barrel into the first fluid tube.

In one embodiment, a second fluid dispensing opening located at the distal end of the second syringe barrel is preferably in fluid communication with a second fluid tube for directing the second fluid of a mixture from the second syringe barrel into the second fluid tube.

In one embodiment, a third dispensing opening at the distal end of the third syringe barrel is preferably in fluid communication with a third fluid tube for directing the third fluid of the mixture from the third syringe barrel into the third fluid tube.

In one embodiment, the applicator instrument may include a fluid tube enclosure including an upper fluid tube enclosure and a lower fluid tube enclosure that are assembled together and secured to a distal end of the fluid manifold. The fluid tubes preferably pass through the fluid tube enclosure. In one embodiment, the distal ends of the respective fluid tubes are preferably coupled with a fluid connector of the spray tip assembly.

In one embodiment, the distal end of the applicator instrument preferably includes a spray tip assembly, which may be secured to the distal ends of upper and lower fluid tube enclosures. In one embodiment, the spray tip assembly preferably includes a fluid connector having a distal end that is secured to a proximal end of a spray tip housing, and an O-ring that forms a fluid-tight seal between the fluid connector and the spray tip housing. The spray tip assembly desirably includes a mixing element that is disposed inside the spray tip housing. A dispensing cap may be secured to the distal end of the spray tip housing by inserting the dispensing cap into the elongated conduit of the spray tip housing.

In one embodiment, the first syringe barrel is adapted to receive a first fluid having a first reactive component (e.g., an electrophile) of a biocompatible reactive formulation. In one embodiment, the second syringe barrel is adapted to receive a second fluid having a second reactive component (e.g., a nucleophile) of a biocompatible reactive formulation, whereby the first and second fluids may be mixed together to form a first mixture. In one embodiment, the first and second fluids have reactive components that are adapted to chemically react with one another to form a biocompatible reactive formulation (e.g., an adhesive; a sealant) that is applied to tissue.

In one embodiment, the applicator instrument desirably includes a third syringe barrel that is adapted to contain a third fluid (e.g., a neutralizing buffer; a diluent) that may be added into the first mixture of the first and second fluids. In one embodiment, the third fluid may be added into and/or mixed with the first mixture of the first and second fluids to form a final mixture that is expressed from the spray tip assembly located at the distal end of the applicator instrument.

In one embodiment, the first fluid within the first syringe barrel may include an electrophile (e.g., PEG-NHS). In one embodiment, the second fluid within the second syringe barrel may include a nucleophile at high pH (e.g., PEG-NH2). In one embodiment, the third fluid within the third syringe barrel may include a pH modifying buffer.

In one embodiment, the first fluid within the first syringe barrel may include an electrophile at high concentration (e.g., PEG-NHS), the second fluid within the second syringe barrel may include a nucleophile at high concentration (e.g., PEG-NH2), and the third fluid within the third syringe barrel may include a diluent (e.g., H2O; a buffer).

In one embodiment, the first and second fluids may include additions of polyelectrolytes such as alginate, heparin, hyaluronic acid, and chitosan.

In one embodiment, the third fluid may include polyvalent ions, such as Calcium.

In one embodiment, the first fluid includes Fibrinogen, the second fluid includes Thrombin, and the third fluid includes a diluent, such as H2O.

In one embodiment, the spray tip assembly preferably includes the spray tip housing having a proximal end, a distal end, an outer wall that extends from the proximal end to the distal end of the spray tip housing, and an elongated conduit surrounded by the outer wall that extends from the proximal end to the distal end of the spray tip housing.

In one embodiment, the spray tip assembly desirably includes a mixing element disposed within the elongated conduit of the spray tip housing, and a mixing chamber located between an outer surface of the mixing element and an inner surface of the outer wall of the spray tip housing.

In one embodiment, the mixing element desirably includes a proximal end adjacent the proximal end of the spray tip housing and a distal end adjacent the distal end of the spray tip housing, a third fluid inlet opening at the proximal end of the mixing element, and one or more third fluid exit openings formed in the outer surface of the mixing element that are in fluid communication with the third fluid inlet opening, whereby the one or more third fluid exit openings extend laterally through the mixing element to the outer surface of the mixing element for being in fluid communication with the mixing chamber.

In one embodiment, the spray tip assembly preferably includes the fluid connector secured to the proximal end of the spray tip housing and opposing the proximal end of the mixing element. The fluid connector desirably includes first and second fluid channels in fluid communication with the mixing chamber, and a third fluid channel in fluid communication with the third fluid inlet opening of the mixing element.

In one embodiment, the mixing element preferably has a third fluid conduit extending distally from the third fluid inlet opening of the mixing element toward the distal end of the mixing element for interconnecting the third fluid inlet opening and the one or more third fluid exit openings of the mixing element.

In one embodiment, the fluid connector has a proximal end and a distal end, and the distal end of the fluid connector is disposed within the elongated conduit of the spray tip housing and opposes the proximal end of the mixing element.

In one embodiment, the first, second and third fluid channels of the fluid connector extend from the proximal end to the distal end of the fluid connector, and the first, second and third fluid channels are isolated from one another within the fluid connector.

In one embodiment, the third fluid channel of the fluid connector preferably extends through a central region of the fluid connector, and the first and second fluid channels of the fluid connector extend on opposite sides of the third fluid channel.

In one embodiment, the one or more third fluid exit openings are located adjacent the distal end of the mixing element, and the third fluid conduit of the mixing element extends to the distal end of the mixing element for being in fluid communication with the one or more third fluid exit openings.

In one embodiment, the one or more third fluid exit openings are located midway between the proximal and distal ends of the mixing element, and the third fluid conduit of the mixing element extends to the midway location of the mixing element for being in fluid communication with the one or more third fluid exit openings.

In one embodiment, the one or more third fluid exit openings are located adjacent the proximal end of the mixing element, and the third fluid inlet opening is in fluid communication with the one or more third fluid exit openings.

In one embodiment, a system and/or an applicator instrument may be designed so that the third fluid may be added into a first mixture of the first and second fluids at any location along the length of the spray tip assembly so as to control, adjust and/or modify the chemical reaction of the first and second reactive fluids.

In one embodiment, the inner surface of the outer wall of the spray tip housing has internal threads that are located adjacent the proximal end of the spray tip housing. In one embodiment, the distal end of the fluid connector has external threads that are configured to mesh with the internal threads of the spray tip housing for securing the distal end of the fluid connector with the proximal end of the spray tip housing.

In one embodiment, the first fluid channel of the fluid connector is aligned with a first lateral side of the mixing chamber, the second fluid channel of the fluid connector is aligned with a second lateral side of the mixing chamber, and the third fluid channel of the fluid connector is aligned with the third fluid inlet opening and the third fluid conduit of the mixing element.

In one embodiment, an applicator instrument for dispensing a biocompatible reactive formulation preferably includes a first chamber containing a first fluid having a first reactive component. In one embodiment, the first chamber is in fluid communication with the first fluid channel of the fluid connector.

In one embodiment, the applicator instrument preferably includes a second chamber containing a second fluid having a second reactive component that is reactive with the first reactive component. In one embodiment, the second chamber is in fluid communication with the second fluid channel of the fluid connector.

In one embodiment, the applicator instrument preferably includes a third chamber containing a third fluid. In one embodiment, the third chamber is in fluid communication with the third fluid channel of the fluid connector.

In one embodiment, a system for dispensing a biocompatible reactive formulation is configured to direct the first and second fluids in series through the respective first and second fluid channels of the fluid connector and into the mixing chamber for forming a first mixture.

In one embodiment, the system is configured to direct the third fluid in series through the third fluid channel of the fluid connector, into the third fluid inlet opening of the mixing element, through the third fluid conduit of the mixing element, and laterally through the one or more third fluid exit openings of the mixing element for entering into the mixing chamber for being added into the first mixture of the first and second fluids to form a final mixture.

In one embodiment, a dispensing cap is disposed within the elongated conduit of the spray tip housing and is secured to the distal end of the spray tip housing for opposing the distal end of the mixing element. In one embodiment, the dispensing cap preferably includes a dispensing opening that is in fluid communication with a distal end of the mixing chamber for expressing the final mixture of the first, second, and third fluids.

In one embodiment, a system for dispensing biocompatible reactive formulations desirably includes a first chamber containing a first fluid having a first reactive component, a second chamber containing a second fluid having a second reactive component that is reactive with the first reactive component, and a third chamber containing a third fluid.

