Medical ice slurry production and delivery system, and method

Abstract

To provide an improved system and method for medical ice slurry production.SOLUTION: A housing includes: an actuator; and a cooling apparatus which is cooperative with the housing so as to cool non-freezing slurry compositions held in a disposable cartridge down to a temperature cool enough to form ice crystals. A medical ice slurry production system includes: an agitator which is cooperative with the actuator of the housing for agitating medical slurry compositions containing reduced ice crystals through a tip end of a needle so as to reduce the ice crystals down to the size small enough to be delivered; and an access port which is configured and provided to allow the medical slurry compositions containing the reduced ice crystals to be collected or injected from the disposable cartridge while maintaining sterility of the medical slurry compositions containing the reduced ice crystals.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Cross - Reference to Related Applications) Not applicable.

[0002] (Statement Regarding Federally Sponsored Research) Not applicable.

[0003] The present disclosure relates generally to ice slurries for medical applications, and more specifically to systems and methods for the production and withdrawal or infusion of medical ice slurries.

Background Art

[0004] Ice slurries used in the medical field generally contain partially frozen saline. Medical ice slurries are used in surgical applications to induce hypothermia and protect a patient's organs during surgery by slowing the metabolic rate of the organs and tissues. Medical ice slurries are also infused into patients for selective or non - selective cryotherapy and / or cryoablation.

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present disclosure provides a system and method for generating a medical ice slurry. Specifically, a medical ice slurry generation system and method are disclosed that enable an end - user / clinician to generate and deliver a sterile medical ice slurry composition at the point of care.

Means for Solving the Problems

[0006] In one aspect, the present disclosure provides a medical ice slurry generation system comprising a disposable cartridge that holds a non-frozen, sterile medical slurry composition. The system further comprises a housing that supports the disposable cartridge. The housing includes an actuator and a cooling device that is cooperable with the housing to cool the non-frozen slurry composition held in the disposable cartridge to a temperature sufficient for ice crystals to form. The medical ice slurry generation system further comprises a stirrer that is cooperable with the actuator of the housing to stir the medical slurry composition to reduce the ice crystals to a size sufficient to deliver the medical slurry composition containing the reduced ice crystals through the tip of a needle to a patient, and an access port configured and provided to allow recovery or injection of the medical slurry composition containing the reduced ice crystals from the disposable cartridge while maintaining the sterility of the medical slurry composition containing the reduced ice crystals.

[0007] In another aspect, the present disclosure provides a medical ice slurry generation system comprising a disposable cartridge that holds a non-frozen, sterile medical slurry composition. The disposable cartridge includes an access port. The medical ice slurry generation system further comprises a housing that supports the disposable cartridge. The housing includes an actuator. The medical ice slurry generation system further comprises a cooling device that is cooperable with the housing to cool the non-frozen slurry composition held in the disposable cartridge to a temperature sufficient for ice crystals to form within the composition, a stirrer that is cooperable with the actuator of the housing to stir the medical slurry composition to reduce the ice crystals to a size sufficient to deliver the medical slurry composition containing the reduced ice crystals through the tip of a needle to a patient, and a pump operable to pump the medical slurry composition containing the reduced ice crystals out of the access port of the disposable cartridge through a disposable supply tube while maintaining the sterility of the medical slurry composition containing the reduced ice crystals.

[0008] In yet another aspect, the present disclosure provides a method for generating a medical ice slurry, comprising the steps of providing a disposable cartridge that holds a non-frozen, sterile medical slurry composition within a housing, and cooling the disposable cartridge to a temperature sufficient to form ice crystals within the disposable cartridge while the disposable cartridge is disposed within the housing. The method for generating a medical ice slurry further comprises agitating the medical slurry composition held within the disposable cartridge to reduce the size of the ice crystals within the disposable cartridge to a size sufficient to deliver the medical slurry composition containing the reduced ice crystals through the tip of a needle to a patient.

[0009] [Invention 1001] A disposable cartridge that holds a non-frozen, sterile medical slurry composition, A housing that supports the disposable cartridge and includes an actuator, A cooling device that is operable with the housing to cool the non-frozen slurry composition held within the disposable cartridge to a temperature sufficient to form ice crystals within the disposable cartridge, An agitator that is operable with the actuator of the housing to agitate the medical slurry composition to reduce the size of the ice crystals to a size sufficient to enable the medical slurry composition containing the reduced ice crystals to be delivered through the tip of a needle to a patient, An access port that is constructed and arranged to enable the medical slurry composition containing the reduced ice crystals to be withdrawn from or injected into the disposable cartridge while maintaining the sterility of the medical slurry composition containing the reduced ice crystals, A medical ice slurry generation system. [Invention 1002] The medical ice slurry generation system of Invention 1001, wherein the disposable cartridge comprises one of a syringe or a cannister. [The present invention 1003] The medical ice slurry generation system of the present invention 1001, wherein the access port is constructed and arranged to enable the syringe to engage with the access port and recover the slurry composition. [The present invention 1004] The medical ice slurry generation system of the present invention 1001, wherein the agitator comprises at least one vibration device or rotating device. [The present invention 1005] The medical ice slurry generation system of the present invention 1001, wherein the agitator comprises a rotating device constructed and arranged to rotate back and forth. [The present invention 1006] The medical ice slurry generation system of the present invention 1001, wherein the agitator is attached to the disposable cartridge. [The present invention 1007] The medical ice slurry generation system of the present invention 1001, wherein the agitator is attached to the actuator supported by the housing. [The present invention 1008] The actuator is a motor constructed and arranged to agitate the medical slurry composition inside the disposable container to the agitator so that the ice crystals inside the disposable cartridge are reduced to a size sufficient to allow the medical slurry composition containing the reduced ice crystals to be delivered through the tip of the needle for injection into the patient. The medical ice slurry generation system of the present invention 1001 comprising. [The present invention 1009] The medical ice slurry generation system of the present invention 1001, wherein the access port is defined within the disposable cartridge. [The present invention 1010] The access port is a first access port defined within the disposable cartridge, the system includes a second access port defined within the housing, and the first access port and the second access port are in fluid communication to enable the medical ice slurry composition to be recovered from the disposable cartridge while maintaining the sterility of the medical slurry composition, the medical ice slurry generation system of the present invention 1001. [The present invention 1011] The cooling device includes at least one of standard refrigeration, magnetic refrigeration, electrical cooling, or chemical cooling, the medical ice slurry generation system of the present invention 1001. [The present invention 1012] (i) A luer lock with a stopper, (ii) a pressure valve, (iii) a quick disconnect, (iv) a one-way valve with a luer lock, and (v) at least one of a sterile rubber stopper is cooperable with the access port to selectively enable the sterile medical slurry composition to be recovered from the disposable cartridge through the access port, the medical ice slurry generation system of the present invention 1001. [The present invention 1013] The crystallized ice that has become smaller is less than about 1 mm, the medical ice slurry generation system of the present invention 1001. [The present invention 1014] The actuator is operable to rotate the agitator at a rotational speed of about 1000 revolutions per minute to 45000 revolutions per minute, the medical ice slurry generation system of the present invention 1001. [The present invention 1015] The agitator includes one or more blades sized to define a length of about 12.5% to about 99% of the diameter of the disposable cartridge, respectively, the medical ice slurry generation system of the present invention 1001. [The present invention 1016] A disposable cartridge that holds a non-frozen sterile medical slurry composition and includes an access port, A housing that supports the disposable cartridge and includes an actuator, A cooling device cooperable with the housing for cooling the unfrozen slurry composition held within the disposable cartridge to a temperature sufficient for ice crystals to form within the disposable cartridge; An agitator cooperable with the actuator of the housing for agitating the medical slurry composition such that the ice crystals become small enough to a size sufficient for the medical slurry composition containing the reduced-size ice crystals to be delivered to a patient through the tip of a needle; A pump operable to pump the medical slurry composition containing the reduced-size ice crystals out of the access port of the disposable cartridge through a disposable delivery tube while maintaining the sterility of the medical slurry composition containing the reduced-size ice crystals; A medical ice slurry generation system comprising the above. [Invention 1017] Installing a disposable cartridge holding an unfrozen sterile medical slurry composition within a housing; Cooling the disposable cartridge to a temperature sufficient for ice crystals to form within the disposable cartridge while the disposable cartridge is installed within the housing; Agitating the medical slurry composition held within the disposable cartridge such that the ice crystals within the disposable cartridge become small enough to a size sufficient for the medical slurry composition containing the reduced-size ice crystals to be delivered to a patient through the tip of a needle; A medical ice slurry generation method including the above steps. [Invention 1018] The medical slurry generation method of Invention 1017, including the step of recovering the medical slurry composition containing the reduced-size ice crystals from the disposable cartridge while maintaining the sterility of the medical slurry composition. [Invention 1019] A method for generating a medical slurry according to the present invention 1017, comprising the step of pumping the medical slurry composition containing smaller ice crystals from a disposable cartridge while maintaining the sterility of the medical slurry composition. [The present invention 1020] The method for generating a medical slurry according to the present invention 1017, wherein the stirring step comprises stirring the medical slurry composition by an actuator so that the ice crystals inside the disposable cartridge become small enough to allow the medical slurry composition containing the smaller ice crystals to be delivered to a patient through the tip of a needle. The foregoing and other aspects and advantages of the present invention will become apparent from the following description. In the specification, reference is made to the accompanying drawings, which form a part hereof, and preferred embodiments of the present invention are shown therein by way of illustration. Such embodiments do not necessarily represent the full scope of the present invention, but accordingly the claims are referred to herein for the purpose of interpreting the scope of the present invention.

