Patent Publication Number: US-9844461-B2

Title: Home-use applicators for non-invasively removing heat from subcutaneous lipid-rich cells via phase change coolants

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application claims priority to the following U.S. Provisional Patent Applications, each of which is incorporated herein by reference: 61/298,175, filed Jan. 25, 2010 and 61/354,615, filed Jun. 14, 2010. To the extent that the materials in the foregoing references and/or any other references incorporated herein by reference conflict with the present disclosure, the present disclosure controls. 
    
    
     TECHNICAL FIELD 
     The present application relates generally to home-use applicators for non-invasively removing heat from subcutaneous lipid-rich cells via phase change coolants, and associated devices, systems and methods. In particular, several embodiments are directed to devices that a user may easily recharge or regenerate using a conventional commercial, clinical, institutional or domestic freezer. 
     BACKGROUND 
     Excess body fat, or adipose tissue, may be present in various locations of the body, including, for example, the thighs, buttocks, abdomen, knees, back, face, arms, chin, and other areas. Moreover, excess adipose tissue is thought to magnify the unattractive appearance of cellulite, which forms when subcutaneous fat protrudes into the dermis and creates dimples where the skin is attached to underlying structural fibrous strands. Cellulite and excessive amounts of adipose tissue are often considered to be unappealing. Moreover, significant health risks may be associated with higher amounts of excess body fat. 
     A variety of methods have been used to treat individuals having excess body fat and, in many instances, non-invasive removal of excess subcutaneous adipose tissue can eliminate unnecessary recovery time and discomfort associated with invasive procedures such as liposuction. Conventional non-invasive treatments for removing excess body fat typically include topical agents, weight-loss drugs, regular exercise, dieting or a combination of these treatments. One drawback of these treatments is that they may not be effective or even possible under certain circumstances. For example, when a person is physically injured or ill, regular exercise may not be an option. Similarly, weight-loss drugs or topical agents are not an option when they cause an allergic or other negative reaction. Furthermore, fat loss in selective areas of a person&#39;s body often cannot be achieved using general or systemic weight-loss methods. 
     Other methods designed to reduce subcutaneous adipose tissue include laser-assisted liposuction and mesotherapy. Newer non-invasive methods include applying radiant energy to subcutaneous lipid-rich cells via, e.g., radio frequency and/or light energy, such as is described in U.S. Patent Publication No. 2006/0036300 and U.S. Pat. No. 5,143,063, or via, e.g., high intensity focused ultrasound (HIFU) radiation such as is described in U.S. Pat. Nos. 7,258,674 and 7,347,855. In contrast, methods and devices for non-invasively reducing subcutaneous adipose tissue by cooling are disclosed in U.S. Pat. No. 7,367,341 entitled “METHODS AND DEVICES FOR SELECTIVE DISRUPTION OF FATTY TISSUE BY CONTROLLED COOLING” to Anderson et al. and U.S. Patent Publication No. 2005/0251120 entitled “METHODS AND DEVICES FOR DETECTION AND CONTROL OF SELECTIVE DISRUPTION OF FATTY TISSUE BY CONTROLLED COOLING” to Anderson et al., the entire disclosures of which are incorporated herein by reference. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Many features of the present technology are illustrated in simplified, schematic and/or partially schematic formats in the following Figures to avoid obscuring significant technology features. Many features are not drawn to scale so as to more clearly illustrate these features. 
         FIG. 1  is a partially schematic, partially cut-away illustration of a cooling device having a coolant vessel and heat exchanger configured in accordance with an embodiment of the disclosure. 
         FIG. 2  is a partially schematic, partially cut-away illustration of a particular embodiment of the device shown in  FIG. 1 . 
         FIG. 3  is a partially schematic illustration of a device having an overall arrangement generally similar to that shown in  FIG. 1 , configured in accordance with still another embodiment of the disclosure. 
         FIG. 4  is a partially schematic illustration of a device having a heat exchanger and a removable coolant vessel configured in accordance with another embodiment of the disclosure. 
         FIG. 5A  is a partially schematic, enlarged illustration of an embodiment of the coolant vessel and heat exchanger shown in  FIG. 4 . 
         FIG. 5B  is a partially schematic, cross-sectional illustration of the heat exchanger and coolant vessel taken substantially along line  5 B- 5 B of  FIG. 5A . 
         FIG. 6A  is a partially schematic, partially cut-away illustration of a coolant vessel and heat exchanger configured in accordance with another embodiment of the disclosure. 
         FIG. 6B  is a partially schematic, cross-sectional illustration of an embodiment of the heat exchanger and coolant vessel, taken substantially along line  6 B- 6 B of  FIG. 6A . 
         FIG. 7  is a partially schematic illustration of a device having a coolant vessel and heat exchanger that are separable from an applicator in accordance with yet another embodiment of the disclosure. 
         FIG. 8  is a partially schematic illustration of a portion of the coolant vessel and heat exchanger, taken substantially along line  8 - 8  of  FIG. 7 . 
         FIG. 9  is a partially schematic, cross-sectional illustration of an applicator having non-elastic and elastic materials arranged in accordance with an embodiment of the disclosure. 
         FIG. 10  is a partially schematic, cross-sectional illustration of an applicator having an internal support structure in accordance with an embodiment of the disclosure. 
         FIG. 11  is an enlarged illustration of a portion of the applicator shown in  FIG. 10 . 
     
    
    
     DETAILED DESCRIPTION 
     1. Overview 
     Several examples of devices, systems and methods for cooling subcutaneous adipose tissue in accordance with the presently disclosed technology are described below. Although the following description provides many specific details of the following examples in a manner sufficient to enable a person skilled in the relevant art to practice, make and use them, several of the details and advantages described below may not be necessary to practice certain examples and methods of the technology. Additionally, the technology may include other examples and methods that are within the scope of the claims but are not described here in detail. 
     References throughout this specification to “one example,” “an example,” “one embodiment” or “an embodiment” mean that a particular feature, structure, or characteristic described in connection with the example is included in at least one example of the present technology. Thus, the occurrences of the phrases “in one example,” “in an example,” “one embodiment” or “an embodiment” in various places throughout this specification are not necessarily all referring to the same example. Furthermore, the particular features, structures, routines, steps or characteristics may be combined in any suitable manner in one or more examples of the technology. The headings provided herein are for convenience only and are not intended to limit or interpret the scope or meaning of the claimed technology. 
