TEMPERATURE REGULATION SYSTEM Field of the Invention

This invention relates to a temperature regulation system which may be useful for warming or cooling articles including mammals particularly human beings.

Background to the Invention

In an environment where there is no simple access to electricity, if is difficult to quickly or efficiently regulate the temperature of a body or article. A typical, portable temperature stabilising method for a body or article (such as a foodstuff) is the use of insulation such as padding or a blanket. An alternative standard for humans in danger of hypothermia is the use of a thermal blanket. This has no insulation properties, but is highly radiative for body heat. Such simple methods however may be insufficient to save the life of a patient.

More sophisticated and rapid temperature regulation methods have been devised but they are typically not portable, or if so, are complicated or messy to implement. US 6,800,087 discloses a blanket system for controlling a patient's body temperature which comprises a blanket under which are an air inlet and outlet. Warmed or cooled air can be supplied depending upon need. A pump is used to supply the air and a vacuum system to remove it.

US 6,969,399 discloses an enclosure for a patient's body. This enclosure allows heat transfer liquid to be contained and to pass over the patient's body. The enclosure has a liquid inlet and outlet, and allows for the heat transfer liquid to be in direct contact with the patient.

US 7,101,386, US 6,991,645 and related patents disclose more intervention based method and apparatus. A patient's body temperature is regulated by altering directly the temperature of blood flowing in a large vein feeding the heart. The temperature of this vein can be regulated by local heating, with an external heat applicator or by using a heating blanket for the whole body, such as those which use forced warm or cool air blowers.

In this specification, where reference has been made to external sources of information, including patent specifications and other documents, this is generally for the purpose of providing a context for discussing the features of the present invention. Unless stated otherwise, reference to such sources of information is not to be construed, in any jurisdiction, as an admission that such sources of information are prior art or form part of

' the common general knowledge in the art.

Object of the Invention It is an object of the present invention to provide a temperature regulation system which is portable, or which may be used to regulate body temperature without reliance on electricity or to provide a temperature regulation system which at least provides the public with a useful choice.

Summary of the Invention

Broadly according to a first aspect of the invention there is provided a temperature regulation system for a body or article comprising: >

(i) a body temperature regulation fluid source ("the source") containing a precursor to a temperature regulation fluid, said precursor capable of being activated to form said

temperature regulation fluid, and said source capable of releasing said temperature regulation fluid following activation of said precursor,

(ii) a panel including a fluid circulation network ("the network") that includes at least one inlet for said temperature regulation fluid; said panel to receive said temperature regulation fluid from said source to thereby transfer heat between the panel and said body or article or vice versa.

Preferably said system is used for transferring heat to or from a human or animal body. Preferably said fluid circulation network has at least one outlet. Preferably said fluid circulation network has a plurality of outlets.

Preferably said source contains two or more substances partitioned or separated from one another, wherein said activation comprises mixing said two or more substances to either release energy as heat via an exothermic process or absorb energy via an endothermic process.

Preferably the product of said activation of said precursor results in a liquid phase product.

In one embodiment said two or more substances react according to a chemical exothermic pathway or chemical endothermic pathway. Preferably said two or more substances are selected from one of the following list: calcium chloride and water, anhydrous magnesium sulphate and water, calcium chloride, water and glycerol, ammonium nitrate and water.

In an alternative embodiment said two or more substances react according to a biochemical exothermic pathway or biochemical endothermic pathway.

Preferably said biochemical pathway is an enzyme catalysed pathway. Preferably said two or more substances are glucose oxidase/catakse and a sugar molecule. Preferably said two or more substances are glucose oxidase/catalase and β— D-glucose.

Preferably the source takes the form of a capsule or cartridge. Preferably said activation can be conducted manually. Preferably the connection of the source to the network can be conducted manually.

Preferably said connection of the source to the network is conducted following said activation of the precursor.

Preferably said panel includes one or more layers of insulative material. Preferably said panel includes one or more layers of material having water resistive properties.

Preferably said network is arranged in a tortuous pattern within the panel.

Preferably said network is arranged in a substantially regular serpentine pattern within the panel. Preferably said network is regularly arranged within the panel.

Preferably said system includes one or more valves capable of adjusting the pressure within the network.