[0010] In view of the following detailed description, the present invention will be better understood and features, aspects, and advantages other than those described above will become apparent. Such detailed description refers to the following drawings.

Brief Description of the Drawings

[0011]

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Mode for Carrying Out the Invention

[0012] Detailed Description Medical ice slurry manufactured off-site (i.e., not at the point of care) requires cold chain transportation to transport the ice slurry to the point of care. Off-site generation imposes a significant burden on the end-user / clinician who administers the ice slurry to the patient. For example, the ice slurry must maintain sterility to ensure patient safety. The ice slurry must also be maintained at an appropriate temperature to maintain the ice crystal size, crystal shape, and ice content of the slurry, as well as to ensure that the slurry maintains its cooling performance and ability to be injected through a needle (i.e., stability). Thus, off-site ice slurry production may require manipulation of the ice slurry by the end clinician, which can potentially endanger patient safety and / or the effectiveness of the ice slurry.

[0013] Accordingly, it is desirable to have a medical ice slurry generation system that enables an end-user to generate and supply sterile medical ice slurry at the point of care. A system that generates medical ice slurry at the point of care while maintaining the sterility and stability of the slurry (e.g., ice crystal size, shape, ice content) can reduce the burden imposed on the end-user and simplify the overall process of producing and providing medical ice slurry to patients.

[0014] Figure 1 shows one non-limiting example of a medical ice slurry generation system 100. The medical ice slurry generation system 100 includes a disposable cartridge 102 configured to be supported within a housing 104. The illustrated disposable cartridge 102 is in the shape of a sterile pre-filled canister. The disposable cartridge 102 is pre-filled with a sterile slurry composition 106. For example, the disposable cartridge 102 may be pre-filled with one of the slurry compositions described in International Patent Application No. PCT / US2015 / 047301, which is hereby incorporated by reference in its entirety. For example, as described in PCT / US2015 / 047301, such a slurry composition can have a preferred ice content range and temperature range and can include one or more additional ice particle smoothing agents and / or biocompatible surfactants (such as glycerol), which can, for example, make the slurry easier to inject. In any of the systems described herein, it is preferred that such agents or surfactants be added after the system has agitated, blended, mixed, or pulverized the medical ice slurry (as described below) and immediately before injecting the slurry. Pre-filling the disposable cartridge 102 with the sterile slurry composition 106 ensures that the sterile slurry composition 106 is self-contained within a closed environment. This helps to reduce the burden on the end user who attempts to maintain the sterility of the slurry composition 106 while handling the disposable cartridge 102. In some non-limiting examples, the disposable cartridge 102 can be surrounded by a heat insulating material (not shown) to improve its thermal stability.

[0015] The disposable cartridge 102 can be made of plastic, glass, or metal materials. The disposable cartridge 102 can be sized to hold a slurry volume of from about 1 cubic centimeter (cc) to about 1 liter (L), depending on the medical application. The disposable cartridge 102 is rotatably coupled to the agitator 108. The agitator 108 includes an agitator shaft 110 and fins 112 disposed within the disposable cartridge 102. The fins 112 are coupled to the agitator shaft 110 and are helical in the longitudinal direction along the shaft 110. The agitator shaft 110 is partially housed within the disposable cartridge 102. That is, the agitator shaft 110 is received in the first side 114 of the disposable cartridge 102 such that the distal end 116 of the agitator shaft 110 protrudes from the first end 114 of the disposable cartridge 102. The agitator shaft 110 is rotationally sealed with respect to the first end 114 of the disposable cartridge 102 to enable rotation of the agitator shaft 110 with respect to the disposable cartridge 102 while maintaining a seal between the sterile slurry composition 106 and the surrounding environment. The seal between the agitator shaft 110 and the first end 114 of the disposable cartridge 102 can be obtained by utilizing at least one of, for example, a hydrostatic seal, a hydrodynamic seal, a fluid bearing, or an O-ring.

[0016] The disposable cartridge 102 includes an access port 118 disposed on a second side 120 of the disposable cartridge 102. The access port 118 is configured and arranged to enable the medical ice slurry composition 106 to be recovered from the disposable cartridge 102 while maintaining the sterility of the slurry composition 106. For example, the access port 118 can be configured to enable the medical ice slurry composition to be recovered from the access port using a syringe. Alternatively or additionally, although details will be described later, the user can pump the fluid of the medical ice slurry composition from the access port using a pump and a disposable supply tube. In certain implementations, the pump or a control device configured to operate the pump can be configured to have a maximum allowable pressure resistance at the end of the supply tube, supply needle, or cannula. The pump can include an adjustable constant volume pump, and the pump or a control device configured to operate the pump can be configured such that a user-specified stop occurs when a predetermined amount of the slurry is supplied. The user can also enable the medical ice slurry composition to be recovered from the access port via gravity flow. Of course, it is never intended to limit the location of the access port 18 of the disposable cartridge 102, and the access port 118 can be located at other locations on the disposable cartridge 102.

[0017] The housing 104 defines an internal cavity 122 sized to receive the disposable cartridge 102 and includes a pair of opposing side walls 124 extending from a base 126. The side walls 124 extend from the base 126 to a substantially open upper surface 128. In another non-limiting example, as shown in FIG. 2, the housing 104 can include a removable cover 129 attached to the substantially open upper surface 128 to further insulate the internal cavity 122 from the surrounding environment.