     Certain embodiments of the technology described below may take the form of computer-executable instructions, including routines executed by a programmable computer or controller. Those skilled in the relevant art will appreciate that the technology can be practiced on computer or controller systems other than those shown and described below. The technology can be embodied in a special-purpose computer, controller, or data processor that is specifically programmed, configured or constructed to perform one or more of the computer-executable instructions described below. Accordingly, the terms “computer” and “controller” as generally used herein refer to any data processor and can include internet appliances, hand-held devices, multi-processor systems, programmable consumer electronics, network computers, mini computers, and the like. The technology can also be practiced in distributed environments where tasks or modules are performed by remote processing devices that are linked through a communications network. Aspects of the technology described below may be stored or distributed on computer-readable media, including magnetic or optically readable or removable computer discs as well was media distributed electronically over networks. In particular embodiments, data structures and transmissions of data particular to aspects of the technology are also encompassed within the scope of the present technology. The present technology encompasses both methods of programming computer-readable media to perform particular steps, as well as executing the steps. 
     One embodiment of a cooling device for cooling subcutaneous lipid-rich cells in a human includes an applicator that is releasably positionable in thermal communication with human skin. The device further includes a coolant vessel having a coolant and a heat transfer conduit having a heat transfer fluid that is isolated from fluid contact with the coolant. A heat exchanger is operatively coupled between the coolant vessel and heat transfer conduit to transfer heat between the heat transfer fluid and the coolant, and a fluid driver is operatively coupled to the heat transfer conduit to direct the heat transfer fluid between the applicator and the heat exchanger. 
     In a further particular embodiment, the coolant has a liquid/solid phase transition temperature greater than the liquid/solid phase transition temperature of the heat transfer fluid. The heat exchanger is positioned within the coolant vessel and includes a heat exchanger conduit that, together with the heat transfer conduit and the applicator, form a sealed, closed-loop path for the heat transfer fluid. Accordingly, the entire device can be placed in a freezer (e.g., a domestic freezer) to freeze the coolant in preparation for treating lipid-rich cells in a human. In other embodiments, only selected components of the device are removable to freeze or otherwise cool the coolant. 
     A method for cooling human tissue in accordance with a particular embodiment of the disclosure includes releasably attaching an applicator to a human, and removing heat from subcutaneous lipid-rich tissue of the human via the applicator to selectively reduce lipid-rich cells of the tissue (e.g., via the body&#39;s reaction to cooling). The heat is removed by directing a chilled heat transfer fluid to applicator and transferring absorbed heat from the heat transfer fluid to a coolant. In particular embodiments, the coolant can remain solid, remain liquid or change phase from a solid to a liquid as it receives heat from the heat transfer fluid. The method still further includes re-cooling the coolant. Selected methods in accordance with another embodiment of the disclosure include removing the heat by directing a chilled heat transfer fluid into a flexible envelope and through a porous internal support structure within the envelope, while the porous internal structure at least restricts fluid pressure in the envelope from (a) bulging the envelope outwardly, or (b) collapsing the internal structure, or (c) both (a) and (b). Still another method includes directing the chilled heat transfer fluid into an applicator, between two flexible portions of the applicator, each having a different elasticity. 
     Without being bound by theory, the selective effect of cooling on lipid-rich cells is believed to result in, for example, membrane disruption, cell shrinkage, disabling, damaging, destroying, removing, killing or other methods of lipid-rich cell alteration. Such alteration is believed to stem from one or more mechanisms acting alone or in combination. It is thought that such mechanism(s) trigger an apoptotic cascade, which is believed to be the dominant form of lipid-rich cell death by non-invasive cooling. In any of these embodiments, the effect of tissue cooling is to selectively reduce lipid-rich cells. 
     Apoptosis, also referred to as “programmed cell death”, is a genetically-induced death mechanism by which cells self-destruct without incurring damage to surrounding tissues. An ordered series of biochemical events induce cells to morphologically change. These changes include cellular blebbing, loss of cell membrane asymmetry and attachment, cell shrinkage, chromatin condensation and chromosomal DNA fragmentation. Injury via an external stimulus, such as cold exposure, is one mechanism that can induce cellular apoptosis in cells. Nagle, W. A., Soloff, B. L., Moss, A. J. Jr., Henle, K. J. “Cultured Chinese Hamster Cells Undergo Apoptosis After Exposure to Cold but Nonfreezing Temperatures”  Cryobiology  27, 439-451 (1990). 
     One aspect of apoptosis, in contrast to cellular necrosis (a traumatic form of cell death causing local inflammation), is that apoptotic cells express and display phagocytic markers on the surface of the cell membrane, thus marking the cells for phagocytosis by macrophages. As a result, phagocytes can engulf and remove the dying cells (e.g., the lipid-rich cells) without eliciting an immune response. Temperatures that elicit these apoptotic events in lipid-rich cells may contribute to long-lasting and/or permanent reduction and reshaping of subcutaneous adipose tissue. 
     One mechanism of apoptotic lipid-rich cell death by cooling is believed to involve localized crystallization of lipids within the adipocytes at temperatures that do not induce crystallization in non-lipid-rich cells. The crystallized lipids selectively may injure these cells, inducing apoptosis (and may also induce necrotic death if the crystallized lipids damage or rupture the bi-lipid membrane of the adipocyte). Another mechanism of injury involves the lipid phase transition of those lipids within the cell&#39;s bi-lipid membrane, which results in membrane disruption or disfunction, thereby inducing apoptosis. This mechanism is well-documented for many cell types and may be active when adipocytes, or lipid-rich cells, are cooled. Mazur, P., “Cryobiology: the Freezing of Biological Systems” Science, 68: 939-949 (1970); Quinn, P. J., “A Lipid Phase Separation Model of Low Temperature Damage to Biological Membranes” Cryobiology, 22: 128-147 (1985); Rubinsky, B., “Principles of Low Temperature Preservation”  Heart Failure Reviews,  8, 277-284 (2003). Another mechanism of injury may involve a disfunction of ion transfer pumps across the cellular membrane to maintain desired concentrations of ions such as potassium (K+) or sodium (Na+). An ion imbalance across the cell membrane may result from lipid phase transition of lipids within the cell&#39;s bi-lipid membrane or by another mechanism, thereby inducing apoptosis. Other yet-to-be-understood apoptotic mechanisms may exist, based on the relative sensitivity to cooling of lipid-rich cells compared to non-lipid rich cells. 
     In addition to the apoptotic mechanisms involved in lipid-rich cell death, local cold exposure is also believed to induce lipolysis (i.e., fat metabolism) of lipid-rich cells and has been shown to enhance existing lipolysis which serves to further increase the reduction in subcutaneous lipid-rich cells. Vallerand, A. L., Zamecnik. J., Jones, P. J. H., Jacobs, I. “Cold Stress Increases Lipolysis, FFA Ra and TG/FFA Cycling in Humans”  Aviation, Space and Environmental Medicine  70, 42-50 (1999). 
