Medical ice slurry production and delivery system and method

Abstract

The present disclosure provides systems and methods for medical ice slurry production. In particular, systems and methods for medical ice slurry production are provided that allow an end user to produce and deliver sterile medical ice slurry at the point of care.

Description

[0001] This patent application is a continuation-in-part of International Application No. PCT / US2017 / 019268, International Filing Date, February 24, 2017, which entered the National Stage in the United States Patent and Trademark Office on August 24, 2017 as U.S. Patent Application No. 15 / 692,833, entitled "Medical Ice Slurry Production and Delivery System and Method," the contents of which are incorporated herein by reference in their entirety.

[0002] Cross Reference to Related Applications

[0003] Not Applicable.

[0004] Statement as to Federally Sponsored Research

[0005] Not Applicable. BACKGROUND

[0006] The present disclosure relates generally to ice slurry for medical use, and more particularly to systems and methods for medical ice slurry production and extraction or injection.

[0007] Ice slurry for use in medical applications generally comprises a partially frozen saline solution. Medical ice slurry is used in surgical applications to induce therapeutic hypothermia and slow the metabolic rate of organs and tissues, thereby protecting the patient's organs during surgical procedures. Medical ice slurry is also injected into a patient's body for selective or non-selective cryotherapy and / or cryolysis. SUMMARY

[0008] The present disclosure provides systems and methods for medical ice slurry production. In particular, medical ice slurry production systems and methods are disclosed that allow an end user / clinician to produce and deliver a sterile medical ice slurry composition at the point of care.

[0009] In one aspect, the present disclosure provides a medical ice slurry production system comprising a disposable cartridge that holds a non-frozen sterile medical ice slurry composition. The system further comprises a housing that supports the disposable cartridge. The housing includes an actuator and a cooling device operable with the housing to cool the non-frozen ice slurry composition held in the disposable cartridge to a temperature sufficient to form ice crystals. The medical ice slurry production system further comprises an agitator operable with the actuator of the housing to agitate the medical ice slurry composition such that the ice crystals are reduced in size to a size sufficient to allow the medical ice slurry composition including the reduced ice crystals to be delivered through an end of a needle to a patient, and an access port constructed and arranged to allow the medical ice slurry composition including the reduced ice crystals to be extracted or injected from the disposable cartridge while maintaining the sterility of the medical ice slurry composition including the reduced ice crystals.

[0010] In yet another aspect, the present disclosure provides a medical slush production system including a disposable cartridge holding a non-frozen, sterile medical slush composition. The disposable cartridge includes an access port. The medical slush production system further includes a housing supporting the disposable cartridge. The housing includes an actuator. The medical slush production system further includes a cooling device operable with the housing to cool the non-frozen slush composition held in the disposable cartridge to a temperature sufficient to form ice crystals in the composition, an agitator operable with the actuator of the housing to agitate the medical slush composition so that the ice crystals are reduced in size to a size sufficient to allow the medical slush composition including the reduced ice crystals to be delivered through an end of a needle to a patient, and a pump operable to pump the medical slush composition including the reduced ice crystals out of the access port of the disposable cartridge through a disposable delivery tube while maintaining sterility of the medical slush composition including the reduced ice crystals.

[0011] In yet another aspect, the present disclosure provides a method of medical slush production including placing a disposable cartridge holding a non-frozen, sterile medical slush composition in a housing and cooling the disposable cartridge to a temperature sufficient to form ice crystals inside the disposable cartridge while placed in the housing. The method of medical slush production further includes agitating the medical slush composition held in the disposable cartridge so that the ice crystals inside the disposable cartridge are reduced in size to a size sufficient to allow the medical slush composition including the reduced ice crystals to be delivered through an end of a needle to a patient.

[0012] The foregoing and other aspects and advantages of the present application will appear from the following description. In the description, reference is made to the accompanying drawings which form a part hereof, and in which are shown by way of illustration preferred embodiments of the present application. Such embodiments do not necessarily represent the full scope of the present application, however, and the present application should be construed to encompass not only the embodiments depicted but also embodiments falling within the scope of the appended claims, and their equivalents. BRIEF DESCRIPTION OF DRAWINGS

[0013] The present application will be better understood with reference to the following detailed description and accompanying drawings, of which:

[0014] Figure 1 is a schematic illustration of the principles of a medical slush production system according to one non-limiting example of the present disclosure.

[0015] Figure 2 shows a medical slush production system of Figure 1 with a lid.

[0016] Figure 3 shows a medical slush production system of Figure 1 with a liquid in an internal cavity defined by the housing.

[0017] Figure 4 A medical ice slurry production system is shown in Figure 1 , wherein the syringe is positioned adjacent to an inlet port of the medical ice slurry production system.

[0018] Figure 5 A medical ice slurry production system is shown in Figure 1 , wherein the syringe holder is coupled to a housing of the medical ice slurry production system.

[0019] Figure 6 A medical ice slurry production system is shown in Figure 4 , wherein one or more filter elements are arranged within a disposable cartridge of the medical ice slurry production system.

[0020] Figure 7 A medical ice slurry production system is shown in Figure 4 , wherein one or more filter elements are arranged within the syringe.

[0021] Figure 8 A disposable cartridge of a medical ice slurry production system is shown in Figure 1 with another non-limiting example of an agitator.

[0022] Figure 9 A disposable cartridge of a medical ice slurry production system is shown in Figure 1 with yet another non-limiting example of an agitator.

[0023] Figure 10 A disposable cartridge of a medical ice slurry production system is shown in Figure 1 with a further non-limiting example of an agitator.

[0024] Figure 11 A disposable cartridge of a medical ice slurry production system is shown in Figure 1 with another non-limiting example of an agitator.

[0025] Figure 12 A disposable cartridge of a medical ice slurry production system is shown in Figure 1 with an additional port.

[0026] Figure 13 is a schematic representation of a medical ice slurry production system according to another non-limiting example of the present disclosure.

[0027] Figure 14 A medical ice slurry production system is shown in Figure 11 , wherein a disposable tube and needle are coupled thereto.

[0028] Figure 15 A medical ice slurry production system is shown in Figure 12A medical ice slurry production system in which the pump is inline with the disposable tubing.

[0029] Figure 16 Another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 11 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0030] Figure 17 Yet another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 11 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0031] Figure 18 Still another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 11 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0032] Figure 19 Another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 11 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0033] Figure 20 A schematic representation of a medical ice slurry production system according to yet another non-limiting example of the present disclosure.

[0034] Figure 21 Another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0035] Figure 22 Yet another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0036] Figure 23 Still another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0037] Figure 24 Another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0038] Figure 25 Another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0039] Figure 26 Yet another non-limiting example of a medical ice slurry production system in which the pump is inline with the disposable tubing is shown. Figure 20 A disposable sleeve for a medical ice slurry production system in which the pump is inline with the disposable tubing.

[0040] Figure 27 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0041] Figure 28 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0042] Figure 29 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0043] Figure 30 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0044] Figure 31 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0045] Figure 32 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0046] Figure 33 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 20 A disposable cartridge of a medical ice slurry production system is shown in

[0047] Figure 34 A schematic representation of a medical ice slurry production system according to another non-limiting example of the present disclosure.

[0048] Figure 35 A schematic representation of a medical ice slurry production system according to another non-limiting example of the present disclosure.

[0049] Figure 36 A schematic representation of a medical ice slurry production system according to another non-limiting example of the present disclosure.

[0050] Figure 37 A schematic representation of a medical ice slurry production system according to another non-limiting example of the present disclosure.

[0051] Figure 38 A further non-limiting example of a medical ice slurry production system is shown having a stirrer Figure 37 A disposable cartridge of a medical ice slurry production system is shown in

[0052] Figure 39FIG. 1 illustrates a medical ice slurry production system in accordance with a non-limiting example of the present disclosure. Figure 37

[0053] Figure 40 FIG. 1 illustrates a medical ice slurry production system in accordance with a non-limiting example of the present disclosure.

[0054] Figure 41 FIG. 1 illustrates a medical ice slurry production system in accordance with a non-limiting example of the present disclosure.

[0055] Figure 42 FIG. 1 illustrates a medical ice slurry production system in accordance with a non-limiting example of the present disclosure. Figure 41 DETAILED DESCRIPTION

[0056] Off-site (i.e., not at the point of care) manufactured medical ice slurry requires cold chain transportation to deliver the ice slurry to the point of care. Off-site production adds burden to the end user and / or clinician administering the ice slurry to the patient. For example, the ice slurry must be kept sterile to ensure patient safety. The ice slurry must also be maintained at the proper temperature to preserve the ice crystal size, crystal shape, and ice content of the ice slurry and to ensure that the ice slurry maintains its cooling properties and ability to be injected through a needle (i.e., stability). Thus, off-site ice slurry manufacturing can require manipulation of the ice slurry by the end clinician, which can compromise patient safety and / or the effectiveness of the ice slurry.

