WO2021148389A1 - Targeted temperature management using booster - Google Patents

Abstract

A targeted temperature management system (300) includes: a cooling container configured to carry a fluid to be cooled; a cooling assembly (125) positioned and arranged to cool the cooling container; a heat sink (140) positioned and arranged to conduct heat away from the cooling assembly (125); and a nozzle arrangement (350) configured to accept pressurized gas and to cool the pressurized gas via a geometry of the nozzle arrangement (350), the nozzle arrangement (350) positioned and arranged to convectively cool the heat sink (140) using the cooled gas.

Description

TITLE

TARGETED TEMPERATURE MANAGEMENT USING BOOSTER

BACKGROUND

[0001] The present disclosure relates generally to medical treatments and in particular to systems employing target temperature management in combination with a medical fluid treatment.

[0002] Target temperature management (“TTM”) is a growing medical procedure in which a patient's core temperature is rapidly lowered and then controlled at a desired temperature for a period of time, for example, over a number of days. The goal of TTM is to improve health outcomes during recovery after a period of stopped blood flow to the brain. TTM is used to reduce the risk of tissue injury following the lack of blood flow, which may be due to cardiac arrest or the blockage of an artery by a clot as a result of a stroke.

[0003] TTM following cardiac arrest typically brings the patient's body temperature to 33°C (91°F) or 36°C (97°F). TTM is thought to prevent brain injury by several methods including decreasing the brain's oxygen demand, reducing the production of neurotransmitters like glutamate, and reducing free radicals that may damage the brain.

[0004] TTM has been accomplished using cooling blankets, cooling helmets, cooling catheters, ice packs and ice water rinsing. One product on the market circulates compressor- cooled water through water- filled pads placed on the patient's body. Another product on the market circulates compressor-cooled saline via a catheter that is inserted into the bladder of a patient. In both instances, the compressors are noisy, bulky, heavy and may not start if placed upside down, which may occur in an intensive care unit (“ICU”).

[0005] Additionally, to the extent that known TTM devices require AC power, there are instances in which TTM is required in the field and elsewhere where no AC power is available. TTM devices in particular may be required out in the field, while the patient is being transported to a hospital, and/or while the patient is being transported between departments of a hospital.

[0006] Multiple needs accordingly exist for a better TTM solution including one that addresses problems associated with compressor-based TTM units, and another that can at least maintain a lowered temperature of a patient while the patient is in a location in which the TTM unit is not able to receive AC power. SUMMARY

[0007] The present disclosure relates to a device and system that provides target temperature management (“TTM”) for a patient. In one embodiment, the TTM device of the present disclosure cools fluid using thermoelectric cooling modules or elements. The thermoelectric cooling modules or elements may include a solid-state active heat pump that transfers heat from one side of the element to the other upon the consumption of electrical energy, creating a warmed side and a cooled side. The warmed and cooled sides are determined by the direction of electrical current flowing through the thermoelectric cooling module.

[0008] In an embodiment, the TTM device includes or is provided with a cooling bag or container that transports a fluid to be cooled. The cooling bag or container may include or form a meandering or serpentine path that carries the fluid to be cooled multiple times across upper and lower cooling plates placed in contact the cooling bag or container. The cooling bag or container may be made of a thermoplastic material that is suitable for sterilization, so as to be capable of carrying a body fluid if desired. The material may include polyvinyl chloride (“PVC”) or be made of a suitable non-PVC material, such as polyurethane (“PU”) due to its desirable thermal properties.. The material may be heat sealed or sonically sealed to form the serpentine pathway. The cooling bag or container may be disposable and discarded after use with a particular patient.

[0009] The upper and lower cooling plates are made in an embodiment of a thermally conductive material such as aluminum, copper, stainless steel, and combinations and alloys thereof. The upper and lower cooling plates are cooled by the cooled side(s) of at least one thermoelectric element, which is/are placed in thermal (e.g., physical) contact with at least one of the upper and lower cooling plates.

[0010] One or more heat sink is placed in thermal (e.g., physical contact) with the warmed side(s) of the one or more thermoelectric element(s). The one or more heat sink may also be made of a thermally conductive material such as aluminum, copper, stainless steel, and combinations and alloys thereof. The one or more heat sink may include a plurality of heat fins. The heat sink and heat fins employ a convective thermal exchange with the environment so as to conductively remove heat from the warmed side(s) of the one or more thermoelectric element(s). Doing so increases the efficiency of the one or more thermoelectric element in transferring heat from its one or more warmed side to its corresponding one or more cooled side. The efficiency- increased one or more one or more thermoelectric element in turn increases the ability of the upper and lower cooling plates in removing heat from liquid flowing through the cooling bag or container.

[0011] In an embodiment, there is direct contact between at least one of the upper and lower cooling plates and the thermoelectric element(s). In another embodiment, the upper and lower cooling plates and the thermoelectric element(s) are coupled via a thermal transfer compound. In an embodiment, there is direct contact between the thermoelectric element(s) and the heat sink. In another embodiment, the thermoelectric element(s) and the heat sink are coupled via a thermal transfer compound.

[0012] In an embodiment, there is a first temperature sensor positioned and arranged to measure and monitor the temperature of the fluid to be cooled in the inlet line.

[0013] In an embodiment, there is a second temperature sensor positioned and arranged to measure and monitor the temperature of the cooled fluid in the outlet line.

[0014] In an embodiment, there is a control unit adapted for powering said at least one thermoelectric element, said control unit being adapted for receiving data in real time from said first temperature sensor and said second temperature sensor, wherein the control unit is set up to calculate in real time a first control parameter Ci based on data received from the first temperature sensor, and wherein the control unit is set up to calculate in real time a second control parameter C₂ based on said first control parameter Ci and data received from said second temperature sensor, said powering of said at least one thermoelectric element being based on said second control parameter C₂.

[0015] It is contemplated that the liquid to be cooled includes water that is then pumped through water- filled pads or blankets that are placed on the patient's body. In another embodiment, the fluid is saline, which is pumped into a catheter inserted into a patient's bladder. In a third embodiment, the fluid is the patient's blood, which is extracted from the patient, e.g., via a central venous catheter (“CVC”), pumped through the cooling bag or container and returned to the patient, e.g., via the CVC. The third embodiment may be employed in combination with a blood treatment, such as continuous renal replacement therapy, which is performed when the patient experiences acute kidney failure. In the second (saline) and third (blood) embodiments, the cooling container or bag is sterilized prior to use, e.g., via steam, ethylene oxide or gamma radiation, and disposed after use. In the water cooling embodiment, the cooling container or bag does not need to be sterilized and may be reused for different patients as long as it is sanitized between uses. In an alternative water cooling embodiment, the cooling container is not provided and the water instead flows into and out of an enclosure, which may for example be formed by the upper and lower cooling plates, e.g., in a hinged clamshell fashion.

[0016] To aid the convective cooling of the heat sink and its fins if provided (and thus the thermal chain discussed above), a fan may be provided to blow air across the heat sink and heat fins. In an alternative embodiment, the heat sink and heat fins may be water cooled. Water cooling may be more viable when the liquid to be cooled within the cooling bag or container is water.

[0017] In a further alternative embodiment a convective booster is provided, which either replaces the fan or is provided in addition to the fan. The booster in an embodiment uses the hospital’s compressed air to form a system that operates with the TTM device just described. The system passes pressurized air through one or more restriction or nozzle, which removes heat and chills the air exiting the nozzle. The one or more nozzle may be placed directly adjacent to the heat fins of the heat sink or the heat fins may be modified to become part of or be incorporated into the one or more nozzle.

[0018] Besides the nozzle, the system may also include one or more pressure regulator placed between the hospital’s compressed air and the one or more nozzle. The pressure regulator provides a continuous and accurate output air pressure to the one or more nozzle, so that an expected pressure that yields a known and tested cooling effect is provided consistently. The pressure regulator also accounts for different supply pressures provided by different hospitals, ensuring that the output pressure from the regulator to the one or more nozzle is not too high.

[0019] The booster system includes all hoses and connectors to connect the hospital’s pressurized air supply to the one or more pressure regulator. The system may further include one or more valve, such as an electrically actuated solenoid valve, and/or a manual gate valve. The gate valve may be used for on/off control of the pressurized air. The one or more electrically actuated solenoid valve may be used for on/off control of pressurized air and/or for controlling the amount of convective cooling provided to the heat sink and heat fins.

[0020] The booster of the system is used in one embodiment to initially cool the patient at a fast rate, for example, to a temperature of 33°C (91°F) or 36°C (97 °F). The booster may be able to reduce the time needed to cool the patient to a desired temperature, for example, in half. After the patient is cooled to the desired temperature, the booster of the system may not be needed to maintain the patient at the desired temperature, which is then performed with the TTM without the booster.