In one embodiment, the system preferably includes a spray tip assembly that is configured for spraying a final mixture of the first, second and third fluids. In one embodiment, the spray tip assembly desirably includes a spray tip housing having a proximal end, a distal end, an outer wall that extends from the proximal end to the distal end of the spray tip housing, and an elongated conduit surrounded by the outer wall that extends from the proximal end to the distal end of the spray tip housing.

In one embodiment, a mixing element is disposed within the elongated conduit of the spray tip housing, and a mixing chamber is located between an outer surface of the mixing element and an inner surface of the outer wall of the spray tip housing.

In one embodiment, the mixing element desirably has a proximal end adjacent the proximal end of the spray tip housing and a distal end adjacent the distal end of the spray tip housing. In one embodiment, the mixing element has a third fluid inlet opening at the proximal end of the mixing element, and one or more third fluid exit openings formed in the outer surface of the mixing element that are in fluid communication with the third fluid inlet opening and that extend laterally to the outer surface of the mixing element for being in fluid communication with the mixing chamber.

In one embodiment, the spray tip assembly includes a fluid connector secured to the proximal end of the spray tip housing and opposing the proximal end of the mixing element. In one embodiment, the fluid connector preferably includes first and second fluid channels that are in fluid communication with the mixing chamber, and a third fluid channel that is in fluid communication with the third fluid inlet opening of the mixing element.

In one embodiment, the system desirably includes a pump assembly (e.g., syringe plungers) that is coupled with the first, second and third chambers for simultaneously forcing the first, second and third fluids to flow through the first, second and third fluid channels of the fluid connector and into the proximal end of the spray tip housing.

In one embodiment, the mixing element preferably includes a third fluid conduit extending distally from the third fluid inlet opening of the mixing element toward the distal end of the mixing element. In one embodiment, the third fluid conduit is in fluid communication with the one or more third fluid exit openings for directing the third fluid from the third fluid inlet opening to the one or more third fluid exit openings.

In one embodiment, a spray tip assembly may utilize a first mixing element having laterally extending third fluid exit openings that are located adjacent the distal end of the mixing element. In this embodiment, the first and second fluids are first mixed together within a mixing chamber at the proximal end of the first mixing element to form a first mixture, and, after the first mixture flows downstream through the mixing chamber toward the distal end of the mixing element, the third fluid is added to the first mixture, via the third fluid exit openings, adjacent the distal end of the first mixing element.

In one embodiment, a spray tip assembly may utilize a second mixing element having laterally extending third fluid exit openings that are located midway between the proximal end and the distal end of the second mixing element. In this embodiment, the first and second fluids are mixed together within the mixing chamber at the proximal end of the second mixing element to form a first mixture, and, as the first mixture flows downstream through the mixing chamber toward the distal end of the mixing element, the third fluid is added to the first mixture, via the third fluid exit openings, at a location that is midway between the proximal end and the distal end of the second mixing element.

In one embodiment, a spray tip assembly may utilize a third mixing element having laterally extending third fluid exit openings that are located adjacent the proximal end of the mixing element. In this embodiment, the first and second fluids are mixed together within the mixing chamber at the proximal end of the third mixing element to form a first mixture, and the third fluid is also added to the first mixture at the proximal end of the third mixing element, via the third fluid exit openings, to form a final mixture. The final mixture then travels the length of the mixing element for further mixing until it is dispensed via the dispensing opening of the dispensing cap.

In one embodiment, a system may include a kit having a first spray tip assembly that has the first mixing element, a second spray tip assembly that has the second mixing element, and a third spray tip assembly that has the third mixing element, whereby only one of the three spray tip assemblies is secured to the distal end of the applicator instrument at any one time. Thus, an operator may modify the characteristics of a biocompatible reactive formulation (i.e., by controlling how the first and second reactive components react with one another) that is dispensed from the applicator instrument by changing the spray tip assembly that is secured to the distal end of the applicator instrument. In one embodiment, a first spray tip assembly may be disconnected from a fluid connector and replaced by a second spray tip assembly that is secured to the fluid connector for changing how the three fluids are mixed together within the spray tip housing.

In other embodiments, the third fluid exit openings may be positioned at any location along the length of a mixing element to further modify and control how reactive components of a biocompatible reactive formulation react with one another. Thus, an infinite number of different types of reactions may be attained by modifying the structure of the mixing elements and/or where along the length of a spray tip assembly a third fluid is added into a first mixture of first and second reactive fluids.

In one embodiment, a method of making a biocompatible reactive formulation preferably includes using a mixing element for mixing a first fluid having a first reactive component and a second fluid having a second reactive component to form a first mixture, and, after forming the first mixture, adding a third fluid into the first mixture of the first and second fluids to form a final mixture. The method may include expressing the final mixture of the first mixture and the third fluid onto a surface (e.g., tissue).

In one embodiment, the first and second fluids are mixed together to form the first mixture adjacent a proximal end of the mixing element and the third fluid is added into the first mixture adjacent a distal end of the mixing element.

In one embodiment, the first and second fluids are mixed together to form the first mixture adjacent a proximal end of the mixing element and the third fluid is added into the first mixture at a location that is midway between the proximal and distal ends of the mixing element.

In one embodiment, the first and second fluids are mixed together to form the first mixture adjacent a proximal end of the mixing element and the third fluid is added into the first mixture adjacent the proximal end of the mixing element.

In one embodiment, the first fluid may include an electrophile, the second fluid may include a nucleophile at high pH, and the third fluid may include a pH modifying buffer or a diluent (e.g., H2O; a buffer).

In a high concentration embodiment, both the electrophile and the nucleophile preferably have higher respective concentrations. In one embodiment, the initial mixture was 43 mg/mL 4 Arm PEG-Amine-10k, and 112.5 mg/mL 4 Arm PEG-SG-20k. After introduction of the third fluid, the concentration was 28.5 mg/mL PEG-Amine, and 75 mg/mL PEG-SG.

These and other preferred embodiments of the present patent application will be described in more detail herein.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Referring toFIGS. 1A and 1B, in one embodiment, an applicator instrument100for mixing and expressing a composition, such as a biocompatible reactive formulation (e.g., a tissue adhesive; a tissue sealant), preferably has a proximal end102and a distal end104. In one embodiment, the applicator instrument100is desirably configured for mixing together two or more fluid components to form a final mixture of a composition, such as a biocompatible reactive formulation. In one embodiment, the final mixture of the biocompatible reactive formulation is preferably expressed (e.g., sprayed) via a spray tip assembly125, which is located at the distal end104of the applicator instrument100.

Referring toFIGS. 2 and 3, in one embodiment, the applicator instrument100preferably includes a plunger head106located at the proximal end102thereof, which is adapted to be assembled with proximal ends of a first syringe plunger108, a second syringe plunger110, and a third syringe plunger112, respectively. In one embodiment, the first and second syringe plungers108,110may have larger cross-sectional diameters, respectively, than the cross-sectional diameter of the third syringe plunger122.

In one embodiment, a first piston114may be secured to the distal end of the first syringe plunger108, and a second piston116may be secured to the distal end of the second syringe plunger110.

In one embodiment, the applicator instrument100preferably includes a first syringe barrel118that is adapted to receive a first fluid having a first reactive component (e.g., an electrophile) of a biocompatible reactive formulation. In one embodiment, the first syringe barrel118is adapted to receive the first piston114and the first syringe plunger108, which may be used for forcing the first fluid from the distal end of the first syringe barrel118.

In one embodiment, the applicator instrument100preferably includes a second syringe barrel120that is adapted to receive a second fluid having a second reactive component (e.g., a nucleophile) of a biocompatible reactive formulation, whereby the first and second fluids may be mixed together to form a first mixture. In one embodiment, the second syringe barrel120is adapted to receive the second piston116and the second syringe plunger110, which may be used for forcing the second fluid from the distal end of the second syringe barrel120. In one embodiment, the first and second fluids have reactive components that are adapted to chemically react with one another to form a biocompatible reactive formulation that is applied to tissue or biomaterial.

In one embodiment, the applicator instrument100desirably includes a third syringe barrel122that is adapted to receive the third syringe plunger112. In one embodiment, the third syringe barrel122is adapted to contain a third fluid (e.g., a pH modifying buffer; a diluent such as H2O or a buffer) that may be added into the first mixture of the first and second fluids. In one embodiment, the third plunger112may be used for forcing the third fluid from the distal end of the third syringe barrel, whereupon it may be added into and/or mixed with the first mixture of the first and second fluids to form a final mixture that is expressed from the distal end104of the applicator instrument100.