[0057] Accordingly, it is desirable to have a medical ice slurry production system that enables an end user to produce and deliver sterile medical ice slurry at the point of care. A system that produces medical ice slurry at the point of care while maintaining the sterility and stability (e.g., ice crystal size and shape and ice content) of the ice slurry can reduce the burden on the end user and simplify the overall process of producing and delivering medical ice crystals to a patient.

[0058] Figure 1 ​​One non-limiting example of a medical ice slurry production system 100 is shown. The medical ice slurry production system 100 includes a disposable cartridge 102 configured to be supported within a housing 104. The illustrated disposable cartridge 102 is in the form of a sterile pre-filled cartridge. The disposable cartridge 102 is pre-filled with a sterile ice slurry composition 106. For example, the disposable cartridge 102 can be pre-filled with an ice slurry composition described in International Patent Application Publication No. PCT / US2015 / 047301, which is incorporated by reference herein in its entirety. As described, for example, in PCT / US2015 / 047301, such an ice slurry composition can have a preferred ice content range, temperature range, and include one or more added ice particle smoothing agents and / or biocompatible surfactants (e.g., glycerol), which can, for example, make the ice slurry more injectable. In any of the systems described herein, it can be preferred to add such an agent or surfactant after the system stirs, blends, mixes, or grinds the medical ice slurry (as described below) and just prior to injecting the ice slurry. Pre-filling the disposable cartridge 102 with the sterile ice slurry composition 106 ensures that the sterile ice slurry composition 106 is self-contained within a closed environment. This helps to alleviate the burden on the end user to somehow maintain the sterility of the ice slurry composition 106 while handling the disposable cartridge 102. In some non-limiting examples, the disposable cartridge 102 can be surrounded by a thermal insulating material (not shown) to improve thermal stability.

[0059] The disposable cartridge 102 can be manufactured from a plastic, glass, or metallic material. The disposable cartridge 102 can be sized to hold an ice slurry volume of between about one cubic centimeter (cc) to about one liter (L), depending on the medical application. The disposable cartridge 102 is rotationally coupled to an 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 helically shaped along the length of the shaft 110. The agitator shaft 110 is partially received within the disposable cartridge 102. That is, the agitator shaft 110 is received in a first side 114 of the disposable cartridge 102 such that a 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 to the first end 114 of the disposable cartridge 102 to allow the agitator shaft 110 to rotate relative to the disposable cartridge 102 while maintaining a seal between the sterile ice 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 using, for example, at least one of a sealed hydrostatic bearing, a sealed hydrodynamic bearing, a fluid bearing, or an O-ring.

[0060] The disposable sleeve 102 includes an access port 118 disposed in the second side 120 of the disposable sleeve 102. The access port 118 is configured and arranged to allow withdrawal of the medical slush composition 106 from the disposable sleeve 102 while maintaining sterility of the slush composition 106. For example, the access port 118 can be configured to allow withdrawal of the medical slush composition from the access port using a syringe. Alternatively or additionally, as discussed in greater detail below, a user can pump the medical slush composition from the access port using a pump and a disposable delivery tube. In particular embodiments, the pump or a controller configured to operate the pump can be configured to have a maximum allowable pressure tolerance at the end of the delivery tube, delivery needle, or cannula. The pump can include an adjustable constant volume pump, and the pump or the controller configured to operate the pump can be configured with a user-specified stop that functions when a predetermined volume of slush has been delivered. A user can also allow withdrawal of the medical slush composition from the access port by gravity flow. It should be understood that the location of the access port 118 on the disposable sleeve 102 is not intended to be limiting in any way, but rather the access port 118 can be disposed in other locations on the disposable sleeve 102.

[0061] The housing 104 defines an interior cavity 122 sized to receive the disposable sleeve 102, and the housing 104 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 top side 128. In other non-limiting examples, the housing 104 can include a removable lid 129 attached to the substantially open top side 128 to further thermally insulate the interior cavity 122 from the ambient environment, as shown in Figure 2

[0062] With continued reference to Figure 1 , the base 126 of the housing 104 includes an actuator 130 coupled to an actuator shaft 132. The actuator shaft 132 extends into the interior cavity 122 of the housing 104 and is configured to be operably coupled to the agitator 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 actuator shaft 132, and thereby the disposable sleeve 102, at a given frequency, such as an ultrasonic frequency. In other non-limiting examples, the actuator 130 can be in the form of another rotational or vibrational mechanism known in the art. The actuator 130 is configured to selectively rotate the actuator shaft 132 and, when coupled to the agitator shaft 110, cause turbulent agitation or mixing of the sterile slush composition 106 within the disposable sleeve 102.

[0063] The medical slush production system 100 includes a cooling device 134. In one example, the cooling device 134 is at least partially supported within the housing 104. In Figure 1 ​In the non-limiting example shown, the sidewall 124 of the housing 104 defines a channel 136 extending between the top side 128 and the base 126. In one non-limiting example, the channel 136 can define a generally helical path through the sidewall 124. The channel 136 is configured to receive a cooling liquid or gas provided by the cooling device 134. Alternatively or additionally, the cooling liquid or gas provided by the cooling device 134 can be provided to a coil (e.g., a copper coil) that can be received within the channel 136. The cooling device 134 can include, for example, a condenser, a compressor, and an evaporator. In other non-limiting examples, the cooling device 134 can utilize magnetic refrigeration, electrical cooling, chemical cooling, conventional refrigeration, compressed gas (Joule-Thomson) cooling, thermoelectric (Peltier) cooling, or another slush outside of the sterile ice slush composition 106. The housing 104 can be fabricated from a material having high thermal conductivity (e.g., stainless steel, copper, aluminum) to reduce thermal resistance between the sterile ice slush composition 106 within the disposable sleeve 102 and the cooling liquid or gas within the channel 136. It should be appreciated that, in some non-limiting examples, the housing 104 can be fabricated from one or more materials. For example, an inner portion of the housing 104 adjacent to the disposable sleeve 102 can be fabricated from a material having high thermal conductivity, and an outer portion of the housing 104 can be fabricated from a thermally insulating material (e.g., plastic or foam).

[0064] A power source 138 supplies electrical power to the cooling device 134, the actuator 130, and the controller 140. The power source 138 can be in the form of an alternating current wall plug power source. Alternatively or additionally, the power source 138 can be in the form of a portable direct current power source (e.g., a battery) to facilitate portability of the medical ice slush production system 100. The controller 140 is in electrical communication with the actuator 130 and the cooling device 134, and is configured to selectively instruct the actuator 130 to rotate the actuator shaft 132 at a desired rotational speed. The controller 140 is also configured to control the cooling device 134, and thereby the temperature of the cooling liquid or gas within the channel 136. One or more sensors (not shown) can be in communication with the controller 140 to sense, for example, the temperature of the cooling liquid or gas within the channel 136 and the temperature of the sterile ice slush composition 106 within the disposable sleeve 102. The temperature of the cooling liquid or gas within the channel 136 and the temperature of the sterile ice slush composition 106 can be measured by using a thermocouple, a thermistor, or another electrical temperature sensor known in the art. Alternatively or additionally, a radiative temperature sensor can be implemented as an infrared detector and a thermoelectric sensor. The one or more sensors can provide feedback to the controller 140 to enable the controller 140 to actively control the cooling device 134 to achieve and maintain a desired temperature of the sterile medical ice slush composition 106.

[0065] In operation, the housing 104 of the medical ice slurry production system 100 is placed at a point of care (e.g., near a patient). Next, the disposable cartridge 102 having a pre-filled non-frozen, sterile ice slurry composition 106 is placed within the internal cavity 122 of the housing 104, and the agitator shaft 110 is coupled to the actuator shaft 132 for rotation therewith. In some non-limiting examples, the internal cavity 122 of the housing includes a gas or air. In other non-limiting examples, the internal cavity 122 can be filled with a liquid, such as Figure 3 The controller 140 is configured to instruct the cooling device 134 to cool the liquid or gas within the passageway 136 to a desired temperature (i.e., a temperature that causes ice crystals to form in the ice slurry composition held within the cartridge 102). In one non-limiting example, a desired temperature of the sterile ice slurry composition 106 can be input to the controller 140, and the controller 140 can automatically control the cooling device 134 to reach and maintain the desired ice slurry temperature. In some non-limiting examples, the desired temperature of the sterile ice slurry composition can be between about -10 °C to about 4 °C.