     One expected advantage of the foregoing techniques is that the subcutaneous lipid-rich cells can be reduced generally without collateral damage to non-lipid-rich cells in the same region. In general, lipid-rich cells can be affected at low temperatures that do not affect non-lipid-rich cells. As a result, lipid-rich cells, such as those associated with cellulite, can be affected while other cells in the same region are generally not damaged even though the non-lipid-rich cells at the surface may be subjected to even lower temperatures than those to which the lipid-rich cells are exposed. 
     2. Representative Devices and Methods that Include Applicators, Coolant Vessels, and Heat Exchangers Arranged as a Single Unit 
       FIG. 1  is a partially schematic, partially cut-away illustration of a device  100  having an applicator  120  operatively coupled to a coolant vessel  140  to cool human tissue  110 . In particular, the device  100  is configured to cool a subcutaneous, lipid-rich tissue  112 , without damaging the overlying dermis  111 , generally in the manner described above. The applicator  120  is coupled to the coolant vessel  140  by a heat transfer conduit  150  that carries a heat transfer fluid  155 . Accordingly, the heat transfer conduit  150  includes a supply portion  151   a  that directs the heat transfer fluid  155  to the applicator  120 , and a return portion  151   b  that receives heat transfer fluid  155  exiting the applicator  120 . The heat transfer fluid  155  is propelled through the heat transfer conduit  150  by a fluid driver  170 , e.g., a pump or other suitable device. The heat transfer conduit  150  is typically insulated to prevent the ambient environment from heating the heat transfer fluid  155 . Other elements of the device (aside from the cooling surface of the applicator  120  in contact with the tissue  110 ) are also insulated from the ambient environment to prevent heat loss and frost formation. 
     The heat transfer conduit  150  is connected to a heat exchanger  160  having a heat exchanger conduit (e.g., tubing)  161  that is positioned within or at least partially within the coolant vessel  140 . The coolant vessel  140  contains a coolant  141  that is in close thermal contact with the heat exchanger  160 , but is isolated from direct fluid contact with the heat transfer fluid  155  contained within the heat exchanger tubing  161 . Accordingly, the heat exchanger  160  facilitates heat transfer between the heat transfer fluid  155  and the coolant  141 , while preventing these fluids from mixing. As a result, the coolant  141  can be selected to have a composition different than that of the heat transfer fluid  155 . In particular embodiments, the coolant  141  can be selected to have a phase transition temperature (from liquid/gel to solid) that is less than normal body temperature (about 37° C.) and in particular embodiments, in the range of from about 37° C. to about −20° C., or about 25° C. to about −20° C., or about 0° C. to about −12° C., or about −3° C. to about −6° C., to present a constant temperature environment to the heat transfer fluid  155  as the coolant  141  transitions from a solid to a liquid/gel. The heat transfer fluid  155  in such embodiments has a phase transition temperature that is less than that of the coolant  141 . Accordingly, the heat transfer fluid  155  remains in a fluid state even when the coolant  141  or a portion of the coolant  141  is in a solid state. As a result, the heat transfer fluid  155  can flow within the heat transfer conduit  150  to convey heat away from the human tissue  110  even when the coolant  141  is frozen or at least partially frozen. 
     In operation, the device  100  can be prepared for use by placing the major components (e.g., the applicator  120 , the heat transfer conduit  150 , the heat exchanger  160  and the coolant vessel  140 ), as a unit, in a suitably cold environment. In a particular embodiment, the cold environment includes a freezer (e.g., a domestic freezer), in which the temperature typically ranges from about −10° C. to about −20° C., sufficient to freeze the coolant  141 . After the coolant  141  is frozen, the device  100  can be removed from the freezer or other cold environment, as a unit, and the applicator  120  can be attached to the human tissue  110  using a cuff or other suitable attachment device (e.g., having a Velcro® closure, a buckle, or other releasable feature). Optionally, the user can apply a lotion between the applicator  120  and the skin to facilitate heat transfer and/or provide a moisturizing or other cosmetic effect. Whether or not the user applies a lotion or another intermediate constituent, the applicator  120  is positioned in thermal communication with the user&#39;s skin, so as to effectively remove heat from the lipid-rich tissue  112 . The fluid driver  170  is then activated to drive the heat transfer fluid  155  through the heat transfer conduit  150 , thus transferring heat from the subcutaneous lipid-rich tissue  112  to the frozen coolant  141  via the heat exchanger  160 . As the coolant  141  melts, the temperature within the coolant vessel  140  remains approximately constant so as to provide a constant or nearly constant heat transfer fluid temperature to the human tissue  110 . After the human tissue  110  has been cooled for an appropriate period of time, causing some or all of the coolant  141  to melt, the device  100  can be removed as a unit from the human tissue  110 , as indicated by arrow A, and the coolant  141  can be re-frozen by placing the device  100  in the freezer. Accordingly, the cooling capacity of the coolant vessel  140  can be readily recharged or regenerated prior to a subsequent treatment process. The appropriate tissue-cooling period of time can be controlled by properly selecting the cooling capacity of the coolant  141 , or via a controller and/or sensor, as described in further detail later with reference to  FIG. 2 . 
     In particular embodiments described above with reference to  FIG. 1  and below with reference to  FIGS. 2-8 , the coolant  141  changes phase as it is heated by the heat transfer fluid  155 , and then changes back again when it is cooled. In other embodiments, the coolant  141  can be heated and cooled without undergoing phase changes. For example, the coolant  141  can remain in a solid phase throughout both the heating and cooling processes, or can remain in a liquid phase throughout both processes. In such cases, the cooling process (whether it takes place in a freezer or other environment) does not freeze the coolant. When the coolant  141  remains a solid, its phase transition temperature is above that of the heat transfer fluid. When the coolant  141  remains a liquid, its phase transition temperature can be above, below, or equal to that of the heat transfer fluid  155 . In such cases, the heat transfer fluid  155  and the coolant  141  can have different or identical compositions, while remaining isolated from direct fluid contact with each other. 
       FIG. 2  is a partially schematic, partially cut-away illustration of an embodiment of the device  100  that operates in accordance with the general principles described above with reference to  FIG. 1 . Accordingly, the device  100  shown in  FIG. 2  includes an applicator  120  and a coolant vessel  140  thermally connected to the applicator  120  via a heat exchanger  160  and a heat transfer conduit  150 . 
