# Patent

## Title
System and method for perfusing biological organs

## Abstract

A system for perfusing a biological organ for use as an experimental model includes a housing having sides that define a cavity for containing a biological organ model within a solution. The housing includes a plurality of apertures defined therethrough configured to mechanically interface with a filter, one or more heating elements and one or more sensors. A peristaltic pump is configured to withdraw and pressurize the solution from the housing and reintroduce the solution under pressure into the biological organ. A heat control module operatively connects to the heating elements and is configured to regulate the temperature of the solution within the housing. A data acquisition system operatively connects to the heat control module, the peristaltic pump and the sensor(s) and regulates and monitors the pressure, flow rate and temperature of the solution during electrical treatment of the biological organ.

## Background
BACKGROUND
The present disclosure relates to a system and method for modeling the heat loss of an organ during energy-based ablation treatments. More particularly, the present disclosure relates to a bench-top, perfusion system and methods for simulating heat loss of a liver during radiofrequency and/or microwave ablation procedures.
TECHNICAL FIELD
In the treatment of diseases such as cancer, certain types of cancer cells have been found to denature at elevated temperatures that are slightly lower than temperatures normally injurious to healthy cells. Known treatment methods, such as hyperthermia therapy, use electrosurgical energy (e.g., electromagnetic radiation) to heat diseased cells to temperatures above 41° C. while maintaining adjacent healthy cells below the temperature at which irreversible cell destruction occurs. These methods involve applying electrosurgical energy to heat, ablate and/or coagulate tissue. Radiofrequency (RF) or Microwave energy is sometimes utilized to perform these procedures.
Treatment may involve inserting ablation probes into tissues or organs where cancerous tumors have been identified. Once the probes are positioned, electrosurgical energy is passed through the probes into surrounding tissue which heats to a certain temperature to destroy malignant tissue. There are a number of different types of apparatus that can be used to perform ablation procedures. Typically, microwave apparatus for use in ablation procedures include a microwave generator, which functions as an energy source, and a microwave surgical instrument having an antenna assembly for directing the energy to the target tissue. The microwave generator and surgical instrument are typically operatively coupled by a cable assembly having a plurality of conductors for transmitting microwave energy from the generator to the instrument, and for communicating control, feedback and identification signals between the instrument and the generator. RF probes may also be utilized to accomplish the same or similar purposes.
Energy is typically applied via antenna assemblies that penetrate tissue. For example and with particular respect to microwave energy probes, several types of antenna assemblies are known, such as monopole and dipole antenna assemblies. In monopole and dipole antenna assemblies, microwave energy generally radiates perpendicularly away from the axis of the conductor. A monopole antenna assembly includes a single, elongated conductor that transmits microwave energy. A typical dipole antenna assembly has two elongated conductors, which are linearly aligned and positioned end-to-end relative to one another with an electrical insulator placed therebetween. Each conductor may be about 1⁄4 of the length of a wavelength of the microwave energy, making the aggregate length of the two conductors about 1⁄2 of the wavelength of the supplied microwave energy. During certain procedures, it can be difficult to assess the extent to which the microwave energy will radiate into and heat the surrounding tissue, making it difficult to determine the area or volume of surrounding tissue that will be ablated. In addition, in certain instances it may also be difficult to assess the extent to which heat is lost inside the tissue or organ during the ablation procedure.
SUMMARY
The present disclosure relates to a system for perfusing a biological organ, e.g., a liver, for use as an experimental model and includes a housing having sides that define a cavity for containing a biological organ model within a solution. The housing includes a plurality of apertures defined therethrough configured to mechanically interface with one or more heating element and/or one or more sensors. One or more filters may also be mechanically interfaced with the apertures. A peristaltic pump is included and configured to withdraw and pressurize the solution from the housing and reintroduce the solution under pressure into the biological organ. A heat control module is configured to regulate the temperature of the solution within the housing and a data acquisition system controls and monitors the heat control module, the peristaltic pump and the sensor(s) to monitor the pressure, flow rate and temperature of the solution during electrical treatment of the biological organ. The sensor may be a pressure transducer, thermocouple or flow rate monitor.
In one embodiment, a conductive ground plate may be disposed in the housing and configured to provide a return path during radio frequency electrical treatment of the biological organ. The ground plate may be selectively removed for cleaning and/or replacement purposes. A specimen table may also be included for supporting the biological organ within the housing. The specimen table may be configured to nestingly-receive the ground plate. The specimen table may also include perforations to allow the solution to freely circulate around the biological organ when disposed in the housing.
In one embodiment, the data acquisition system includes a computer for analyzing data received from the sensor, the heat control module and/or the peristaltic pump. In yet another embodiment, the peristaltic pump includes pressurized tubes for supplying solution to the biological organ, e.g., a liver, each tube configured to accommodate an entry vessel of the liver, e.g., about 0.8 centimeters in diameter for the tube attached to the portal vein and about 0.2 centimeters in diameter for the tube attached to the hepatic artery. The differently sized tubes create a subdivided flow ratio of about 70:30 between the portal vein and hepatic artery. The peristaltic pump may be configured to create a flow rate of about 1500 ml/min. through the liver.
In still another embodiment, the solution includes saline, heparin or other commonly used blood substitutes. The system may also include one or more filters configured to reduce blood clots within the circulating solution. Yet in another embodiment, the system includes an electrode holder for supporting one or more electrodes during electrical activation thereof.
The present disclosure also relates to a method for perfusing a biological organ (e.g., a liver) and includes the initial step of flushing blood from the biological organ utilizing one or more commonly known flushing procedures, e.g., utilizing a saline flushing solution or a saline and Heparin flushing solution (or other commonly known solution) to prevent or clear clotting (e.g., coagulation of smaller capillaries in the liver). The method also includes the steps of: placing the biological organ into a housing containing a perfusing solution; pumping the solution from the housing and reintroducing the solution under pressure into the biological organ through one or more natural orifices; regulating the temperature of the solution (via one or more heating elements and sensors) with a heat control module; and acquiring data relating to the pressure, flow rate and temperature of the solution during electrical treatment of the biological organ.
In an additional step, the solution may be filtered prior to entering the biological organ. With particular respect to a liver used as a biological organ, the pump may be configured to produce a flow rate of 1500 ml/min. into the liver with a ratio of about 70:30 portal vein to hepatic artery. The heating elements may be utilized to maintain the solution at a temperature of about 37 degrees Celsius.