[0066] While cooling the temperature of the sterile slush composition 106 within the disposable sleeve 102 with the cooling device 134, the controller 140 is configured to instruct the actuator 130 to rotate the actuator shaft 132 and, in turn, the agitator shaft 110. It is understood that the actuator 130 can be instructed to rotate the actuator shaft 132 before, simultaneously with, or after the cooling device 134 begins to cool the disposable sleeve 102. Alternatively or additionally, the disposable sleeve 102 can be pre-cooled outside the housing 104 and then further cooled within the housing 104 to form ice crystals. The desired rotational speed or amount of force provided by the actuator 130 can be input to the controller 140. In some non-limiting examples, the desired rotational speed provided by the actuator 130 can be between about 100 revolutions per minute (rpm) to 45,000 rpm, or between about 5,000 rpm to 40,000 rpm, or between about 10,000 rpm to 30,000 rpm. Rotation of the agitator shaft 110 causes the fins 112 to rotate within the sterile slush composition 106. The rotating fins 112 act to turbulently mix the sterile slush composition 106 for a variety of purposes. First, the turbulent mixing promotes an even temperature distribution in the sterile slush composition 106. Second, the rotation of the fins 112 acts to break up ice crystals that form in the sterile slush composition 106 as the sterile slush mixture 106 is cooled (i.e., the sterile slush composition 106 transitions from a liquid composition to a slush comprising solid ice crystals and liquid). Alternatively or additionally, once ice crystals have formed, the controller 140 can be configured to maintain the homogeneity of the sterile slush composition 106 to prevent the slush from separating. The controller 140 can be configured to instruct the actuator 130 to provide rotation between about 60 rpm to 5,000 rpm to maintain the homogeneity of the sterile slush composition 106, or between about 500 rpm to 4,000 rpm, or between about 1,500 rpm to 2,500 rpm.

[0067] The agitator 108 can be constructed to ensure that the ice crystals formed within the sterile slush 106 are broken up to a particular ice crystal size. In non-limiting examples, the ice crystals formed in the sterile slush composition 106 can be broken up to a size of less than about one millimeter (mm). In another non-limiting and optimized example, the ice crystals formed in the sterile slush composition 106 can be broken up to a size of less than about 0.1 mm. The size of the ice crystals in the sterile slush composition 106 can be verified by using (i) light / laser diffraction methods, (ii) direct measurement by a microscope, and / or (iii) ultrasonic or acoustic methods. In some non-limiting examples, the measured size of the ice crystals in the sterile slush composition 106 is transmitted to the controller 140.

[0068] In particular embodiments, the controller or any other controller for any other embodiment described herein can be configured to perform according to two different agitation cycles. In a first cycle, the controller of any embodiment herein can be configured to instruct the actuator and thus the actuator shaft and the agitator shaft (or any other agitation element described herein) to agitate such that ice crystals are broken up or pulverized to a sufficiently small size to have an injectable quality (e.g., less than about 1 mm or preferably less than about 0.1 mm). In a second cycle, which can be before or after the first cycle, the controller can be configured to instruct the actuator and thus the actuator shaft and the agitator shaft (or any other agitation element described herein) to agitate such that the ice slurry is sufficiently mixed. For example, any system herein can be configured with a controller that provides for rotation of the agitator or agitation element between about 60 rpm and 5000 rpm to ensure or maintain sufficient mixing or homogeneity of the ice slurry, or between about 500 rpm and 4000 rpm, or between about 1500 rpm and 2500 rpm, or any other suitable speed and / or number of revolutions of the agitation element.

[0069] In some non-limiting examples, the cooling device 134 can be further configured as a cooling and heating device to provide cooling and heating to the sterile ice slurry composition 106. This can enable the medical ice slurry production system 100 to first form ice crystals within the sterile ice slurry composition 106 and then provide heating prior to injection to ensure that the ice crystals are formed to be homogenous, spherical, and non-dendritic.

[0070] Once the sterile ice slurry composition 106 is cooled to the desired ice slurry temperature and the ice crystals within the sterile ice slurry composition 106 are the desired size, the sterile ice slurry composition 106 is withdrawn from the disposable sleeve 102 via the access port 118 for the desired medical application on a patient. The disposable sleeve 102 can then be discarded and the above process can be repeated with a new disposable sleeve 102.

[0071] As noted above, the end user or clinician can only need to place the pre-filled disposable sleeve 102 within the inner cavity 122 of the housing 104 and withdraw the sterile slush composition 106 from the access port 118 after the slush composition has reached the desired temperature and has the desired ice crystal size for delivery to the patient. Thus, the sterile slush composition 106 is maintained within the disposable sleeve 102 throughout the entire slush production process until the sterile slush composition 106 is withdrawn for use in the patient (e.g., withdrawn for use in another sterile delivery mechanism, such as a syringe). Thus, it should be appreciated that the sterile slush composition 106 is self-contained throughout the medical slush production process, thereby reducing the burden on the clinician to maintain the sterility of the slush composition 106. Moreover, the production of the sterile slush composition 106 (i.e., the cooling and formation of ice crystals of the appropriate size) is substantially automated through the operation of the controller 140, the cooling device 134, and the actuator 130 together for a given medical application.

[0072] Figure 4 A sterile extraction syringe 200 is shown in one non-limiting embodiment configured to be coupled to the access port 118 for withdrawing the sterile slush composition 106. In some non-limiting examples, the access port 118 can include a rubber stopper, a shut-off valve, and / or a luer lock with a removable sterile cap. The sterile extraction syringe 200 can include a needle (not shown) to facilitate injection of the sterile slush composition 106 into the 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 the ice crystals formed in the sterile slush composition 106 to a size corresponding to the diameter of the needle on the sterile extraction syringe 200 that allows the slush to flow therethrough. In one non-limiting example, the ice crystal size can be, for example, less than about 1 mm or less than about 0.3 mm.

[0073] Turning to Figure 5In some non-limiting examples, the medical ice slurry production system 100 includes a syringe holder 300 coupled to a housing 104. In other non-limiting examples, the syringe holder 300 may be detachable from the housing 104. A sterile extraction syringe 200 may be placed within the syringe holder 300 to insulate the sterile ice 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 to a cooling device 134, to maintain the sterile ice slurry composition 106 within the sterile extraction syringe 200 at a desired ice slurry temperature. Alternatively or additionally, the syringe holder 300 may include a stirrer to prevent the sterile ice slurry composition 106 within the sterile extraction syringe 200 from separating prior to injection. It should be understood that the syringe holder 300 may be integrated into any configuration of the medical ice slurry production system 100 described herein.

[0074] like Figure 6 As shown, in some non-limiting examples, the disposable sleeve 102 includes one or more filters 400 arranged adjacent to the inlet port 118. The one or more filters 400 ensure that ice crystals of a desired size are drawn through the sterile extraction syringe 200 and subsequently injected into the patient. In the non-limiting example shown, the one or more filters 400 include a first filter 402, a second filter 404, and a third filter 406, wherein 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 those skilled in the art will recognize, the size of the ice crystals filtered by the first filter 402, the second filter 404, and the third filter 406 can be used to control the size of the ice crystals in the sterile ice syrup 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 other non-limiting examples, the disposable sleeve 102 may include any number of filter elements 400 to filter ice crystals of any size as desired.

[0075] like Figure 7 As shown, in another non-limiting example, one or more filters 400 are alternatively arranged within the sterile extraction syringe 200.

[0076] Figure 8 -11 shows an additional non-limiting example of a stirrer 108 of a disposable sleeve 102 that can be operated by actuator 130 to break up ice crystals and mix or agitate a sterile ice slurry composition 106. Figure 8It shows that it does not have Figure 1 The agitator 108 with fin 112 in the middle. Figure 9 A stirrer 108 is shown comprising a plurality of ridged protrusions 700 arranged axially along the interior of a disposable sleeve 102. Each ridged protrusion 700 extends toward the stirrer shaft 110 and the fins 112 connected thereto. The plurality of ridged protrusions 700 facilitate the breaking up of ice crystals in the sterile ice slurry composition 106 and the mixing of the sterile ice slurry composition 106.

[0077] Figure 10 A mixer 108 is shown, comprising a plurality of blades 800 coupled to a mixer shaft 110. The blades 800 include multiple tapered edges to facilitate the breaking up of ice crystals and the mixing of a sterile ice slurry composition 106. The size of the ice crystals formed within the sterile ice slurry composition 106 by rotating the blades 800 can be controlled by the degree of tapering of each blade edge and / or the length of each blade 800. In a non-limiting example, each blade 800 may define a length between approximately 12.5% ​​and 99% of the diameter defined by the disposable sleeve.