In one embodiment, the first and second syringe barrels118,120may be larger than the third syringe barrel122. In one embodiment, the first and second syringe barrels have respective inner diameters that are the same. In one embodiment, the first and second syringe barrels118,120may have respective cross-sectional diameters that are larger than the cross-sectional diameter of the third syringe barrel122. In one embodiment, the respective first and second syringe barrels118,120may be configured to hold larger volumes of fluid than the volume of fluid that may be held within the third syringe barrel122. In one embodiment, the first and second syringe barrels may be designated as large syringe barrels and the third syringe barrel may be designated as a small syringe barrel.

In one embodiment, the first fluid within the first syringe barrel may include an electrophile (e.g., PEG-NHS). In one embodiment, the second fluid within the second syringe barrel may include a nucleophile at high pH (e.g., PEG-NH2). In one embodiment, the third fluid within the third syringe barrel may include a pH modifying buffer.

In one embodiment, the first fluid within the first syringe barrel may include an electrophile at high concentration (e.g., PEG-NHS), the second fluid within the second syringe barrel may include a nucleophile at high concentration (e.g., PEG-NH2), and the third fluid within the third syringe barrel may include a diluent (e.g., H2O or buffer).

In one embodiment, the first and second fluids may include additions of polyelectrolytes such as alginate, heparin, hyaluronic acid, and chitosan. In one embodiment, the third fluid may include polyvalent ions, such as Calcium.

In one embodiment, the first fluid comprises Fibrinogen, the second fluid comprises Thrombin, and the third fluid comprises a diluent, such as H2O.

In one embodiment, the applicator instrument100preferably includes a fluid manifold124that is located downstream from the distal ends of the first, second and third syringe barrels118,120,122. In one embodiment, the fluid manifold124preferably includes a first connector126adapted to receive a distal end of the first syringe barrel118, a second connector128adapted to receive a distal end of the second syringe barrel120, and a third connector130adapted to receive a distal end of the third syringe barrel122.

In one embodiment, the first connector126of the fluid manifold124is preferably in fluid communication with the first syringe barrel118. In one embodiment, a first component of a biocompatible reactive formulation (e.g., a first fluid containing a first reactive component) that is pre-loaded into the first syringe barrel118may be forced to flow into the first connector126of the fluid manifold124, such as by depressing the first syringe plunger108.

In one embodiment, the second connector128of the fluid manifold124is preferably in fluid communication with the second syringe barrel120. In one embodiment, a second component of a biocompatible reactive formulation (e.g., a second fluid containing a second reactive component that reacts with the first reactive component) that is pre-loaded into the second syringe barrel120may be forced to flow into the second connector128of the fluid manifold124, such as by depressing the second syringe plunger110.

In one embodiment, the third connector130of the fluid manifold124is preferably in fluid communication with the third syringe barrel122. In one embodiment, a third component of a biocompatible reactive formulation that is pre-loaded into the third syringe barrel122(e.g., a pH modifying buffer; a diluent such as H2O or a buffer) may be forced to flow into the third connector130of the fluid manifold124, such as by depressing the third syringe plunger110.

In one embodiment, proximal ends of the first, second, and third syringe plungers108,110, and112may be coupled together so that they may be depressed simultaneously. In one embodiment, the proximal ends of the three syringe plungers108,110, and112may be connected with the plunger head106, which may be forced to move in the distal direction DIR1(FIGS. 1A and 1B) for simultaneously depressing the syringe plungers108,110, and112.

In one embodiment, the applicator instrument100preferably includes a connecting nut132that may be utilized for securing a distal end of the third syringe barrel122with the third connector130of the fluid manifold124.

In one embodiment, O-ring retainers134and O-rings136are preferably utilized for forming fluid-tight connections between the distal ends of the three syringe barrels118,120,122and the respective connectors126,128,130of the fluid manifold124.

In one embodiment, the applicator instrument100preferably includes a syringe barrel support frame138that is adapted to receive and hold the first, second and third syringe barrels118,120, and122. The syringe barrel support frame138desirably holds the syringe barrels118,120,122together for stabilizing the syringe barrels and enhancing the structural integrity of the applicator instrument100.

In one embodiment, the syringe barrel support frame138preferably has a distal end with a distal projection140having external threads, which are adapted to mesh with internal threads (not shown) of the connecting nut132for securing the distal end of the syringe barrel support frame138to the connecting nut132. Thus, in one embodiment, the connecting nut132may be utilized for securing both the distal projection140of the syringe barrel support frame138and the distal end of the third syringe barrel122to the second connector130of the fluid manifold124.

Referring toFIGS. 2 and 4, in one embodiment the distal end of the applicator instrument100preferably includes an upper fluid tube enclosure142and a lower fluid tube enclosure144that are adapted to be assembled with one another over the distal end of the fluid manifold124. In one embodiment, the upper and lower fluid tube enclosures142,144of the applicator instrument100preferably contain a first fluid tube146that is adapted to be in fluid communication with the distal end of the first syringe barrel118, a second fluid tube148that is adapted to be in fluid communication with the distal end of the second syringe barrel120, and a third fluid tube150that is adapted to be in fluid communication with the distal end of the third syringe barrel122. In one embodiment, the distal ends of the respective fluid tubes146,148, and150preferably pass through a fluid tube channel152that is located at the distal ends of the respective upper and lower fluid tube enclosures142,144. As will be described in more detail herein, in one embodiment, the fluid tube channel152preferably directs the fluid tubes146,148, and150into a proximal end of a fluid connector154.

In one embodiment, the distal end of the applicator instrument100preferably includes a spray tip assembly125that is used for spraying a final mixture of a biocompatible reactive formulation. In one embodiment, the spray tip assembly125desirably includes an O-ring156that is adapted to be assembled with the fluid connector154, a mixing element158that is adapted to be disposed inside a spray tip housing160, and a dispensing cap162that is adapted to be secured to the distal end of the spray tip housing160. In one embodiment, the O-ring156preferably forms a fluid-tight seal between the fluid connector154and an inner surface of the spray tip housing160. In one embodiment, an assembly of the fluid connector154, the O-ring156, the mixing element158, the spray tip housing160, and the dispensing cap162may be referred to as the spray tip assembly125.

In one embodiment, the first and second fluid components supplied via the respective first and second fluid tubes146and148may be mixed together within a mixing chamber located inside the spray tip housing160to form a first mixture. In one embodiment, the third fluid component supplied via the third fluid tube150may be added into the first mixture to form a final mixture. In one embodiment, the third component may be added into the first mixture at a selected location between the proximal end and the distal end of the spray tip housing160.

In one embodiment, the first and second fluids may be mixed together adjacent the proximal end of the mixing element158to form a first mixture and the third fluid may be added to the first mixture adjacent the proximal end of the mixing element158to form a final mixture that is expressed from the distal end of the spray tip housing160.

In one embodiment, the first and second fluids may be mixed together adjacent the proximal end of the mixing element158to form a first mixture and the third fluid may be added to the first mixture at a midsection of the mixing element158to form a final mixture that is expressed from the distal end of the spray tip housing160.

In one embodiment, the first and second fluids may be mixed together adjacent the proximal end of the mixing element158to form a first mixture and the third fluid may be added to the first mixture adjacent the distal end of the mixing element158to form a final mixture that is expressed from the distal end of the spray tip housing160.

In one embodiment, the final mixture of the three components may be expressed (e.g., sprayed) via a dispensing opening in the dispensing cap162.

Referring toFIGS. 5A and 5B, in one embodiment, the distal ends of the respective first, second and third syringe barrels118,120, and122may be assembled with the fluid manifold124by inserting the distal end of the first syringe barrel118into the first connector126, the distal end of the second syringe barrel120into the second connector128, and the distal end of the third syringe barrel122into the third connector130. In one embodiment, the connecting nut132may be utilized for interconnecting the distal end of the third syringe barrel122with the third connector130of the fluid manifold124. Although not shown inFIGS. 5A and 5B, the connecting nut132may also be used for securing the externally threaded distal projection140at the distal end of the syringe barrel support frame138(FIG. 3) with the third connector130of the fluid manifold124.

In one embodiment, the applicator instrument100desirably includes the first fluid tube146that is in fluid communication with the distal end of the first syringe barrel118, the second fluid tube148that is in fluid communication with the distal end of the second syringe barrel120, and the third fluid tube150is in fluid communication with the distal end of the third syringe barrel122. The distal ends of the three fluid tubes146,148, and150preferably pass through the fluid tube channel152of the upper and lower fluid tube enclosures142,144(FIG. 4).