[0018] Continuing to refer to FIG. 1, the base 126 of the housing 104 includes an actuator 130 coupled to the actuator shaft 132. The actuator shaft 132 extends into the internal cavity 122 of the housing 104 and is configured to operably couple to the agitation shaft 110. The illustrated actuator 130 can be in the form of a motor. Alternatively or additionally, the actuator can be configured to vibrate or agitate the disposable cartridge 102 and the actuator shaft 132 at a predetermined frequency (e.g., an ultrasonic frequency). In another non-limiting example, the actuator 130 can be in the form of another rotational or vibrating mechanism well known in the art. The actuator 130 is configured to selectively rotate the actuator shaft 132 and, when coupled to the agitation shaft 110, induces turbulent agitation or mixing of the sterile slurry composition 106 within the disposable cartridge 102.

[0019] The medical ice slurry generation system 100 includes a cooling device 134. In one example, the cooling device 134 is at least partially supported within the housing 104. In the non-limiting example illustrated in FIG. 1, the side wall 124 of the housing 104 defines a passageway 136 that extends between the upper surface 128 and the base 126. In one non-limiting example, the passageway 136 can define a substantially helical path through the side wall 124. The passageway 136 is configured to contain a coolant or gas provided by the cooling device 134. Alternatively or additionally, the coolant or gas provided by the cooling device 134 can be supplied to a coil (e.g., a copper coil) that can be contained within the passageway 136. The cooling device 134 can include, for example, a condenser, a compressor, and an evaporator. In another non-limiting example, the cooling device 134 can utilize magnetic refrigeration, electric cooling, chemical cooling, conventional refrigeration, compressed gas (Joule-Thompson) cooling, thermoelectric (Peltier) cooling, or another slurry other than the sterile slurry composition 106. The housing 104 can be made from a material having a high thermal conductivity (e.g., stainless steel, copper, aluminum) to reduce the thermal resistance between the sterile slurry composition 106 within the disposable cartridge 102 and the coolant or gas within the passageway 136. Of course, in some non-limiting examples, the housing 104 can be made from one or more materials. For example, the inner portion of the housing 104 adjacent to the disposable cartridge 102 can be made from a material having a high thermal conductivity, and the outer portion of the housing 104 can be made from a heat insulating material (e.g., plastic or foam).

[0020] Power supply 138 supplies power to cooling device 134, actuator 130, and control device 140. Power supply 138 can be in the form of an AC wall outlet. Alternatively or additionally, power supply 138 can be in the form of a portable DC power supply (e.g., a battery), which promotes the portability of the medical ice slurry generation system 100. Control device 140 is electrically communicative with actuator 130 and cooling device 134 and is configured to selectively instruct actuator 130 to rotate actuator shaft 132 at a desired rotational speed. Control device 140 is further configured to control cooling device 134, thereby controlling the temperature of the coolant or gas within passageway 136. One or more sensors (not shown) can communicate with control device 140 to sense, for example, the temperature of the coolant or gas within passageway 136 and the temperature of the sterile slurry composition 106 within disposable cartridge 102. The temperature of the coolant or gas within passageway 136 and the temperature of the sterile slurry composition 106 can be measured using a thermocouple, a thermistor, or other electrical temperature sensors known in the art. Alternatively or additionally, radiation temperature sensors such as infrared detectors and pyroelectric sensors can be implemented. One or more sensors can provide feedback to control device 140 so that control device 140 can actively control cooling device 134 to achieve and maintain the desired temperature of the sterile medical ice slurry composition 106.

[0021] During operation, the housing 104 of the medical ice slurry generation system 100 is placed at a point-of-care location (e.g., near the patient). Next, the disposable cartridge 102 having the pre-filled non-frozen sterile slurry composition 106 is placed within the internal cavity 122 of the housing 104 and is coupled to the actuator shaft 132 for co-rotation with the agitation shaft 110. In some non-limiting examples, the internal cavity 122 of the housing 104 contains gas or air. In another non-limiting example, as shown in FIG. 3, the internal cavity 122 can be filled with liquid. The control device 140 is configured to command the cooling device 134 to cool the liquid or gas within the passage 136 to a desired temperature (i.e., the temperature at which ice crystals are formed within the slurry composition held within the disposable cartridge 102). In one non-limiting example, the desired temperature of the sterile slurry composition 106 is input into the control device 140, and the control device 140 can automatically control the cooling device 134 to reach and maintain the desired slurry temperature. In some non-limiting examples, the desired temperature of the sterile slurry composition is between about -10°C and about 4°C.

[0022] While the cooling device 134 is lowering the temperature of the sterile slurry composition 106 within the disposable cartridge 102, the control device 140 is configured to command the actuator 130 to rotate the actuator shaft 132 and thereby rotate the agitation shaft 110. Of course, before, at the same time as, or after the cooling device 134 begins to cool the disposable cartridge 102, the actuator 130 can be commanded to rotate the actuator shaft 132. Alternatively or additionally, the disposable cartridge 102 can be pre-cooled away from the housing 104 and then further cooled within the housing 104 to form ice crystals. A desired rotational speed or force magnitude provided by the actuator 130 can be input into the control device 140. In some non-limiting examples, the desired rotational speed provided by the actuator 130 is from about 100 revolutions per minute (rpm) to 45,000 rpm, or from about 5000 rpm to 40,000 rpm, or from about 10,000 rpm to 30,000 rpm. The rotation of the agitation shaft 110 causes the fins 112 within the sterile slurry composition 106 to rotate. The rotating fins 112 act to turbulently mix the sterile slurry composition 106 and serve multiple purposes. First, the turbulent mixing promotes a uniform temperature distribution within the sterile slurry composition 106. Second, the rotation of the fins 112 acts to break up ice crystals formed within the sterile slurry composition as the sterile slurry composition 106 is cooled (i.e., as the sterile slurry composition 106 transitions from a liquid composition to an ice slurry consisting of solid ice crystals and liquid). Alternatively or additionally, the control device 140 can be configured to maintain the homogeneity of the sterile slurry composition 106 after ice crystals have formed to prevent the slurry from separating. The control device 140 is configured to command the actuator 130 to provide a rotation of from about 60 rpm to 5000 rpm, or from about 500 rpm to 4000 rpm, or from about 1500 rpm to 2500 rpm to maintain the homogeneity of the sterile slurry composition 106.

[0023] The stirrer 108 can be configured to ensure that the ice crystals formed within the sterile slurry composition 106 are divided into specific ice crystal sizes. In one non-limiting example, the ice crystals formed within the sterile slurry composition 106 can be crushed to a size of less than about 1 millimeter (mm). In another non-limiting and optimal example, the ice crystals formed within the sterile slurry composition 106 can be crushed to a size of less than about 0.1 mm. The size of the ice crystals within the sterile slurry composition 106 can be confirmed using, for example, (i) light / laser diffraction methods, (ii) direct measurement with a microscope, and / or (iii) ultrasonic or acoustic methods. In some non-limiting examples, this measured size of the ice crystals within the sterile slurry composition 106 is communicated to the control device 140.