[0078] Figure 11 A stirrer 108 is shown having a plurality of ridged, blade-like protrusions 900 arranged axially along the interior of a disposable sleeve 102. Each of the plurality of ridged, blade-like protrusions 900 extends radially inward. Here, the stirrer shaft 110 is rigidly coupled to a first side 114 of the disposable sleeve 102 such that the entire disposable sleeve 102 can be stirred in response to rotation or vibration provided by the actuator 130. It should be understood that, in Figure 1 and 8 Various combinations of one or more of each configuration of the stirrer 108 shown in -11 are within the scope of this disclosure.

[0079] Figure 12 Another non-limiting example of a disposable sleeve 102 is shown. Figure 12 As shown, the disposable sleeve 102 includes an additional port 1000 disposed in a second side 120 of the disposable sleeve 102. The additional port 1000 is constructed and arranged to allow microbubbles, such as therapeutic agents or therapeutic gases, to be injected, for example, through an additional syringe 1002 into a sterile ice slurry composition 106 within the disposable sleeve 102. The additional port 1000 may include, for example, a rubber stop configured to be punctured by a needle, a shut-off valve, and / or a Luer lock mechanism with a removable sterile cap. Alternatively or additionally, the additional syringe 1002 may be used to inject a heat-insulating agent into the sterile ice slurry composition 106 to facilitate periodic heating and cooling of the sterile ice slurry composition 106, thereby forming smooth ice crystals suitable for injection into a patient.

[0080] Figure 13Another non-limiting example of a medical ice slurry production system 100 is shown. Except as described below or otherwise apparent from the figures, Figure 13 the medical ice slurry production system 100 in Figure 1 is similar to the medical ice slurry production system 100 in Figure 13 As shown in the medical ice slurry production system 100 in

[0081] the medical ice slurry production system 100 in Figure 14 is similar to the medical ice slurry production system 100 in Figure 13 the medical ice slurry production system 100 in 14 the medical ice slurry production system 100 in Figure 1The needle 1204 can be injected into the patient at the treatment site once the sterile slush composition 106 within the disposable sleeve 102 forms ice crystals (as a result of the composition being cooled to the desired temperature by the cooling device 134) and the ice crystals have the desired size (as a result of the actuation of the agitator 108). The controller 140 is then configured to instruct the pumping device 1104 to pump the sterile slush composition 106 into the patient at the desired flow rate for the predetermined period of time. Thus, it should be appreciated that the sterile slush composition 106 is self-contained throughout the process, thereby reducing the burden on the end user to maintain the sterility of the sterile slush composition 106. Moreover, for a given medical application, the production (i.e., the cooling and formation of ice crystals of the appropriate size) and delivery (i.e., injection) of the sterile slush composition 106 is substantially automated through the operation of the controller 140, the cooling device 134, the actuator 130, and the pumping device 1104 together.

[0082] As shown in Figure 15 In another non-limiting example, the pumping device 1104 can be arranged in-line with the disposable tube 1200, where the disposable tube 1200 passes through the pumping device 1104, as shown in

[0083] In particular embodiments, the pumping device 1104 can be configured to have a maximum allowable pressure tolerance at the end of the delivery or disposable tube 1200, or at the end of the delivery needle 1204 or cannula. The pumping device 1104 can also include an adjustable constant volume pump and be configured with a user-specified stop that comes into play after a predetermined amount of slush has been delivered.

[0084] Figure 16 Figure 19 shows an additional non-limiting example of an agitator 108 that can be operated with a disposable sleeve 102. Figure 16 The sleeve 102 and agitator 108 shown in Figure 19 are substantially the same as the sleeve 102 and agitator 108 shown in Figure 8 Figures 11 and 13, 14, except that Figures 16 to 19 The extension 1102 (of the port 1100) in the sleeve 102 in Figure 13 and 14 is oriented horizontally rather than vertically as shown in

[0085] Figure 20 Figure 20 shows another non-limiting example of a medical slush production system 100. Except as described below or as otherwise made apparent from the figures, Figure 20 The medical slush production system 100 in Figure 1The medical ice slurry production system 100. Identical components are indicated by the same reference numerals. (e.g., ...) Figure 20 As shown, the medical ice slurry production system 100 includes a disposable sleeve 1700 configured to be supported within a housing 104. The disposable sleeve 1700 is in the form of a sterile pre-filled syringe. The disposable sleeve 1700 is pre-filled with a sterile, non-frozen ice slurry composition 106. Pre-filling the disposable sleeve 1700 with the non-frozen sterile ice slurry composition 106 ensures that the sterile ice slurry composition 106 remains independent within a closed environment. This helps reduce the burden on end-users attempting to operate the disposable sleeve 1700 while maintaining the sterility of the ice slurry composition 106. In some non-limiting examples, the disposable sleeve 1700 may be surrounded by an insulating material (not shown) to improve thermal stability.

[0086] The disposable sleeve 1700 can be made of plastic, glass, or metal. The size of the disposable sleeve 1700 can be determined according to the medical application to hold an ice slurry volume between approximately one cubic centimeter (cc) and approximately one liter (L). The disposable sleeve 1700 is rotatably connected to a stirrer 108. The disposable sleeve 1700 is rotatably connected to a stirrer 1702. The stirrer 1702 operates similarly to the one described above. Figure 1 The stirrer 108 is described above, except that the stirrer 1702 is configured to be operated using a disposable sleeve 1700. The stirrer 1702 includes a stirrer shaft 1704 and fins 1706 disposed within the disposable sleeve 1700 and coupled to the stirrer shaft 1704. The fins 1706 are helical along the length of the stirrer shaft 1704. The stirrer shaft 1704 is received within the disposable sleeve 1700. The stirrer shaft 1704 is rotatably sealed to the tapered end 1708 of the disposable sleeve 1700 to allow the stirrer shaft 1704 to rotate relative to the disposable sleeve 1700 while maintaining a seal between the sterile ice slurry composition 106 and the surrounding environment. The stirrer shaft 1704 can be rotatably sealed to the tapered end 1708, for example, by using at least one of a sealed hydrostatic bearing, a sealed hydrodynamic bearing, a fluid bearing, and an O-ring.

[0087] The disposable sleeve 1700 includes an inlet port 1710 and a plunger 1712 disposed in a distal end 1712 of a tapered end 1708. The inlet port 1710 is constructed and arranged to allow a medical ice slurry composition 106 to be injected from the disposable sleeve 1700 into a patient. For example, the inlet port 1710 may be configured to be coupled to a needle. The plunger 1712 is slidably received within a second side 1714 of the disposable sleeve 1700 opposite the tapered end 1708. The plunger 1712 is configured to be axially displaced relative to the disposable sleeve 1700 to inject the sterile ice slurry composition 106 within the disposable sleeve 1700.

[0088] Except in the Examples, or where otherwise indicated, all metrics are provided in SI units. Figure 20 The operation of the medical ice slurry production system 100 in Figure 1 the medical ice slurry production system 100 in FIG. 1. Once the sterile ice slurry composition 106 within the disposable sleeve 1700 is cooled to the desired temperature by the cooling device 134 and includes ice crystals of the desired size due to the agitator 1702, the disposable sleeve 1700 is removed from the housing 104 and the needle is coupled to the tapered end 1708 of the disposable sleeve 1700. Alternatively or additionally, the disposable sleeve 1700 can be placed within a syringe holder similar to the syringe holder 300 in Figure 5 for safe storage prior to injection. The sterile ice slurry composition 106 is then injected into the patient at the treatment site. Thus, the sterile ice slurry composition 106 is self-contained during the entire medical ice slurry production process, thereby reducing the burden on the clinician to maintain the sterility of the ice slurry composition 106 during delivery and production. Also, for a given medical application, the production of the sterile ice slurry composition 106 (i.e., the cooling and formation of ice crystals of the appropriate size) is substantially automated by operating the controller 140, the cooling device 134, and the actuator 130 together. The use of the disposable container 1700 to deliver the sterile composition 106 also eliminates the need to transfer the ice slurry composition 106 after production.

[0089] Figure 21 -28 illustrates an additional non-limiting example of an agitator 1702 of a disposable sleeve 1700 that can be operated with the actuator 130 to break up ice crystals and mix the sterile ice slurry composition 106. As shown in Figure 21 the agitator 108 includes a plurality of ridge-like protrusions 1800 arranged axially along the interior of the disposable sleeve 1700. The plurality of ridge-like protrusions 1800 each extend toward the agitator shaft 1704 and the fin 1706 coupled thereto. In operation, rotation of the agitator shaft 1704 and, thus, the fin 1706 causes the fin 1706 to rotate past the plurality of ridge-like protrusions 1800 to facilitate breaking up ice crystals and mixing the sterile ice slurry composition 106.