In one embodiment, as the plunger head106(FIG. 5A) is depressed toward the distal end of the applicator instrument100in the distal direction designated DIR1, the respective syringe plungers108,110, and112move simultaneously with one another to preferably force the three fluids that are within the three syringe barrels118,120, and122into the respective first, second and third fluid tubes146,148, and150for being mixed together within the spray tip assembly125(FIGS. 1A and 1B) that is located at the distal end of the applicator instrument100.

Referring toFIGS. 6A and 6B, in one embodiment, the applicator instrument100(FIG. 1A) preferably includes the syringe barrel support frame138having a proximal end164and a distal end166with the externally threaded projection140extending from the distal end166of the syringe barrel support frame.

In one embodiment, the proximal end164of the syringe barrel support frame138preferably includes syringe barrel securing flanges168A,168B that oppose one another and that are adapted to engage flanges located at the proximal ends of the respective first, second, and third syringe barrels118,120,122(FIG. 3) for securing the proximal ends of the syringe barrels to the syringe barrel support frame138.

In one embodiment, the syringe barrel support frame138preferably includes a first set of C-shaped flanges170A,170B that are adapted to engage an outer wall of the first syringe barrel118(FIG. 2) for securing the first syringe barrel to the syringe barrel support frame138. In one embodiment, the syringe barrel support frame138preferably includes a second set of C-shaped flanges172A,172B that are adapted to engage an outer wall of the second syringe barrel120(FIG. 2) for securing the second syringe barrel to the syringe barrel support frame. In one embodiment, the syringe barrel support frame138preferably includes a central opening174located at the proximal end thereof that is aligned with a central opening176formed in the externally threaded projection140located at the distal end166of the syringe barrel support frame. In one embodiment, the third syringe barrel122(FIG. 2) may be passed through the central opening174at the proximal end and the central opening176of the externally threaded projection140for securing the third syringe barrel with the syringe barrel support frame138.

Referring toFIGS. 7A and 7B, in one embodiment, the fluid manifold124(FIG. 2) preferably has a proximal end178and a distal end180. In one embodiment, the fluid manifold124preferably includes the first connector126having an opening182that is adapted to receive a distal end of the first syringe barrel118(FIG. 2). In one embodiment, the fluid manifold124also desirably includes the second connector128having a central opening184that is adapted to receive a distal end of the second syringe barrel120(FIG. 2). In one embodiment, the fluid manifold124also preferably includes the third connector130having a central opening186that is adapted to receive a distal end of the third syringe barrel122(FIG. 2).

In one embodiment, the central openings182,184,186of the respective first, second and third connectors126,128, and130preferably extend to the distal end180of the fluid manifold124. In one embodiment, proximal ends of the first, second and third fluid tubes146,148,150(FIG. 2) preferably pass through the respective openings182,184, and186at the distal end180of the fluid manifold124for being in fluid communication with the distal ends of the respective first, second, and third syringe barrels118,120, and122(FIG. 2). The distal ends of the fluid tubes146,148, and150are preferably in fluid communication with the spray tip assembly125(FIG. 1A).

Referring toFIGS. 8A and 8B, in one embodiment, the applicator instrument100(FIG. 1A) preferably includes the connecting nut132having a proximal end188and a distal end190with a tube-shaped connector192that is adapted to be secured with the third connector130of the fluid manifold124(FIG. 2). In one embodiment, the connecting nut132preferably has a central conduit194that extends from the proximal end188to the distal end190thereof. In one embodiment, the connecting nut132preferably includes internal threads196adjacent the proximal end188thereof that are adapted to mesh with the external threads of the externally threaded projection140at the distal end of the syringe barrel support frame138for securing the distal end of the syringe barrel support frame138to the fluid manifold124(FIG. 3).

Referring toFIGS. 3, 9A, and 9B, in one embodiment, the applicator instrument100(FIG. 1A) preferably includes one or more O-ring retainers134having a larger diameter section198and a smaller diameter section200with a central opening202passing through both the larger and smaller diameter sections198,200. In one embodiment, the size difference between the larger diameter section198and the smaller diameter section200preferably defines an abutting surface204that is adapted to abut against proximal faces of the respective first, second and third connectors126,128,130of the fluid manifold124(FIG. 2). In one embodiment, an O-ring136(FIG. 3) may be assembled over the outer surface of the smaller diameter section200for facilitating the formation of a water-tight seal between the abutting surface204of the O-ring retainer134and the proximal face of an opposing connector of the fluid manifold. Referring toFIG. 3, in one embodiment, the distal ends of the respective syringe barrels118,120, and122preferably pass through the central opening202of the O-ring retainer134associated therewith.

Referring toFIGS. 10A-10C, in one embodiment, the applicator instrument100(FIG. 1A) preferably includes the plunger head106having a proximal face206that faces toward the proximal end of the applicator instrument and a distal face208that faces toward the distal end of the applicator instrument. In one embodiment, the plunger head106preferably includes a first syringe plunger attachment slot210that is adapted to receive a thumb flange located at the proximal end of the first plunger108(FIG. 3) for securing the proximal end of the first syringe plunger with the plunger head106. In one embodiment, the plunger head106desirably includes a second syringe plunger attachment slot212that is adapted to receive a thumb flange at the proximal end of the second plunger110(FIG. 3) for securing the proximal end of the second syringe plunger110with the plunger head106. In one embodiment, the plunger head106desirably includes a third syringe plunger attachment slot214that is preferably adapted to receive a thumb flange at the proximal end of the third syringe plunger112(FIG. 3) for securing the proximal end of the third syringe plunger with the plunger head106.

In one embodiment, after the proximal ends of the respective syringe plungers108,110,112(FIG. 3) have been secured to the plunger head106, the plungers may be moved simultaneously with one another as the plunger head106is depressed in the distal direction DIR1toward the distal end104of the applicator instrument100(FIG. 1A).

Referring toFIGS. 2, 4, 11 and 12, in one embodiment, the applicator instrument100preferably includes the upper fluid tube enclosure142and the lower fluid tube enclosure144that are assembled together for being secured to the distal end of the fluid manifold124(FIG. 2). In one embodiment, the lower fluid tube enclosure144desirably has an inner face216that includes proximally located projections218A,218B that are adapted to be inserted into female openings220A,220B (FIG. 7A) formed in the fluid manifold124. The upper fluid tube enclosure may have similar projections. The projections may be used for assembling the proximal ends of the respective upper and lower fluid tube enclosures142,144with the distal end of the fluid manifold124(FIG. 7A).

In one embodiment, the distal ends of the respective upper and lower fluid tube enclosures142,144preferably includes the fluid tube channel152that is adapted to guide the distal ends of the first, second and third fluid tubes146,148,150(FIG. 2) into the proximal end of the spray tip assembly125, which is located at the distal end104of the applicator instrument100(FIG. 1A).

Referring toFIG. 12, in one embodiment, the inner face216of the lower fluid tube enclosure144preferably includes at least one male post222and at least one female opening224that are adapted to engage structural features provided on an opposing inner face of the upper fluid tube enclosure142(FIG. 11) for forming a snap-fit connection between the upper and lower fluid tube enclosures142,144. For example, a male post on the upper fluid tube enclosure may be inserted into a female opening on the lower fluid tube enclosure, and a male post on the lower fluid tube enclosure may be inserted into a female opening on the upper fluid tube enclosure.

Referring toFIG. 13, in one embodiment, the first syringe barrel118(FIG. 3) preferably has a proximal end226including a laterally extending flange228and a distal end230having a dispensing opening232. Referring toFIGS. 13 and 14, in one embodiment, the proximal end226of the first syringe barrel118desirable includes a first syringe barrel opening234that is adapted to receive the first syringe plunger108(FIG. 3).

In one embodiment, the first syringe plunger108preferably includes a proximal end236having a thumb engaging flange238and a distal end240that is adapted to be coupled with a first piston114(FIG. 3). In one embodiment, the distal end240including the first piston114(FIG. 2) is adapted to be inserted into the first syringe barrel opening224for being depressed toward the distal end230of the first syringe barrel118.

In one embodiment, the applicator instrument preferably includes the second syringe barrel120and the second syringe plunger110(FIG. 3), which may have a structure, size, shape, and configuration that is similar to that shown and described above inFIGS. 13 and 14for the first syringe barrel118and the first plunger108. In one embodiment, the first and second syringe barrels may have different sizes for holding different volumes of fluid.