[0024] In certain embodiments, the control device 140 or any of the remaining optional control devices for any of the remaining embodiments described herein can also be configured to execute in response to two different cycles of agitation. In a first cycle, the control device of any of the embodiments herein commands the actuator and thus the actuator shaft and the agitation shaft (or any other optional agitation element described herein) to agitate such that the ice crystals are broken or crushed to a size small enough (e.g., less than about 1 mm or preferably less than about 0.1 mm) to be of injectable quality. In a second cycle, which can be either before or after the first cycle, the control device is configured to command the actuator and thus the actuator shaft and the agitation shaft (or any other optional agitation element described herein) to agitate to sufficiently mix the slurry. For example, to ensure or maintain sufficient mixing or homogeneity of the slurry, any of the systems described herein can be configured using a control device that provides rotation of the stirrer or agitation element at a rate of about 60 rpm to 5000 rpm, or about 500 rpm to 4000 rpm, or about 1500 rpm to 2500 rpm, or any other suitable speed and / or rotation rate of the agitation element.

[0025] In some non-limiting examples, the cooling device 134 can further be configured as a cooling and heating device for providing both cooling and heating to the sterile slurry composition 106. This enables a medical ice slurry generation system 100 that first forms ice crystals in the sterile slurry composition 106 and then supplies heat prior to injection to ensure the formation of homogeneous, spherical, and non-dendritic ice crystals.

[0026] Once the sterile slurry composition 106 is cooled to the desired slurry temperature and the ice crystals in the sterile slurry composition 106 reach the desired size, the sterile slurry composition 106 is recovered from the disposable cartridge 102 through the access port 118 for use in the desired medical application in a patient. Thereafter, the disposable cartridge 102 can be discarded, and the above-described process can be repeated using a new disposable cartridge 102.

[0027] As described above, all that is required of the end user or clinician is to place the pre-filled disposable cartridge 102 within the internal cavity 122 of the housing 104 and, after the slurry composition has reached the desired temperature with the desired ice crystal size, recover the sterile slurry composition 106 from the access port 118 for delivery to the patient. Thus, until the sterile ice slurry composition 106 is recovered for use by the patient (e.g., until recovered for use with another sterile delivery mechanism such as a syringe), the sterile slurry composition 106 is maintained within the disposable cartridge 102 throughout the ice slurry manufacturing process. Thus, it goes without saying that the sterile slurry composition 106 is self-contained throughout the medical ice slurry manufacturing process, reducing the clinician's burden of maintaining the sterility of the slurry composition 106. Also, the manufacture of the sterile slurry composition 106 for a given medical application (i.e., cooling and the formation of ice crystals of the appropriate size) is substantially automated by operating the control device 140, the cooling device 134, and the actuator 130 together.

[0028] FIG. 4 shows a sterile extraction syringe 200 configured to be coupled to an access port 118 for retrieving a sterilized slurry composition 106 in one non-limiting example. In some non-limiting examples, the access port 118 comprises a rubber stopper, a shut-off valve, and / or a luer lock with a removable sterile cover. The sterile extraction syringe 200 can comprise a needle (not shown) to facilitate injection of the sterile slurry composition 106 into a patient. In some non-limiting examples, the needle (not shown) can be 19 gauge or smaller. The agitator 108 can be configured to break up ice crystals formed within the sterile slurry composition 106 to a size that allows the slurry to flow through the diameter of the needle of the sterile extraction syringe 200. In one non-limiting example, the size of the ice crystals can be, for example, less than about 1 mm or less than about 0.3 mm.

[0029] Moving on to FIG. 5, in some non-limiting examples, the medical ice slurry generation system 100 comprises a syringe holder 300 coupled to the housing 104. In another non-limiting example, the syringe holder 300 can be separated from the housing 104. The sterile extraction syringe 200 can be disposed within the syringe holder 300 to thermally insulate the sterile slurry composition 106 within the sterile extraction syringe 200. In some non-limiting examples, the syringe holder 300 is actively cooled, for example, by coupling the syringe holder 300 to a cooling device 134 to maintain the sterile slurry composition 106 within the sterile extraction syringe 200 at a desired slurry temperature. Alternatively or additionally, the syringe holder 300 can include an agitator to prevent separation of the sterile slurry composition 106 within the sterile extraction syringe 200 prior to injection. It should be known that the syringe holder 300 can be incorporated into any configuration of the medical ice slurry generation system 100 described herein.

[0030] As shown in FIG. 6, in some non-limiting examples, the disposable cartridge 102 includes one or more filters 400 disposed adjacent to the access port 118. The one or more filters 400 ensure that ice crystals of a desired size are continuously recovered by the sterile extraction syringe 200 and subsequently injected into the patient. In the illustrated non-limiting example, the one or more filters 400 include a first filter 402, a second filter 404, and a third filter 406, and the second filter 404 is disposed between the first filter 402 and the third filter 406. The first filter 402 is configured to filter ice crystals of a first size. The second filter 404 is configured to filter ice crystals of a second size smaller than the first size, and the third filter 406 is configured to filter ice crystals of a third size smaller than the second size. As will be appreciated by those skilled in the art, the sizes of the ice crystals filtered by the first, second, and third filters 402, 404, and 406 can be used to control the size of the ice crystals in the sterile slurry composition 106 injected into the patient. For example, in one non-limiting example, the first size is about 500 micrometers (μm), the second size is about 250 μm, and the third size is about 100 μm. In another non-limiting example, the disposable cartridge 102 can include any number of filters 400 that filter ice crystals of any size, as needed.

[0031] In another non-limiting example, as shown in FIG. 7, the one or more filters 400 are instead disposed within the sterile extraction syringe 200.

[0032] Figures 8 - 11 show additional non - limiting examples of agitator 108 of disposable cartridge 102 that is operable with actuator 130 to crush ice crystals and mix or stir sterile slurry composition 106. FIG. 8 shows agitator 108 without fins 112 of FIG. 1. FIG. 9 shows agitator 108 with a plurality of raised protrusions 700 axially disposed along the interior of disposable cartridge 102. Each raised protrusion 700 extends towards agitator shaft 110 and fins 112 coupled to agitator shaft 110. The plurality of raised protrusions 700 facilitates crushing of ice crystals in sterile slurry composition 106 and mixing of sterile slurry composition 106.

[0033] FIG. 10 shows agitator 108 with a plurality of blades 800 coupled to agitator shaft 110. Blades 800 have tapered edges to facilitate crushing of ice crystals and mixing of sterile slurry composition 106. The size of the ice crystals formed by rotating blades 800 within sterile slurry composition 106 can be adjusted by the degree of taper of the edge of each blade and / or the length of each blade 800. In one non - limiting example, each blade 800 can be of a length between about 12.5% and 99% of the diameter of the disposable cartridge.

[0034] FIG. 11 shows agitator 108 having a plurality of raised blade protrusions 900 axially disposed along the interior of disposable cartridge 102. Each of the plurality of raised blade protrusions 900 extends radially inwardly. Here, agitator shaft 110 is rigidly coupled to the first side 114 of disposable cartridge 102, enabling the entire disposable cartridge 102 to be agitated in response to rotation or vibration provided by actuator 130. It should be known that one or more various combinations of each configuration of agitator 108 shown in FIGS. 1 and 8 - 11 are within the scope of the present disclosure.

[0035] FIG. 12 shows another non-limiting example of the disposable cartridge 102. As shown in FIG. 12, the disposable cartridge 102 includes an additional port 1000 disposed on the second side 120 of the disposable cartridge 102. The additional port 1000 is configured and arranged such that, for example, microbubbles of a therapeutic agent or a therapeutic gas can be injected into the sterile slurry composition 106 within the disposable cartridge 102, for example, with an additional syringe 1002. The additional port 1000 can comprise, for example, a rubber stopper configured to be penetrated by a needle, a shut-off valve, and / or a luer lock mechanism with a removable sterile cover. Alternatively or additionally, an additional syringe 1002 can inject a heat agent into the sterile slurry composition 106 to facilitate periodic heating and cooling of the sterile slurry composition 106 to form smooth ice crystals suitable for injection into a patient.