     One characteristic of the device  100  shown in both  FIG. 1  and  FIG. 2  is that the when the applicator  120  is first placed against the human tissue  110 , the heat transfer fluid  155  in the heat transfer conduit  150  and the applicator  120  will be at or approximately at the temperature of the cold environment in which the device  100  was placed. In at least some cases, this temperature may be uncomfortably low. Accordingly, the device  100  and associated methods can include features for reducing the likelihood that the user will encounter a potentially detrimental effect or uncomfortably cold sensation when first using the device  100 . In a particular embodiment, the device  100  can include a heater  152  positioned to heat the heat transfer fluid  155  entering the applicator  120  via the supply portion  151   a . This arrangement can increase the temperature of the heat transfer fluid  155  by at least an amount sufficient to reduce the user&#39;s discomfort and/or provide a safe and efficacious treatment. In a further particular aspect of this embodiment, the device  100  can be configured to shunt the heat transfer fluid  155  away from the heat exchanger  160  while the heat transfer fluid temperature is initially elevated. This arrangement can avoid unnecessarily melting the coolant  141  before treatment begins. Accordingly, the device  100  can include a shunt channel  153  connected between the supply portion  151   a  and the return portion  151   b  in parallel with the heat exchanger  160  to bypass the heat exchanger  160 . One or more shunt valves  154  (two are shown in  FIG. 2 ) are positioned to regulate flow through the shunt channel  153 , e.g., to open or partially open the shunt channel  153  during initial startup, and then close or partially close the shunt channel  153  after the temperature of the applicator  120  has been elevated by a sufficient amount. 
     The device  100  can include a controller  180  to control the heater  152 , the shunt valves  154 , and/or other features of the device  100 . For example, in a particular embodiment, the controller  180  includes a microprocessor  183  having a timer component  184 . When the device  100  is initially powered (e.g., by activating the fluid driver  170 ), the microprocessor  183  can automatically open the shunt channel  153  via the shunt valves  154 , and activate the heater  152 . The heater  152  and the shunt channel  153  can remain in this configuration for a predetermined time, after which the microprocessor  153  automatically issues control signals deactivating the heater  152  and closing the shunt channel  153 . Accordingly, the timer component  184  operates as a sensor by sensing the passage of time during which the heater  152  is actively heating the heat transfer fluid  155 . In other embodiments described further below, one or more sensors can detect other characteristics associated with the device  100 . 
     In a particular embodiment, the microprocessor  183  can direct the control signals  182  based on inputs  181  received from one or more temperature sensors  186 . For example, the device  100  can include a first temperature sensor  186   a  positioned at the applicator  120 . The microprocessor  183  can automatically activate the heater  152  and the shunt channel  153  until the first temperature sensor  186   a  indicates a temperature suitable for placing the applicator  120  against the human tissue  110 . The device  100  can include a second temperature sensor  186   b  located at the coolant vessel  140  (e.g., the center of the coolant  141 ). The microprocessor  183  can accordingly direct control signals  182  that activate the fluid driver  170  for as long as the second temperature sensor  186   b  indicates a constant and/or suitably low temperature. When the second temperature sensor  186   b  identifies a temperature rise (indicating that the coolant  141  has completely melted), the microprocessor  183  can automatically deactivate the fluid driver  170 . If the coolant  141  is not selected to change phase during heating and cooling, the micro-processor  183  can deactivate the fluid driver  170  when the temperature of the coolant  141  exceeds a threshold temperature. The controller  180  can include an output device  185  that indicates the operational modes or states of the device  100 . For example, the output device  185  can display visual signals (e.g., via different colored LEDs) and/or aural signals (e.g., via an audio speaker) to signify when the applicator  120  is ready to be applied to the human tissue  110 , when the treatment program is over, and/or when temperatures or other characteristics of any of the device components are outside pre-selected bounds. 
     In yet another embodiment, the controller  180  can direct a simplified process for handling the initial temperature of the heat transfer fluid  155 . In particular, the controller  180  can monitor the temperature signal provided by the first temperature sensor  186   a , without activating the fluid driver  170 , and without the need for the heater  152  or the shunt channel  153 . Instead, the controller  180  can generate an output (presented by the output device  185 ) when the ambient conditions cause the heat transfer fluid  155  to rise to an acceptable temperature, as detected by the first temperature sensor  186   a . The user can optionally accelerate this process by applying heat to the applicator  120  and/or the heat transfer conduit  150  via an external heat source. An advantage of this approach is that it can be simpler than the integrated heater  152  described above. Conversely, the heater  152  (under the direction of the controller  180 ) can be more reliable and quicker, at least in part because the heater  152  is positioned within the insulation provided around the heat transfer conduit  150  and other device components. 
     The device  100  can include a variety of features configured to enhance uniform heat distribution and heat transfer. For example, the heat exchanger  160  can include fins  165  on the heat exchanger tubing  161  to increase the surface area available to transfer heat between the heat transfer fluid  155  and the coolant  141 . The coolant vessel  140  can also include a first agitator  101   a  that distributes the melting coolant  141  within the coolant vessel  140  to provide for a more uniform temperature and heat transfer rate within the vessel  140 . In one embodiment, the first agitator  101   a  can include a magnetically driven device, and can be magnetically coupled to a first actuator motor  102   a  positioned outside the coolant vessel  140 . Accordingly, the agitator  101   a  can operate without the need for a sealed drive shaft penetrating into the coolant vessel  140 . A similar arrangement can be used at the applicator  120 . In particular, the applicator  120  can include a second agitator  101   b  driven by a second actuator motor  102   b  to distribute the heat transfer fluid  155  uniformly within the applicator  120 . Suitably positioned internal fluid channels can be used in addition to or in lieu of the second agitator  101   b  to uniformly distribute the heat transfer fluid  155  in the applicator  120 . A representative device that includes such features is a Model No. 10240 pad, available from Breg Polar Care (bregpolarcare.com). The actuator motors  102   a ,  102   b  can be operatively coupled to a power cord  173 , which also provides power to the fluid driver  170  and the heater  152 . In other embodiments, the device  100  can include other elements that agitate and/or distribute the fluid in the applicator  120  and/or the coolant vessel  140 . Such elements can include liquid jets, shaft-driven stirrers, pistons and/or other devices that move the solid and/or liquid portion of the coolant  141  within the coolant vessel  140 , and/or actuators that vibrate, shake, tip or otherwise move the coolant vessel  140  itself or heat exchanger  160  within the coolant vessel. 
     As noted above, the applicator  120 , the heat transfer conduit  150 , the heat exchanger  160 , and the coolant vessel  140  can be moved as a unit between the target tissue  110  and a freezer or other cold environment prior to and after treatment. In a particular embodiment, the remaining components or elements of the device  100  shown in  FIG. 2  can also be placed in the freezer. For example, when the fluid driver  170  includes a pump  171  driven by a pump motor  172 , these components (along with the controller  180 ) can also be placed in the freezer. In other embodiments, one or more of these components may be removed prior to placing the rest of the device  100  in the freezer. For example, the power cord  173  can be removed from the motor  172  and other system components at a junction B 1  as indicated by arrow B. In another embodiment, the pump motor  172  can be removed from the device  100  at a junction Cl as indicated by arrow C. For example, the pump motor  172  can be magnetically coupled to the pump  171 , generally in the manner of the stirrers described above to make connecting and disconnecting the motor  172  easier. In still another aspect of this embodiment, the controller  180  and/or components of the controller  180  can be carried by the motor  172  and can accordingly be removed from the device  100  along with the motor  172 . 