[0021] It is further contemplated to provide the TTM device with battery power that is used to power the device when no AC power is available, e.g., while the patient is out in the field, being transported to a hospital, and/or while the patient is being transported between departments of a hospital. It is also contemplated to power the TTM device in such a way that the battery may be relatively small and the overall TTM device relatively lightweight, such that the TTM device may be readily transported with the patient in the field, on the way to the hospital and between departments of the hospital. In particular, it has been found that suitable thermoelectric elements provide 200 to 300 Watts of cooling power when fully powered. It has also been found that the same thermoelectric elements provide 70 to 100 Watts of cooling power when the thermoelectric elements themselves are not powered but the cooling fan is powered, which may be termed passive cooling. It is therefore contemplated to operate a control unit of the TTM system and associated cooling device to cause the cooling fan but not the thermoelectric elements to be powered when running on battery power. The result is that the battery only needs to supply 70 to 100 Watts of power, which means that the battery may weigh less than one kilogram and have an energy density of 0.1 kWh/kg.

[0022] In another embodiment, it is contemplated to operate a control unit of the TTM system and associated cooling device when no AC power is present to provide only a small amount of DC power to the thermoelectric elements and no power to the cooling fan. It has been found that cooling output is not linear to a power input to the TTM system and that lower power inputs yield a proportionally larger cooling power output.

[0023] A battery again weighing less than one kilogram and having an energy density of 0.1 to 0.26 kWh/kg may be used. The energy density is derived from a number of hours of battery power use without power connection and the amount of power needed in a low power mode taking into account devices requiring power, for example a blood pump (e.g., requiring 20W), the thermoelectric elements (e.g., Peltier requiring 20W), other electronics (e.g., GUI, CPU at 20 W) plus an engineering factor for other electronic devices, resulting in a need of, for example, 100W multiplied by the number of hours of use without AC power. The result in one example is a battery having an energy density of at least 0.1 kWh/kg for one hour.

[0024] In light of the disclosure set forth herein, and without limiting the disclosure in any way, in a first aspect, which may be used with any other aspect described herein, a targeted temperature management device for receiving a cooling container configured to carry a fluid to be cooled is provided where the targeted temperature management device includes: (i) a cooling plate positioned and arranged to cool the cooling container; (ii) at least one thermoelectric element structured to conduct heat from a cooled side to a warmed side when receiving an electrical current, the at least one thermoelectric element positioned and arranged such that the cooled side cools the cooling plate; and (iii) a heat sink positioned and arranged to conduct heat away from the warmed side of the at least one thermoelectric element .

[0025] In a second aspect, which may be used with any other aspect described herein, the cooling plate is made of a conductive material including aluminum, copper, stainless steel, and combinations and alloys thereof.

[0026] In a third aspect, which may be used with any other aspect described herein, the cooling plate is a first cooling plate and which includes a second cooling plate, the second cooling plate positioned and arranged to cool an opposite side of the cooling container cooled by the first cooling plate.

[0027] In a fourth aspect, which may be used with any other aspect described herein, a first cooling plate is in thermal communication with a second cooling plate.

[0028] In a fifth aspect, which may be used with any other aspect described herein, the cooled side of at least one of the thermoelectric elements is positioned and arranged to cool the second cooling plate.

[0029] In a sixth aspect, which may be used with any other aspect described herein, the at least one thermoelectric element is structured to collectively supply up to 500 Watts of cooling power.

[0030] In a seventh aspect, which may be used with any other aspect described herein, the at least one thermoelectric element includes a plurality of thermoelectric elements, the plurality of thermoelectric elements connected electrically in parallel.

[0031] In an eighth aspect, which may be used with any other aspect described herein, the heat sink includes a plurality of heat fins. [0032] In a ninth aspect, which may be used with any other aspect described herein, the targeted temperature management device includes a fan positioned and arranged to blow air across the plurality of heat fins.

[0033] In a tenth aspect, which may be used with any other aspect described herein, at least one of (i) the cooled side of the at least one thermoelectric element is contacted directly with the cooling plate or (ii) the heat sink is contacted directly with the warmed side of the at least one thermoelectric element.

[0034] In an eleventh aspect, which may be used with any other aspect described herein, at least one of (i) the cooled side of the at least one thermoelectric element is contacted with the cooling plate via a thermal transfer compound or (ii) the heat sink is contacted with the warmed side of the at least one thermoelectric element via a thermal transfer compound.

[0035] In a twelfth aspect, which may be used with any other aspect described herein, a targeted temperature management device includes: (i) a thermally conductive enclosure for receiving a fluid to be cooled; (ii) at least one thermoelectric element structured to conduct heat from a cooled side to a warmed side when receiving an electrical current, the at least one thermoelectric element positioned and arranged such that the cooled side cools the thermally conductive enclosure; and (iii) a heat sink positioned and arranged to conduct heat away from the warmed side of the at least one thermoelectric element.

[0036] In a thirteenth aspect, which may be used with any other aspect described herein, the thermally conductive enclosure includes first and second a cooling plates seal together to receive the fluid to be cooled.

[0037] In a fourteenth aspect, which may be used with any other aspect described herein, a targeted temperature management device includes: (i) a cooling container configured to carry a fluid to be cooled; (ii) a cooling plate positioned and arranged to cool the cooling container; (iii) at least one thermoelectric element structured to conduct heat from a cooled side to a warmed side when receiving an electrical current, the at least one thermoelectric element positioned and arranged such that the cooled side cools the cooling plate; and (iv) a heat sink positioned and arranged to conduct heat away from the warmed side of the at least one thermoelectric element.

[0038] In a fifteenth aspect, which may be used with any other aspect described herein, the cooling container is made of a material that is suitable for steam, ethylene oxide or gamma sterilization prior to use. [0039] In a sixteenth aspect, which may be used with any other aspect described herein, wherein the cooling container is made of a material suitable for reuse.

[0040] In a seventeenth aspect, which may be used with any other aspect described herein, the cooling container includes a serpentine fluid cooling pathway.

[0041] In an eighteenth aspect, which may be used with any other aspect described herein, the cooling container is a cooling bag.

[0042] In a nineteenth aspect, which may be used with any other aspect described herein, the targeted temperature management device includes at least one of water-filled pads, a central venous catheter or a catheter configured to access a patient's bladder for fluid communication with the cooling container.

[0043] In a twentieth aspect, which may be used with any other aspect described herein, the targeted temperature management device includes electrical circuit under control of a control unit to power the at least one thermoelectric element in a first direction to cool the cooling plate and in a second direction to warm the cooling plate.

[0044] In a twenty-first aspect, which may be used with any other aspect described herein, a targeted temperature management system includes: (i) a cooling container configured to carry a fluid to be cooled; (ii) a cooling assembly positioned and arranged to cool the cooling container; (iii) a heat sink positioned and arranged to conduct heat away from the cooling assembly; and (iv) a nozzle arrangement configured to accept pressurized gas and to cool the pressurized gas via a geometry of the nozzle arrangement, the nozzle arrangement positioned and arranged to convectively cool the heat sink using the cooled gas.

[0045] In a twenty-second aspect, which may be used with any other aspect described herein, the nozzle arrangement includes a plurality of nozzles, each nozzle having the cooling geometry.

[0046] In a twenty-third aspect, which may be used with any other aspect described herein, the heat sink includes a plurality of heat fins, and wherein each nozzle is dedicated to at least one heat fin.

[0047] In a twenty-fourth aspect, which may be used with any other aspect described herein, the heat sink includes a plurality of heat fins, and wherein each nozzle is formed as part of at least one of the heat fins. [0048] In a twenty-fifth aspect, which may be used with any other aspect described herein, the geometry of the nozzle arrangement is integrated into the heat sink.

[0049] In a twenty-sixth aspect, which may be used with any other aspect described herein, the geometry of the nozzle arrangement is sized to force cooled gas over at least substantially all of the heat sink.

[0050] In a twenty- seventh aspect, which may be used with any other aspect described herein, the heat sink includes a plurality of heat fins, and wherein a geometry of the nozzle arrangement is sized to force cooled gas over the plurality of heat fins.

[0051] In a twenty-eighth aspect, which may be used with any other aspect described herein, the geometry of the nozzle arrangement is configured to constrict and then expand the pressurized gas.

[0052] In a twenty-ninth aspect, which may be used with any other aspect described herein, the geometry of the nozzle arrangement is configured to choke the pressurized gas.

[0053] In a thirtieth aspect, which may be used with any other aspect described herein, the targeted temperature management system includes at least one pressure regulator located between a supply of the pressurized gas and the nozzle arrangement, the pressure regulator oriented to regulate the pressurized gas accepted by the nozzle arrangement.

[0054] In a thirty-first aspect, which may be used with any other aspect described herein, the targeted temperature management system includes at least one valve located between a supply of the pressurized gas and the nozzle arrangement.

[0055] In a thirty-second aspect, which may be used with any other aspect described herein, the targeted temperature management system includes a control unit programmed to allow the nozzle arrangement to accept pressurized gas during an initial cooling of a patient and to operate the fan to maintain the patient at a cooled temperature.

[0056] In a thirty-third aspect, which may be used with any other aspect described herein, the pressurized gas is pressurized air.

[0057] In a thirty-fourth aspect, which may be used with any other aspect described herein, a targeted temperature management device includes: (i) a cooling container configured to carry a fluid to be cooled; (ii) a cooling assembly positioned and arranged to cool the cooling container; (iii) a heat sink positioned and arranged to conduct heat away from the cooling assembly; (iv) a fan positioned and arranged to blow air across the heat sink; (v) a battery positioned and arranged to supply battery power when external power is unavailable; and (vi) a control unit programmed to allow the external power to generate power to the cooling assembly when the external power is available and to allow battery power to be supplied solely to the fan when external power is unavailable.