[0090] As shown in Figure 22As shown, the agitator 1702 includes a plurality of blades 1900 coupled to an agitator shaft 1704. Each blade 1900 includes multiple tapered edges to facilitate the breaking up of ice crystals and the mixing of the sterile ice slurry composition 106. Each blade 800 also includes multiple tapered edges to facilitate the breaking up of ice crystals and the mixing of the sterile ice slurry composition 106. The size of the ice crystals formed within the sterile ice slurry composition 106 by rotating the blades 800 can be controlled by the degree of tapering of the edges of each blade and / or the length of each blade 800. In a non-limiting example, each blade 800 may define a length between approximately 12.5% ​​and 99% of the diameter defined by the disposable sleeve.

[0091] like Figure 23 As shown, the stirrer 1702 includes a plurality of ridged, blade-like protrusions 2000 arranged axially along the interior of the disposable sleeve 1700. Each of the plurality of ridged, blade-like protrusions 2000 extends radially inward. In this non-limiting example, the stirrer 1702 includes a cap 2002 configured to rigidly connect the tapered end 1708 of the disposable sleeve 1700 to the actuator 130, such that the entire disposable sleeve 1700 can be stirred in response to rotation and / or vibration provided by the actuator 130.

[0092] like Figure 24 As shown, the agitator 1702 includes a plurality of particles 2100 pre-filled in a disposable sleeve 1700 along with the sterile ice slurry composition 106. In this non-limiting example, the disposable sleeve 1700 can be operated with a cap 2002, and the plurality of particles 2100 facilitate turbulent mixing and agitation within the disposable sleeve 1700 in response to rotation and / or vibration provided by the actuator 130. Figure 25 As shown, the agitator 1702 includes a plurality of blades 2200. Each of the plurality of blades 2200 includes a plurality of tapered edges to facilitate the breaking up of ice crystals and the mixing of the sterile ice slurry composition 106. The degree of tapering defined by the tapered edges and / or the length defined by each of the plurality of blades 2200 can control the size of the ice crystals formed by rotating the plurality of blades 2200 within the sterile ice slurry composition 106. In a non-limiting example, the plurality of blades 2200 may define a length that is between about 12.5% ​​and 99% of the diameter defined by the disposable sleeve. Furthermore, each of the plurality of blades 2200 may be configured to rotate in opposite directions relative to each other.

[0093] like Figure 26 As shown, the stirrer 1702 includes blades 2300 coupled to the stirrer shaft 1704 for rotation therewith. Figure 27 As shown, the stirrer 1702 includes impeller 2300 and a plurality of fins 2400 coupled to the inner surface of the impeller 2300. Figure 28As shown, the mixer 1702 includes a whisk-like mixing section 2500 coupled to the mixer shaft 1704 for rotation therewith. It should be understood that in Figure 20 Various combinations of the various constructions of the stirrer 1702 shown in -28 are within the scope of this disclosure.

[0094] like Figure 29 As shown, in a non-limiting example, a stirrer 1702 is arranged on the side of a disposable sleeve 1700. Specifically, a stirrer shaft 1704 projects from the side of the disposable sleeve 1700 and includes blades 1900 coupled to the stirrer shaft 1704. It should be understood that in this arrangement, the stirrer 1702 may take any form of construction of the stirrer 1702 described herein. Corresponding to this arrangement of the stirrer 1702, an actuator 130 is arranged in a corresponding interior of a sidewall 124 of the housing 104. An actuator shaft 132 projects from the corresponding sidewall 124 toward the stirrer shaft 1704.

[0095] like Figure 30 As shown, in another non-limiting example, each sidewall 124 of the housing 104 may include a corresponding actuator 130 and actuator shaft 132. This allows the housing 104 to support a plurality of disposable sleeves 1700 and thereby produce a plurality of sterile ice slurry compositions 106 for injection into a patient.

[0096] like Figure 31 As shown, in another non-limiting example where the stirrer 1702 is arranged on one side of the disposable sleeve 1700, the stirrer 1702 may include a plurality of blades 2800 each configured to rotate in opposite directions relative to each other.

[0097] like Figure 32As shown in FIG. 17, in some non-limiting examples, the disposable sleeve 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 sleeve 170. In the non-limiting example shown, the one or more filters 2900 include a first filter 2902, a second filter 2904, and a third filter 2906, wherein 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 having a first size. The second filter 2904 is configured to filter ice crystals having a second size that is smaller than the first size, and the third filter 2906 is configured to filter ice crystals having a third size that is smaller than the second size. As will be appreciated by those of skill in the art, the sizes of the ice crystals filtered by the first filter 2902, the second filter 2904, and the third filter 2906 can be used to control the size of the ice crystals in the sterile slush composition 106 injected into the patient. For example, in one non-limiting example, the first size is about 500 micrometers (pm), the second size is about 250 pm, and the third size is about 100 pm. In other non-limiting examples, the disposable sleeve 102 can include any number of filters 400 to filter ice crystals of any size as desired.

[0098] Figure 33 Another non-limiting example of a disposable sleeve 1700 is shown. As Figure 33 As shown in FIG. 17, in some non-limiting examples, the disposable sleeve 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 sleeve 170. In the non-limiting example shown, the one or more filters 2900 include a first filter 2902, a second filter 2904, and a third filter 2906, wherein 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 having a first size. The second filter 2904 is configured to filter ice crystals having a second size that is smaller than the first size, and the third filter 2906 is configured to filter ice crystals having a third size that is smaller than the second size. As will be appreciated by those of skill in the art, the sizes of the ice crystals filtered by the first filter 2902, the second filter 2904, and the third filter 2906 can be used to control the size of the ice crystals in the sterile slush composition 106 injected into the patient. For example, in one non-limiting example, the first size is about 500 micrometers (pm), the second size is about 250 pm, and the third size is about 100 pm. In other non-limiting examples, the disposable sleeve 102 can include any number of filters 400 to filter ice crystals of any size as desired.

[0099] Figure 34 Another non-limiting example of a medical slush production system 100 is shown. Except as described below or as otherwise apparent from the Figures, Figure 31 The medical slush production system 100 in FIG. 17 is similar to the medical slush production system 100 in Figure 1 and 20 The medical slush production system 100 in FIG. 17 is similar to the medical slush production system 100 in Figure 34As shown, the medical ice slurry production system 100 includes a stirrer 3100 in liquid form (e.g., exalcohol, isopropyl alcohol, or ethanol) supported within an inner cavity 122 of a housing 104. A disposable sleeve 1700 is suspended within the stirrer 3100 and includes a cap 3102 configured to provide a seal between an inlet port 1710 and the surrounding stirrer 3100. An actuator 3104, in the form of an ultrasonic transmitter, is arranged around the disposable sleeve 1700. The actuator 3104 is configured to vibrate at an ultrasonic frequency. The ultrasonic waves generated by the actuator 3104 are transmitted through the stirrer 3104 to the disposable sleeve 1700 to break up ice crystals formed in a sterile ice slurry formulation 106 to a desired ice crystal size. A controller 140 is electrically connected to the actuator 3104 and configured to selectively instruct the actuator 3104 to generate the ultrasonic waves carried by the stirrer 3100. In operation, controller 140 is configured to instruct actuator 3104 to apply ultrasonic waves through stirrer 3100 until ice crystals in the sterile ice slurry composition 106 define a desired size. In a non-limiting example, the duration for which actuator 3104 applies ultrasonic waves on disposable sleeve 1700 may be input to controller 140. Alternatively or additionally, controller 140 may be configured to vary the vibration frequency of actuator 3104 to control the ice crystal size within the sterile ice slurry composition 106.

[0100] Figure 35 Another non-limiting example of a medical ice slurry production system 100 is shown. Except as described below or as evident from the figures, Figure 35 The medical ice slurry production system 100 is similar to Figure 1 and 20 The medical ice slurry production system 100. Identical components are indicated by the same reference numerals. (e.g., ...) Figure 35 As shown, the medical ice slurry production system 100 includes a stirrer 3200 having a mechanical connection mechanism 3202 supported within an inner cavity 122 of a housing 104. The mechanical connection mechanism 3202 is configured to removably couple a disposable sleeve 1700 to a connection mechanism. The mechanical connection mechanism 3202 of the stirrer 3200 is coupled to an actuator shaft 132 of an actuator 130 to facilitate rotation and / or vibration of the mechanical connection mechanism 3202 and thus the disposable sleeve 1700. In operation, the end user places the disposable sleeve 1700 within the inner cavity 122 of the housing 104, such that the disposable sleeve 1700 is coupled to the mechanical connection mechanism 3202. The mechanical connection mechanism 3202 is rotated and / or vibrated by the actuator 130 to break up ice crystals formed during the production of the sterile ice slurry composition 106 prior to injection.