BRIEF DESCRIPTION OF THE DRAWINGS
Various embodiments of the subject instrument are described herein with reference to the drawings wherein:
FIG. 1 is a schematic representation of a biological organ perfusion system shown according to one embodiment of the present disclosure;
FIG. 2 is an enlarged, perspective model view of a biological organ perfusion system according to another embodiment of the present disclosure; and
FIG. 3 is an enlarged, exploded view of the biological organ perfusion system of FIG. 2.



DETAILED DESCRIPTION
Prior to perfusing a biological organ, e.g., a liver 500, for use in gathering heat loss and other experimental data from the liver 500 during an ablation treatment, the liver 500 is initially flushed of blood utilizing one or more suitable flushing procedures utilizing a saline solution or a saline and Heparin solution to prevent clotting (e.g., coagulation of smaller capillaries in the liver).
Referring initially to FIG. 1, a schematically-illustrated system 10 for perfusing a biological organ, e.g., liver 500, is depicted and generally includes a housing 20 having sides 22 that are configured to define a cavity 25 for supporting or containing a liver 500 or other biological tissue therein. The housing 20 acts as a reservoir for containing the liver 500 in a solution 75 (e.g., saline or other suitable liquid of about 30 liters). The housing 20 includes a series of ports 23 defined through one or more of the sides 22 that are configured to operatively couple to one or more mechanical components utilized in the perfusing system 10, e.g., heaters 30a and 30b, fittings with valves 40a and 40b and conductive ground pad 50.
A peristaltic pump 60 is configured to operatively couple to the system 10 and supplies solution 75 (e.g., a saline solution) for infusion into the liver 500. The pump 60 draws solution 75 from a reservoir contained within the cavity 25 for circulation purposes. Solution 75 is drawn from the reservoir into the pump 60, which forces the solution 75 into the liver 500 through one or more vein and/or artery entry points in the liver 500, e.g., the portal vein 502 and/or the hepatic artery 504. The average rate of blood flow through a typical liver is about 1500 ml/min. with the majority of blood flowing through the portal vein (e.g., about 70%). In the present disclosure, the fluid perfuses the liver 500 under about the same flow rate and is forced to exit through the vena cava 506 into the reservoir where it is, again, re-circulated to the pump 60.
In order to simulate blood flow in the perfusing system 10 under real conditions, the tubing 502a and 504a of the perfusing system 10 is adapted to accommodate the different diameter size of the two blood vessels 502 and 504, respectively. For example, the tubing diameter for the portal vein 502 may be nominally sized to about 0.8 cm and the tubing diameter size for the hepatic artery may be sized to about 0.2 cm. The different tubing diameters and the multi-channel or multi-port peristaltic pump 60 establish adjustable flow rates to simulate a working liver model similar to live human liver. As one example, a working pump rate at 280 RPM creates about a 1500 ml/min flow through a model liver 500 and the different diameter tubing sizes allows a subdivided flow of about 70% portal vein and 30% hepatic artery.
In one embodiment, the temperature of the solution 75 is regulated using one or more heaters 30a and 30b, and various controls 85 and 300 and sensors 88 operably connected to the perfusing system 10. For example and as best shown in FIG. 1, the perusing system 10 includes two heaters 30a and 30b coupled to a heat control module 85 for controlling the temperature of the saline solution 75. The heat control module 85, in turn, communicates with one or more thermocouples 88 to sense the temperature of the saline solution 75 in the reservoir and actively adjust the heaters to maintain the reservoir temperature at about 37° C. The thermally regulated saline that perfuses the liver dictates the temperature of the organ nominally at 37° C. Other suitable temperatures are contemplated by the present disclosure. As described in more detail below with respect to FIGS. 2 and 3, various mounting blocks may be utilized to support the thermocouple(s) 88 and heaters 30a and 30b. The heaters 30a and 30b may be directly coupled to one or more sides of the housing 120 or supported upon a support table 170 disposed adjacent the perfusing system 10.
The perfusing system 10 may also be equipped with one or more sensors or transducers 90a and 90b that are configured to monitor the pressure, flow rate and/or temperature in the portal vein 502 and/or the hepatic artery 504. The measured values are communicated back to a computer 200 and/or a data acquisition system 300 that actively monitors, records and/or regulates the various operating and control elements of the perfusing system 10, e.g., heaters 30a and 30b, pump 60, sensors 90a and 90b, thermocouple(s) 88. This enables an operator to vary certain parameters of the perfusing system 10 to simulate various conditions. The valves 40a and 40b may be regulated as well to control the flow of fluid into the system. The control conditions are highly controllable and highly repeatable with limited variability in the testing environment. This enables an operator to test liver reaction and liver response under consistent operating conditions with minimal variation amongst the pre-set operating parameters. The system 10 also enables the operator to vary certain parameters, e.g., temperature, pressure, etc., while maintaining other parameters fixed for experimental purposes.