[0058] In a thirty-fifth aspect, which may be used with any other aspect described herein, the control unit is programmed to allow external power to be supplied to the cooling assembly and the fan when the external power is available.

[0059] In a thirty-sixth aspect, which may be used with any other aspect described herein, the targeted temperature management device includes a transformer configured to convert the external power into a same voltage type as the battery power.

[0060] In a thirty- seventh aspect, which may be used with any other aspect described herein, the cooling assembly includes a cooling plate positioned and arranged to cool the cooling container and a cooling element positioned and arranged to cool the cooling plate.

[0061] In a thirty-eighth aspect, which may be used with any other aspect described herein, the battery weighs less than one kilogram.

[0062] In a thirty-ninth aspect, which may be used with any other aspect described herein, a targeted temperature management device includes: (i) a cooling container configured to carry a fluid to be cooled; (ii) a cooling assembly positioned and arranged to cool the cooling container; (iii) a heat sink positioned and arranged to conduct heat away from the cooling assembly; (iv) a battery positioned and arranged to supply battery power when external power is unavailable; and (v) a control unit programmed to allow a higher power level generated from the external power to be supplied to the cooling assembly when the external power is available and to allow a lower power level of the battery power to be supplied to the to the cooling assembly when external power is unavailable.

[0063] In a fortieth aspect, which may be used with any other aspect described herein, a lower power level is 0.5 to 5 percent of the higher power level.

[0064] In a forty-first aspect, which may be used with any other aspect described herein, the targeted temperature management device includes a transformer configured to convert the external power into a same voltage type as the battery power.

[0065] In a forty-second aspect, which may be used with any other aspect described herein, the targeted temperature management device includes a fan positioned and arranged to blow air across the heat sink, and wherein the control unit is further programmed to allow external power to power the fan when external power is available.

[0066] In a forty-third aspect, which may be used with any other aspect described herein, the fan is unpowered when external power is not available.

[0067] In a forty-fourth aspect, any of the features, functionality and alternatives described in connection with any one or more of Figs. 1A to 8 may be combined with any of the features, functionality and alternatives described in connection with any other of Figs. 1A to 8.

[0068] It is accordingly an advantage of the present disclosure to provide an improved target temperature management (“TTM”) system and device.

[0069] It is another advantage of the present disclosure to provide a TTM system and device that uses thermoelectric cooling.

[0070] It is a further advantage of the present disclosure to provide a TTM system and device that employs a convective cooling booster that uses available pressurized air, such as hospital pressurized air.

[0071] It is still another advantage of the present disclosure to provide a TTM system and device that is battery powered for ready use when AC power is not present.

[0072] It is yet a further advantage of the present disclosure to provide a TTM system and device having a relatively lightweight backup battery.

[0073] Additional features and advantages are described in, and will be apparent from, the following Detailed Description and the Figures. The features and advantages described herein are not all-inclusive and, in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the figures and description. Also, any particular embodiment does not have to have all of the advantages listed herein, and it is expressly contemplated to claim individual advantageous embodiments separately. Moreover, it should be noted that the language used in the specification has been selected principally for readability and instructional purposes, and not to limit the scope of the inventive subject matter.

BRIEF DESCRIPTION OF THE FIGURES

[0074] Fig. 1A is a schematic view of a targeted temperature management device according to an example embodiment of the present disclosure. [0075] Fig. IB is a schematic electrical diagram illustrating one embodiment for wiring the thermoelectric elements of the present disclosure, which may reverse current flow to either cool or heat the patient.

[0076] Fig. 2 is a schematic view of a targeted temperature management device connected to a patient according to an example embodiment of the present disclosure.

[0077] Fig. 3 is a schematic view of a targeted temperature management system connected to a patient according to an example embodiment of the present disclosure.

[0078] Fig. 4 is a schematic view of a regulator and valve system according to an example embodiment of the present disclosure.

[0079] Figs. 5A to 5D illustrate various nozzle assembly arrangements according to example embodiments of the present disclosure.

[0080] Fig. 6 is a schematic view of a nozzle geometry according to an example embodiment of the present disclosure.

[0081] Fig. 7 is a graph illustrating temperate drop plotted against Mach number for a nozzled booster of the present disclosure.

[0082] Fig. 8 is a schematic view of a battery powered targeted temperature management device according to an example embodiment of the present disclosure.

[0083] Fig. 9 is a schematic view of the control strategy for targeted temperature management according to the present disclosure.

[0084] Fig. 10 is a diagram showing a simulation of cooling step response for various patients at a blood flow of 250 ml/min.

[0085] Fig 11 is a schematic view of a control strategy for targeted temperature management according to an embodiment of the present disclosure.

DETAILED DESCRIPTION

Targeted Temperature Management Having Thermoelectric Cooling [0086] Referring now to Fig. 1A, a targeted temperature management (“TTM”) device 100 includes a cooling container 110 configured to carry a fluid to be cooled and a cooling plate (e.g., cooling plate 120a or cooling plate 120b, which may be referred to herein generally as cooling plate 120) positioned and arranged to cool the cooling container 110. The fluid may be water, saline, blood, etc. For example, and as described in more detail below, cooling container 110 may carry water that is then pumped through water-filled pads or blankets that are placed on the patient's body. In another embodiment, the fluid is saline, which may pumped into a catheter inserted into a patient's bladder. The fluid may also be the patient's blood, which is extracted from the patient, e.g., via a central venous catheter (“CVC”), pumped through the cooling container 110 (e.g., cooling bag) and returned to the patient, e.g., via the CVC.

[0087] In an embodiment, an inside 112 of cooling container 110 is sterilized prior to use for saline, blood, or any other intravenous fluid that may be inserted or injected into the patient. Here, container 110 is typically disposable. Sterilization may be via steam, ethylene oxide or gamma radiation. Container 110 is made of any medically acceptable material capable of withstanding such sterilization, e.g., polyvinylchloride (“PVC”) or a non-PVC material. If the fluid is water or other liquid that does not come into contact with the patient, container 110 does not need to be sterilized and may be reused. Here, container 110 may be made of a thicker material, which may also be PVC or a polyurethane.

[0088] The TTM device 100 may include multiple cooling plate(s) (e.g., cooling plate 120a and cooling plate 120b). For example, cooling plate 120a may be positioned to cool one side of the cooling container 110, while cooling plate 120b is positioned to cool the other side of cooling container 110. The cooling plates 120a, 120b may be in thermal communication with each other, e.g., via the cooling container 110 or via other means. Cooling plates 120a and 120b are made of a conductive material such as aluminum, copper, stainless steel, and combinations and alloys thereof.

[0089] It is also contemplated that if the fluid is water or other liquid that does not come into contact with the patient, container 110 may not be needed. Instead, cooling plate 120a and cooling plate 120b are sized and shaped so as to seal together, e.g., as hinged clamshells, to form an enclosure that receives and cools the fluid. One of cooling plates 120a and 120b may hold an o-ring type gasket, e.g., silicone, that is compressed by the other of the cooling plates when closed to form the enclosure. One or both cooling plates 120a and 120b may form, or cooperate to form, a thermally conductive serpentine fluid pathway that forces the fluid to be cooled to meander along the pathway, increasing contact time and cooling efficiency. Inlet line 114 and outlet line 116 that extend to and from container 114 and 116 in Figs. 1A, 2 and 3 extend instead to the enclosure formed by cooling plate 120a and cooling plate 120b. Lines 114 and 116 may be permanently attached to, or plugged into, one of the plates. Lines 114 and 116 may be reusable or disposable. If disposable, lines 122 and 124 may be attached to water-filled pads 210 that are applied on the patient's body (Fig. 2) and plug into one of the plates. In an alternative embodiment, the enclosure is formed, e.g., stamped, from a single thermally conductive blank, or is otherwise formed without requiring cooling plates 120a and 120b.

[0090] TTM device 100 also includes at least one thermoelectric element 130a to 130c structured to conduct heat from a cooled side 132 to a warmed side 134 when receiving an electrical current. The thermoelectric element(s) 130a to 130c is positioned and arranged such that the cooled side 132 cools the cooling plate 120. Additionally, a cooled side of one or more additional thermoelectric element (not illustrated) may be positioned and arranged to cool cooling plate 120b. The thermoelectric elements may be a single element or may include a plurality (three illustrated but could be two or more than three) of thermoelectric elements 130a to 130c electrically connected in parallel. It should be appreciated however that with a coordinated placement of thermoelectric elements 130a ... 130n, the elements may be electrically connected in parallel.

[0091] Thermoelectric elements 130a to 130d may be applied to both plates 120a and 120b or to one plate only (e.g., 120a), wherein that plate is in thermal contact with the other cooling plate (e.g., 120b). The cooling plate(s) 120a and 120b and cooling elements, such as thermoelectric elements 130a to 130c, may form a cooling assembly 125. In an example, thermoelectric elements 130a to 130c are structured to collectively supply 200 Watts of cooling power. Cooling power output is dependent on a number of factors, including driving current and ambient temperature. Experiments involving prototypes showed a cooling output of around 200W of cooling at ambient temp of 23 to 24°C, where power to the elements was typically 24V*6A=144W. The experiments used water to simulate blood, where energy was removed from the water to ambient air, cooling the water. It should be appreciated however that adding additional thermoelectric elements and/or increasing input power may easily bring the total cooling output of cooling assembly 125 to around 500W.