     Certain features described above in the context of a processor-based automatic control system can, in other embodiments, operate without a processor, or can operate manually. For example, the shunt valves  154  can include thermostatic radiator values, or similar valves that have an integrated temperature sensor (e.g., a mechanical thermostat) that autonomously drives the valve without the need for a processor. In other embodiments, the coolant  141  can change color as it undergoes its phase change, which can eliminate the need for the second temperature sensor  186   b . In one aspect of this embodiment, the coolant vessel  140  is transparent, allowing the user to readily see both when the coolant  141  is frozen and when the coolant  141  has melted. In the event the device  100  loses coolant  141  over the course of time, the coolant vessel  140  can include a fill/drain port  142 . In a particular aspect of this embodiment, the fill/drain port  142  can have a removable plug  148  that is transparent, in addition to or in lieu of the coolant vessel  140  being transparent. Similarly, the heat transfer fluid  155  can include constituents that change color when the heat transfer fluid attains a temperature that is no longer suitable for properly chilling the tissue  110 . The applicator  120  and/or the heat transfer conduit  150  (or portions thereof) can be made transparent to allow the user to easily determine when this temperature threshold has been exceeded. 
     Both the coolant  141  and the heat transfer fluid  155  are selected to be highly thermally conductive. Suitable constituents for the coolant  141  include water in combination with propylene glycol, ethylene glycol, glycerin, ethanol, isopropyl alcohol, hydroxyethyl cellulose, salt, and/or other constituents. In at least some embodiments, the same constituents can be used for the heat transfer fluid  155 , but the ratios of the constituents (and therefore the overall composition of the heat transfer fluid) are selected to produce a lower liquid/solid phase transition temperature. Both the heat transfer fluid  155  and the coolant  141  can be selected to have high heat conductivity and low toxicity in case of a leak. Both can include an anti-microbial agent to restrict or prevent algae formulation and/or propagation of other undesirable life forms. The coolant  141  can be selected to have a high heat capacity to better absorb heat from the heat transfer fluid  155 . The heat transfer fluid  155  can have a relatively low heat capacity so that it readily heats up when the heater  152  is activated. The heat transfer fluid  155  can also be selected to have a low viscosity at operating temperatures to facilitate flow through the heat transfer conduit  150 , the heat exchanger  160  and the applicator  120 . In any of these embodiments the coolant vessel  140  in which the coolant  141  is disposed can be flexible and elastic, and/or can include a vent or other feature to accommodate volume changes as the coolant  141  changes phase. 
       FIG. 3  is a partially schematic, isometric illustration of an embodiment of the device  100  described above with reference to  FIG. 2 . As shown in  FIG. 3 , the applicator  120  has a generally flexible configuration, allowing it to conform to the shape of the tissue to which it is applied. An attachment device  123  releaseably attaches the applicator  120  to the tissue and can accordingly include a strap (e.g. Velcro), a cuff (e.g., generally similar to a blood pressure cuff) or another suitable device. The coolant vessel  140  is housed in a coolant vessel housing  143  that is in turn attached to or otherwise includes the support structure  121 . The support structure  121  can be at least partially flexible so that when it is attached to the applicator  120 , it does not overly inhibit the ability of the applicator  120  to conform to the human tissue. In one embodiment, the support structure  121  and the coolant vessel housing  143  can be supported relative to the applicator  120  with standoffs. In another embodiment, an optional foam or other flexible layer (e.g. an inflatable air bladder)  122  can be positioned between the support structure  121  and the applicator  120  to further facilitate the ability of the applicator  120  to flex relative to the coolant vessel housing  143 . 
     In one aspect of an embodiment shown in  FIG. 3 , the power cord  173  can be releasably attached directly to the pump motor  172 , thus allowing the power cord  173  to be removed before the device  100  is placed in the freezer. The power cord  173  can be connected directly to an AC outlet, and can include a DC converter if the pump motor  172  is a DC motor. If the pump motor  172  is coupled to a rechargeable battery located within the housing  143 , the power cord  173  can be used to recharge the battery. 
     In another aspect of this embodiment, the pump motor  172  itself can be removed from the coolant vessel housing  143 , along with the power cord  173 , generally in the manner described above with reference to  FIG. 2 . In still a further particular aspect of this embodiment, the controller  180  (not visible in  FIG. 3 ) and associated output device  185  can be carried by the pump motor  172  and can accordingly be readily removed from the coolant vessel housing  143  along with the pump motor  172 . 
     One feature of particular embodiments of the device  100  described above with reference to the  FIGS. 1-3  is that the applicator  120 , the coolant vessel  140 , the heat exchanger  160 , and the heat transfer conduit  150  can be configured as an inseparable unit (at least during normal use—components may be separated by an authorized servicer if necessary during a maintenance or repair process). Accordingly, these components form a sealed, closed-loop path for the heat transfer fluid  155 . An advantage of this feature is that it is simple to use. In particular, the user can place the entire device  100  (or at least the above components) in the freezer or other cold environment until the coolant  141  is frozen, and can remove the entire device  100  as a unit from the freezer or other cold environment prior to cooling the target tissue. Because the arrangement is simple to use, it can be particularly suitable for home use. Because it does not include removable components (in certain embodiments) or separable fluid connections, it is expected to be more robust than systems that do include such features. Because the coolant  141  has a fixed liquid/solid phase transition temperature, the device  100  can easily control the temperature of the heat transfer fluid  155  with a reduced level of active control, and the device  100  can be thermally recharged in any environment having a temperature less than the phase transition temperature. 
     Another feature of particular embodiments of the device  100  described above is that the volume of heat transfer fluid  155  contained in the system can be made relatively low by using short lengths and/or small diameters for the heat transfer conduit  150  and the heat exchanger tubing  161 , and a low (e.g., thin) profile for the applicator  120 . Accordingly, the coolant  141  can more quickly cool the heat transfer fluid  155  and the entirety of the effective heat transfer surface of the applicator  120 . Having a low thermal mass for the heat transfer fluid  155  will also reduce the amount of time and/or energy required to elevate the temperature of the applicator  120  to a comfortable level after the device  100  has been removed from the freezer. 
     Still another feature of particular embodiments of the device  100  described above is that the unitary arrangement of the device is expected to produce a compact size and therefore low mass. These features in turn can make it easier to position the device in a freezer (e.g., a domestic freezer), and can make the device more comfortable and convenient to wear during use. 
     Yet another feature of at least some of the foregoing embodiments is that the simplicity of the device can reduce manufacturing costs and therefore the costs to the user. In at least some instances, the device need not include the serviceable component features described above because the device may be cheaper to replace than repair. The device can include an automated lock-out or shut-down feature that activates after a predetermined number of uses to prevent use beyond an expected period of threshold efficacy or useful life. 