[0036] FIG. 13 shows another non-limiting example of a medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 13 is the same as the medical ice slurry generation system 100 of FIG. 1, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in FIG. 13, the disposable cartridge 102 includes an access port 1100 disposed on a first side portion 114 of the disposable cartridge 102. The access port 1100 has an extension 1102 that fluidly connects the access port 1100 to a pump device 1104 supported by the housing 104. The illustrated pump device 1104 is integrated into the base 126 of the housing 104 and is configured to supply the sterile slurry composition 106 from the disposable cartridge 102. In another non-limiting example, the pump device 1104 can be disposed remote from the housing 104. In various examples, the pump device 1104 can include a volumetric infusion pump or other pumping mechanisms known in the art. The pump device 1104 can be coupled to the extension 1102, for example, using a luer lock connection with a sterile removable cap, a rubber stopper configured to be pierced by a needle, and / or a shut-off valve. The control device 140 is configured to communicate with the pump device 1104 and selectively instruct the pump device 1104 to supply the sterile slurry composition 106 from the disposable cartridge 102 for injection. The control device 140 is further configured to control the flow rate provided by the pump device 1104. In one non-limiting example, the pump device 1104 can be an infusion pump, a diaphragm pump, a peristaltic pump, a piston pump, a rotary vane pump, or other pump suitable for withdrawing a medical slurry composition from a disposable container. Of course, in alternative embodiments, the port 1100 can communicate directly with another second port defined within the housing or directly with the pump (i.e., without the extension 1102).

[0037] As one non-limiting example, FIG. 14 shows a pump device 1104 that operates with a disposable tube 1200 and a needle 1204. The needle 1204 can be removably coupled to the disposable tube 1200 via a needle coupling 1202. The disposable tube 1200 can be coupled to the pump device 1104 using, for example, a rubber stopper configured to be penetrated by a needle, a luer lock connection with a sterile removable cap, and / or a shut-off valve. The operation of the medical ice slurry generation system 100 of FIGS. 13 and 14 is equivalent to that of the medical ice slurry generation system 100 of FIG. 1, except as apparent from the following description and the drawings. Once the sterile slurry composition 106 in the disposable cartridge 102 forms ice crystals (by cooling the composition to the desired temperature via the cooling device 134) and the ice crystals are of the desired size (due to the operation of the agitator 108), the needle 1204 can be injected into a patient in the treatment position. The control device 140 is then configured to instruct the pump device 1104 to pump the sterile slurry composition 106 to the patient at a desired flow rate for a predetermined time. Thus, it goes without saying that since the sterile slurry composition 106 is self-contained throughout the process, the burden on the end user to maintain the sterility of the sterile slurry composition 106 can be reduced. Also, the production (i.e., cooling and formation of ice crystals of the appropriate size) and delivery (i.e., injection) of the sterile slurry composition 106 for a given medical application are substantially automated by the integrated operation of the control device 140, the cooling device 134, the actuator 130, and the pump device 1104.

[0038] As shown in FIG. 15, in another non-limiting example, the pump device 1104 can be disposed in-line with the disposable tube 1200, where the disposable tube 1104 threads through the pump device 1104. In this way, the pump device 1104 is not in direct contact with the disposable tube 1104.

[0039] In some embodiments, the pump device 1104 can be configured to have maximum allowable pressure resistance at the end of the delivery or disposable tube 1200, or at the end of the delivery needle 1204 or cannula. The pump device 1104 can also include an adjustable constant volume pump and can be configured such that a user-specified stop occurs when a predetermined amount of slurry has been delivered.

[0040] Figures 16 - 19 show additional non-limiting examples of the agitator 108 that can cooperate with the disposable cartridge 102. The agitator 108 and cartridge 102 shown in Figures 16 - 19 are substantially identical to the agitator 108 and cartridge 102 shown in Figures 8 - 11 and 13, 14, except that the extension 1102 (of port 1100) within the cartridge 102 in Figures 16 - 19 extends from different sides of the cartridge 102 towards the side wall 124 in an overall horizontal orientation rather than the vertical orientation of the examples shown in Figures 13 and 14.

[0041] Figure 20 shows another non-limiting example of the medical ice slurry generation system 100. The medical ice slurry generation system 100 of Figure 20 is equivalent to the medical ice slurry generation system 100 of Figure 1, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in Figure 20, the medical ice slurry generation system 100 includes a disposable cartridge 1700 configured to be supported within the housing 104. The illustrated disposable cartridge 1700 is in the shape of a sterile pre-filled syringe. The disposable cartridge 1700 is pre-filled with a sterile, non-frozen slurry composition 106. Pre-filling the disposable cartridge 1700 with the sterile, non-frozen slurry composition 106 ensures that the sterile slurry composition 106 is self-contained within a closed environment. This helps to reduce the burden on the end-user who attempts to maintain the sterility of the slurry composition 106 while handling the disposable cartridge 1700. In some non-limiting examples, the disposable cartridge 1700 is surrounded by a thermal insulation material (not shown) to improve its thermal stability.

[0042] The disposable cartridge 1700 can be made of plastic, glass, or metal materials. The disposable cartridge 1700 can be sized to hold a slurry volume between about 1 cubic centimeter (cc) and about 1 liter (L) depending on the medical application. The illustrated disposable cartridge 1700 is rotatably coupled to the agitator 108. The disposable cartridge 1700 is rotatably coupled to the agitator 1702. The agitator 1702 operates similarly to the agitator 108 of FIG. 1 described above, except that it is configured to operate with the disposable cartridge 1700. The agitator 1702 includes a stirring shaft 1704 and fins 1706 disposed within the disposable cartridge 1700 and coupled to the stirring shaft 1704. The fins 1706 are helical in the longitudinal direction along the stirring shaft 1704. The stirring shaft 1704 is housed within the disposable cartridge 1700. The stirring shaft 1704 is rotationally sealed with respect to the tapered tip 1708 of the disposable cartridge 1700 to allow rotation of the stirring shaft 1704 with respect to the disposable cartridge 1700 while maintaining a seal between the sterile slurry composition 106 and the surrounding environment. For example, by utilizing at least one of a hydrostatic seal, a hydrodynamic seal, a fluid bearing, and an O-ring, the stirring shaft 1704 can be rotationally sealed with respect to the tapered tip 1708.

[0043] The disposable cartridge 1700 includes an access port 1710 provided at the distal end 1712 of the tapered tip 1708 and a plunger 1712. The access port 1710 is configured and arranged to allow the medical ice slurry composition 106 to be injected from the disposable cartridge 1700 into the patient. For example, the access port 1710 can be configured to couple to a needle. The plunger 1712 is slidably housed within the second face 1714 opposite the tapered tip 1708 of the disposable cartridge 1700. The plunger 1712 is configured to be axially displaced with respect to the disposable cartridge 1700 to inject the sterile slurry composition 106 into the disposable cartridge 1700.