[0092] The side of thermoelectric elements 130a to 130c from which heat is transferred depends on the direction of current through the elements. For example, when current is applied in a first direction through thermoelectric elements 130a to 130c, one side of the thermoelectric elements warms or becomes warm (e.g., warmed side 134) while the opposite side cools or becomes cool (e.g., the cooled side 132). If the current is reversed, the heating and cooling and the warmed and cooled sides are also reversed. To this end, it is expressly contemplated to wire a voltage supply to TTM device so that power may be reversed to instead warm the patient, for example, when treatment has been completed.

[0093] Fig. IB illustrates an example electrical circuit 30 for powering thermoelectric elements 130a to 130c (and additional elements 130d .... 130n). In the illustrated embodiment, elements 130a to 130c are powered in parallel but could alternatively be powered in parallel. Fig. IB illustrates that a power source 32 is provided, which is connected electrically to main power lines 34 and 36. Legs 38 extend from main power lines 34 and 36 to elements 130a to 130c, creating a parallel power arrangement. A bypass line 40 is provided extending between power lines 34 and 36. A return line 42 is provided which extends between power lines 34 and 36. Switch 44a is located in power line 36, while switch 44b is located in power line 34. Switch 44c is located in bypass line 40, while switch 44d is located in return line 42. Switches 44a to 44d are placed under control of a control unit 50 as indicated by the dotted control lines. To cool the patient, control unit 50 powers thermoelectric elements 130a to 130c in a first direction, e.g., by closing switches 44a and 44b (allowing current flow through those switches) and opening switches 44c and 44d (preventing current flow through those switches). To cool the patient, control unit 50 powers thermoelectric elements 130a to 130c in a second direction, e.g., by closing switches 44c and 44d (allowing current flow through those switches) and opening switches 44a and 44b (preventing current flow through those switches).

[0094] Cooling plates 120a and 120b may be thermally insulated on their outer surfaces to help prevent ambient heat from heating the cooling plates. The thermal insulation helps to maintain the cooling capacity of plates 120a and 120b. The thermal insulation may for example be a lightweight foam that is applied to the outer surfaces of plates 120a and 120b, e.g., around the thermoelectric elements 130a to 130c operably coupled to the cooling plates.

[0095] In the illustrated embodiment, TTM device 100 includes a heat sink 140 positioned and arranged to conduct heat away from the warmed side 134 of the at least one thermoelectric element 130. Heat sink 140 may include a plurality of heat fins 142. Heat sink 140 and heat fins 142 are likewise made of a conductive material, such as aluminum, copper, stainless steel, and combinations and alloys thereof. As illustrated in Fig. 1A, the TTM device 100 may also include a fan 150 positioned and arranged to blow air across the plurality of heat fins 142. Fan 150 cools heat fins 142, which in turn pull heat from thermoelectric elements 130a to 130c.

[0096] The heat sink 140, thermoelectric elements 130a to 130c and cooling plate(s) 120 may be thermally coupled in various arrangements. For example, the cooled side 132 of the thermoelectric element 130 may be in direct contact with the cooling plate 120 or the cooled side 132 of the thermoelectric element 130 may be in contact with the cooling plate A20 via a thermal transfer compound. Additionally, the heat sink 140 may be in direct contact with the warmed side 134 of the thermoelectric element 130 or heat sink 140 may be in contact with the warmed side 134 of thermoelectric element 130 via a thermal transfer compound.

[0097] In an example, thermoelectric elements 130a to 130c may be Peltier modules or devices. Instead of using a compressor-cooled system that is noisy, bulky, heavy and may not start if placed upside down, which may occur in an intensive care unit, fluid is cooled by thermoelectric elements 130a to 130c, such as Peltier modules or devices. Peltier modules are solid-state active heat pumps, which transfer heat from one side of the device to the other side of the device with the consumption of electrical energy.

[0098] Thermoelectric performance is a function of ambient temperature, heat exchanger or heat sink performance, thermal load, thermoelectric element 130 geometry (e.g., Peltier geometry), and thermoelectric element 130 electrical parameters (e.g., Peltier electrical parameters). The amount of heat that can be moved is proportional to the current and time. The possible cooling effect is described by Equation 1 where ( q ) is the cooling effect in Watts [W], (P) is the Peltier coefficient, (I) is the current and (/) is the time.

Q = ^Plt Equation 1

[0099] The Peltier coefficient ( P ) depends on temperature and materials from which the Peltier module is made. Peltier modules are made of two dissimilar materials, which are typically semi-conductors. The materials may be placed thermally in parallel and electrically in series and may be joined by thermal plates to allow heat to flow from one side of the element to the another when an electric current or an electromagnetic field is applied to the element. In the illustrated embodiment, heat is transferred from the cooled side 132 of elements 130a to 130c the warmed side 134. Heat sink 140 is accordingly positioned and arranged to on warmed side 134 to conduct heat away from the warmed side 134. [00100] A magnitude of 10W/A for the cooling effect of elements 130a to 130c is common. Some of that magnitude may be lost however via waste heat described in Equation 2 and a phenomena of heat moving back from the warmed side 134 to the cooled side 132 inside the Peltier module as the temperature difference between each side increases. The result is that the amount of heat effectively moved lessens as the temperature difference between the cooled side 132 and the warmed side 134 grows, causing elements 130a to 130c to become less efficient. At a certain temperature difference, waste heat and heat returning to cooled side 132 overcomes the moved heat, such that element 103a to 130c starts to heat cooled side 132 instead of cooling it further.

Q_waste = RI²t Equation 2

[00101] In Equation 2, ( R ) is the resistance and (Q_waste) is the waste heat produced by the Peltier module.

[00102] As illustrated in Fig. 1A, the fluid to be cooled is pumped through cooling container 110, which may define an internal meandering or serpentine fluid path or pathway 220 (see Fig. 2). Cooling container 110 is inserted and clamped between two cooling plates 120 so that there is good thermal contact. Thermoelectric element(s) 130a to 130c, such as Peltier modules, are attached, by direct contact or a thermal transfer compound, to the bottom side of cooling plate 120a. Heat sink 140 as discussed above may include a plurality of projecting heat fins 142 is similarly attached to the Peltier modules (e.g., via direct contact or thermal compound). Additionally, a fan 150 is arranged to produce a flow of cooling air onto the projecting heat fins 142 of heat sink 140. In an alternative implementation, the thermoelectric element(s) 130 (e.g., Peltier modules) may be water-cooled.

[00103] Referring now to Fig. 2, a TTM system 200 that includes a TTM device 210 coupled to a patient. TTM system 200 may be used with different fluids (e.g., water, blood, saline, etc.). In an example, the fluid is water, which is pumped through water- filled pads 210 applied to the patient's body. In another example, the fluid is saline which is pumped through a catheter 210 inserted into the patient's bladder. In yet another example, the fluid is blood, which is extracted from the patient, e.g. via a central venous catheter (“CVC”) 210, pumped through the cooling container 110, and then returned to the patient, e.g. via the standard CVC. [00104] As illustrated in Fig. 2, cooling container 110 may include a flexible bag having a serpentine fluid cooling pathway 220. The material of the cooling bag may for example be heat sealed or sonically sealed to form the serpentine pathway 220.

[00105] An important aspect of target temperature management is the process to control the core temperature of a patient in need of therapeutic hypothermia. The scope is to deliver a higher level of controllability to the medical device intended to perform the treatment in order to improve its performance. Temperature control is often quite slow, the actuator is working with a fast time response, however, the controlled process is often slow. In the scope of target temperature management, TTM, the patient weight, Mbody, is typically +70 kg, with an average specific heat capacity, Cp_body of 3470 J/(kg*K) [https://www.engineeringtoolbox.com/human-body-specific-heat-d_393.html]. Thus, it takes time to alter the body temperature. The specific heat capacity of blood, Cp_blood, is 2968 J/(kg*K) [Lloyd, British Medical Journal, vol. 2, p. 1072, 1897].

[00106] “Cascade control can be used when there are several measurement signals and one control variable. It is particularly useful when there are significant dynamics, e.g., long dead times or long time constants, between the control variable and the process variable. One example is shown in Fig. 9.

[00107] The task to control the core temperature of a patient is an excellent example of where cascade control is highly suitable. This is since the actuator will apply the cooling effect to a sort of heat transfer device, e.g. an aluminum block. The device has got a certain weight, typically in the range 0.1-1 kg. This block will change its temperature quick compared to the core temperature of a patent that will be altered slowly, since the full body mass is typically around 75 kg. To apply this methodology to Fig. 9, P₁ would be the thermal dynamic process of the aluminum block, y_s the temperature sensor at the actuator, i.e. the aluminum block, P₂ the patient thermal dynamic process, y the temperature out from the patient, i.e. the blood temperature coming from the patient, or a temperature sensor placed in the patient. C_s would be the fast control loop controlling the P₁ temperature and C_p would be the slow loop controlling the patient temperature by setting the reference value to the C_s loop.