     3. Representative Devices and Methods that Include Separable Coolant Vessels 
       FIG. 4  is a partially schematic, partially cut-away illustration of an embodiment of a device  400  having a user-removable or separable coolant vessel  440 , unlike the configurations described above with reference to  FIGS. 1-3 . In particular, the device  400  can include a heat exchanger  460  having a heat exchanger conduit (e.g., tubing)  461  positioned external to the coolant vessel  440 , allowing the coolant vessel  440  to be removed from the device  400  (as indicated by arrow D) for thermal recharging or regeneration. Accordingly, the coolant vessel  440  can be placed in a cold environment (e.g., a freezer) to re-cool (e.g., re-freeze) the coolant  141 , without placing the entire device  400  in the cold environment. This arrangement may be suitable for applications in which freezer space is limited and thus placing only the coolant vessel  440  in the freezer is advantageous. As a result, certain aspects of the device  400  can be simpler than the device  100  described above with reference to  FIGS. 1-3 . For example, the heat transfer conduit  150  is not cooled along with the coolant vessel  440  and accordingly the need for the heater  152  and/or shunt channel  153  and shunt valves  154  described above with reference to  FIG. 2  can be eliminated. Conversely, an advantage of the arrangement described above with reference to  FIGS. 1-3  is that the interface between heat exchanger tubing  161  and the coolant vessel  140  need not be disturbed when the coolant vessel  140  is chilled. As described further below with reference to  FIGS. 5A-6B , certain aspects of the device  400  are designed to mitigate the potential impact of detaching and reattaching the heat exchanger  460  and the coolant vessel  440 . 
       FIG. 5A  is an enlarged, partially schematic illustration of an embodiment of the coolant vessel  440  and the heat exchanger  460  in which the heat exchanger tubing  461  is positioned around the outside of the coolant vessel  440 . In particular, the heat exchanger tubing  461  can have a serpentine shape extending upwardly and downwardly along the longitudinal axis of the coolant vessel  440 . The heat transfer fluid  155  passes through the heat transfer tubing  461  as indicated by arrows E. To remove the coolant vessel  440  from the heat exchanger  460 , the user pulls the coolant vessel  440  upwardly as indicated by arrow D in  FIG. 5A . The heat exchanger tubing  461  can be “springy” and can accordingly be resiliently biased inwardly toward the coolant vessel  440  to releasably secure the coolant vessel  440  in position, and to provide intimate thermal contact between the heat exchanger tubing  461  and the exterior surface of the coolant vessel  440 . This feature can also promote a “scrubbing” mechanical contact between the heat exchanger tubing  461  and the exterior surface of the coolant vessel  440  to remove frost build-up or other residue to ensure good thermal contact as these components are connected. Further details of the foregoing arrangement are described below with reference to  FIG. 5B . 
       FIG. 5B  is a partially schematic, cross-sectional illustration of the heat exchanger  460  and the coolant vessel  440 , taken substantially along line  5 B- 5 B of  FIG. 5A . As shown in  FIG. 5B , the coolant vessel  440  can have an outer surface with a series of recesses  449 , each of which is sized and positioned to receive a portion of the heat exchanger tubing  461 . The exterior surface of the coolant vessel  440  can include a first thermally conductive surface  462   a  that is in intimate thermal and physical contact with a corresponding second thermally conductive surface  462   b  of the heat exchanger tubing  461 . Accordingly, this arrangement can readily transfer heat between the heat transfer fluid  155  within the heat exchanger tubing  461 , and the coolant  141  within the coolant vessel  440 . The coolant vessel  440  can include features for uniformly distributing the liquid portion of the coolant  141  (e.g., agitators) in a manner generally similar to that described above with reference to  FIG. 2 . 
       FIGS. 6A and 6B  illustrate another arrangement of a coolant vessel  640  that is removably attached to a corresponding heat exchanger  660  in accordance with another embodiment of the technology. In one aspect of this embodiment, the coolant vessel  640  includes multiple vertically extending blind channels  644  defined at least in part by a thermally conductive channel wall  645 . The heat exchanger  660  includes thermally conductive heat exchanger tubing  661  that directs the heat transfer fluid  155  into and out of the blind channels  644 . In particular, the heat exchanger tubing  661  can include supply sections  664   a  that extend into the blind channels  644  and are coupled to a supply manifold  663   a . The heat exchanger tubing  661  can further include corresponding return sections  664   b  that also extend into each of the blind channels  644  and are coupled to a return manifold  663   b . In a particular embodiment, the return sections  664   b  are located annularly inwardly within the corresponding supply sections  664   a . Accordingly, the heat transfer fluid enters the supply sections  664   a , rises within the blind channels  664  and then descends through the return sections  664   b , as indicated by arrows E. The coolant vessel  640  is removed from the heat exchanger  660  by pulling it upwardly away from the heat exchanger  660  as indicated by arrow D, and is replaced by placing it downwardly over the heat exchanger  660 , with the blind channels  644  aligned with the corresponding supply sections  664   a . The blind channels  644  and the corresponding supply sections  664   a  can be tapered and/or otherwise biased into contact with each other to promote thermal contact and to facilitate mechanically scraping frost from surfaces of either element. 
       FIG. 6B  is a partially schematic, cross-sectional illustration of the coolant vessel  640  and the heat exchanger  660 , taken substantially along line  6 B- 6 B of  FIG. 6A . As shown in  FIG. 6B , the blind channels  664  include thermally conductive channel walls  665  that are in intimate thermal contact with the outer surfaces of the supply sections  664   a . Arrows E indicate the radially inward path of the heat transfer fluid  155  as it moves from the supply sections  664   a  to the return sections  664   b.    
     4. Representative Devices and Methods that Include Separable Coolant Vessels and Heat Exchangers 
       FIG. 7  is a partially schematic, partially cut-away illustration of a device  700  having a releasable coupling  756  between a heat exchanger  760  and a coolant vessel  740  on one hand, and the heat transfer conduit  150  on the other. Accordingly, the releasable coupling  756  can include a supply coupling  757   a  at the supply portion  151   a  of the heat transfer conduit  150 , and a return coupling  757   b  at the return portion  151   b  of the heat transfer conduit  150 . The couplings  757   a ,  757   b  can include any suitable fluid-tight, easily releasable and reattachable elements. For example, the couplings  757   a ,  757   b  can include quick-release couplings generally similar to those used for intravenous fluid connections. 
     One feature of an embodiment shown in  FIG. 7  is that, like the embodiments described above with reference to  FIGS. 4-6B , the entire device  700  need not be placed in the freezer or other cold environment to re-solidify or otherwise re-cool the coolant  141 . In addition, the device  700  does not require that the thermal connection between the heat exchanger  760  and the coolant vessel  740  be disturbed in order to recharge the coolant vessel  740 . Conversely, an advantage of the arrangements described above with reference to  FIGS. 1-6B  is that they do not require connecting and disconnecting fluid conduits. 