FIGS. 2 and 3 show a working model representation of a liver perfusion system 100 in accordance with the schematic embodiment of the present disclosure shown in FIG. 1. More particularly, the liver perfusing system 100 includes a nonconductive housing 120 having sides 122 that form an internal cavity 135 for containing a saline solution 75 or other suitable solution as mentioned above (See FIG. 1). The system 100 is designed as a modular unit with selectively adjustable and removable components, which permits more adaptability of the system to simulate working conditions.
The sides 122 of the housing 120 are configured with various mechanical interfaces, e.g., apertures or ports 123, slits, cutouts 121, ridges 137, etc., that allow the user to easily mount and/or couple the various components that make up the system 100, e.g., filters or valves 125, thermocouples 88, lid 131 and electrode holder assembly 160, etc. For example, a slit 121 is defined in a side 122 of the housing 120 and is dimensioned to matingly receive a filter block 145 for supporting one or more filters or filter valves 125 thereon; fitting block 166 may be utilized to support a plurality of filters or valves 125 within the filter block 145 mounted to the inside of housing 120.
In another example, a heater control box mount 130 may be coupled atop table 170 to support a heater, e.g., heater 30a, 30b (See FIG. 1) thereon for regulating the temperature of the solution 75 (See FIG. 1) inside the housing 120. The heater control box 130 also prevents the temperature controller (heater 30a and 30b) from accidental exposure to the solution 75. Moreover, one or more thermocouple ports 140 may be defined in one or more sides 122 of the housing 120 to mount or support thermocouples 88 (See FIGS. 1 and 3) that monitor the temperature of the solution 75 and provides information relating thereto back to the heat control module 85 (See FIG. 1). A removable thermocouple block 168 may also be employed to support an array or series of thermocouples 88 and other sensors (not shown) utilized with the system 100 within the thermocouple port(s) 140. The various mounts 130 and support blocks 145, 168 are all selectively removeably to facilitate cleaning and/or replacement of accessories.
The housing 20 is configured to accommodate a specimen table 150 therein that supports the treatment specimen, e.g., liver 500. The specimen table 150 includes perforations 152 to facilitate circulation of the solution 75 around the liver 500. Conductive ground plate 165 is disposed in the housing 120 below the specimen table 150 in a nested-like arrangement and may be dimensioned to connect to a ground plug (not shown) that connects through the housing 120. Conductive ground plate 165 provides return path back to the electrosurgical generator (not shown) during electrical activation. The conductive ground plate 165 simulates the ground return for radiofrequency applications but can easily be removed during microwave ablation. An accessory table 170 and computer shelf 175 may also be utilized to support various electronic accessories proximate the system 100.
In use the liver perfusion system 10 (or 100) may be utilized to regulate, monitor and/or adjust the pressure, flow rate and temperature of the solution 75 flowing into the hepatic artery 504 and portal vein 502, through the liver 500 and out the vena cava 506 The system 10 (or 100) allows for a highly repeatable and highly controllable testing environment for modeling heat loss within a liver 500 during the application of electrical energy, such as microwave ablation or radiofrequency application.
The present disclosure also relates to a method for perfusing a biological organ (e.g., a liver 500) and includes the initial step of flushing blood from the biological organ 500 utilizing one or more commonly known flushing procedures utilizing a saline flushing solution or a saline and Heparin flushing solution to prevent clotting (e.g., coagulation of smaller capillaries in the liver). The method also includes the steps of: placing the biological organ 500 into a housing 20 containing a solution 75; pumping the solution 75 from the housing 20 and reintroducing the solution 75 under pressure into the biological organ 500 through a natural orifice (e.g., in the case of a liver the portal vein 502 or hepatic artery 504); regulating the temperature of the solution 75 with the housing 20 utilizing one or more heating elements 30a and 30b and sensors 90a, 90b, 88 that are regulated and monitored with a heat control module 85; and acquiring data relating to the pressure, flow rate and temperature of the solution 75 during electrical treatment of the biological organ 500.
In an additional step, the solution 75 is filtered prior to entering the biological organ 500. The pump 60 of the pumping step may be configured to produce a flow rate of about 1500 ml/min. into the biological organ 500 with a ratio of about 70:30 portal vein to hepatic artery. Other pumping speeds and flow rates are also contemplated depending upon a particular purpose or when perfusing a particular organ. One or more heating elements 30a and 30b may be utilized to maintain the solution 75 at a temperature of about 37 degrees Celsius.
From the foregoing and with reference to the various figure drawings, those skilled in the art will appreciate that certain modifications can also be made to the present disclosure without departing from the scope of the present disclosure. While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of particular embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