[00108] If parameters of the patient are known to the machine, a feedforward algorithm could be added to speed up the control response and allow for a quicker convergence to a steady state temperature. As an example, the Miffin St Jeor Equation t https://en.wikipedia.org/wki/Basal_metabolic_rate ] can be used to estimate the average power produced by the patient as follows:

[00109]

Equation 3

[00110] Where P is power in W, m is body mass in kg, h is height in cm, a is age in years, s is correction for male and female corresponding to 5 and -161 respectively. 0.0484 is the conversion factor from kcal/day to W.

[00111] As an example, let’s assume a male patient of 75kg, 75 years of age and 175 cm of height. This would result in an average power produced 71W according to Error! Reference source not found..

[00112] This information could be used as a feedforward in the control strategy, this will create an offset (which would have been obtained eventually from the integral part of a PID control). However, knowing the controller gets a head start of where the nominal needed power will be and thus may lead to quicker converging without the need of an overly aggressively tuned PID.

[00113] If a good model is available, various control strategies utilizing this model could be applied, e.g. model predictive controller, linear quadratic controller or similar that utilize the system knowledge.

[00114] The patient thermal model can be setup as a change in the energy balance of the patient, with the blood flow in and out affecting it.

[00115]

Equation 4

[00116] is the specific heat capacity for the patient,

is the specific heat capacity of blood, M_body k [g ] is the patient's weight,

T_care [^ºC], is the core temperature of the patient, is the blood flow, the temperature of the blood going to the patient,

T_{fromPatien t} [°C·] the temperature of the blood going out of the patient for normal flow rates this can be assumed to be equal to the patient core temperature. If Error! Reference source not

found, is Faplace transformed and the temperature from the patient is assumed to mimic the core temperature the equation can be written as follows:

[00118] From Error! Reference source not found, we can see that the form of the equation is a first order system with a time constant of τ_ραtimt

this time

constant will set the control strategy needed for this medical device. Most of the variables in the time constant are known constant, except for the patient weight (it could be a user input), this could be identified through an initial controlled step response. Below is a table [Table 1] of what the time constant of the patient will be for a couple of blood flows and body sizes.

[00119] The Error! Reference source not found, is a simplification in two main aspects. Firstly, the time constant is capturing the system well enough, however, the time delay is not considered in this model, a more detailed model would have a time delay adjusting for the transport from the cooler to the patient core. This time will be set proportional to the blood volume from the cooling actuator to the core of the body, typically a few hundred milliliters, and the flow rate, typically a few hundred milliliters per minute, thus yielding a time delay in the size of minutes. This is several times smaller than the time constant as seen in the table above. The second simplification is that the metabolic rate as mentioned in Error! Reference source not found, is not accounted for. Typically, during a TTM treatment the patient is will be undressed to speed up the cooldown and dissipate the power through the skin. The conclusion is that the patient thermal process can be modelled more accurately with a first order time delayed system, as the equation below:

[00120] Equation 6

[00121] Where K_p is the static gain of the system, T is the time constant of the system and L is the time delay of the system. K_y will be one as seen in Equation 5Error!

Reference source not found.and the time constant will be in the magnitude of hours and the time delay is in the magnitude of minutes.

[00122] The two variables that sets the system dynamics are the blood flow and the patient weight, the blood flow will be known by the device and the weight can be calculated from the initial step response from the system.

[00123]

Equation 7

[00124] For example, let the initial step be 10°C and, i.e. the blood to the patient is 10°C below the temperature of the blood coming from the patient ΔT = 10. The patient would slow converge towards this new setpoint, the samples of the core temperature, i.e. the temperature of the blood from the patient can be made periodically, e.g. every 15 min. Let us assume the patient initial temperature is 37°C then the behavior shown in Fig. 10 would be observed.

[00125] The data points are roughly 37, 36.45, 35.93 35.44 34.97 34.53 34.12 33.73 33.36 °C. From these data points the Error! Reference source not found. Error! Reference source not found.can be used to estimate the time constant of the system with linear regression. This yields a time constant of 4.416 hours, and since the blood flow is known as well as the other constants the weight can be estimated to 60 kg. If a 0.1 °C gaussian noise error is applied to the data the estimate will be 59.99 kg, which is good enough as an estimation.

[00126] A linear regression to find the time constant can be done with a rewrite of Error! Reference source not found, as follows:

[00127] Equation 8

[00128] If t is exchanged for a time vector with time stamps > 0 and T₁ is exchanged for a temperature vector with the same length and temperature at the corresponding time stamps Error! Reference source not found.Error! Reference source not found, will give the time constant that best fit the data samples.

[00129] The cooler model is composed of two equations, the first describes the cooling powers effect on the cooling block temperature and the second describes the cooling block temperatures effect on the blood outflow temperature. The following parameters are used in the first equation; Pcooier is the cooling source [W] acting on the cooling block, h which is the coefficient of heat transfer [W/(m²*K)] between cooling source and blood, i.e. an average of the total heat transfer coefficient, A is the average area that the heat is transferred crosses [m²], T_cooler is the temperature of the cooling block, M_cooleris the mass of the cooling block [kg] and Cp_cooler is the specific heat of the cooling block. This can be represented as follows:

9

[00131] The second equation uses the following parameters; T_out is the blood temperature out from the cooling block [°C], Cp_cooler is the specific heat of blood [J/(kg*K)], ρ_blood is the density of blood [kg/ml], Q_blood is the blood flow rate [ml/s], V_bag is the volume of the heater transfer bag, i.e. the disposable with a fixed blood volume [ml], h which is the coefficient of heat transfer [W/(m²*K)] between cooler and the blood in the disposable bag, A is the average area that the heat is transferred across to blood [m²], T_in is the blood temperature in to the cooling block [°C], i.e. the same as from patient, c.f. T_core in Equation 5, T_cooler is the cooler block temperature [°C], c.f. Error! Reference source not found.9. The equation can be represented as follows:

Equation 10

[00133] The Equation 9 and Equation 10 together describes the process PI, c.f. Fig. 9. From these equations the equations to calculate the time constant from each subsystem can be derived.

[00136] It can be seen that it is the lowest heat transfer coefficient that has the largest impact on the overall heat transfer. Since that is accounted for, the estimation has a correct magnitude. In case a better estimation is to be made, all layers should be added but the impact is expected to be small.

[00137] If the following values are assumed: Cp_Cooler = 900 [J/kg*K], M_Cooler = 0.81 [kg], h_c = 41000[W/(m²*K)]{ assumes aluminium, i.e. 205 W/(m*K) and that the plate is roughly 5 mm thick], V_bag = 30 [ml] {The bag volume is estimated as follows: 200 x 150 x 1 mm = 30 ml, the same proportions are used for area estimations], h_b = 270 [W/(m² * K)] {The thermal conductivity of polyurethane is 0.27 W/(m*K) and the bag thickness is assumed to be 1 mm. This is a simplification since the overall heat transfer coefficient will depend on flow turbulence etc.}, and a blood flow, Q_blood, of 250 ml/min, i.e. 4.17 [ml/s]. The time constants can be estimated to 45.3 seconds for the cooler and 3.3 seconds for the cooling for the blood. Both time constants are significantly smaller than the main process, i.e. the cooling of the patient, which is in the size of several hours, c.f. Error! Reference source not found.. The following table [Table 2] shows the time constant for several blood flow rates:

[00138] Since the time constant of the blood temperature change is significantly faster (regardless of blood flow rate, cf. Error! Reference source not found.) the system can be represented with a first order system with the dominate pole from the cooler time constant. A rule of thumb is that a system can be adequately represented by the dominant pole, if it is more than 5 times slower than the fast pole. In this system, with the assumptions that has been made, the difference is between 10-15 times, thus a first order time delayed, FOTD, system can represent the system well enough. This system will not change with patient, however, it will have change with the blood flow (the non-dominant pole), thus a simple look-up table for various blood flows would be enough to get the model parameters as needed in the FOTD model, cf. Error! Reference source not found.. An initial step response could also be used to identify the system, the time constant is roughly 45 seconds, so 3 - 4 time constants should be enough to make an identification of the static gain and time delay. It should be noted that the static gain will be affected by the blood flow, higher blood flow yields lower static gain, i.e. power input to temperature output gain.

[00139] Since the systems have such a great difference in their individual time constants, it would be recommended to limit the inner loops controller, this is since the outer loop will show no change in its temperature before the inner loop controller is saturated. Since the cooling transport media is blood, it is undesired to cool it too much, it will result in a system that can't be operated, either the blood freezes and cause a blockage or the pump will have trouble moving the blood due to increased viscosity. Regardless limits on the inner loops control output is needed, i.e. limits on T_out cf. Equation 10.

[00140] Suggested solution: [00141] The simplest way would be to limit the output from the inner control loop and add tracking of the output signal with integral acting on the difference between the saturated output signal, u, and the desired output signal, v, from the PID. This would typically kick in when the blood temperature is outside the desired limits, e.g. 10°C and 40°C.