[0101] Figure 36Another non-limiting example of a medical ice slurry production system 100 is shown. Except as described below or otherwise apparent from the figures, Figure 36 the medical ice slurry production system 100 in Figure 1 and 20 is similar to the medical ice slurry production system 100 in Figure 36 The medical ice slurry production system 100 includes a sleeve support 3300 defining a generally cylindrical shape. The sleeve support 3300 is configured to be removably coupled to one or more disposable sleeves 1700. The sleeve support 3300 is coupled to the actuator shaft 132 of the actuator 130 to facilitate movement and / or rotation of the sleeve support 3300 in one or more of the x-direction, y-direction, and z-direction. The illustrated disposable sleeve 1700 includes an agitator 1702 including a plurality of ridge-like lobe-like protrusions 2000 arranged axially along the interior of the disposable sleeve 1700 as illustrated in Figure 23 It will be appreciated that alternative configurations of agitation described herein can be implemented in this non-limiting example.

[0102] The movement imparted on the agitator by the actuator 130 and, in turn, by the disposable sleeve 1700 breaks up ice crystals formed in the sterile ice slurry composition 106 prior to injection. It will be appreciated that, in order to properly balance the agitator 3300 during movement, the disposable sleeve 1700 should be coupled to the agitator 3300 relatively and in pairs.

[0103] Figure 37 Another non-limiting example of a medical ice slurry production system 100 is shown. Except as described below or otherwise apparent from the figures, Figure 37 the medical ice slurry production system 100 in Figure 1 is similar to the medical ice slurry production system 100 in Figure 37 The medical ice slurry production system 100 includes a disposable sleeve 3400 configured to be supported within the housing 104. The illustrated disposable sleeve 3400 is in the form of a sterile pre-filled, compressible bag. In some non-limiting examples, the disposable sleeve 3400 is an intravenous (IV) infusion bag. The disposable sleeve 3400 is pre-filled with the sterile ice slurry composition 106. Pre-filling the disposable sleeve 3400 with the sterile ice slurry composition 106 ensures that the sterile ice slurry composition 106 is self-contained within an enclosed environment. This helps to alleviate the burden on the end user to manipulate the disposable sleeve 3400 while attempting to maintain the sterility of the ice slurry composition 106. In some non-limiting examples, the disposable sleeve 3400 can be surrounded by a thermal insulating material (not shown) to improve thermal stability.

[0104] The disposable sleeve 3400 can be sized to hold a volume of ice slurry between about one cubic centimeter (cc) and about one liter (L), depending on the medical application. The illustrated disposable sleeve 3400 includes an access port 3402 fluidly coupled to a pumping device 3404. The pumping device 3404 is similar in construction and operation to the pumping device 1104 in Figure 13 . That is, a controller 140 is in communication with the pumping device 3404 and is configured to selectively instruct the pumping device 3404 to pump the sterile ice slurry composition 106 from the disposable sleeve 3400 for injection. The controller 140 is also configured to control the flow rate provided by the pumping device 3404. In one non-limiting example, the pumping device 3404 can be an infusion pump or any other pump described herein. Further, the pumping device 3402 can be coupled to a disposable tubing and needle to enable injection into a patient, as illustrated in Figure 14

[0105] In particular embodiments, the pumping device 3404, like the pumping device 1104, can be configured to have a maximum allowable pressure tolerance at the end of the delivery or disposable tubing, or at the end of the delivery needle or cannula. The pumping device 3404 can also include an adjustable constant volume pump and be configured with a user-specific stop that functions after a predetermined amount of ice slurry has been delivered.

[0106] The illustrated agitator 3406 and actuator 3408 are similar to the agitator 3100 and actuator 3104 in Figure 34 . That is, the actuator 3408 is configured to generate ultrasonic vibrations that are carried through the agitator 3406 to the disposable container 3400 to break up ice crystals in the sterile ice slurry composition 106 prior to injection.

[0107] As illustrated in Figure 38 , in another non-limiting example, the disposable sleeve 3400 is coupled to an agitator 3500. The agitator 3500 includes an agitator shaft 3502 coupled to a plurality of blades 3504 disposed within the disposable sleeve 3400. The agitator shaft 3502 is coupled to the actuator shaft 132 to enable the blades 3504 to rotate within the disposable sleeve 3400 and break up ice crystals formed in the sterile ice slurry composition 106 to a desired size.

[0108] As illustrated in Figure 39 ​As shown, in yet another non-limiting example, the disposable sleeve 3400 can be operated using a stirrer 3600. The stirrer 3600 includes a pair of opposing supports 3602, each support 3602 coupled to an actuator 3604 disposed in a corresponding one of the sidewalls 124 of the housing 104. The pair of opposing supports 3202 are each configured to move to compress the disposable sleeve 3400 and provide agitation to break up ice crystals formed in the sterile ice slurry composition 106. In operation, the controller 140 is configured to apply agitation to the disposable sleeve 3400 via one or more stirrers 3606 coupled to the actuators 3604. Once the sterile ice syrup composition 106 reaches the desired temperature and includes ice crystals of the desired size, the controller 140 is configured to instruct the actuator 3604 to displace to compress the disposable sleeve 3400, thereby forcing the sterile ice syrup composition 106 through the inlet port 3402 for injection into the patient.

[0109] Figure 40 Another non-limiting example of a medical ice slurry production system 100 is shown. Except as described below or as evident from the figures, Figure 40 The medical ice slurry production system 100 is similar to Figure 1 and 20 The medical ice slurry production system 100. Identical components are indicated by the same reference numerals. (e.g., ...) Figure 40 As shown, the medical ice slurry production system 100 includes a first cooling channel 3702 connected to a first cooling device 3700 and a second cooling channel 3708 connected to a second cooling device 3706. The first cooling channel 3702 is arranged within the side 124 of the housing to provide cooling to a first cavity 3710 arranged within the housing 104. The second cooling channel 3708 is arranged within the side 124 of the housing 104 to provide cooling to a second cavity 3712 arranged within the housing 104.

[0110] The medical slush production system 100 includes a disposable cartridge 3714. The disposable cartridge 3714 includes a first syringe chamber 3716, a second syringe chamber 3718, and a droplet device 3720 disposed between the first syringe chamber 3716 and the second syringe chamber 3718. When placed in 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 3712. The first syringe chamber 3716 is pre-filled with a sterile first liquid 3722, a sterile second liquid 3724, and a collapsible partition 3726 disposed between the first liquid 3722 and the second liquid 3724. The second liquid 3724 is disposed adjacent to the droplet device 3720. A plunger 3728 is slidably received within the first syringe chamber 3716 and is configured to inject the first liquid 3722 into the second syringe chamber 3718 and, in turn, the second liquid 3724 (the liquids are substantially incompressible).

[0111] In operation, the controller 140 controls the first cooling device 3700 to maintain the first cavity 3710 at a cold temperature (e.g., about 2°C) and the second cooling device 3706 to maintain the second cavity 3712 at a much lower temperature than the freezing point (e.g., -100°C). Once the desired temperatures are achieved in the first cavity 3710 and the second cavity 3712, the plunger 3728 is displaced to inject the second liquid 3724 through the droplet device 3720 and into the second syringe chamber 3718. The freezing temperature of the droplet device 3720 and the second cavity 3712 allows ice crystals to form in the second syringe chamber 3718 having a desired size (controlled by the droplet device 3720). Next, the collapsible partition 3726 is crushed or displaced to allow the first liquid 3722 to fall into the second syringe chamber 3718, thereby suspending the previously formed ice crystals in the first liquid 3722 (i.e., a sterile slush composition is produced at a desired temperature with ice crystals having a desired size). The resulting sterile slush mixture can then be injected into a patient.

[0112] Figure 41 A non-limiting example of a medical slush production system 100 is shown. Except in the following description or as otherwise indicated herein, Figure 41 the medical slush production system 100 in Figure 40 the medical slush production system 100 in. The same parts are designated by the same 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 42As shown in FIG. 38, the ice tray 3800 defines a plurality of ice cavities 3900, each ice cavity 3900 pre-filled with a liquid 3902 and sized to form ice crystals having a desired size and shape.