Preferably said panel includes one or more fittings allowing the panel to be interlocked or attached to at least a second panel.

Preferably said one or more inlets and/ or one or more outlets are capable of interlocking or engagement -with said second (or further) panel.

Preferably said panel may contain one or more temperature sensors to record and/or transmit and/ or display a temperature.

According to a second aspect of the invention there is provided a source of temperature regulation fluid suitable for use with the temperature regulation system, including two or more substances partitioned or separated from one another, which upon mixing, will either release energy as heat via an exothermic process or absorb energy via a endothermic process.

Preferably the product of the exothermic or endothermic process is a liquid. Preferably said source comprises a cartridge or capsule adapted to interlock or engage with an inlet of the fluid circulation network of the system. Preferably said mixing can be instigated manually.

Preferably said manual instigation is by hand pressure causing rupture of the partitioning between the substances.

In one embodiment the two or more substances when mixed will react according to a chemical exothermic pathway or chemical endothermic pathway. Preferably the two or more substances are selected from one of the following list: calcium chloride and water, anhydrous magnesium sulphate and water. - calcium chloride, water and glycerol.

ammonium nitrate and water.

In an alternative embodiment the two or more substances when mixed will react according to a biochemical exothermic pathway or biochemical endothermic pathway.

Preferably said biochemical pathway is an enzyme catalysed pathway.

Preferably said two or more substances are glucose oxidase/catalase and a sugar molecule.

Preferably said two or more substances are glucose oxidase/catalase and β— D-glucose.

According to a third aspect of the invention there is provided a panel including a fluid circulation network suitable for use in the body regulation system above.

Preferably said panel includes one or more layers of insulative material.

Preferably said panel includes one or more layers of material having water resistive properties.

Preferably said network is arranged in a tortuous pattern within the panel.

Preferably said network is arranged in a substantially regular serpentine pattern within the panel.

Preferably said network is regularly arranged within the panel. Preferably said panel includes one or more fittings allowing the panel to be interlocked or attached to a second (or further) panel.

Preferably said one or more inlets and/ or one or more outlets are capable of interlocking or engagement with said second (or further) panel.

Preferably said panel contains one or more temperature sensors to record and/ or transmit and/ or display the temperature of said panel or the body or article iα contact with said panel.

According to a further aspect of the invention there is provided a temperature regulation covering comprising one or more of the panels above interlocked together and one or more sources of temperature regulation fluid.

According to a further aspect of the invention there is provided a kitset for temperature regulation of a body or article including one or more panels above and one or more sources of temperature regulation fluid above.

According to a further aspect of the invention there is provided a method of temperature regulation of a body or an article comprising the steps of engaging a said source of temperature regulation fluid with an inlet of a said panel, and activating the source either before, substantially simultaneous with, or after the step of engaging the source with the inlet.

Preferably the method includes the step of interlocking one or more of said panels together.

Preferably the method includes engaging one or more of said sources with said network either simultaneously or sequentially.

Preferably the method includes draining the network of the temperature regulation fluid by gravity or suction.

To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims. The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting.

Other aspects of the invention may become apparent from the following description which is given by way of example only and with reference to the accompanying drawings.

Definitions

"The term "comprising" as used in this specification and claims means " consisting at least in part of; that is to say when interpreting statements in this specification and claims which include "comprising", features, other than those prefaced by this term in each statement, can also be present. Related terms such as "comprise" and "comprised" are to be interpreted in similar manner."

The term "tortuous" as used in this specification means marked by repeated turns and bends.

The term "serpentine" as used in this specification, means a winding path or line.

The term "temperature regulation" as used in this specification includes temperature adjustment whether it be by heating or cooling.

The term "glucose oxidase/catalase" as used in this specification, refers to the glucose oxidase system which is an enzyme highly specific for D-glucose producing hydrogen peroxide which can be followed by treatment with catalase to convert hydrogen peroxide to water. In many applications these two enzymatic activities are not separated. Glucose oxidase and catalase may be used together when hydrogen peroxide is to be avoided. This is generally the case in the present invention. However use of this term does not preclude use of the glucose oxidase enzyme only.