       FIG. 8  is a partially schematic, cross-sectional illustration of a portion of the heat exchanger  760  and the coolant vessel  740 , taken substantially along line  8 - 8  of  FIG. 7 . As shown in  FIG. 8 , the coolant vessel  740  can include a vessel wall  746  having an insulative portion  747   a  over a portion of its surface, and a conductive portion  747   b  in areas adjacent to the heat exchanger tubing  761 . For example, the insulative portion  747   a  can include a material such as a plastic that has a low thermal conductivity to prevent or at least restrict heat transfer to the coolant vessel  740  except as it is received from the heat exchanger tubing  761 . The conductive portion  747   b  can include copper or another highly thermally conductive material that readily transfers heat between the coolant  141  and the heat exchanger tubing  761 , which can also include copper or another highly thermally conductive material. The heat exchanger tubing  761  can be welded to or otherwise intimately bonded to the conductive portion  747   b  in a way that provides high thermal conductivity between the two. In other embodiments, the heat exchanger tubing  761  can take the form of a channel that is integrally formed with the conductive portion  747   b , e.g., in a casting process. 
     When the coolant  141  is selected to undergo a phase change during operation, it can include a solid component  141   a  generally positioned away from the vessel wall  746  once the coolant  141  begins to melt, and a liquid component  141   b  generally in contact with the inner surface of the vessel wall  746  and conductive portion o the vessel wall  747   b . As described above, the coolant vessel  740  can include an agitator or other device to enhance the uniform distribution of heat transfer within the coolant vessel  740  by circulating the liquid component  141   b , moving the solid component  141   a , and/or vibrating or otherwise moving the coolant vessel  740 . 
     5. Representative Applicators and Associated Methods 
       FIGS. 9-11  illustrate particular features of applicators that may form a portion of any of the devices described above with reference to  FIGS. 1-8 . In other embodiments, these applicators may be used with devices other than those expressly shown and described above with reference to  FIGS. 1-8 . The size and shape of the applicator can be selected based on the user&#39;s physiology and the location on the user&#39;s body to which the applicator will be attached. 
       FIG. 9  illustrates an applicator  920  that includes an envelope  924  having an entry port  928   a  coupled to a heat transfer fluid supply portion  151   a , and an exit port  928   b  coupled to a return portion  151   b . The envelope  924  can include a flexible first portion  925  in contact with the human tissue  110 , and a flexible second portion  926  facing away from the human tissue  110 . The flexible first portion  925  can be attached to the flexible second portion  926  at corresponding bonds  927  formed by an adhesive, thermal welding, or other suitable process. The first portion  925  has a first elasticity, and the second portion  926  has a second elasticity less than the first elasticity. Accordingly, the second portion  926  can, in at least some embodiments, be non-elastic. As used herein, the term “non-elastic” applies to a material that does not stretch, or stretches by only an insignificant amount when the applicator  920  is subjected to normal operating pressures. The term “elastic” as used herein applies to a material that does stretch when the applicator is subjected to normal operating pressures provided by the attachment of the device to the patient and/or heat transfer fluid  155 . Because the first portion  925  is more elastic than the second portion  926 , it can readily conform to the local shape of the human tissue  110 . In particular, the first portion  925  can conform to the underlying tissue  110  without forming creases  930  (shown in dotted lines in  FIG. 9 ), which form in some existing devices and can interfere with skin/applicator thermal contact and/or internal flow within the applicator  920 . As a result, the first portion  925  is more likely to remain in close thermal contact with the human tissue  110  and can therefore more efficiently transfer heat away from the tissue  110 . The second portion  926  can flex in a manner that accommodates the contour of the human tissue  110 , without stretching at all, or without stretching in a manner that might cause the envelope to bulge outwardly away from the tissue  110  (e.g., at the ends of the applicator  920 ) and thereby reduce the degree of thermal contact between the envelope  924  (and more particularly, the heat transfer fluid  155 ) and the tissue  110 . 
     In particular embodiments, the second portion  926  can include polyethylene, polypropylene, nylon, vinyl, and/or another suitable plastic film. The first portion  925  can include latex rubber, nitrile, polyisoprene and/or urethane, and/or another suitable elastomeric material. An optional elastic mesh  929  can be positioned adjacent to the first portion  925  (or the entire envelope  924 ), and can include an elastic nylon, rubber and/or other suitable elastic material. The mesh  929  can prevent the first portion  925  from undergoing excessive wear and/or bulging during handling. It can accordingly be strong, but thin enough to avoid significantly interfering with the heat transfer process between the applicator  920  and the tissue  110 . 
     In a particular embodiment, the applicator  920  can also include a flexible support structure  921  that provides additional support for the envelope  924 , without inhibiting the ability of the envelope  924  to conform to the tissue  110 . The support structure  921  can also function as the releasable coupling (e.g., a cuff) securing the applicator  920  to the tissue  110 . In any of these embodiments, the support structure  921  can have a pre-formed shape (e.g., a downwardly-facing concave shape) and can be resiliently biased toward the pre-formed shape. Accordingly, the applicator  920  can more readily conform to a convex tissue surface. In particular embodiments, a family of applicators having different shapes can be coupled to a similar type of overall cooling device to provide for system commonality and interchangeability. 
       FIG. 10  is a partially schematic, cross-sectional illustration of an applicator  1020  having an envelope  1024 , an external support structure  1021   a  generally similar to that described above with reference to  FIG. 9 , and an internal support structure  1021   b  located within the envelope  1024 . The internal support structure  1021   b  can be porous, e.g., 50% porosity or higher in some embodiments, and in particular embodiments, in the range of from about 75% porosity to about 95% porosity. Accordingly, the internal support structure  1021   b  can diffuse the heat transfer fluid  155  throughout the envelope  1024  from an entry port  1028   a  to an exit port  1028   b , without overly restricting the flow of the heat transfer fluid  155 . The particular porosity value selected for the internal support structure  1021   b  can depend on factors that include the viscosity and/or flow rate of the heat transfer fluid  155 . In a particular embodiment, the internal support structure  1021   b  can include a porous matrix material having one or multiple layers  1031  (three are shown in  FIG. 10  for purposes of illustration) that can slide relative to each other, as indicated by arrows F. In a further particular embodiment, the internal support structure  1021   b  is attached to the inner surfaces of the envelope  1024  to prevent the envelope from overly stretching. The envelope  1024  can also include spaced-apart connections  1035  (e.g., stitches or perforated panels) that extend from the envelope upper surface through the internal support structure  1021   b  to the envelope lower surface to prevent or restrict the envelope  1024  from ballooning when pressurized with the heat transfer fluid  155  while allowing the layers  1031  to slide laterally relative to each other. Accordingly, when the applicator  1020  is coupled to an upstream fluid driver  1070   a , the pressure exerted by the incoming heat transfer fluid  155  on the envelope  1024  will be less likely to expand the envelope  1024 . 