[0113] In operation, the controller 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 warmer temperature (e.g., 2°C). Once the desired temperatures are achieved in the first cavity 3710 and the second cavity 3712 and ice crystals have formed in the ice tray 3800, the ice tray 3800 is inverted Figure 42 ) to release the formed ice crystals 3902 from their respective ice cavities 3900. When released, the ice crystals 3902 fall into the second syringe chamber 3718, thereby suspending the previously formed ice crystals in the first liquid 3802 (i.e., producing a sterile ice slush composition at a desired temperature, wherein the ice crystals have a desired size). The formed sterile ice slush mixture can then be agitated, if desired, and injected into a patient. In particular embodiments, the first liquid 3802 can include saline, lactated Ringer's solution, or a solution prepared to emulsify, generally a fine dispersion of insoluble droplets or particles.

[0114] In each of the above embodiments, it is also understood that the temperature within the medical ice slush mixing chamber (e.g., any of the canisters or disposable sleeves described herein) can be equilibrated with any one or more of the cooling devices, liquids, or gases discussed herein, to provide a uniformly cooled medical ice slush. For example, with reference to Figure 1 -3, these systems can be configured such that the temperature within the sleeve 102 is equilibrated with the cooling liquid or gas in the channel or coil 136, or with the cooling liquid or gas in the cavity 122.

[0115] Thus, although the present application has been described in connection with specific embodiments and examples, it is not necessarily limited to the embodiments and examples described, but rather, the scope of the present application is to be determined entirely by the appended claims, and equivalents thereof. The entire disclosure of each of the various patents and publications referred to herein is hereby incorporated by reference, as if each were individually incorporated by reference.

Claims

1. A medical slush production system, comprising: a disposable cartridge, comprising: a first chamber pre-filled with non-frozen sterile first liquid and non-frozen sterile second liquid, the non-frozen sterile first liquid and the non-frozen sterile second liquid separated by a collapsible divider such that the non-frozen sterile first liquid and the non-frozen sterile second liquid are independent within an enclosed environment; a second chamber; a microdroplet device disposed between the first chamber and the second chamber; a housing supporting the disposable cartridge, the housing defining a first cavity and a second cavity and configured and arranged to receive the disposable cartridge such that the first chamber is disposed within the first cavity and the second chamber is disposed within the second cavity; a first cooling device operable with the housing to provide cooling to the first cavity and to cool the first chamber and the non-frozen sterile first liquid and the non-frozen sterile second liquid in the first chamber to a first temperature; a second cooling device operable with the housing to provide cooling to the second cavity and to cool the second chamber to a second temperature; a plunger operable with the disposable cartridge to: inject the non-frozen sterile second liquid through the microdroplet device into the second chamber such that the second temperature is capable of forming ice crystals in the second chamber; and manipulate the collapsible divider to thereby cause the non-frozen sterile first liquid to enter the second chamber, suspending ice crystals in the non-frozen sterile first liquid, thereby forming a medical slush composition comprising ice crystals; and an access port configured and arranged to allow withdrawal or injection of the medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition comprising ice crystals of a desired size; wherein the access port is defined in the disposable cartridge; and wherein the disposable cartridge is removably placed in the housing.

2. The medical slush production system of claim 1, wherein, the first temperature is above 0°C.

3. The medical slush production system of claim 1, wherein, the second temperature is below 0°C.

4. The medical slush production system of claim 1, wherein, the housing includes a first cooling channel coupled to the first cooling device and disposed within a side of the housing to provide cooling to the first cavity.

5. The medical slush production system of claim 1, wherein, the housing includes a second cooling channel coupled to the second cooling device and disposed within a side of the housing to provide cooling to the second cavity.

6. The medical slush production system of claim 1, wherein, the collapsible divider is crushed.

7. The medical slush production system of claim 1, wherein, the collapsible divider is displaced.

8. The medical slush production system of claim 1, wherein, the plunger is slidingly received within the first chamber.

9. The medical slush production system of claim 1, wherein, the microdroplet device is configured to be capable of forming ice crystals of a desired size upon injection of the non-frozen sterile second liquid into the second chamber.

10. The medical slush production system of claim 1, wherein, a power source coupled to a controller configured to operate the first cooling device and the second cooling device is also included.

11. A medical slush production system, comprising: a disposable cartridge, comprising: a first chamber; an ice tray disposed within the first chamber, the ice tray comprising a plurality of ice cavities pre-filled with a non-frozen sterile first liquid; and a second chamber coupled to the first chamber, the second chamber holding a non-frozen sterile second liquid, such that the ice tray, the non-frozen sterile first liquid, and the non-frozen sterile second liquid are independent in a closed environment; a housing supporting the disposable cartridge, the housing defining a first cavity and a second cavity, and configured and arranged to receive the disposable cartridge such that the first chamber is disposed within the first cavity and the second chamber is disposed within the second cavity; a first cooling device operable with the housing to provide cooling to the first cavity and to cool the first chamber, the ice tray, and the non-frozen sterile first liquid to a first temperature sufficient to form ice crystals in the plurality of ice cavities; a second cooling device operable with the housing to provide cooling to the second cavity and to cool the second chamber and the non-frozen sterile second liquid to a second temperature; the ice tray configured to be inverted after ice crystals are formed, thereby releasing the ice crystals from the first chamber into the second chamber, thereby suspending the ice crystals in the non-frozen sterile second liquid, thereby forming a medical slush composition comprising ice crystals; and an access port configured and arranged to allow withdrawal or injection of the medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition comprising ice crystals; wherein the access port is defined in the disposable cartridge; and wherein the disposable cartridge is removably placed in the housing.

12. The medical slush production system of claim 11, wherein, the first temperature is sufficient to freeze the non-frozen sterile first liquid in the plurality of ice cavities.

13. The medical slush production system of claim 11, wherein, the second temperature is above 0°C.

14. The medical slush production system of claim 11, wherein, the second temperature is higher than the first temperature.

15. The medical slush production system of claim 11, wherein, the plurality of ice cavities are sized to form ice crystals of a desired size.

16. The medical slush production system of claim 11, wherein, the first temperature is sufficient to form ice crystals of a desired size in the ice tray.

17. The medical slush production system of claim 11, wherein, the second chamber is configured to agitate the medical slush composition.

18. The medical slush production system of claim 11, wherein, the ice tray is made of a flexible material.

19. The medical slush production system of any one of claims 1 or 11, wherein, the disposable cartridge comprises one of a syringe or a cartridge.

20. The medical slush production system of any one of claims 1 or 11, wherein, the access port is configured and arranged to allow a syringe to engage the access port and withdraw the medical slush composition.

21. The medical slush production system of any one of claims 1 or 11, wherein, the access port is a first access port defined in the disposable cartridge, and it comprises a second access port defined in the housing, the first access port and the second access port being in fluid communication, thereby allowing withdrawal of the medical slush composition from the disposable cartridge while maintaining sterility of the medical slush composition.

22. The medical slush production system of any one of claims 1 or 11, wherein, the first cooling device comprises at least one of standard cooling, magnetic cooling, electrical cooling, or chemical cooling.

23. The medical slush production system of any one of claims 1 or 11, wherein, the second cooling device comprises at least one of standard cooling, magnetic cooling, electrical cooling, or chemical cooling.

24. The medical slush production system of any one of claims 1 or 11, wherein, At least one of (i) a luer lock with a shut-off valve, (ii) a pressure valve, (iii) a quick disconnect device, (iv) a one-way valve with a luer lock, and (v) a sterile rubber stopper is operable through the access port to selectively allow withdrawal of a sterile medical slush composition comprising ice crystals from the disposable cartridge through the access port.

25. The medical slush production system of any one of claims 1 or 11, wherein, The ice crystals have a maximum diameter of less than one millimeter.

26. The medical slush production system of any one of claims 1 or 11, wherein, The ice crystals have a maximum cross-sectional diameter of less than 0.3 millimeters.

27. The medical slush production system of any one of claims 1 or 11, wherein, The ice crystals have a maximum cross-sectional diameter of less than 0.1 millimeters.

28. The medical slush production system of any one of claims 1 or 11, wherein, Also included are: a pump operable to pump a medical slush composition comprising ice crystals out of the access port of the disposable cartridge through a disposable delivery tube while maintaining sterility of the medical slush composition comprising ice crystals.

29. The medical slush production system of any one of claims 1 or 11, wherein, At least one of the non-frozen sterile first liquid or the non-frozen sterile second liquid comprises saline, lactated Ringer's solution, or a solution for making an emulsion.

30. The medical slush production system of any one of claims 1 or 11, wherein, The first cooling device is configured to provide uniform cooling to the first chamber.

31. The medical slush production system of any one of claims 1 or 11, wherein, The second cooling device is configured to provide uniform cooling to the second chamber.

