Aerosol devices and methods for inhaling a substance and uses thereof

Abstract

Devices, cartridges, and method are described herein for emulating smoking wherein a device generates an aerosol for inhalation by a subject by heating a viscous material that can have a tactile response in the mouth or respiratory tract, while reducing Hoffman analytes and mutagenic compounds delivered to the user as compared to a common tobacco cigarette.

Claims

1. A device for aerosolizing a material comprising: a body including a heater; a vaporizable material contained in a cartridge; and a lid sealed upon the cartridge, wherein the lid comprises apertures or vents; wherein the vaporizable material comprises propylene glycol, glycerin, and a tobacco material comprising pieces of tobacco; wherein the device is configured to generate an aerosol by heating the vaporizable material to a target temperature at which the vaporizable material forms an aerosol substantially free from at least one Hoffmann analyte; wherein the propylene glycol and glycerin are present in an amount to produce a visible aerosol; and wherein the apertures or vents of the lid allow an exit of the aerosol generated from heating the vaporizable material.

2. The device of claim 1, wherein the vaporizable material is a fluidic or viscous vaporizable material.

3. The device of claim 1, wherein the cartridge comprises a flange.

4. The device of claim 3, wherein the lid is sealed upon the flange.

5. The device of claim 1, wherein the lid is metallic.

6. The device of claim 1, wherein the lid comprises a heat-sealable film or aluminum.

7. The device of claim 1, wherein the at least one Hoffmann analyte is selected from the group consisting of: ammonia, aminonaphthalenes, benzopyrene, formaldehyde, acetaldehyde, acetone, methyl ethyl ketone, butyraldehyde, hydrogen cyanide, nitrous oxides, tobacco-specific nitrosamines (TSNAs), pyridine, quinolone, hydroquinone, phenol, cresols, tar, carbon monoxide, 1,3-butadiene, isoprene, acrylonitrile, benzene, toluene, and styrene.

8. The device of claim 1, wherein the pieces of tobacco are less than 2 mm in diameter.

9. The device of claim 1, wherein the target temperature is 100° C. to 200° C.

10. The device of claim 1, wherein the aerosol contains at least 70% less Hoffman analytes than a common tobacco cigarette.

11. The device of claim 1, wherein the glycerin is present in an amount to produce a visible vapor when the aerosol is exhaled by a user.

12. A cartridge for use in a vaporizer device comprising an oven chamber configured for the cartridge to be inserted therein, the cartridge comprising: a shell containing a vaporizable material comprising propylene glycol, glycerin, and a tobacco material comprising pieces of tobacco; and a lid sealed upon the shell, wherein the lid comprises a plurality of apertures or vents; wherein the plurality of apertures or vents of the lid are configured to allow exit of an aerosol generated from heating the vaporizable material within the cartridge to a target temperature by a heater of the vaporizer device; and wherein the propylene glycol and glycerin are present in an amount to produce a visible aerosol.

13. The cartridge of claim 12, wherein the shell comprises a flange and the lid is sealed upon the flange.

14. The cartridge of claim 12, wherein the pieces of tobacco are less than 2 mm in diameter.

15. The cartridge of claim 12, wherein the target temperature is 100° C. to 200° C.

16. An aerosol-generating device comprising: a body comprising a heater and an oven chamber; a mouthpiece connected to the body such that the mouthpiece is configured to be hinged open to provide access to the oven chamber; and a cartridge configured to be inserted into the oven chamber, the cartridge comprising: a shell containing a vaporizable material comprising propylene glycol, glycerin, and a tobacco material comprising pieces of tobacco, wherein the heater is configured to heat the vaporizable material within the cartridge within the oven chamber to a target temperature; and a lid sealed upon the shell, the lid comprising a plurality of apertures or vents configured to allow exit from the cartridge of an aerosol generated by heating the vaporizable material within the cartridge; wherein the propylene glycol and glycerin are present in an amount to produce a visible aerosol.

17. The device of claim 16, wherein the shell comprises a flange and the lid is sealed upon the flange.

18. The device of claim 16, wherein the pieces of tobacco are less than 2 mm in diameter.

19. The device of claim 16, wherein the target temperature is 100° C. to 200° C.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are used, and the accompanying drawings of which:

(2) FIG. 1 illustrates a device of the invention comprising a mouthpiece and a body having a heater, an oven chamber, a fuel tank, and an igniter with controller for maintaining the operating temperature;

(3) FIG. 2 illustrates a device of the invention comprising a fuel tank that is meant to be refillable, and has a port for that purpose;

(4) FIG. 3 illustrates a device of the invention comprising a heater assembly, which can be powered by any combustible fuel, and a series of bimetallic objects to control the flow of the combustible fuel to heater assembly;

(5) FIG. 4 demonstrates a device wherein fuel is supplied to the tank through a filling valve and compressed liquid fuel can be drawn for use by a wick;

(6) FIG. 5 illustrates a device of the invention comprising a single elastomeric stopper which prohibits the movement of gas and wherein the flow of gaseous fuel is limited by a compressed foam flow restrictor and may only leave through a valve orifice;

(7) FIG. 6 demonstrates a device in which the plastic body exhaust apertures are located above the heater exhaust apertures and the escaping gas must pass along the heater body and exchange even more of its heat, thereby improving efficiency of the device;