Brief Description of the Drawings The invention will now be dissented by way of example only and with reference to the drawings which:

Figure 1 shows a cross section of one embodiment of a panel of the invention;

Figure 2 shows a cross section of an alternative embodiment of a panel of the invention with the tubular channel in a collapsed configuration; Figure 3 shows a cross section of the panel of Figure 2, but with the tubular channel filled; Figure 4 shows a plan view of one possible arrangement of the tubular network within a panel of the invention;

Figure 5 shows a plan view of multiple panels in accordance with the invention, interlocked together;

Figure 6 shows a schematic side cross sectional view of one source of temperature regulation fluid in accordance with the invention; Figure 7 Shows a schematic experimental set, up testing a biochemical reaction pathway.

Detailed Description of the Invention

The present invention provides a novel approach to temperature regulation of an article or body. , Although the following description relates predominantly to regulating the temperature of a human (whether by heating or cooling) it will be understood by one skilled in the art that the invention and the method of its use can be employed for a wider range of purposes. This will include the temperature modification or maintenance of food stuffs and beverages for example, and also to the temperature regulation of animals.

The following describes one preferred form of a heat regulation system in accordance with the invention.

One preferred embodiment of the invention comprises a panel having therein a network capable of containing a temperature regulation fluid, and a temperature regulation fluid capable of acting as a heating source or temperature drain.

The Panel

The panel of invention may be of varying sizes. The panel may be large enough to cover or even wrap a human. Alternatively the panel may be sized to cover only a single body part. In one embodiment, panels of the invention may also be capable of interlocking with one another to provide a much larger blanket of modular interlocked panels. In such an embodiment, it is envisaged that the network for containing the temperature regulation fluid may also interconnect if desired, to allow the fluid to pass through a plurality of interlocked panels.

Each panel may be merely a simple fabric, membrane or support structure for the fluid network system. Alternatively the panel may be a more complex structure of layers including insulation and/ or waterproof layers for example. One preferred form of the invention involves three principle lightweight layers, with insulated, tubular and laminated water-proof layers. The device may also include an elastic fabric layer and sealed collapsible channel network. Specific materials which could be incorporated include: neoprene insulation, Aerogel™ insulation, synthetic foam, bubblewrap, elastomers, natural and synthetic fibres e.g. polypropylene - waterproofing such as hospital grade PVC, latex, synthetic film, nylon, Gortex™

Tubular Network

Essentially, any form of tubing or sealed channel which can contain water is possible. However, the nature of the tubing may depend upon the temperature regulation fluid which is employed. It should be invert to the fluid.

In preferred forms the tubing may comprise plastic piping such as PVC oxygen line, laminated public channels or alternatively metal foil lubing or other materials as known in the art.

In one embodiment the tubular network may comprise a single pathway arranged throughout a panel. It may or may not have an outlet capable of draining the fluid, depending upon whether or not the system is intended to be reused. In a preferred embodiment one or more outlets are included to allow efficient fluid drainage once used. The network system may also include partitioned regions that is, regions which may be

closed off to the fluid or opened up should it be desired. As mentioned previously the fluid network system may also be capable of being interlocked with the analogous system of another panel. The interlocking can be of many different forms as known by one skilled in the art. Screw fittings, modular click-fit fittings, for example are included.

With reference to the Figures, Figure 1, 2 and 3 show cross-section views of a panel of the invention.

Figure 1 is cross section of one embodiment of a panel. This panel has an inner side 1, closest to the body of a patient with a temperature to be regulated and an outer side 2, farthest away from the body.

In this preferred embodiment, both the inner 1 and outer 3 layers have a waterproof layer 3. It may be strictly waterproof or may be a breathable membrane material as is known in the art.

In this embodiment, closer to the outer side 2, there is an insulative layer 4. In this Figure one layer of insulative material is illustrated. However as would be envisaged by one skilled in the art, a plurality of layers of such material could be used. Varying degrees of thickness could also be employed. As would be appreciated, the less the number of layers of insulative or other materials, the more portable and packable the panel wiJl be. Thus all

• variations may have desirable properties and be suitable for different purposes. There are included within the scope of the invention. Figure 2 also illustrates a tubular network or channel 5 within which the temperature regulation fluid is contained within the panel.