Referring toFIGS. 3, 15, and 16, in one embodiment, the applicator instrument100preferably includes the third syringe located in the center of the device, which preferably includes the third syringe barrel122and third syringe plunger112. In one embodiment, the third syringe barrel122preferably has a proximal end242having a laterally extending flange244and a distal end246having a dispensing opening248adapted to dispense a third fluid component disposed within the third syringe barrel122. In one embodiment, the third syringe barrel122preferably includes a third barrel opening250that preferably extends from the proximal end242to the fluid dispensing opening248located at the distal end246of the third syringe barrel122.

In one embodiment, the third syringe plunger112preferably includes a proximal end252having a thumb engaging flange254that may be engaged for depressing the third syringe plunger112toward the distal end246of the third syringe barrel122. In one embodiment, the third syringe plunger112preferably includes a distal end256that is adapted to be inserted into the central opening250of the third syringe barrel122. In one embodiment, the third syringe plunger112may be depressed in a distal direction DIR1(FIG. 1A) toward the distal end246of the third syringe barrel122for dispensing a third fluid component that is pre-loaded into the third syringe barrel122from the dispensing opening248located at the distal end246of the third syringe barrel122.

Referring toFIG. 17, in one embodiment, the distal ends of the syringe plungers108,110,112are desirably inserted into the respective syringe barrels118,120, and122. The proximal ends of the syringe plungers108,110,112may be secured within the syringe plunger receiving slots210,212,214(FIG. 10C) that are accessible at the distal face of the plunger head106to provide for simultaneous distal movement of the syringe plungers108,110,112in the direction designated DIR1toward the distal end104of the applicator instrument100. In one embodiment, the first piston head114is secured to the distal end of the first syringe plunger108and the second piston head116is secured to the distal end of the second syringe plunger110. In one embodiment, the distal ends of the first, second and third syringe barrels118,120, and122are secured to the respective connectors126,128and130of the fluid manifold124.

Referring toFIG. 18, in one embodiment, the distal end230A of the first syringe barrel118is inserted into the first fluid inlet opening of the first connector126of the fluid manifold124. A first O-ring retainer134A and a first O-ring136A are utilized to form a fluid-tight coupling between the distal end230A of the first syringe barrel118and the first connector126of the fluid manifold124.

In one embodiment, the distal end230B of the second syringe barrel120is inserted into the third fluid inlet opening of the second connector128of the fluid dispensing manifold124. A second O-ring retainer134B and a second O-ring136B are utilized for forming a fluid-tight coupling between the distal end230B of the second syringe barrel120and the second connector128of the fluid manifold124.

In one embodiment, the distal end230C of the third syringe barrel122is inserted into the third fluid inlet opening of the third connector130of the fluid dispensing manifold124. A third O-ring retainer134C and a third O-ring136C are utilized for forming a water-tight coupling between the distal end230C of the third syringe barrel122and the third connector130of the fluid manifold124.

In one embodiment, the first fluid dispensing opening232A located at the distal end230A of the first syringe barrel118is preferably in fluid communication with the first fluid tube146for directing the first fluid of a mixture from the first syringe barrel118into the first fluid tube146.

In one embodiment, the second fluid dispensing opening232B located at the distal end230B of the second syringe barrel120is preferably in fluid communication with the second fluid tube148for directing the second fluid of a mixture from the second syringe barrel120into the second fluid tube148.

In one embodiment, the third fluid dispensing opening232C located at the distal end230C of the third syringe barrel122is preferably in fluid communication with the third fluid tube150for directing the third fluid of the mixture from the third syringe barrel122into the third fluid tube150.

Referring toFIGS. 17, 19A, and 19B, in one embodiment, the distal end104of the applicator instrument100preferably includes the spray tip assembly125, which is coupled with the distal ends of the respective upper and lower fluid tube enclosures142,144(FIG. 4). In one embodiment, the spray tip assembly125preferably includes the fluid connector154having a distal end that is secured to a proximal end of the spray tip housing160, and the dispensing cap162that is preferably assembled with the distal end of the spray tip housing160.

Referring toFIGS. 20A and 20B, in one embodiment, the spray tip assembly125preferably includes the fluid connector154and the O-ring156, which is assembled over a neck of the fluid connector154. The spray tip assembly125desirably includes the spray tip housing160having an elongated conduit extending along the length thereof that is adapted to receive the mixing element158. After the O-ring156and the fluid connector154are assembled together, the O-ring/fluid connector subassembly is preferably inserted into a proximal end of the elongated conduit of the spray tip housing160so that the fluid connector154may be secured within the proximal end of the spray tip housing160. The dispensing cap162is preferably inserted into a distal end of the elongated conduit of the spray tip housing160for being secured to the distal end of the spray tip housing160.

Referring toFIG. 20B, in one embodiment, the spray tip housing160preferably has internal threads161that are located adjacent a proximal end of the spray tip housing. In one embodiment, the external threads164of the fluid connector154are preferably adapted to mesh with the internal threads161of the spray tip housing160for securing the distal end of the fluid connector154with the proximal end of the spray tip housing160.

Referring toFIG. 21A, in one embodiment, the fluid connector154preferably includes a proximal end260that is adapted to be coupled with the distal ends of the upper and lower fluid tube enclosures142,144(FIG. 2) and a distal end262having the external threads264, which are adapted to engage the internal threads161of the spray tip housing160(FIG. 20B).

Referring toFIGS. 21B-21D, in one embodiment, the proximal end260of the fluid connector154preferably includes a first fluid tube opening266that is adapted to receive the first fluid tube146(FIG. 2), a second fluid tube opening268that is adapted to receive the second fluid tube148(FIG. 2), and a third fluid tube opening270that is adapted to receive the third fluid tube150(FIG. 2).

Referring toFIGS. 21D-21G, in one embodiment, the first fluid tube opening266of the fluid connector154is preferably in fluid communication with a first fluid channel272, which is open at the distal end262of the fluid connector154. In one embodiment, the second fluid tube opening268is preferably in fluid communication with a second fluid channel274, which is open at the distal end266of the fluid connector154. In one embodiment, the third fluid tube opening270of the fluid connector154is preferably in fluid communication with a third fluid channel276, which is open at the distal end262of the fluid connector154. The respective first, second and third fluid channels272,274,276preferably maintain the three fluids of the three component mixture separated and spaced away from one another until they are introduced into the spray tip housing for being mixed together.

Referring toFIGS. 17, 22A, and 22B, in one embodiment, the spray tip assembly125of the applicator instrument100(FIG. 1A) preferably includes a mixing element158that is disposed inside the spray tip housing160. The mixing element158may have the shape of a cylinder or a cylindrical-shaped rod. In one embodiment, the mixing element158, which is preferably located downstream of the fluid connector154, is adapted for mixing together the three fluids that pass through the fluid connector. In one embodiment, the mixing element158preferably has a proximal end278and a distal end280. The outer surface of the mixing element158preferably includes a plurality of static mixing fins282that are spaced from one another over the outer surface of the mixing element158for mixing together the three fluids as the fluids flow downstream through the mixing chamber. In one embodiment, the mixing element158preferably includes one or more laterally extending third fluid exit openings284that may be used for dispensing the third fluid into the mixing space (e.g., an annular mixing space) that surrounds the outer surface of the mixing element158. In one embodiment, the annular mixing space is preferably located between the outer surface of the mixing element and the inner surface of the spray tip housing160.

Referring toFIGS. 17, and 23A-23C, in one embodiment, the spray tip housing160of the spray tip assembly125preferably has a cylindrical or tube-shaped body with a proximal end288, a distal end290and an elongated conduit292that extends from the proximal end to the distal end thereof. In one embodiment, the spray tip housing160preferably includes an outer wall having an inner surface with internal threads161that are located adjacent the proximal end288thereof. In one embodiment, the internal threads161of the spray tip housing160preferably engage the external threads264of the fluid connector154(FIG. 21A) for securing the distal end of the fluid connector154to the spray tip housing160.

Referring toFIGS. 17 and 23D, in one embodiment, the elongated conduit292of the spray tip housing160is preferably adapted to receive the mixing element158. The internal threads161at the proximal end288of the spray tip housing160are desirably adapted to engage the external threads264(FIG. 21B) located at the distal end of the fluid connector154.

Referring toFIGS. 17 and 24A, in one embodiment, the spray tip assembly125of the applicator instrument100preferably includes the dispensing cap162that is adapted to be assembled with the distal end290of the spray tip housing160(FIG. 23D). In one embodiment, the dispensing cap162preferably has an open proximal end296that opposes a distal end of the mixing element and a closed distal end298having an end wall300with a dispensing opening302.