## Claims

1. A system for perfusing a biological organ for use as an experimental model, the system comprising:
a housing having sides that define a cavity for containing a biological organ within a solution, the housing including a plurality of apertures defined therethrough configured to mechanically interface with at least one heating element and at least one sensor;
a removable conductive ground plate disposed in the housing, the removable conductive ground plate including a plurality of legs extending therefrom and configured to provide a return path during radiofrequency electrical treatment of the biological organ;
a specimen table for supporting the biological organ within the housing, the specimen table including a plurality of legs extending therefrom and configured to nestingly-receive the removable conductive ground plate below the specimen table;
a peristaltic pump configured to withdraw the solution from the housing and reintroduce the solution under pressure into the biological organ;
a heat control module operatively connected to the at least one heating element, the heat control module configured to regulate the temperature of the solution within the housing; and a data acquisition system operatively connected to the heat control module, the peristaltic pump and the at least one sensor, the data acquisition system configured to regulate the pressure, flow rate and temperature of the solution during electrical treatment of the biological organ, the data acquisition system includes a computer for analyzing data received from the at least one sensor, heat control module and peristaltic pump.

2. The system for perfusing a biological organ according to claim 1, wherein the at least one sensor includes at least one of a pressure transducer, thermocouple, and flow rate monitor.

3. The system for perfusing a biological organ according to claim 1, wherein the specimen table includes perforations configured to allow the solution to freely circulate around the biological organ.

4. The system for perfusing a biological organ according to claim 1, wherein the peristaltic pump includes pressurized tubes for supplying solution to the biological organ, each pressurized tube configured to accommodate an entry vessel of the biological organ.

5. The system for perfusing a biological organ according to claim 4, wherein the biological organ is a liver and the pressurized tube attached to a portal vein of the liver is about 0.8 centimeters in diameter and the pressurized tube attached to a hepatic artery of the liver is about 0.2 centimeters in diameter.

6. The system for perfusing a biological organ according to claim 1, wherein the biological organ is a liver and the peristaltic pump creates a flow rate of about 1500 ml/min. through the liver.

7. The system for perfusing a biological organ according to claim 5, wherein the differently sized pressurized tubes create a subdivided flow ratio of about 70:30 between the portal vein and hepatic artery.

8. The system for perfusing a biological organ according to claim 1, wherein the solution includes saline.

9. The system for perfusing a biological organ according to claim 1, wherein the solution includes heparin.

10. The system for perfusing a biological organ according to claim 1, wherein one of the plurality of apertures defined through the housing is dimensioned to matingly receive a filter block mounted within the housing, the filter block including at least one filter configured to reduce blood clots within the solution.

11. The system for perfusing a biological organ according to claim 1, further comprising an electrode holder for supporting at least one electrode during electrical activation thereof.

12. The system for per fusing a biological organ according to claim 3, wherein the removable conductive ground plate includes a plurality of openings defined therein.