[00142] Another alternative is to control the inner loop using a model predictive control, MPC, since the process is well known cf. Equation 9 and Equation 10. The benefit of an MPC is that it handles constrains on all the signals in its implementation, i.e. if the output temperature should be above a certain value, e.g. 10°C it will handle this constraint. Another benefit with the MPC is that it can handle multi order system which the system is, even though as mentioned before it will behave close to a first order system. A first order system controlled with an MPC (without signal constrains) can be realized with a regular PI controller.

[00143] The Amigo method is a convenient way of tuning a control loop where the process can be well represented with a first order time delayed process. Since this is the case for the patient thermal system representation this method can be applied.

[00144] Since our system has a time constant much larger than the time delay a PI controller would suffice to control the process. The Amigo method have got two equations to calculate the corresponding P and I value for the process represented on the form of seen in Equation 6.

[00145]

Equation 11

[00146] The parameters from Equation 9is the parameters for an ideal PI control representation, i.e.

0 Targeted Temperature Management Using Booster [00147] Referring now to Fig. 3, a targeted temperature management system 300 includes a cooling container 110 configured to carry a fluid to be cooled and a cooling assembly 125 positioned and arranged to cool the cooling container 110. TTM system 300 also includes a heat sink 140 positioned and arranged to conduct heat away from the cooling assembly 125. Additionally, the TTM system 300 includes a nozzle arrangement 350 configured to accept pressurized air and to cool the pressurized air via a geometry of the nozzle arrangement 350. Nozzle arrangement 350 in the illustrated embodiment is positioned and arranged to convectively cool heat sink 140 using the cooled air.

[00148] As described above with respect to Fig. 1A, the cooling assembly 125 includes at least one cooling plate 120a and 120b (which may be thermally coupled to one another) positioned and arranged to cool the cooling container 110 and a at least one cooling element 130a to 130d positioned and arranged to cool cooling plates 120a and 120b. Similar to the TTM device 100 illustrated in Fig. 1A, the TTM system 300 may include a heat sink 140 positioned and arranged to conduct heat away from the warmed side of the cooling element 130a to 130d.

[00149] The TTM system 300 may be implemented in a hospital and connected to a hospital air pressure system 352. The pressurized air provides a cooling effect when released over a restriction nozzle (e.g., nozzle 500 described in Fig. 6). As illustrated in Fig. 3, cooling container 110 may be supplied fluid from a source container 360, which for example supplies saline to the cooling container 110. Cooling assembly 125 cools the saline, which may be pumped via a pump through a catheter inserted into a patient's bladder. If the catheter is a dual lumen catheter, the cooled saline may be continually circulated from cooling container 110, to the patient, and back to the cooling container until the patient reaches the desired temperature. If the catheter is a single lumen catheter, saline may be delivered batch wise from cooling container 110 to the patient.

[00150] As primarily illustrated in Fig. 3, in another example, the fluid cooled is the patient's blood, which is extracted from the patient, e.g., via a CVC, pumped through cooling container 110 (e.g., cooling bag) via a blood pump 370 and returned to the patient through a drip chamber 340 and associated level sensors that removes any air from the blood back to the patient, e.g., via the CVC. Container 360 in the blood cooling embodiment may also store saline, e.g., for priming and blood rinseback. TTM system 300 in Fig. 3 also includes an arterial blood pressure sensor located upstream of blood pump 370, a system pressure sensor located between blood pump 370 and cooling container 110, a venous pressure sensor coupled with drip chamber 340, an air detector located downstream from blood pump 370, and clamps for clamping the arterial and venous lines. It should be appreciated what while a CVC is one suitable blood catheterization technique, other techniques including a separate or single need access to the patient's blood vessels via the patient's arm are also suitable. [00151] In an embodiment, the cooled blood is provided in combination with a blood cleansing treatment such as hemodialysis (“HD”), hemofiltration (“HF”), hemodiafiltration (“HDF”), isolated ultrafiltration (“UF”), slow continuous ultrafiltration (“SCUF”), continuous renal replacement therapy (“CRRT”), continuous veno-venous hemodialysis (“CVVHD”), continuous veno-venous hemofiltration (“CVVH”), and continuous veno-venous hemodiafiltration (“CVVHDF”). Here, a dialyzer (not illustrated) is located upstream or downstream from cooling container 110. A separate blood pump may be provided between cooling container 110 and the dialyzer to repressurize the blood for whichever is located downstream from the other. Treatment fluid pumps and treatment fluid sources are also provided to pump treatment fluid to and from the dialyzer and/or directly to the extracorporeal circuit, e.g., directly to cooling container 110 in which the treatment fluid is also cooled. A treatment fluid volume and ultrafiltration (“UF”) control mechanism, such as a flow meter system, balance chambers or weight scales may also be provided to track how much treatment fluid is delivered to the dialyzer and/or extracorporeal circuit, how much fluid is removed from the dialyzer and how much UF has been removed from the patient.

[00152] All electrically actuated components illustrated in Fig. 3 and any electrically actuated components added for any blood cleansing treatment are operated under the control of a control unit, which includes one or more processor, one or more memory and a user interface, which may be operated via a touch screen and one or more membrane switches. For any of the blood cleansing treatments listed above, the control unit may be provided with the blood treatment device.

[00153] In the illustrated embodiment, TTM system 300 includes at least one air pressure regulator 420 (see Fig. 4) located between a supply of the pressurized air (e.g., hospital air pressure system 352) and the nozzle arrangement 350 and oriented to regulate the pressurized air accepted by the nozzle arrangement 350. System 300 also includes all of the hose, tubing fittings and connectors needed to connect nozzle arrangement to the hospital’s pressurized air supply. Additionally, the TTM system 300 may also include at least one valve (e.g., gate valve or electronic valves) located between the supply of the pressurized air and the nozzle arrangement 350. A control unit may be programmed to allow the nozzle arrangement 350 to accept pressurized air during an initial cooling of a patient and to operate the fan 150 and/or valves (e.g., electronic solenoid valves 430a to 430e of Fig. 4) to maintain the patient at a cooled temperature, e.g., 3°C (91°F) or 36°C (97 °F).

[00154] Fig. 4 illustrates that TTM system 300 includes pressure regulator 420, which accounts for differences between air pressure systems 352 of different hospitals and for variations in air pressure within any given hospital. Without at least one pressure regulator 420, the feed pressure provided by the hospital may result in too high a cooling effect on the patient's blood or other fluid. In an example, one or more valves, such as a gate valve 410 and/or electronic solenoid valve 430a to 430e are provided instead of or in addition to pressure regulator 420. Gate valve 410 is in one embodiment an on/off valve, which may be manually operated to turn nozzle arrangement 350 on and off. Pressure regulator 420 sets the pressure at each nozzle 500a to 500e. Solenoid valves 430a to 430e automatically control whether pressurized air is received respectively at nozzles 500a to 500e.

[00155] Solenoid valves 430a to 430e may be “toggled” on/off under control of the control unit to achieve an appropriate cooling effect. Here, valves 430a to 430e may negate the need for regulator 420. In the example illustrated in Fig. 4, a separate electrically actuated solenoid valve 430a to 430e is provided for each nozzle 500a to 500e. Here, each nozzle 500a to 500e may be “toggled” on/off by its corresponding electronic solenoid valves to achieve an appropriate cooling effect.

[00156] Referring now to Figs. 5A to 5D, nozzle arrangement 350 may include a plurality of nozzles 500, wherein each nozzle has the cooling geometry (see Fig. 6). In one example, each nozzle 500 is dedicated to one or more heat fin 142 and/or portions thereof. As illustrated in Fig. 5A, nozzle 500a is dedicated to heat fins 142a, 142b; nozzle 500b is dedicated to heat fins 142b, 142c; nozzle 500c is dedicated to heat fins 142c, 142d; and nozzle 500d is dedicated to heat fins 142d, 142e. Alternatively illustrated in Fig. 5B, nozzle 500a is dedicated to heat fins 142a and 142b, while nozzle 500b is dedicated to heat fins 142d and 142e. Both nozzles 500a and 500b are dedicated to heat fin 142c.

[00157] Referring again to Fig. 5A, each nozzle 500 may be formed as part of at least one heat fin 140. For example, nozzle 500a is formed as part of heat fins 142a, 142b, while nozzle 500b is formed as part of heat fins 142b, 142c. As illustrated alternatively in Figs. 5C and 5D, heat fins 142a to 142f may be formed together with the nozzle assembly 350, which here includes a single nozzle. The geometry of the nozzle arrangement 350 is integrated into the heat sink 140 in Figs. 4C and 4D. In one example, nozzle arrangement 350 is sized to force cooled air over at least substantially all of the heat sink 140 and therefore over the plurality of heat fins 142. In another example, nozzle arrangement 350 replaces heat fins 142a to 142f such that the contour of the one or more nozzle forms a surface of heat sink 140.

[00158] Referring now to Fig. 6, an example geometry of nozzle arrangement 350 is illustrated showing that the geometry of the nozzle arrangement 350 is configured to constrict and then expand the pressurized air. The pressurized air may be choked at a choke point or throat of the nozzle geometry. Fig. 6 illustrates a nozzle 500 with a chocked throat, wherein the mass flow rate through nozzle 500 has reached its maximum at the current feeding pressure and feeding temperature.