Referring toFIGS. 24A-24D, in one embodiment, the end wall300of the dispensing cap162preferably has an inner face304that surrounds the dispensing opening302. The dispensing cap162preferably includes a swirl chamber306having radially extending grooves308that direct fluids (e.g., the three fluids from the three syringes) from an outer perimeter310of the inner face304toward a circular depression312that surrounds the dispensing opening302. The swirl chamber306preferably provides for enhanced mixing of the fluids of a multiple component mixture prior to being dispensed through the dispensing opening302of the dispensing cap162.

In one embodiment, the dispensing cap162may have one or more of the structural features of the dispensing caps disclosed is commonly assigned U.S. patent application Ser. No. 16/593,783, filed on Oct. 4, 2019, the disclosure of which is hereby incorporated by reference herein.

In one embodiment, the dispensing cap162may have one or more of the structural features of the orifice cups disclosed is commonly assigned U.S. patent application Ser. No. 16/593,799, filed on Oct. 4, 2019, the disclosure of which is hereby incorporated by reference herein.

Referring toFIG. 25, in one embodiment, the spray tip assembly125of the applicator instrument100is preferably secured to the distal ends of the upper and lower fluid tube enclosures142,144(FIG. 2) so that the three fluids directed through the respective first, second and third fluid tubes146,148, and150may be directed into the three fluid tube openings266,268, and270(FIGS. 21C and 21G) located at the proximal end of the fluid connector154. In one embodiment, the external threads264(FIG. 21B) at the distal end of the fluid connector154mesh with the internal threads161(FIG. 20B) at the proximal end288of the spray tip housing160for securing the spray tip housing to the fluid connector. In one embodiment, the mixing element158is preferably disposed within the elongated conduit of the spray tip housing160, with the mixing chamber being located between the inner surface of the outer wall of the spray tip housing160and the outer surface of the mixing element158. Upon depressing the plunger head106in the distal direction DIR1(FIG. 17), the three fluids contained within the respective first, second and third fluid tubes146,148, and150are forced to flow downstream into the three fluid inlet openings of the fluid connector154, whereupon the three fluids pass through the respective fluid channels of the fluid connector154and are directed toward the proximal end of the mixing element158. The mixing element158preferably mixes the three fluids within the mixing chamber of the spray tip housing160prior to the final mixture being expressed from the dispensing opening of the dispensing cap162.

In one embodiment, the first fluid having the first reactive component (e.g., Fibrinogen) and the second fluid having the second reactive component (e.g., Thrombin) are mixed together within the mixing chamber of the spray tip assembly125to form a first mixture, and then the third fluid (e.g., a diluent or pH modifying buffer) is added to the first mixture within the mixing chamber to form a final mixture that is expressed (e.g., sprayed) from the dispensing opening of the dispensing cap162.

In one embodiment, the mixing chamber is an elongated mixing chamber that is located inside the spray tip housing160. The elongated mixing chamber may have an annular shape. In one embodiment, the spray tip housing160has a proximal end for receiving the respective first, second, and third fluids and a distal end that receives the dispensing cap162.

Referring toFIG. 26, in one embodiment, the spray tip assembly125may include a set of interchangeable mixing elements284A,284B, and284C having different structural characteristics for changing how, when and/or where along the length of the spray tip assembly the third fluid of the biocompatible reactive formulation is added to a first mixture of the first and second fluids. For example, each of the different mixing elements284A,284B, and284C may alter how the third fluid is added into a first mixture of first and second fluids to generate a final mixture that is expressed (e.g., sprayed) onto tissue. In certain preferred embodiments, only one of the mixing elements284A,284B, and284C is disposed inside the spray tip housing160at any one time. Thus, the reaction of the first and second reactive components may be controlled by selecting which of the unique mixing elements158A,158B, and158C is utilized.

In one embodiment, the spray tip assembly125may utilize a first mixing element158A having laterally extending third fluid exit openings284A that are located adjacent the distal end280A of the mixing element158A. In this embodiment, the first and second fluids are first mixed together within a mixing chamber at the proximal end of the first mixing element158A to form a first mixture, and, after the first mixture flows downstream through the mixing chamber toward the distal end of the mixing element158A, the third fluid is added to the first mixture, via the third fluid exit openings284A, adjacent the distal end of the first mixing element158A.

In one embodiment, the spray tip assembly125may utilize a second mixing element158B having laterally extending third fluid exit openings284B that are located midway between the proximal end278B and the distal end280B of the second mixing element. In this embodiment, the first and second fluids are mixed together within the mixing chamber at the proximal end of the second mixing element158B to form a first mixture, and, as the first mixture flows downstream through the mixing chamber toward the distal end of the mixing element158B, the third fluid is added to the first mixture, via the third fluid exit openings284B, at a location that is midway between the proximal end and the distal end of the second mixing element158B.

In one embodiment, the spray tip assembly125may utilize a third mixing element158C having laterally extending third fluid exit openings284C that are located adjacent the proximal end278C of the mixing element. In this embodiment, the first and second fluids are mixed together within the mixing chamber at the proximal end of the third mixing element158C to form a first mixture, and the third fluid is also added to the first mixture at the proximal end of the third mixing element158C, via the third fluid exit openings284C, to form a final mixture. The final mixture then travels the length of the mixing element for further mixing until it is dispensed via the dispensing opening of the dispensing cap162.

In other embodiments, the third fluid exit openings may be positioned at any location along the length of a mixing element to further modify and control how reactive components react with one another. Thus, an infinite number of different types of reactions may be attained by modifying the structure of the mixing elements.

In one embodiment, a system may include a kit having a first spray tip assembly that has the first mixing element158A, a second spray tip assembly that has the second mixing element158B, and a third spray tip assembly that has the third mixing element158C, whereby only one of the three spray tip assemblies is secured to the distal end of the applicator instrument at any one time. Thus, an operator may modify the characteristics of a biocompatible reactive formulation (i.e., by controlling how, when and/or where the first and second reactive components react with one another) that is dispensed from the applicator instrument by changing the spray tip assembly that is secured to the distal end of the applicator instrument. In one embodiment, a first spray tip assembly may be disconnected from a fluid connector and replaced by a second spray tip assembly that is secured to the fluid connector for changing how the three fluids are mixed together within the spray tip housing.

Referring toFIGS. 27A-27D, in one embodiment, the first mixing element158A (FIG. 26) preferably has an outer surface with a cylindrical shape (e.g., a cylindrical rod) that extends between a proximal end278A and a distal end280A thereof. The outer surface of the first mixing element158A preferably has a plurality of static mixing fins282A that are spaced from one another along the length of the first mixing element. The first mixing element158A preferably has a third fluid inlet opening314A, and a third fluid conduit316A that is in fluid communication with the third fluid inlet opening314A and that extends from the third fluid inlet opening314A to the laterally extending third fluid exit openings284A located adjacent the distal end280A of the first mixing element158A. In one embodiment, the third fluid flows into the third fluid inlet opening314A, flows downstream through the third fluid conduit316A, and then flows laterally through the third fluid exit openings284A for being directed into the mixing chamber so that the third fluid may be added into the first mixture of the first and second fluids.

Referring toFIG. 28A, in one embodiment, the distal end262of the fluid connector154may be inserted into the opening at the proximal end288of the spray tip housing160, whereupon the external threads264at the distal end of the fluid connector154engage the internal threads161adjacent the proximal end of the spray tip housing160for securing the distal end of the fluid connector154to the proximal end of the spray tip housing160. The O-ring154preferably forms a fluid-tight seal between the distal end of the fluid connector154and the inner surface of the spray tip housing160. In one embodiment, the third fluid channel276at the distal end of the fluid connector154is preferably aligned with the third fluid inlet opening314A and the third fluid conduit316A of the first mixing element158A. In one embodiment, the third fluid is preferably dispensed from the third fluid channel276and is directed into the third fluid conduit316A of the mixing element158A.

Referring toFIGS. 28A and 28B, in one embodiment, the first fluid is preferably dispensed from the first fluid channel272of the fluid connector154, and the second fluid is preferably dispensed from the second fluid channel274of the fluid connector154. The dispensed first and second fluids preferably flow downstream (i.e., in the distal direction DIR1) through an annular mixing space285that is located between an outer surface of the first mixing element158A and an inner surface of the spray tip housing160. As the first and second fluids flow downstream (in the direction DIR1) through the annular mixing space285, the first and second fluids are preferably mixed together by the static mixing fins282, which are spaced over the outer surface of the first mixing element158A.