Figure 2 is a cross section of an alternative embodiment of a panel of the invention. Again the inner layer 1 and outer layer 2 are illustrated and shown to have outer waterproof layers 3. This embodiment however has an elastic fabric layer 21 which can be for example a Lycra™ based material or similar where the material has significant elastic properties in ideally both directions. Figure 2 also illustrates the tubular network or channel 22 in a collapsed configuration. In some preferred embodiments of the invention, this channel 22 prior to use is collapsed, thereby reducing the volume of the panel. This can be performed by applying manual pressure to the panel to evacuate the network of any gas or fluid.

Alternatively, this could be achieved by vacuum for example and the panel vacuum packed before use. In a preferred form the panel of the invention is reusable. Thus it may be that it is initially sold or presented vacuum packed and after its first use the network is cleared manually, vacuum pumped or drained by gravity, as would be envisaged by one skilled in the art.

Figure 3 illustrates the panel of Figure 2 differing only in that the tubular channel or network 5 is not filled with the temperature regulation fluid 31 and the elastic fabric layer 21 is now stretched.

Figure 4 illustrates a plan view of one panel 41 of the invention. In this case, the tubular fluid network 42 is shown along with a fluid inlet 43 and three fluid outlets 44. IN the case where the panel of the inventions is disposable and will only be used once, no fluid outlet 44 is necessary although even then it is preferred (to facilitate fluid flow into the network). However in other embodiments there may be one or more outlets 33. As illustrated in

Figure 4 the fluid network 42 is regularly arranged within the panel 41 in a regular serpentine arrangement.

In this, Figure three outlets 44 are shown. These outlets or connection points 44 can be used to connect with other panels, or to connect to a pumping or other circulation device as might be expected in the art (discussed below). The use of multiple panels such as that of Figure 4, interlocked together, is illustrated in Figure 5. In this Figure two panels 41 are illustrated each with a tubular fluid network 42. They are interlocked together with one inlet 43 and one outlet 44. However also connected into the fluid network is a separate modular pump 51 capable of fitting with the standard inlets 43 and outlets 44 of the panels 41. The pump 51 assists with the circulation of the heat regulation fluid within the fluid network 42. Such a pump 51 may be used in the case of multiple panels or equally it may be used when there is only one panel employed.

In general when there is a single inlet and outlet, or with multiple inlets and outlets, it is preferred each inlet and outlet is valve controlled. This can be by manual valve control or in conjunction with a pressurising device that enables unidirectional or bidirectional flow depending on requirements or modular connections. Each valve can be connected to each other by in some fashion, preferably by twist lock mechanisms. In a preferred embodiment the valves have specialised adaptors which only permit the head of the injecting tubes to fit and unlock the valve, allowing one possible flow pathway (illustrated for example with the arrows indicating the direction of temperature regulating fluid circulation through the tubular network in Figures 4 and 5).

Temperature Regulation Fluid

The temperature regulation fluid has the general characteristic of being a source or drain of heat, in other words the fluid is hotter than or cooler than the body 'or article which is to have its temperature altered. In the simplest sense, this may mean hot or cold water may act as a temperature regulation fluid for example. However our preferred temperature regulation fluid is one which can be provided in a precursor form and activated to give rise to a heating or cooling effect. One embodiment uses a chemical pathway to achieve the effect. An alternative embodiment uses a biochemical pathway.

A number of constituents may be used to form the temperature regulation fluid. Our preference is to use those (for heating and for cooling) which will remain as a liquid once activated.

In terms of the chemical pathway, preferably the chemicals are non- toxic, biodegradable and easily handled. This allows easy flushing/removal afterwards. Thus we ensure we remain below the saturation point of the fluid. However, those that do crystallise or form a solid upon activation are also within the scope of the invention. It may or may not be possible to regenerate the crystallised fluid and re-use the network and panel(s) but this is also within the scope of the invention. There are a number of chemical combinations which can be used to give rise to a heating or cooling effect. These include: -Heating (exothermic): calcium chloride and water, Enthalpy of heat: - 82.6 kj mol ^"1 anhydrous magnesium sulphate and water. Solid reactions includes calcium chloride, water and glycerol. -Cooling (endo thermic): - ammonium nitrate and water. Enthalpy of heat: + 23 kj mol ^"1

However there can be many more as would be known by those skilled in the art. See for example I. Martinez, "Termodinάmica bάsicaj ap/icada", Ed. Dossat, 1992, ISBN 84-237-0810- 1.