[00159] The nozzle geometry illustrated in Fig. 6 may also be referred to as a converging/diverging (“CD”) nozzle. Gas flows through the nozzle 500 from a region of high pressure (referred to in Fig. 6 as the chamber) to one of low pressure (referred to in Fig. 6 as the ambient or tank). Typically, the chamber is large enough such that any changes in velocity in the chamber are negligible. The pressure in the chamber is denoted by the symbol (p_c). Gas flows from the chamber into the converging portion of the nozzle, past the throat, through the diverging portion and is then exhausted into the ambient as a jet. The pressure of the ambient is referred to as the “back pressure” and given the symbol (/%)_.

[00160] In nozzle arrangement 350, the chamber in Fig. 6 accepts hospital air at the pressure regulated by regulator 420 as (p_c), which may be assumed to be a regulated pressure of approximately 4 bar, where the temperature of the chamber (T_c) is assumed to be approximately 30°C. The back pressure in Fig. 6 represents an ambient pressure, assumed to be approximately 1 atmosphere. The diverging section in Fig. 6 may align with or replace heat fins 142 of heat sink 140 in a TTM device 100. Alternatively, diverging section 610 may terminate at the beginning of heat fins 142 of heat sink 140 so as to blow chilled air over the heat fins.

[00161] Besides the assumption of a regulated pressure for (p_c) of approximately 4 bar and a chamber temperature (T_c) of approximately 30°C, the calculations provided below assume the following: (i) the throat 610 of the nozzle 400 is choked, i.e., the maximum mass flow rate is reached with the current feeding pressure and the selected throat area; (ii) hospital air system 352 can deliver a mass flow rate of air of at least 0.005 kg/s; (iii) the hospital can handle a continuous air flow of several cubic meters of air per hour (which is highly likely); (iv) any increased noise level due to the air flow is tolerable or may be muffled; and (v) the simplification that air flow can be described as adiabatic is made, e.g., that there is no thermal interaction of the pressurized air with the surroundings prior to exiting the nozzle 400.

[00162] The temperature drop through a nozzle 500 at supersonic conditions can be described with Equation 12. To achieve supersonic conditions in the diverging section 650, the converging section 640 needs to be subsonic while the throat 610 is sonic, i.e., having a Mach number (“Ma”) of 1 at the throat 610 (occurs in chocked throats).

TQ

T = -

1 T- 0.2 Ma² Equation 12

[00163] In Equation 12, (To) is the temperature of the air supplied by the hospital air system, (T_e) is the exit temperature and (Ma) is the Mach number at the exit. From Equation 12, the exit temperature rapidly decreases with an increased Mach number, which is illustrated in Fig. 7. At a chocked flow through a nozzle 500, the local Mach number can be calculated with Equation 13.

0.5 · (k + 1)

Equation 13

[00164] In Equation 4, (A) is the area at a certain position in the nozzle 500, (A*) is the area at the throat 610 of the nozzle 500, (Ma) is the Mach number at the selected position, (k) is the specific heat ratio for the fluid flowing through the nozzle 500 (normally a number between 1.1 and 1.7, 1.4 for air at normal temperatures). Equation 13 lacks an algebraic solution, however, it can be solved numerically with various solvers, such as the Newton- Raphson method.

[00165] The appropriate throat area for a certain mass flow ( ΎTΊ ^max) can be calculated according to Equation 14, where 7Ύ7 ^max is the maximum mass flow that the throat can deliver with a feeding pressure (Po) and an initial temperature (To). In Equation 5, (k) is still the specific heat ration and (R) is the specific gas constant.

Equation 14

[00166] Under the assumption that the hospital's pressurized air can deliver at least at 0.005 kg/s in mass flow rate and assuming that the feeding pressure (P₀) is

approximately 4 bar with a temperature (T₀) of 30°C and that normal air is supplied (e.g., (k) =

1.4006 and (R) = 287 m²/(s²K)), then Equation 5 yields: A ^* = 5.4 _· 10 ⁶m² or a circular throat 610 with a dimeter of 2.6mm.

[00167] If it is assumed that the area exit of the nozzle 500 is equal to one of the fin channels of a cooling fin in the TTM device, then A = 38.4 ^· 10 ⁶m² and combining (A) with the previous result of (A*) in Equation 13 results in a Mach number (Ma) = 3.55². The calculated Mach number yields a temperature drop of almost 72 percent when used in Equation 12.

[00168] Assuming that the pressure is fairly stable in TTM device 100), i.e., assuming close to atmospheric pressure, the specific heat for constant pressure ( C_P ) can be used. The possible cooling effect is described by Equation 15 where (Q) is the cooling effect in Watts [W], (T₀) is the feeding temperature [K], (T_e) is the exit temperature [K], ( C_P ) is the specific heat for constant pressure

is the maximum mass flow [kg/s]. Equation 15

[00169] In an example, Q — 1090 W when the following parameters are used: which corresponds to a feeding temperature of 30°C;

calculated with Equation 12;

numerical solution to Equation 13;

which is a valid assumption during constant pressure, that is, for an open hospital room with atmospheric pressure. [00170] Then, if it is assumed that the efficiency between the air to heat fin 142 heat exchange is approximately 30 percent efficient, the above cooling effect ( Q ) is reduced to a true cooling effect (Q_{t e}) of approximately Qtrue 10901K (0.30) 327W p_rom (p_e assumptions made above, the assumption that is least likely to be achieved is the Mach number of 3.55. However, by conservatively assuming that a chocked throat 610 is achieved without supersonic conditions in the diverging section 650, the system may provide a cooling effect or cooling power of approximately 250W. The cooling effect of 250W is determined using Ma = 1, (T_c) = 30°C, and excluding any heat exchanger effects. Heat exchanger effects are due to nozzle 500 acquiring energy through conduction, which will occur. Energy acquired via conduction is neglected for simplicity however in the equation quantifying the cooling effect.

[00171] The nozzle geometry of nozzle arrangement 350 may include each of the portions described in Fig. 6. In another example, the nozzle geometry or nozzle arrangement 350 may include a subsection of the portions described in Fig. 6, for example, the diverging section 650 may be removed from the nozzle 500. However, removing the diverging section 650 may result in a less effective cooling effect for the device by limiting the Mach number achievable by the device to sonic air flow speeds (e.g., Ma = 1).

[00172] The nozzle geometry of Fig. 6 is illustrated as being circular over its changing cross-section. It is contemplated to make the nozzle geometry of nozzle arrangement 350 oblong or elliptical so that the nozzle may cool multiple heat fins or a larger portion of heat sink 140. In the oblong or elliptical geometry, the choked geometry is a choked slit or narrow oblong or elliptical shape. A single oblong or elliptical nozzle may be provided to chill an entire heat sink 140 or multiple oblong or elliptical nozzles may be provided for same.

[00173] The control unit for nozzle arrangement 350 is in one embodiment programmed to use or actuate the nozzle arrangement at the beginning of the chilling process in which the patient's body temperature is lowered from normal body temperature (e.g., 37°C (98°F) to the desired lowered temperature of 33°C (91°F) or 36°C (97°F). After the patient reaches this temperature, nozzle arrangement 350 is deactivates and the cooling proceeds in a maintain mode to maintain the patient at the desired lowered temperature.

[00174] It should be appreciated that pressurized air cooling is not limited nozzle arrangement 350 discussed above, or even to use within a hospital. For example, it is contemplated to use the pressurized air in fluid communication with one or more perforated pad placed where needed on the patient's body or skin. Pressurized air leaks of jets out of the perforated holes arranged in an array on the pad to provide direct air cooling to the patient. Pressurized air may be provided by a battery powered or fuel powered compressor, or via a canister of pressurized air, such that AC power is not needed. Such a structure is well suited for remote areas and emergencies in the field.

[00175] It should also be appreciated that pressurized cooling is not limited to air and may include other gases, such as carbon dioxide, CO2, which is typically produced as a byproduct of industrial processes, or nitrogen, which is the most plentiful of the air gases. Such gases may be supplied under pressure in canisters, bottles or cylinders. The gas type only affects the k and Cp value in the equations above.

Targeted Temperature Management Having Passive Cooling [00176] In the illustrated embodiment of Fig. 8, TTM device 100 includes a battery 810 that is used to power the device 100 when no AC power is available, e.g., while the patient is out in the field, while being transported to a hospital, and while being transported between departments of a hospital. Battery 810 may be relatively small and the overall TTM device 100 relatively lightweight, such that the TTM device 100 may be readily transported with the patient in the field, on the way to the hospital and between departments of the hospital.

[00177] A battery weighing approximately 0.3 to 1.0kg may be provided to produce 0.1 kWh of power. Different types of rechargeable batteries exist with energy densities between 0.1 to 0.3 kWh/kg, but batteries that are capable of withstanding several charge cycles and temperature swings often have energy densities between 0.1 to 0.2 kWh/kg.

[00178] In particular, it has been found that suitable thermoelectric elements provide 200 to 300 Watts of cooling power when fully powered, which correlates to approximately to a 1.5 to 4kg battery for one hour of drift. Instead of powering thermoelectric elements 130a to 130c to produce 200 to 300 Watts in cooling efficiency at environmental temperatures (e.g., 22°C to 24°C), the elements 130a to 130c may instead be cooled with a fan 150 to provide a cooling effect of approximately 70 to 100W. For example, it has also been found that the same thermoelectric elements 130a to 130c provide 70 to 100 Watts of cooling power when the thermoelectric elements themselves are not powered (or powered very low, e.g., at 2 to 10W to start the transport) but cooling fan 150 is powered, which has been termed passive cooling.