     The internal support structure  1021   b  can resist buckling, in addition to or in lieu of resisting bulging or ballooning. For example, the internal support structure  1021   b  can have a high enough buckling strength so that when the applicator  1020  is coupled to a downstream fluid driver  1070   b , the envelope  1024  will not collapse upon itself due to external, ambient pressure (e.g., to the point that it inhibits the flow of heat transfer fluid  155 ) when the heat transfer fluid  155  is withdrawn through the exit port  1028   b . In particular embodiments, the heat transfer fluid  155  may be withdrawn via a pressure that is up to about 2 psi below the pressure outside the envelope  1024 . In other embodiments, the foregoing pressure differential can be up to about 5 psi or 10 psi without the envelope  1024  collapsing on itself. This will help keep the envelope from ballooning due to positive internal pressure. Another advantage of the downstream fluid driver  1070   b  is that if the envelope  1024  is inadvertently punctured, the downstream fluid driver  1070   b  will suck air through the puncture, while the upstream fluid driver  1070   a  will continue to pump heat transfer fluid  155  through such a puncture. 
       FIG. 11  is a partially schematic, enlarged illustration of a portion of the applicator  1020  circled in  FIG. 10 . As shown in  FIG. 11 , the internal support structure  1021   b  can include small pores  1034  distributed throughout the structure. At the interface with the tissue  110 , the pores can form a distributed arrangement of generally hemispherical dimples. When the envelope  1024  includes a material that is not elastic, the material will tend to crease when folded over a convex portion of the tissue  110 . The pores  1034  are small enough so that they accommodate or receive small “microcreases”  1033  that can form along the surface of the envelope  1024 . Unlike the creases  930  described above with reference to  FIG. 9 , the microcreases  1033  are very small and accordingly do not significantly inhibit the internal flow within the applicator and do not significantly disrupt the uniformity of the heat transfer between the heat transfer fluid  155  within the envelope  1024 , and the tissue  110  outside the envelope  1024 . In effect, the microcreases  1033  can distribute the creasing effect of the envelope material over a larger area that reduces the overall impact of the effect on fluid flow and heat transfer. In particular embodiments, the microcreases  1033  can have a generally hemispherical shape that is pre-set into the envelope material using a thermoset process. In other embodiments, the shape and/or formation process of the microcreases  1033  can be different. In still another embodiment, the entire portion of the envelope  1024  in contact with the patient tissue can have a pre-set or pre-formed shape (e.g., a hemispherical or other concave shape) that is maintained as the envelope is placed in contact with the patient tissue; 
     In a particular embodiment, the internal support structure  1021   b  can include a TN Blue non-abrasive non-woven polyester pad available from Glit/Microtron. This material can be made in multiple layers (e.g., two layers, each 0.35 of an inch thick) encased in a polyether-polyurethane film envelope  1024  having a thickness of 0.006-0.012 inches. The internal support structure  1021   b , which is already porous due to the fibrous make-up of the material, can be even further perforated with a hole pattern, producing small diameter holes spaced uniformly spaced apart, and oriented generally perpendicular to the major surfaces of the envelope  1024 . These holes can facilitate bending the internal support structure  1021   b  to conform to convex and/or concave shapes. It is expected that the relatively thin overall dimensions of the resulting applicator  1020  (e.g., from about 0.25 inch to about 0.50 inch) will allow the applicator  1020  to readily conform to the human anatomy. The low flow impedance of the internal support structure  1021   b  is expected to allow flow rates of approximately 0.1 to 5 liters per minute, suitable for adequately cooling the adjacent tissue. In addition, the three-dimensional nature of the fibrous, porous structure can facilitate a uniform distribution of the heat transfer fluid  155  within the applicator  1020 , producing a more uniform treatment of the adjacent tissue  110 . 
     The porosity of the internal support structure  1021   b  can vary from one portion of the applicator  1020  to another, and/or can vary depending upon the local flow direction desired for the heat transfer fluid  155 . For example, the porosity of the internal support structure  1021   b  can be selected to enhance heat transfer from the tissue in the peripheral areas of the applicator  1020 , e.g., to account for the expected increase in heat transfer losses to the ambient environment in these areas. The porosity can be altered by adjusting the number and/or size of the pores within the internal support structure  1021   b , as well as the spatial orientation of the pores. 
     From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but that various modifications can be made without deviating from the technology. For example, the devices described above can include components that provide mechanical energy to create a vibratory, massage and/or pulsatile effect in addition to cooling the subcutaneous tissue. Representative components are described in U.S. Pat. No. 7,367,341 and in commonly assigned U.S. Patent Publication No. 2008/0287839, both of which are incorporated herein by reference. While certain features of the devices described above make them particularly suitable for home use, such features do not preclude the devices from being used in hospital or clinical office settings. In such embodiments, the devices or portions of the devices can be cooled in commercial, clinical or institutional freezers and/or coolers. The shapes, sizes and compositions of many of the components described above can be different than those disclosed above so long as they provide the same or generally similar functionalities. For example, the conduits and tubing described above can have other shapes or arrangements that nevertheless effectively convey fluid. The fluid driver can be operatively coupled to the heat transfer conduit without being directly connected to the heat transfer conduit, e.g., by being connected to the heat exchanger that conveys the heat transfer fluid, or by being connected to the applicator. The controller can implement control schemes other than those specifically described above, and/or can be coupled to sensors other than those specifically described above (e.g., pressure sensors) in addition to or in lieu of temperature and time sensors, to detect changes associated with the cooling device. The controller can in some cases accept user inputs, though in most cases, the controller can operate autonomously to simplify the use of the device. As discussed above, the coolant in some embodiments can go through a phase change during heating and cooling, so that the cooling process freezes or solidifies the coolant. In other embodiments for which no phase change occurs, the cooling process does not freeze or solidify the coolant. 
     Certain aspects of the technology described in the context of particular embodiments may be combined or eliminated in other embodiments. For example, the applicators described above in the content of  FIGS. 9-11  can be used with any of the devices described above with reference to  FIGS. 1-8 . The thermal connections between the heat exchanger tubing and the coolant vessel described in the content of  FIG. 8  can be applied to the arrangement shown and described in the content of  FIGS. 1-3 . The heaters and flow agitators described in the context of certain embodiments can be eliminated in other embodiments. Further, while advantages associated with certain embodiments of the technology have been described within the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the present disclosure. Accordingly, the present disclosure and associated technology can encompass other embodiments not expressly shown or described herein.