[0044] The operation of the medical ice slurry generation system 100 of FIG. 20 is equivalent to that of the medical ice slurry generation system 100 of FIG. 1, except as apparent from the following description and drawings. Once the sterile slurry composition 106 within the disposable cartridge 1700 is cooled to a desired temperature via the cooling device 134 and contains ice crystals of a desired size by the agitator 1702, the disposable cartridge 1700 is removed from the housing 104 and a needle is coupled to the tapered tip 1708 of the disposable cartridge 1700. Alternatively or additionally, the disposable cartridge 1700 can be placed within a syringe holder similar to the syringe holder 300 of FIG. 5 for safe storage prior to injection. Next, the sterile slurry composition 106 is injected into the patient at the treatment site. Thus, since the sterile slurry composition 106 is self - contained throughout the manufacturing process of the medical ice slurry, it reduces the burden on the clinician to maintain the sterility of the sterile slurry composition 106 during delivery and manufacture. To repeat, the manufacture of the sterile slurry composition 106 for a given medical use (i.e., cooling and formation of ice crystals of appropriate size) is substantially automated via the control device 140, the cooling device 134, and the actuator 130 operating together. Using the disposable container 1700 to deliver the sterile composition 106 also eliminates the need to move the slurry composition 106 after manufacture.

[0045] FIGS. 21 - 28 show additional non - limiting examples of the agitator 1702 of the disposable cartridge 1700 that can cooperate with the actuator 130 to crush ice crystals and mix the sterile slurry composition 106. As shown in FIG. 21, the agitator 108 includes a plurality of raised protrusions 1800 axially disposed along the interior of the disposable cartridge 1700. Each of the plurality of raised protrusions 1800 extends towards the agitator shaft 1704 and the fins 1706 coupled thereto. During operation, the rotation of the agitator shaft 1704 and thus the fins 1706 rotates the fins 1706 so as to pass through the plurality of raised protrusions 1800 to facilitate crushing of the ice crystals and mixing of the sterile slurry composition 106.

[0046] As shown in FIG. 22, the agitator 1702 includes a plurality of blades 1900 connected to the agitation shaft 1704. The blades 1900 include a plurality of tapered edges that facilitate the crushing of ice crystals and the mixing of the sterile slurry composition 106. The blade 800 includes a tapered edge for facilitating the crushing of ice crystals and the mixing of the sterile slurry composition 106. The size of the ice crystals formed by rotating the blade 800 within the sterile slurry composition 106 can be adjusted by the degree of taper of the edge of each blade and / or the length of each blade 800. In one non-limiting example, each blade 800 can be sized to be between about 12.5% and 99% of the diameter of the disposable cartridge.

[0047] As shown in FIG. 23, the agitator 1702 includes a plurality of raised blade protrusions 2000 axially disposed along the interior of the disposable cartridge 1700. Each of the plurality of raised blade protrusions 2000 extends radially inward. In this non-limiting example, the agitator 1702 includes a cap 2002 configured to rigidly couple to the tapered tip 1708 of the disposable cartridge 1700 and the actuator 130, enabling the entire disposable cartridge 1700 to be agitated in response to the rotation and / or vibration provided by the actuator 130.

[0048] As shown in FIG. 24, agitator 1702 includes a plurality of particles 2100 pre-filled in disposable cartridge 1700 together with sterile slurry composition 106. In this non-limiting example, disposable cartridge 1700 is operable with cap 2002, and the plurality of particles 2100 facilitate turbulent mixing agitation within disposable cartridge 1700 in response to rotation and / or vibration provided by actuator 130. As shown in FIG. 25, agitator 1702 includes a plurality of blades 2200. Each of the plurality of blades 2200 includes a tapered edge for facilitating the crushing of ice crystals and the mixing of sterile slurry composition 106. The size of the ice crystals formed by rotating blades 2200 within sterile slurry composition 106 can be adjusted by the degree of taper of the tapered edge of each blade 2200 and / or the length of each blade 2200. In one non-limiting example, each blade 2200 can be of a length between about 12.5% and 99% of the diameter of the disposable cartridge. Additionally, each of the plurality of blades 2200 can be configured to rotate in opposite directions relative to each other.

[0049] As shown in FIG. 26, agitator 1702 includes paddles 2300 coupled to agitator shaft 1704 for rotation with agitator shaft 1704. As shown in FIG. 27, agitator 1702 includes a plurality of fins 2400 coupled to paddles 2300 and to the inner surface of paddles 2300. As shown in FIG. 28, agitator 1702 includes a whisk 2500 coupled to agitator shaft 1704 for rotation with agitator shaft 1704. It should be understood that the various combinations of the configurations of agitator 1702 shown in FIGS. 20 - 28 are within the scope of the present disclosure.

[0050] As shown in FIG. 29, in one non-limiting example, the agitator 1702 is disposed on the side surface of the disposable cartridge 1700. Specifically, the agitation shaft 1704 protrudes from the side surface of the disposable cartridge 1700 and includes a blade 1900 coupled to the agitation shaft 1704. Of course, in this configuration, the agitator 1702 can be in the shape of the agitator 1702 of any configuration described herein. Corresponding to this arrangement of the agitator 1702, the actuator 130 is disposed within one of the corresponding side walls 124 of the housing 104. The actuator shaft 132 protrudes from the corresponding side wall 124 toward the agitation shaft 1704.

[0051] In another non-limiting example, as shown in FIG. 30, each of the side walls 124 of the housing 104 can include a corresponding actuator 130 and an actuator shaft 132. This enables a housing 104 to support a plurality of disposable cartridges 1700, thereby enabling the generation of a plurality of sterile slurry compositions 106 for injection into a patient.

[0052] As shown in FIG. 31, in another non-limiting example where the agitator 1702 is provided on the side surface of the disposable cartridge 1700, the agitator 1702 can include a plurality of blades 2800 configured to rotate in opposite directions relative to each other.

[0053] As shown in FIG. 32, in some non-limiting examples, the disposable cartridge 1700 includes one or more filters 2900 disposed adjacent to the access port 1710. The one or more filters 2900 ensure that ice crystals of a desired size are injected by the disposable cartridge 1700. In the illustrated non-limiting example, the one or more filters 2900 include a first filter 2902, a second filter 2904, and a third filter 2906, and the second filter 2904 is disposed between the first filter 2902 and the third filter 2906. The first filter 2902 is configured to filter ice crystals of a first size. The second filter 2904 is configured to filter ice crystals of a second size smaller than the first size, and the third filter 2906 is configured to filter ice crystals of a third size smaller than the second size. As will be recognized by those skilled in the art, the sizes of the ice crystals filtered by the first, second, and third filters 2902, 2904, 2906 can be used to control the size of the ice crystals in the sterile slurry composition 106 injected into the patient. For example, in one non-limiting example, the first size is about 500 μm, the second size is about 250 μm, and the third size is about 100 μm. In another non-limiting example, the disposable cartridge 102 can include any number of filters 400 that filter ice crystals of any size, as needed.

[0054] FIG. 33 shows another non-limiting example of the disposable cartridge 1700. As shown in FIG. 33, the disposable cartridge 1700 includes an additional port 3000 provided on its side surface. The additional port 3000 is configured and arranged to allow an additional syringe 3002 to inject, for example, a therapeutic agent into the sterile slurry composition 106 within the disposable cartridge 1700. The access port 3000 can comprise, for example, a rubber stopper configured to be penetrated by a needle, a luer lock connection with a sterile removable cap, and / or a shut-off valve. Alternatively or additionally, the additional syringe 3002 can inject a heat agent into the sterile slurry composition 106 to facilitate the periodic heating and cooling of the sterile slurry composition 106 required to form smooth ice crystals.