Antifreeze may also be included to allow operation at sub-zero temperatures. Propylene glycol and other non-toxic varieties e.g. Noburst, RV antifreeze, may be added to provide sub-zero reactions.

A number of biochemical and bioactive constituents may be used to form the temperature regulation fluid. Our preference is to use those (for heating or for cooling) which will remain liquid once activated. Preferably the bioactive reagents are non- toxic, biodegradable and easily handled. This allows easy flushing/removal afterwards. Thus we ensure we remain below the saturation point of the fluid. It may or may not be possible to regenerate the bioreactive fluid and re-use the network and panel(s) but this is also within the scope of the invention.

We are particularly interested in enzyme catalysed reactions although others include bacterial growth. In terms of exothermic reactions, those which release more than lOOkJmol ^"1 are particularly of interest although those which release less could also have some limited application. Table 1 is derived from Goldberg's (2004) "Thermodynamics of Enzyme-Catalysed Reactions — a Database for Quantitative Biochemistry". It lists 13 reactions (of 263 detailed) which release more than lOOkJmol ^"1

Table 1

Typical biochemical and bioreactive combinations include all of the above. Our preferred combinations include (but are not restricted to)

Heating (exothermic):

• Glucose Oxidase/Catalase oxidising Glucose/Dextrose buffer solution. Cooling (endo thermic):

• Nitrogenase in the presence of MgATP and sodium dithionite in imidazole buffer. (Heat enthalpy = +36 kj mol ^"1 .) See Throneley R.N.F et el. λ transient- kinetic study of the nitrogenise of Klebsiella pneumoniae by stoppedfl- ow calorimetry. BiochemJ. (1989) 264, 657-661

It is desirable that the temperature regulation device for use on surfaces allows relatively rapid warming or cooling of the inner surface, and then maintains a temporary but constant temperature throughout the device for the duration of the aqueous chemical or biochemical reagent reactions.

The preferred system of the invention relies upon external injection of the temperature regulation fluid (or its precursors) into the fluid network. This input of fluid can come from many difference sources. As an example Figure 6 illustrates a capsule 60 capable of interlocking with the fluid system. This is preferably via connection or interlocking of the nozzle of the capsule that can attach and lock onto a valve similar to inlet 43 of Figures 4 and 5, allowing for fluid in capsule to transfer the contents without leakage or spillage. The capsule 60 contains a small sealed sachet or reservoir 61 of preferably aqueous solution surrounded by a flexible tubular container 62 enclosing solid or liquid chemical or biochemical reagents.

The operating mechanism of the device requites the rupture of the sachet (typically by hand) and mixing of the reagents within the tube before pressure induced squeeze injection

through the specialised nozzle into the valve. However it is possible that the cartridge or other container holding these reagents is connected before activation or even could be provided in place in the network prior to use. The chemicals can be permitted to flow through the miniature tubular network such as the flow direction as shown in Figures 4 or 5 to distribute heat evenly throughout the device. Once the chemicals reach the ends of the valves, pressure is necessary to close the valve of that outlet point and prevent die fluid leaking. Pressure release can be achieved by a manual lock on each valve.

Preferably the invention is designed for immediate and temporary generation of heat as required in the situation and not exceeds safe exposure levels where adverse temperatures can inflict injury. The insulation layer should provide enough thermal resistance that allows the thermal conduction to be minimised externally and heat distribution only towards the inner layer. Once the reaction of the aqueous chemicals reach equilibrium, the reaction will remain in liquid state that can be drained from the tubular system and the device can be reusable thereafter. The different chemical and biochemical precursors can be obtained separately, as a capsule for example and preferably will be labelled with what temperature effect can be gained by its use.