32. A method for producing a medical slush, the method comprising: removably placing a disposable cartridge in a housing, the disposable cartridge comprising: a first chamber pre-filled with a non-frozen sterile first liquid and a non-frozen sterile second liquid, the non-frozen sterile first liquid and the non-frozen sterile second liquid separated by a collapsible partition such that the non-frozen sterile first liquid and the non-frozen sterile second liquid are independent within an enclosed environment; a second chamber; a microdroplet device disposed between the first chamber and the second chamber; the housing defining a first cavity and a second cavity and configured and arranged to receive the disposable cartridge such that the first chamber is disposed within the first cavity and the second chamber is disposed within the second cavity; cooling the first cavity when placed in the housing using a first cooling device operable with the housing and cooling the first chamber and the non-frozen sterile first liquid and the non-frozen sterile second liquid in the first chamber to a first temperature; cooling the second cavity using a second cooling device operable with the housing and cooling the second chamber to a second temperature; injecting the non-frozen sterile second liquid into the second chamber through the microdroplet device using a plunger operable with the disposable cartridge such that the second temperature is capable of forming ice crystals in the second chamber; and manipulating the collapsible partition using the plunger to bring the non-frozen sterile first liquid into the second chamber, suspending ice crystals in the non-frozen sterile first liquid, thereby forming a medical slush composition comprising ice crystals; wherein an access port is configured and arranged to allow withdrawal or injection of a medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition comprising ice crystals.

33. A method for producing a medical slush, the method comprising: A disposable cartridge is removably placed in a housing, the disposable cartridge comprising: a first chamber; an ice tray disposed within the first chamber, the ice tray comprising a plurality of ice cavities pre-filled with a non-frozen sterile first liquid; and a second chamber coupled to the first chamber, the second chamber holding a non-frozen sterile second liquid, such that the ice tray, the non-frozen sterile first liquid, and the non-frozen sterile second liquid are independent in an enclosed environment; the housing defines a first cavity and a second cavity, and is constructed and arranged to receive the disposable cartridge such that the first chamber is disposed within the first cavity and the second chamber is disposed within the second cavity; when placed in the housing, the first cavity is cooled using a first cooling device operable with the housing, and the first chamber, ice tray, and non-frozen sterile first liquid are cooled to a first temperature sufficient to form ice crystals in the plurality of ice cavities; the second cavity is cooled using a second cooling device operable with the housing, and the second chamber and non-frozen sterile second liquid are cooled to a second temperature; and after the ice crystals are formed, the ice tray is inverted, the ice crystals are released from the first chamber into the second chamber, and the ice crystals are suspended in the non-frozen sterile second liquid, thereby forming a medical slush composition comprising ice crystals; wherein the access port is constructed and arranged to allow withdrawal or injection of the medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition comprising ice crystals.

34. The method of any one of claims 32 or 33, wherein, includes withdrawing the medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition.

35. The method of any one of claims 32 or 33, wherein, includes pumping the medical slush composition comprising ice crystals from the disposable cartridge while maintaining sterility of the medical slush composition.

36. A method of producing a medical slush, the method comprising: receiving at a point of care a disposable cartridge comprising an access port, the disposable cartridge containing a sterile slush composition, wherein the sterile slush composition is independent within an enclosed environment, and wherein the disposable cartridge comprises one of a syringe or a cartridge; removably placing the disposable cartridge within a housing, wherein the housing comprises a cooling device operable to cool the sterile slush composition to a temperature sufficient to form ice crystals; cooling the disposable cartridge to a temperature sufficient to form ice crystals in the sterile slush composition inside the disposable cartridge; removing the disposable cartridge from the housing at the point of care; and agitating the sterile slush composition such that the ice crystals are reduced to a size sufficient to allow the sterile slush composition comprising reduced ice crystals to be delivered through the access port to a patient through an end of a needle, wherein the sterile slush composition remains independent of the enclosed environment throughout the production process, and wherein the access port is constructed and arranged to allow withdrawal or injection of the sterile slush composition comprising ice crystals from the disposable cartridge at the point of care while maintaining sterility of the sterile slush composition comprising ice crystals.

37. A method of producing medical ice slurry at a point of care, the method comprising: receiving at the point of care a pre-filled disposable cartridge containing a non-frozen sterile ice slurry composition, wherein the sterile ice slurry composition is self-contained within an enclosed environment, wherein the disposable cartridge comprises one of a syringe or a cartridge; cooling the pre-filled disposable cartridge to a temperature sufficient to form ice crystals in the sterile ice slurry composition inside the pre-filled disposable cartridge; and agitating the sterile ice slurry composition held in the disposable cartridge such that the ice crystals are reduced in size to a size sufficient to allow the sterile ice slurry composition including the reduced ice crystals to be delivered through an end of a needle to a patient through an access port defined in the disposable cartridge.

38. The method of any one of claims 36-37, wherein, the temperature is between -10°C and 4°C.

39. The method of any one of claims 36-37, wherein, the sterile ice slurry composition includes an agent or a biocompatible surfactant.

40. The method of claim 39, wherein, the agent or the biocompatible surfactant is capable of making the sterile ice slurry composition more injectable.

41. The method of claim 39, wherein, the sterile ice slurry composition includes a biocompatible surfactant, and wherein the biocompatible surfactant is glycerol.

42. The method of any one of claims 36-37, wherein, the syringe is a pre-filled syringe.

43. The method of any one of claims 36-37, wherein, at least one of (i) a luer lock with a shut-off valve, (ii) a pressure valve, (iii) a quick disconnect, (iv) a one-way valve with a luer lock, and (v) a sterile rubber stopper is operable through the access port to selectively allow withdrawal of the sterile medical ice slurry composition from the disposable cartridge through the access port.

44. A sterile ice slurry production system, the system comprising: a pre-filled disposable cartridge holding a non-frozen sterile ice slurry composition, the non-frozen sterile ice slurry composition being self-contained in an enclosed environment; an access port defined in the disposable cartridge; a housing defining an internal cavity sized to receive the pre-filled disposable cartridge; a cooling device operable within the housing to cool the non-frozen sterile ice slurry composition to a temperature sufficient to form ice crystals in a sterile ice slurry; an agitator operable with the disposable cartridge to agitate the sterile ice slurry composition such that the ice crystals are reduced in size to a size sufficient to allow the sterile ice slurry composition including the reduced ice crystals to be delivered through an end of a needle to a patient; and wherein the sterile ice slurry composition is configured to remain self-contained within the pre-filled disposable cartridge throughout the sterile ice slurry production process.

45. A sterile ice slurry production system, the system comprising: a disposable cartridge receiving a sterile ice slurry composition, wherein the sterile ice slurry composition is self-contained in an enclosed environment; an access port defined in the disposable cartridge; a housing defining an internal cavity sized to receive the disposable cartridge; and a cooling device operable within the housing to cool the sterile ice slurry composition to a temperature sufficient to form ice crystals; and a sterile ice slurry production system, the system comprising: an agitator operable with the disposable sleeve to agitate the sterile slush composition such that the ice crystals are reduced to a size sufficient to permit the sterile slush composition including the reduced ice crystals to be delivered through the end of the needle to the patient; wherein the sterile slush composition is configured to remain independent within the disposable sleeve throughout the sterile slush production process.

46. The sterile ice-mush production system according to any of claims 44 or 45, characterized in that, the housing further comprises an actuator, and wherein the actuator is configured to impart motion to the agitator to agitate the sterile slush composition such that the ice crystals inside the disposable sleeve are reduced to a size sufficient to permit the sterile slush composition including the reduced ice crystals to be withdrawn or injected from the disposable sleeve while maintaining the sterility of the sterile slush composition including the reduced ice crystals.

47. The sterile ice-mush production system according to any of claims 44 or 45, characterized in that, at least one of (i) a luer lock with a shut-off valve, (ii) a pressure valve, (iii) a quick disconnect, (iv) a one-way valve with a luer lock, and (v) a sterile rubber stopper is operable through the access port to selectively permit withdrawal of the sterile medical slush composition from the disposable sleeve through the access port.

48. The sterile ice-mush production system according to any of claims 44 or 45, characterized in that, the temperature is between -10°C and 4°C.

49. The sterile ice-mush production system according to any of claims 44 or 45, characterized in that, the sterile slush composition includes an agent or a biocompatible surfactant.

50. The sterile ice slush production system of claim 49, wherein, the agent or the biocompatible surfactant is capable of making the sterile slush composition more injectable.

51. The sterile ice slush production system of claim 49, wherein, the sterile slush composition includes a biocompatible surfactant, and wherein the biocompatible surfactant is glycerol.

52. The sterile ice-mush production system according to any of claims 44 or 45, characterized in that, the disposable sleeve includes one of a syringe or a cartridge.

53. The sterile ice slush production system of claim 52, wherein, the syringe is a pre-filled syringe.

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