[0055] FIG. 34 shows another non-limiting example of the medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 31 is similar to the medical ice slurry generation system 100 of FIGS. 1 and 20, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in FIG. 34, the medical ice slurry generation system 100 includes a stirrer 3100 in the shape of a liquid (e.g., alcohol, isopropenyl, or ethanol) supported within the internal cavity 122 of the housing 104. The disposable cartridge 1700 floats within the stirrer 3100 and includes a cap 3102 configured to provide a seal between the access port 1710 and the surrounding stirrer 3100. An actuator 3104 in the shape of an ultrasonic vibrator is disposed around the disposable cartridge 1700. The actuator 3104 is configured to vibrate at an ultrasonic frequency. The ultrasonic waves generated by the actuator 3104 are transmitted to the disposable cartridge 1700 by the stirrer 3104, facilitating crushing the ice crystals formed within the sterile slurry formulation 106 to a desired ice crystal size. The control device 140 is electrically in communication with the actuator 3104 and is configured to selectively instruct the actuator 3104 to generate ultrasonic waves transmitted by the stirrer 3100. During operation, the control device 140 is configured to instruct the actuator 3104 to transmit ultrasonic waves through the stirrer 3100 until the ice crystals within the sterile slurry composition 106 reach a desired size. In one non-limiting example, the length of time the actuator 3104 transmits ultrasonic waves to the disposable cartridge 1700 can be input to the control device 140. Alternatively or additionally, the control device 140 can be configured to vary the vibration frequency of the actuator 3104 to control the size of the ice crystals within the sterile slurry composition 106.

[0056] FIG. 35 shows another non-limiting example of a medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 35 is similar to the medical ice slurry generation system 100 of FIGS. 1 and 20, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in FIG. 35, the medical ice slurry generation system 100 includes an agitator 3200 having a mechanical link mechanism 3202 supported within an internal cavity 122 of a housing 104. The mechanical link mechanism 3202 is configured such that the link mechanism is removably coupled to a disposable cartridge 1700. The mechanical link mechanism 3202 of the agitator 3200 is coupled to an actuator shaft 132 of an actuator 130 to facilitate rotation and / or vibration of the mechanical link mechanism 3202 and thereby the disposable cartridge 1700. During operation, an end user disposes of the disposable cartridge 1700 within the internal cavity 122 of the housing 104 such that the disposable cartridge 1700 is coupled to the mechanical link mechanism 3202. The mechanical link mechanism 3202 is rotated and / or vibrated by the actuator 130 to crush ice crystals formed during the generation of the sterile slurry composition 106 prior to injection.

[0057] FIG. 36 shows another non-limiting example of the medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 33 is similar to the medical ice slurry generation system 100 of FIGS. 1 and 20, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in FIG. 36, the medical ice slurry generation system 100 includes a cartridge support 3300 that defines a generally cylindrical shape. The cartridge support 3300 is configured to removably couple one or more disposable cartridges 1700. The cartridge support 3300 is coupled to the actuator shaft 132 of the actuator 130 to facilitate movement and / or rotation of the cartridge support 3300 in one or more of the x, y, and z directions. The illustrated disposable cartridge 1700 includes an agitator 1702 having a plurality of raised blade protrusions 2000 axially disposed along the interior of the disposable cartridge 1700 as shown in FIG. 23. Of course, alternative configurations of agitation described herein can be implemented with this non-limiting example.

[0058] The movement transmitted to the agitator by the actuator 130 and thereby the disposable cartridge 1700 crushes the ice crystals formed within the sterile slurry composition 106 prior to injection. Of course, the disposable cartridge 1700 should be coupled to the agitator 3300 as opposing pairs to properly balance the agitator 3300 during movement.

[0059] FIG. 37 shows another non-limiting example of a medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 37 is similar to the medical ice slurry generation system 100 of FIGS. 1 and 20, except as apparent from the following description and drawings. Like components are identified with like reference numerals. As shown in FIG. 37, the medical ice slurry generation system 100 includes a disposable cartridge 3400 configured to be supported within a housing 104. The illustrated disposable cartridge 3400 is in the shape of a sterile pre-filled compression bag. In some non-limiting examples, the disposable cartridge 3400 is an intravenous (IV) bag. The disposable cartridge 3400 is pre-filled with a sterile slurry composition 106. Pre-filling the disposable cartridge 3400 with the sterile slurry composition 106 ensures that the sterile slurry composition 106 is self-contained within a closed environment. This helps to reduce the burden on the end-user to maintain the sterility of the slurry composition 106 while handling the disposable cartridge 3400. In some non-limiting examples, the disposable cartridge 3400 may be surrounded by a thermal insulation material (not shown) to improve its thermal stability.

[0060] The disposable cartridge 3400 can be sized to hold a volume of slurry between about 1 cubic centimeter (cc) and about 1 liter (L), depending on the medical application. The illustrated disposable cartridge 3400 includes an access port 3402 that is fluidly coupled to a pump device 3404. The pump device 3404 is similar in construction and operation to the pump device 1104 of FIG. 13. That is, the control device 140 is configured to communicate with the pump device 3404 and selectively instruct the pump device 3404 to pump the sterile slurry composition 106 from the disposable cartridge 3400 for injection. The control device 140 is further configured to control the flow rate provided by the pump device 3404. In one non-limiting example, the pump device 3404 can be an infusion pump or any other pump described herein. Additionally, as shown in FIG. 14, the pump device 3402 can be coupled to a disposable tube and needle to enable infusion to a patient.

[0061] In certain embodiments, the pump device 3404 can be configured, similar to the pump device 1104, to have a maximum allowable pressure tolerance at the end of the delivery or disposable tube or at the end of the delivery needle or cannula. The pump device 3404 can also include an adjustable constant volume pump and can be configured to cause a user-specified stop when a predetermined amount of slurry has been delivered.

[0062] The illustrated agitator 3406 and actuator 3408 are similar to the agitators 3100 and 3104 of FIG. 34. That is, the actuator 3408 is configured to generate ultrasonic vibrations that are transmitted through the agitator 3406 to the disposable container 3400 to break up ice crystals in the sterile slurry composition 106 prior to injection.

[0063] As shown in FIG. 38, in another non-limiting example, the disposable cartridge 3400 is coupled to a stirrer 3500. The stirrer 3500 includes a stirring shaft 3502 coupled to a plurality of blades 3504 disposed within the disposable cartridge 3400. The stirring shaft 3502 is coupled to the actuator shaft 132 to enable the blades 3504 to rotate within the disposable cartridge 3400 and break the ice crystals formed in the sterile slurry composition 106 to a desired size.

[0064] In yet another non-limiting example, as shown in FIG. 39, the disposable cartridge 3400 is operable with a stirrer 3600. The stirrer 3600 includes a pair of opposing supports 3602 each coupled to an actuator 3604 disposed on a corresponding one of the side walls 124 of the housing 104. The pair of opposing supports 3202 are each configured to be movable to compress the disposable cartridge 3400 and provide agitation to break the ice crystals formed in the sterile slurry composition 106. During operation, the control device 140 is configured to apply agitation to the disposable cartridge 3400 via one or more agitators 3606 coupled to the actuator 3604. Once the sterile slurry composition 106 reaches the desired temperature and contains ice crystals of the desired size, the control device 140 is configured to instruct the actuator 3604 to move so as to compress the disposable cartridge 3400 and thereby force the sterile slurry composition 106 through the access port 3402 for injection to the patient.