The above describes a preferred embodiment of the present invention and indicates some optional modifications. Other useful modifications can be made without departing from the scope of the invention as has been broadly defined above. One embodiment would include the use of sensors to monitor the temperature flow within the network and on the inner side of the device, and that creating the device in multiple forms of which that can be wrapped, worn and encased a surface, object or persons using the principles of the device. Other modifications include automated or mechanical injecting or pumping systems

attached at the valve (shown in Figure 5) of pre-mixed aqueous chemicals or biochemical reagents at the appropriate thermo-regulating temperature as required by the feedback sensors.

It should be noted that the invention can have a number of different embodiments which are included within the scope of the claimed invention. These include (but are not limited to): a single panel with single inlet and outlet; a panel with single or multiple inlet(s) and outlet(s) - panels which may be flat or shaped (such as tents, gloves, hoods, chilly bins.

Potential applications of the invention are widespread, and include (but are not restricted to):

• outdoor market for the consumer — clothing, garments, hoods, gloves, safely devices (e.g. for hypothermia); Consumer equipment — tenting, sleeping bags defrosting, chilly bags for food;

• industrial safety (e.g. for people working under extreme conditions);

• emergency services (e.g. in ambulances);

• hospitals (e.g. cooling for stroke patients — in the form of a collar or a hood, full body blanket for example, or to heat intravenous infusion liquid bags)

• defence and military services - for army, navy and air force personnel, humanitarian aid.

One principal advantage is that no external power supply (battery or mains) is necessarily required.

EXPERIMENTAL

The following experiments have been performed to verify the reaction protocols:

Chemical Reaction Pathways

Calcium Chloride and Water reaction, performed with 3Og of granulised GaCl ₂ and 60ml of H ₂ O reacted under atmospheric temperatures of 18.5°C and liquid temperature of 18.2°C. The reaction produced a heat increase to a maximum of 44.6°C within four minutes before receding to 41.8°C at 15 minutes under a mildly insulated environment.

Calcium Chloride and Water reaction, performed with 13g of granuHsed CaCl ₂ and 60ml of H ₂ O reacted under atmospheric temperatures of 18.2 ⁰ C and Hquid temperature of 17.2°C. The reaction produced a heat increase to a maximum of 38.9°C within five minutes before receding to 32.8 ⁰ C at 15 minutes under a mildly insulated environment

Anhydrous Magnesium Sulphate and Water reaction, performed with 25g of powderised crystalline MgSO ₄ and 60ml of H ₂ O reacted under atmospheric temperatures of 17.5°C and liquid temperature of 16.2°C. The reaction produced a heat increase to a maximum of 26.8°C within five minutes before receding to 23.4 ⁰ C at 15 minutes under a mildly insulated environment

Ammonium Nitrate and Water reaction, performed with 11.5g of granulised NH ₄ Cl and 60ml of H ₂ O reacted under atmospheric temperatures of 18.9 ⁰ C and liquid temperature of 18.1 ⁰ C. The reaction produced a heat decrease to a minimum of 6.2°C within three minutes before increasing to 9.6°C at 15 minutes under a mildly insulated environment

Ammonium Nitrate and Water reaction, performed with 3Og of granulised NH ₄ Cl and 60ml of H ₂ O reacted under atmospheric temperatures of 18.5°C and liquid temperature of 17.9°C. The reaction produced a heat decrease to a minimum of -4.1 ⁰ C within three minutes before receding to 0.4 ⁰ C at 15 minutes under a mildly insulated environment.

Biochemical Pathway

Figure 7 shows our experimental set up for investigation of the β-D-glucose-glucose oxidase system. A 300ml plastic cylinder 71 is employed as the reaction vessel. Air is pumped in from an air pump 72 to a diffuser 73 below the level of the reaction solution 74. pH, temperature, pressure and dissolved oxygen, probes are housed with the housing 75.

The solution is stirred by a magnetic stirring rod 76, powered by a magnetic stirrer 77. A phosphate buffer system was employed to alter the pH of the system.

First, appropriate amount of potassium hydrogen phosphate, potassium dihydrogen phosphate and glucose powder are weighted and mixed in about 300 ml of cold tap water. Then, the solution is transferred to a 300ml plastic measuring cylinder.

Before the experiment is started, the air pump and magnetic stirrer are turned on for 5-10 minutes to allow thorough mixing and aeration. As soon as the enzyme is added, logging of the multi-parameter In-Situ Inc Troll 9500 probe (to measure pH, redox potential, dissolved oxygen, temperature and pressure) and the picologger PC-08 to measure temperature are started.