In one embodiment, after the third fluid exits the third fluid channel276of the fluid connector154, the third fluid preferably travels downstream through the third fluid inlet opening314A and the third fluid conduit316A, whereupon the third fluid is directed laterally through the third fluid exit openings284A and into the annular mixing space285for being added into the first mixture of the first and second fluids. In the embodiment shown inFIGS. 28A and 28B, the third fluid is added into the first mixture adjacent the distal end of the first mixing element158A.

Referring toFIG. 28A, in one embodiment, the final mixture of the first, second and third fluids is desirably directed downstream toward the end wall300of the dispensing cap162, and is further directed into the swirl chamber306of the dispensing cap for further mixing. The final mixture is preferably expressed from the distal end of the spray tip assembly125via the dispensing opening302formed in the end wall300of the dispensing cap162.

Referring toFIGS. 29A and 29B, in one embodiment, the second mixing element158B (FIG. 26) preferably has an outer surface with a cylindrical shape that extends between a proximal end278B and a distal end280B of the second mixing element. The outer surface of the second mixing element158B preferably has a plurality of static mixing fins282B that are spaced from one another along the length of the second mixing element. The second mixing element158B preferably has a third fluid inlet opening314B and a third fluid conduit316B that extends distally from the third fluid inlet opening314B to third fluid exit openings284B, which are located about midway between the proximal end278B and the distal end280B of the second mixing element158B. In one embodiment, the third fluid is added to a first mixture of the first and second fluids via the third fluid exit openings284B, which are midway between the proximal and distal ends of the second mixing element158B. A final mixture, comprising the first, second, and third fluids, then flows in the downstream direction DIR1over the outer surface of the second mixing element158B. The final mixture is preferably further mixed as it travels downstream over the remaining length of the second mixing element158B.

Referring toFIGS. 30A and 30B, in one embodiment, the distal end262of the fluid connector154is preferably inserted into the opening at the proximal end288of the spray tip housing160, whereupon the external threads264at the distal end of the fluid connector154engage the internal threads161adjacent the proximal end288of the spray tip housing160for securing the distal end of the fluid connector154with the proximal end of the spray tip housing160. The O-ring154(FIG. 30A) preferably forms a fluid-tight seal between the fluid connector154and the inner surface of the outer wall of the spray tip housing160.

In one embodiment, when the syringe plungers are depressed, the first fluid is preferably dispensed from the first fluid channel272of the fluid connector154and the second fluid is preferably dispensed from the second fluid channel274of the fluid connector154, whereupon the first and second fluids are mixed together within the annular mixing space285that surrounds the second mixing element158B, thereby forming a first mixture. As the first and second fluids travel downstream toward the distal end290(FIG. 30A) of the spray tip housing160, the first and second fluids are preferably mixed together by the static mixing fins282B located over the outer surface of the second mixing element158B.

In one embodiment, the third fluid channel276located at the distal end of the fluid connector154is preferably aligned with the third fluid inlet opening314B and the third fluid conduit316B of the second mixing element158B. In one embodiment, the third fluid is preferably dispensed from the third fluid channel276and into the third fluid inlet opening314B, whereupon the third fluid is directed downstream into the third fluid conduit316B of the second mixing element158B. The third fluid preferably travels downstream to a midway location of the second mixing element158B, whereupon the third fluid is directed laterally through the third fluid exit openings284B and into the annular mixing space285that surrounds the outer perimeter of the second mixing element158B for being added into the first mixture of the first and second fluids to form a final mixture.

In the particular embodiment shown inFIGS. 30A and 30B, the first and second fluids are first mixed together at the proximal end of the second mixing element158B and within the annular mixing space285to form a first mixture, and the third fluid is added into the first mixture via the laterally extending third fluid exit openings284A. The final mixture of the first, second and third fluids is preferably directed through the annular mixing space285from a midsection of the second mixing element158B toward the end wall of the dispensing cap162, and is further directed into the swirl chamber306of the dispensing cap for further mixing. The final mixture is preferably expressed from the distal end of the spray tip assembly125via the dispensing opening302formed in the end wall300of the dispensing cap162.

Referring toFIGS. 31A and 31B, in one embodiment, the third mixing element158C (FIG. 26) preferably has an outer surface with a cylindrical shape (e.g., a cylindrical rod) that extends between a proximal end278C and a distal end280C of the third mixing element. The outer surface of the third mixing element158C preferably has a plurality of static mixing fins282C that are spaced from one another along the length of the third mixing element. The third mixing element158C preferably has a third fluid inlet opening314C that is in fluid communication with laterally extending third fluid exit openings284C, which are located adjacent the proximal end278C of the third mixing element158C. In one embodiment, the third fluid is added to the first mixture of the first and second fluids via the third fluid exit openings284C. The final mixture, comprising the first, second, and third fluids, preferably flows in the downstream direction DIR1toward the distal end280C of the third mixing element158C. The static mixing fins282C mix the first, second and third fluids together as the three fluids flow over the outer surface of the third mixing element158C.

Referring toFIGS. 32A and 32B, in one embodiment, the distal end262of the fluid connector154is desirably inserted into the opening at the proximal end288of the spray tip housing160, whereupon the external threads264at the distal end of the fluid connector154engage the internal threads161adjacent the proximal end288of the spray tip housing160for securing the distal end of the fluid connector154with the proximal end of the spray tip housing160. The O-ring156(FIG. 32A) preferably forms a fluid-tight seal between the fluid connector154and the inner surface of the outer wall of the spray tip housing160.

In one embodiment, when syringe plungers are depressed, the first fluid is preferably dispensed from the first fluid channel272of the fluid connector154and the second fluid is preferably dispensed from the second fluid channel274of the fluid connector, whereupon the first and second fluids are mixed together within an annular mixing space285located between the outer surface of the third mixing element158C and an inner surface of the spray tip housing160to form a first mixture.

In one embodiment, the third fluid channel276, located at the distal end of the fluid connector154, is preferably aligned with the third fluid inlet opening314C of the third mixing element158C. In one embodiment, the third fluid is preferably dispensed from the third fluid channel276of the fluid connector154and into the third fluid inlet opening314C, whereupon the third fluid is directed laterally through the third fluid exit openings284C located adjacent the proximal end278C of the third mixing element158C. The third fluid is preferably directed through the third fluid exit openings284C and into the annular mixing space285that surrounds the outer perimeter of the third mixing element158C for being added into the first mixture of the first and second fluids, which forms a final mixture.

In the particular embodiment shown inFIGS. 32A and 32B, the final mixture of the first, second and third fluids are desirably joined together adjacent the proximal end278C of the third mixing element158C, whereupon the final mixture (i.e., a mixture of the first, second and third fluids) flows downstream in the direction DIR1as it is further mixed by the fluid mixing fins282C spaced over the outer surface of the third mixing element158C. The final mixture preferably flows downstream through the annular mixing space285toward the end wall300of the dispensing cap162, whereupon the final mixture flows into the swirl chamber306of the dispensing cap162for further mixing. The final mixture is preferably expressed from the distal end of the spray tip assembly125via the dispensing opening302formed in the end wall300of the dispensing cap162.

Referring toFIGS. 33 and 34, in one embodiment, an applicator instrument100′ for mixing and expressing a composition, such as a biocompatible reactive formulation, preferably has one or more of the structural elements and/or features shown and described above inFIGS. 1A-32B. In one embodiment, the applicator instrument100′ preferably has a proximal end102′ and a distal end104′ including a spray tip assembly125′ located at the distal end. In one embodiment, the applicator instrument100′ is preferably configured for mixing together two or more fluid components (e.g., three components) to form a final mixture of a biocompatible reactive formulation (e.g., a tissue adhesive; a tissue sealant). In one embodiment, the final mixture of the biocompatible reactive formulation is preferably expressed from the spray tip assembly125′, which is located at the distal end104′ of the applicator instrument100′.

In one embodiment, the applicator instrument100′ preferably includes three syringe plungers108′,110′, and112′ that have the same size, shape and dimension. In one embodiment, the applicator instrument100′ preferably includes three syringe barrels118′,120′, and122′ that have the same size, shape, configuration, and dimension.

In one embodiment, the applicator instrument100′ preferably includes the first syringe barrel118′ that is adapted to contain a first reactive fluid of a multiple component tissue adhesive. In one embodiment, the first syringe barrel118′ is adapted to receive the first syringe plunger108′, which may be used for forcing the first reactive fluid from the distal end of the first syringe barrel118′.