[0065] FIG. 40 shows another non-limiting example of the medical ice slurry generation system 100. The medical ice slurry generation system 100 of FIG. 40 is the same as the medical ice slurry generation system 100 of FIGS. 1 and 20, except as apparent from the following description and drawings. Similar components are identified by similar reference numerals. As shown in FIG. 40, the medical ice slurry generation system 100 includes a first cooling passage 3702 coupled to a first cooling device 3700 and a second cooling passage 3706 coupled to a second cooling device 3706. The first cooling passage 3702 is disposed within a side surface 124 of the housing to cool a first cavity 3710 disposed within the housing 104. The second cooling passage 3708 is disposed within a side surface 124 of the housing 104 to cool a second cavity 3712 disposed within the housing 104.

[0066] The medical ice slurry generation system 100 includes a disposable cartridge 3714. The disposable cartridge 3714 includes a first syringe chamber 3716, a second syringe chamber 3718, and a microdroplet device 3720 provided between the first syringe chamber 3716 and the second syringe chamber 3718. When disposed within the housing 104, the first syringe chamber 3716 is disposed within the first cavity 3710 and the second syringe chamber 3718 is disposed within the second cavity 3718. The first syringe chamber 3716 is pre-filled with a sterile first liquid 3722, a sterile second liquid 3724, and a foldable separator 3726 disposed between the first liquid 3722 and the second liquid 3724. The second liquid 3724 is disposed adjacent to the microdroplet device 3720. A plunger 3728 is slidably received within the first syringe chamber 3716 and is configured to inject the first liquid 3722 and thereby the second liquid 3724 (the liquid is substantially incompressible) toward the second syringe chamber 3718.

[0067] During operation, the control device 140 controls the first cooling device 3700 to maintain the first cavity 3710 at a cold temperature (e.g., about 2°C), and controls the second cooling device 3706 to maintain the second cavity 3712 at a temperature substantially below the freezing temperature (e.g., -100°C). Once the desired temperatures are achieved in the first and second cavities 3710 and 3712, the plunger 3728 is moved to inject the second liquid 3724 into the second chamber 3718 via the microdroplet device 3720. The freezing temperatures of the microdroplet device 3720 and the second cavity 3712 allow for the formation of ice crystals of a desired size (controlled by the microdroplet device 3720) within the second syringe cavity 3718. Next, the collapsible separator 3726 is crushed or moved to allow the first liquid 3722 to fall into the second syringe chamber 3718, thereby suspending the ice crystals previously formed in the first liquid 3722 (i.e., producing a sterile slurry composition of a desired temperature with ice crystals of a desired size). Next, the formed sterile slurry mixture can be injected into a patient.

[0068] Figure 41 shows one non-limiting example of a medical ice slurry generation system 100. The medical ice slurry generation system 100 of Figure 41 is similar to the medical ice slurry generation system 100 of Figure 40, except as apparent from the following description and the drawings. Similar components are identified by similar reference numerals. As shown in Figure 41, the first syringe chamber 3716 includes an ice tray 3800 disposed therein, and the second syringe chamber 3718 is pre-filled with a first liquid 3802. The ice tray 3800 can be made of a flexible material. As shown in Figure 42, the ice tray 3800 defines a plurality of ice cavities 3900 that are each pre-filled with a liquid 3902 and are sized to form ice crystals of a desired size and shape.

[0069] During operation, the control device 140 controls the first cooling device 3700 to maintain the first cavity 3710 at a freezing temperature (e.g., about -20°C), and controls the second cooling device 3706 to maintain the second cavity 3712 at a higher temperature (e.g., 2°C). Once the desired temperatures are achieved in the first and second cavities 3710 and 3712 and ice crystals are formed in the ice tray 3800, the ice tray 3800 is inverted (Figure 42) to release the ice crystals 3902 formed from the respective ice cavities 3900. Once released, the ice crystals 3902 fall into the second syringe chamber 3718, thereby suspending the ice crystals previously formed in the first liquid 3802 (i.e., producing a sterile slurry composition of the desired temperature with ice crystals of the desired size). Next, if necessary, the formed sterile slurry mixture is agitated and made ready for injection into a patient. In certain embodiments, the first liquid 3802 can include saline, lactated Ringer's solution, or a solution for making an emulsion that is an overall fine dispersion of insoluble droplets or particles.

[0070] In each of the above-described embodiments, it is of course also possible that the temperature within the mixing chamber of the medical ice slurry (e.g., either the canister or the disposable cartridge described herein) can be equalized with any one or more of the cooling devices, liquids, or gases described herein so as to provide a uniformly cooled medical ice slurry. For example, referring to the systems of Figures 1 - 3, these systems can be configured such that the temperature within the cartridge 102 is equalized with the coolant or gas within the passageway, or the coil 136, or the coolant or gas within the cavity 122.

[0071] Although the present invention has been described above in connection with specific embodiments and examples, the present invention is not necessarily so limited, and numerous other embodiments, examples, uses, and variations and developments from such embodiments, examples, and uses are intended to be encompassed by the claims appended hereto. The entire disclosure of each patent and publication cited herein is incorporated by reference as if each such patent or publication was individually incorporated herein by reference.

Claims

1. receiving a disposable cartridge with an access port, wherein the closed environment within the disposable cartridge is pre-filled with an unfrozen, sterile medical slurry composition; placing the disposable cartridge within a housing, the housing comprising a cooling device operable to cool the unfrozen sterile medical slurry composition to a temperature sufficient to form a sterile medical slurry composition comprising a plurality of ice crystals; cooling the disposable cartridge to a temperature sufficient to form a sterile medical slurry composition; coupling an extraction syringe to an access port for withdrawing the sterile medical slurry composition; withdrawing the sterile medical slurry composition from the disposable cartridge through the access port of the disposable cartridge using the extraction syringe; Including, the unfrozen sterile medical slurry composition is self-contained within the closed environment during formation of the sterile medical slurry composition; and the access port is constructed and arranged to allow the sterile medical slurry composition to be withdrawn or injected from the disposable cartridge while maintaining the sterility of the sterile medical slurry composition; A method for producing a sterile medical slurry composition.

2. agitating the sterile medical slurry composition held in the disposable cartridge so that the plurality of ice crystals is reduced in size to a size sufficient to allow the sterile medical slurry composition to be delivered to a patient through the tip of a needle operably connected to the disposable cartridge or to the extraction syringe. The method of claim 1 further comprising:

3. 3. The method of claim 1 or 2, wherein the temperature sufficient to form the sterile medical slurry composition is about -10°C to about 4°C.

4. 3. The method of claim 1 or 2, wherein the non-frozen, sterile medical slurry composition comprises an agent or a biocompatible surfactant.

5. 5. The method of claim 4, wherein the agent or biocompatible surfactant is configured to make the sterile medical slurry composition more injectable.

6. 6. The method of claim 5, wherein the unfrozen, sterile medical slurry composition comprises a biocompatible surfactant, and the biocompatible surfactant is glycerol.

7. 5. The method of claim 4, wherein the unfrozen, sterile medical slurry composition comprises an agent, the agent being an ice particle smoothing agent.

8. 3. The method of claim 1 or 2, wherein the disposable cartridge is a pre-filled syringe.

9. 3. The method of claim 1 or 2, wherein at least one of: (i) a luer lock with a stopper; (ii) a pressure valve; (iii) a quick disconnect; (iv) a one-way valve with a luer lock; or (v) a sterile rubber stopper is cooperable with the access port to selectively allow the sterile medical slurry composition to be withdrawn from the disposable cartridge through the access port.

10. The method of claim 1 or 2, wherein the disposable cartridge includes an agitator.

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