The experiment was finished when there was no significant increase of temperature of the solution.

ICH ₂ PO ₄ 22.98g

K ₂ HPO ₄ 7.53g

Glucose 60.02g

Cold tap water 300ml

Magnetic Stirrer Speed 7

Flow rate —

Air pump low

Enzyme (glucose oxidase

3ml + catalase (OxyGO 1500)

End = Time=0 Time=2000s

5555s

Temperature ( °C) 18.49 22.07 24.71

^" pH 5^69 5A4 4.32

Dissolved oxygen

97.77 40.27 46.55

DO ( ⁰ A)

Note: from Time=0 to Time=2000s, Temperature increase is linear whereas DO level is constant. Calculations Enzymatic reaction: β - D - glucose + O ₂ + H ₂ O ^" ^{∞se oxidase} > £> - gluconic acid + H ₂ O ₂ (-125 kj mol ⁴ )

2H ₂ O ₂ ^cala!ase > 2H ₂ O + O ₂ (-100 kj mol ^"1 )

Reaction rate of enzyme:

OxyGO enzyme at 35°C pH 5.1 is rated at >1500 Titrimetric Unit per ml 1 Titrimetric unit will oxidize 3.0 mg glucose to gluconic acid in 15 minutes, i.e. 0.2 mg glucose oxidized per minute for each titrimetric unit

Therefore, 0.2 mg min ^'1 í 18Og mol ^"1 — 1.1 x 10 ^"6 mol glucose oxidised per itninute per titrimetric unit

ImI of enzyme contains 1500 unit, i.e. 1.1 x 10 ^"6 mol min ^"1 x 1500 unit = 0.00165 mol of glucose oxidised per min per ml of enzyme

Glucose C ₆ H ₁₂ O ₆ - M ₁ = 180 g mol ⁴

Heat of reaction: Breakdown of glucose into gluconic acid and hydrogen peroxide yield -125kJ mol ^"1 while complete breakdown of glucose and its by-product hydrogen peroxide yield -223 kj mol ^"1 when oxygen is used as electron acceptor. As a reference, standard heat of combustion of glucose is about -280OkJ mol ^"1

Reaction rate needed to increase water by 1 ⁰ C:

Heat capacity for IL of water is 4186 J ⁰ C ^"1

Assuming 20OkJ mol ^"1 generated from the enzymatic reaction,

4186 J ⁰ C ^"1 í 20OkJ mol ^"1 = 0.021 mol of glucose needed to be oxidised to increase IL of water for 1°C. Therefore, 0.021 mol ⁰ C ^"1 x 180 g mol ^"1 = 3.78 g glucose oxidised to increase IL of water for 1°C.

Glucose oxidase requires oxygen as an electron acceptor to be present for the reaction to work. Therefore

oxygen consumption from air consisting of 20% oxygen is included with the reaction.

Amount of enzyme needed:

0.021 rnol ⁰ C ^"1 í 0.00165 mol/min ml = 12.7 ml enzyme needed to oxidise glucose to generate enough heat to raise IL of water by 1 ⁰ C every minute

Maximum temperature increase for complete glucose oxidation: At 20 ⁰ C, saturated d-glucose solution can reach about 50% by weight.

Hence, assuming 20% glucose solution is used, that would mean 200g L ^"

Resulting 200g í 3.78g ⁰ C ^"1 = 52.9 ⁰ C temperature increase in IL of solution if all available glucose is completely oxidised.

Experimental Conclusions

The experiments above demonstrate the validity of using small volumes of mixed precursors to form liquid chemical or biochemical reagents that regulate heat within set temperature ranges. The application of endothermic or exothermic reagents in small volumes can provide controlled warmth or cooling as circulated within a close-loop flow network as outlined in the invention.

Where in the foregoing description reference has been made to elements or integers having known equivalents, then such equivalents are included as if they were individually set forth.

Although the invention has been described by way of example and with reference to particular embodiments, it is to be understood that modifications and/ or improvements may be made without departing from the scope or spirit of the invention.

In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognise that the invention is, also thereby described in terms of any individual member or subgroup of members of the Markush group