In one embodiment, the applicator instrument100preferably includes the second syringe barrel120′ that is adapted to contain a second reactive fluid of the multiple component tissue adhesive. In one embodiment, the second syringe barrel120′ is adapted to receive the second syringe plunger110′, which may be used for forcing the second reactive fluid from the distal end of the second syringe barrel120′. The first and second reactive fluids may be mixed together to form a first mixture. In one embodiment, the first and second reactive fluids may be adapted for chemically reacting with one another to form a biocompatible reactive formulation, such as a tissue adhesive or a tissue sealant.

In one embodiment, the applicator instrument100desirably includes the third syringe barrel122′, which is adapted to receive the third syringe plunger112′. In one embodiment, the third syringe barrel122′ is adapted to contain a third fluid component (e.g., a neutralizing buffer; a diluent, such as H2O). In one embodiment, the third syringe plunger112′ may be depressed for forcing the third fluid component from the distal end of the third syringe barrel122′, whereupon the third fluid may be added into and/or mixed with the first mixture of the first and second reactive fluids.

In one embodiment, proximal ends of the syringe plungers108′,110′, and112′ are preferably secured to a plunger head106′, which may be depressed in the distal direction DIR1for simultaneously moving the syringe plungers in the distal direction DIR1to simultaneously dispense the first, second and third fluids from the respective first, second and third syringe barrels118′,120′, and122′.

In one embodiment, the first, second and third syringe barrels118′,120′, and122′ are the same size and may have respective cross-sectional diameters that are the same size. In one embodiment, the respective first, second, and third syringe barrels118′,120′, and122′ are configured to hold an equal volume of fluid. Thus, the volume of the first fluid held in the first syringe barrel118′ may equal the volume of the second fluid held in the second syringe barrel120′, which, in turn, may be equal to the volume of the third fluid held in the third syringe barrel122′.

In one embodiment, the applicator instrument100′ preferably includes a fluid manifold124′ that is located downstream from the distal ends of the first, second and third syringe barrels118′,120′,122′. In one embodiment, the fluid manifold124′ preferably includes a first connector126′ adapted to receive a distal end of the first syringe barrel118′, a second connector128′ adapted to receive a distal end of the second syringe barrel120′, and a third connector130′ adapted to receive a distal end of the third syringe barrel122′.

In one embodiment, the first connector126′ of the fluid manifold124′ is preferably in fluid communication with the first syringe barrel118′. In one embodiment, a first component of a multiple component adhesive that is pre-loaded into the first syringe barrel118′ may be forced to flow into the first connector126′ of the fluid manifold124′, such as by depressing the first syringe plunger108′.

In one embodiment, the second connector128′ of the fluid manifold124′ is preferably in fluid communication with the second syringe barrel120′. In one embodiment, a second component of a multiple component adhesive that is pre-loaded into the second syringe barrel120′ may be forced to flow into the second connector128′ of the fluid manifold124′, such as by depressing the second syringe plunger110′.

In one embodiment, the third connector130′ of the fluid manifold124′ is preferably in fluid communication with the third syringe barrel122′. In one embodiment, a third component of a multiple component adhesive that is pre-loaded into the third syringe barrel122′ may be forced to flow into the third connector130′ of the fluid manifold124′, such as by depressing the third syringe plunger110′.

In one embodiment, the applicator instrument100′ preferably includes a syringe barrel support frame138′ that is adapted to receive and hold the first, second and third syringe barrels118′,120′, and122′. The syringe barrel support frame138′ desirably holds the syringe barrels118′,120′,122′ together for stabilizing the syringe barrels and enhancing the structural integrity and consistent performance of the applicator instrument100.

In one embodiment, the syringe barrel support frame138preferably has a distal end with a distal projection140′ having internal threads, which are adapted to mesh with external threads of a connecting nut132′ for securing the distal end of the syringe barrel support frame138′ to the connecting nut132′. In one embodiment, the connecting nut132′ may also be utilized for securing both the distal projection140′ of the syringe barrel support frame138′ and the distal end of the third syringe barrel122′ to the second connector130′ of the fluid manifold124′.

Referring toFIG. 35, in one embodiment, the distal end230A′ of the first syringe barrel118′ is inserted into the third fluid inlet opening of the first connector128′ of the fluid manifold124′. A first O-ring retainer134A′ and a first O-ring136A′ are utilized to form a fluid-tight coupling between the distal end230′ of the first syringe barrel118′ and the first connector126′ of the fluid manifold124′.

In one embodiment, the distal end230B′ of the second syringe barrel120′ is inserted into the third fluid inlet opening of the second connector128′ of the fluid dispensing manifold124′. A second O-ring retainer134B′ and a second O-ring136B′ are utilized for forming a fluid-tight coupling between the distal end of the second syringe barrel120′ and the second connector128′ of the fluid manifold124′.

In one embodiment, the distal end230C′ of the third syringe barrel122′ is inserted into the third fluid inlet opening of the third connector130′ of the fluid dispensing manifold124′. A third O-ring retainer134C′ and a third O-ring136C′ are utilized for forming a water-tight coupling between the distal end of the third syringe barrel122′ and the third connector130′ of the fluid manifold124′.

In one embodiment, the first fluid dispensing opening232A′ located at the distal end of the first syringe barrel118′ is preferably in fluid communication with the first fluid tube146′ for directing the first fluid of a mixture from the first syringe barrel118′ into the first fluid tube146′.

In one embodiment, the second fluid dispensing opening248B′ located at the distal end230B′ of the second syringe barrel120′ is preferably in fluid communication with the second fluid tube148′ for directing the second fluid of a mixture from the second syringe barrel120′ into the second fluid tube148′.

In one embodiment, the third dispensing opening248C′ at the distal end230C′ of the third syringe barrel122′ is preferably in fluid communication with the third fluid tube150′ for directing the third fluid of the mixture from the third syringe barrel122′ into the third fluid tube150′.

In one embodiment, the distal end104′ of the applicator instrument100′ preferably includes the spray tip assembly125′, which is secured to the distal ends of the respective upper and lower fluid tube enclosures142′,144′. In one embodiment, the spray tip assembly125′ preferably includes the fluid connector154′ having a distal end that is secured to a proximal end of the spray tip housing160′. An O-ring156′ forms a fluid-tight seal between the fluid connector154′ and the spray tip housing160′ A mixing element158′ is disposed inside the spray tip housing160′. A dispensing cap162′ is preferably assembled within an opening provided at the distal end of the spray tip housing160′.

Referring toFIG. 36, in one embodiment, a dispensing system100″ for dispensing a tissue adhesive preferably includes a first syringe barrel118″ adapted to contain a first fluid having a first reactive component, a second syringe barrel120″ adapted to contain a second fluid having a second reactive component, and a third syringe barrel122″ adapted to receive a third fluid (e.g., a neutralizing buffer; a diluent such as H2O). In one embodiment, a first syringe plunger108″ having a first piston114″ secured to a distal end thereof is assembled with the first syringe barrel118″, a second syringe plunger110″ having a second piston116″ secured to a distal end thereof is assembled with the second syringe barrel120″, and a third syringe plunger112″ having a third piston117″ secured to a distal end thereof is assembled with the third syringe barrel122″.

In one embodiment, proximal ends of the first, second and third syringe plungers108″,110″ and112″ are desirably secured to the plunger head106″. The plunger head106″ may be pushed in the distal direction DIR1for forcing the pistons114″,116″ and117″ toward the distal ends of the respective syringe barrels118″,120″, and122″ to simultaneously force the first, second and third fluids from the distal ends of the syringe barrels.

In one embodiment, when the plunger head106″ is depressed, the first fluid in the first syringe barrel118″ flows downstream through the first fluid tube146″ and into the spray tip assembly125″, and the second fluid in the second syringe barrel120″ flows downstream through the second fluid tube148″ and into the spray tip assembly125″ for being mixed with the first fluid to form a first mixture. Simultaneously, the third fluid in the third syringe barrel122″ flows downstream through the third fluid tube150″ and into the spray tip assembly125″ for being added into the first mixture of the first and second fluids. The third fluid is preferably added into the first mixture of the first and second fluids at a location that is downstream of the location where the first and second fluids are first mixed together within the spray tip assembly125″. The location where the third fluid tube150″ enters the spray tip assembly125″ may be modified for changing how the first and second reactive components react with one another.

While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, which is only limited by the scope of the claims that follow. For example, the present invention contemplates that any of the features shown in any of the embodiments described herein, or incorporated by reference herein, may be incorporated with any of the features shown in any of the other embodiments described herein, or incorporated by reference herein, and still fall within the scope of the present invention.