[00179] Referring again to Figs. 1A to 3, a control unit (not illustrated) of TTM device 100 or TTM systems 200, 300 may be programmed or operated to cause the cooling fan 150 but not the thermoelectric elements 130 to be powered when running on battery or DC power and when AC power is not available. The result is that the battery 810 of Fig. 8 only needs to supply 70 to 100 Watts of power, which means that the battery 810 may weigh less than one kilogram and have an energy density of 0.1 kWh/kg.

[00180] In an alternative embodiment, a control unit (not pictured) of the TTM device 100 or TTM system 200, 300 is programmed or operated to provide only a small amount of power to the thermoelectric elements 130a to 130c and no power to the cooling fan 150 when AC power is unavailable. In an example, the lower power level is on the order of a few, e.g., less than 20W. The lower power level may be, for example, 0.5 to 5% of the higher power level. The lower power level only needs to start thermoelectric elements 130a to 130c. The amount of the lower power level depends on the geometry and thickness of elements 130a to 130c and their material.

[00181] It has been found that cooling output is not linear to power input such that the initial power input (e.g., first 100 Watts) yields a proportionally larger cooling power output than an additional power input (e.g., a second 100 Watts when 200 Watts are applied in total). For example, the first Watt of power provides more cooling efficiency than the last Watt of power provided (e.g., up to approximately two to three times more cooling efficiency). By applying 10 to 30W of DC power from battery 810 to the thermoelectric elements 130a to 130d, an efficient cooling effect may be achieved for the TTM device 100 and allow battery 810 to be less than 1 kg with an energy density of approximately 0.1 to 0.26 kWh/kg. That is, assuming 100W of power is needed to run a blood pump, the thermoelectric elements, electronics such as user interface, lights, etc., and an engineering factor, over a period of an hour without AC power, then a battery having a density of at least 0.1 kWh/kg is needed.

[00182] In an example, the entire TTM device 100 weights less than 8 kg, which may include a smaller blood pump with a flow rate of approximately 300ml/min and a working delta pressure of up to 250 mmHg. In one example, the components of the TTM device may include a blood pump (approximately 0.5 to 1.0 kg), a clamp (approximately 0.3 to 0.5 kg), a cooling unit (approximately 1.5 to 2.5 kg), a battery 810 (approximately 0.5 to 1.0 kg) and housing or casing components (approximately 1.5 to 2.0 kg), which results in a device that weights approximately 4.3 to 7.0 kg.

[00183] The TTM device 100 may include or may be in communication with a control unit 820 programmed to allow battery power to be supplied to the cooling assembly 125 and fan 150 when the external power is unavailable. Additionally, control unit 820 may be programmed to allow external power to power cooling assembly 125 and the fan 150 when the external power is available. Control unit 820 may be provided externally to TTM device 100 as illustrated in Fig. 8 (e.g., be located in a blood treatment device). Control unit 820 is provided alternatively within TTM device 100.

[00184] In one example, control unit 820 is programmed to cause full power from the external power to be supplied to the cooling assembly 125 when the external power is available and to cause a lower power level of the battery power of battery 810 to be supplied to cooling assembly 125 when external power is unavailable. In another example, control unit 820 is programmed to automatically cause (i) power to be supplied to fan 150 and full power to be supplied thermoelectric elements 130a to 130c when external AC power is available and (ii) battery power to be supplied to fan 150 only when AC power is unavailable.

[00185] In an embodiment, TTM device 100 illustrated in Fig. 1A and having the additional components of Fig. 8 is powered via DC power whether AC power is available or not. A transformer 830 is provided to transform the AC power into the same voltage DC power as provided by battery 810. The power supplied by transformer 830 is greater than that of battery 810 in one embodiment.

[00186] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims. For example, it is expressly contemplated that the nozzled booster cooling described above may be used with other types of coolers or chillers than one using thermoelectric cooling.

Claims

CLAIMS The invention is claimed as follows:

1. A targeted temperature management system (300) comprising: a cooling container (110) configured to carry a fluid to be cooled, said cooling container (110) comprising an inlet line (114) adapted to forward said fluid to be cooled from a body to cool (210), said cooling container (110) comprising an outlet line (116) adapted for forwarding cooled fluid from the cooling container (110) back to the body to cool (210); a cooling assembly (125) positioned and arranged to cool the cooling container (110), said cooling assembly (125) comprising a cooling plate (120a, 120b), at least one thermoelectric element (130a to 130c) structured to conduct heat from a cooled side (132) to a warmed side (134) when receiving an electrical current, the at least one thermoelectric element (130a to 130c)postitioned and arranged such that the cooled side (132)cools the cooling plate (120a, 120b); a heat sink (140) positioned and arranged to conduct heat away from the cooling assembly (125); a first temperature sensor (T1) positioned and arranged to measure and monitor the temperature of the fluid to be cooled in inlet line (114); a second temperature sensor (T2) positioned and arranged to measure and monitor the temperature of the cooled fluid in outlet line (116); a control unit (50) adapted for powering said at least one thermoelectric element (130a to 130c), said control unit being adapted for receiving data in real time from said first temperature sensor (T1) and said second temperature sensor (T2), wherein the control unit (50) is set up to calculate in real time a first control parameter C₁ based on data received from the first temperature sensor (T1); the control unit (50) is set up to calculate in real time a second control parameter C₂ based on said first control parameter C₁ and data received from said second temperature sensor (T2), said powering of said at least one thermoelectric element (130a to 130c) being based on said second control parameter C₂, and further comprising a nozzle arrangement (350) configured to accept pressurized gas and to cool the pressurized gas via a geometry of the nozzle arrangement (350), the nozzle arrangement (350) positioned and arranged to convectively cool the heat sink (140) using the cooled gas.

2. The targeted temperature management system (300) according to Claim 1, wherein the cooling assembly (125) includes a cooling plate (120a, 120b) positioned and arranged to cool the cooling container (110) and a cooling element (130a to 130d) positioned and arranged to cool the cooling plate (120a, 120b).

3. The targeted temperature management system (300) according to Claim 2, wherein the cooling element (130a to 130d) includes at least one thermoelectric element (130a to 130d) structured to conduct heat from a cooled side (132) to a warmed side (134) when receiving an electrical current, the at least one thermoelectric element (130a to 130c) positioned and arranged such that the cooled side (132) cools the cooling plate (120a, 120b).

4. The targeted temperature management system (300) according to Claim 3, wherein the heat sink (140) is positioned and arranged to conduct heat away from the warmed side (134) of the at least one thermoelectric element (130a to 130c).

5. The targeted temperature management system (300) according to any of the preceding claims, wherein the nozzle arrangement (350) includes a plurality of nozzles (500a to 500e), each nozzle having the cooling geometry.

6. The targeted temperature management system (300) according to Claim 5, wherein the heat sink (140) includes a plurality of heat fins (142), and wherein each nozzle (500a to 500e) is dedicated to at least one heat fin (142a to 142f).

7. The targeted temperature management system (300) according to Claim 5, wherein the heat sink (140) includes a plurality of heat fins (142a to 142f), and wherein each nozzle (500a to 500e) is formed as part of at least one of the heat fins (142a to 142f).

8. The targeted temperature management system (300) according to any of the preceding claims, wherein the geometry of the nozzle arrangement (350) is integrated into the heat sink (140).

9. The targeted temperature management system (300) according to any of the preceding claims, wherein the geometry of the nozzle arrangement (350) is sized to force cooled gas over at least substantially all of the heat sink (140).

10. The targeted temperature management system (300) according to any of the preceding claims, wherein the heat sink (140) includes a plurality of heat fins (142a to 142f), and wherein a geometry of the nozzle arrangement (350) is sized to force cooled gas over the plurality of heat fins (142a to 142f).

11. The targeted temperature management system (300) according to any of the preceding claims, wherein the geometry of the nozzle arrangement (350) is configured to constrict and then expand the pressurized gas.

12. The targeted temperature management system (300) according to any of the preceding claims, wherein the geometry of the nozzle arrangement (350) is configured to choke the pressurized gas.

13. The targeted temperature management system (300) according to any of the preceding claims, which includes at least one pressure regulator (420) located between a supply of the pressurized gas and the nozzle arrangement (350), the pressure regulator (420) oriented to regulate the pressurized gas accepted by the nozzle arrangement (350).

14. The targeted temperature management system (300) according to any of the preceding claims, which includes at least one valve (410, 430a to 430e) located between a supply of the pressurized gas (352) and the nozzle arrangement (350).

15. The targeted temperature management system (300) according to any of the preceding claims, which includes a fan (150) positioned and arranged to blow gas across the heat sink (140).

16. The targeted temperature management system (300) according to Claim 15, which includes a control unit programmed to allow the nozzle arrangement (350) to accept pressurized gas during an initial cooling of a patient and to operate the fan (150) to maintain the patient at a cooled temperature.

17. The targeted temperature management system (300) according to any of the preceding claims, wherein the pressurized gas is pressurized air.