(8) FIG. 7 illustrates a device of the invention with a hinged mouthpiece;

(9) FIG. 8A demonstrates a device wherein the user can slide a strip of material towards the mouthpiece end of the device to turn it on, and then slide the strip back towards the fill port to turn it off;

(10) FIG. 8B illustrates the device of FIG. 8A from a different perspective;

(11) FIG. 9 illustrates a cartridge that can contains a moist vaporizable product for use with a device capable of vaporizing the product comprising a shell, a lid, and a flange for adhering the lid to the shell;

(12) FIG. 10 shows a basic heat-sealable film with PET base layer and APET heat-sealing layer;

(13) FIG. 11 shows a composite film with a PET base layer and APET heat-sealing layer, but with additional metal layer and metal adhesion layer;

(14) FIG. 12 illustrates a cartridge of the invention containing a moist vaporizable product and comprising apertures or vents to allow the content within the cartridge to have access to the environment;

(15) FIGS. 13A-B illustrate cartridges with two portions that can fit together and may have apertures or vents for releasing a vapor from the contents of the cartridges;

(16) FIG. 14 demonstrates an exemplary method of use of a device of the invention that can emulate smoking by still providing many of the desirable effects of smoking required by a user while reducing Hoffman analyte intake;

(17) FIG. 15 demonstrates an exemplary method of use of a device of the invention wherein the user has received inhaled tobacco substances from a device of the invention in a manner that has reduced the Hoffman analyte intake of the user by at least 70% and the user may exhale a visible vapor from the vapor-forming medium to provide a similar visual aide to that of exhaled smoke in the act of smoking; and

(18) FIG. 16 shows the results of a bacterial mutagenesis test (Ames assay) indicating that particulate generated by smoking the device of the present invention is non-mutagenic.

DETAILED DESCRIPTION OF THE INVENTION

(19) The invention described herein has a wide range of applications for inhalation of an active substance as will be appreciated by persons of skill in the art upon reviewing the disclosure. For example, the devices, cartridges, systems, kits and methods could be used, for example, to inhale a tobacco product through the mouth or nose. The devices, cartridge, systems, kits, and methods could also be used to reduce the Hoffmann analytes provided to user by inhaling a tobacco product, as compared to smoking or burning of tobacco. Additionally, the devices, systems, kits and methods could be used, for example, to inhale any substance, such as a botanical, pharmaceutical, nutraceutical, or any other substance providing a benefit or sensation to an end user.

(20) I. Aerosol Generating Device

(21) An exemplary device of the invention is illustrated in FIG. 1. The device 100 is capable of creating temperatures high enough to aerosolize a product contained within the device 100. A device of the invention can comprise a mouthpiece 110 and a body 120 having a heater 122, an oven chamber 124, a fuel tank 126, and an igniter with controller for maintaining the operating temperature. Examples of operating temperature regulators of a device include a bimetallic actuator. Alternatively, a paraffin-filled component that expands and contracts to modulate butane flow could be employed. Alternatively, a system could be employed to measure the current temperature, for example, with a thermocouple sensor and compare it to a prescribed temperature, for example, with a micro-controller, and by controlling an electromechanical valve, for example, servo or solenoid valve. A user-selected temperature, as described above, the selected temperature could be used as an input to this system.

(22) A device can be constructed without an active regulating element. This can result in reduced complexity and in lowering the overall cost of manufacture of the device. For example, the flow of fuel to the heater 122 can be set at a low level. In use, the temperature inside the oven chamber 124 increases until an equilibrium point where additional heat introduced equals the heat lost to the environment. Heat is lost by conduction through the body of the device 100, and with the vapor delivered to the user. This equilibrium point determines the operating temperature of the device 100. By changing the fuel flow rate, size and material of the burner, and other factors, the system can be calibrated to provide a fairly stable desired operating temperature.

(23) A piezo-electric igniter can be used. Other igniters can be used, such as, a flint starter or battery-powered resistive coil.

(24) As illustrated in FIG. 2, a device 200 of the invention can also comprise a fuel tank 226 that is meant to be refillable, and has a port 230 for that purpose. The tank 226 can be disposable once its fuel is exhausted. A release mechanism such as a pin or cam can be employed allowing the user to quickly remove the depleted tank 226 and replace it with a full tank. A replaceable tank might include additional parts of the device such as the igniter and heater. A liquid fuel is the preferable fuel source, however the liquid fuel can be complimented or replaced by a battery-powered electric heater or other compact heat source. The tank 126 can be filled by a fill valve mechanism 128 as shown in FIG. 1 with a specialized fuel source or a standard commercial fuel source.

(25) The fuel tank can hold enough fuel for repeated uses of the device. The device can be used for up to 10, 20, 30, 40, 50, or 60 uses. In some embodiments, the device can be used for more than 60 uses. The device can also be used for up to 1, 2, 3, 4, 5, 6, 7, or 8 hours of continuous or non-continuous use. A cartridge for use with the device can be disposed after each use or used for multiple uses. The long lasting use of a device of the invention provides the user the advantage of not having to service the device or refill the fuel tank on a regular basis. The advantage of multiple uses can be preferably obtained by using a larger sized fuel tank and/or the use of butane as a fuel, which can produce the necessary temperatures to use the device in an efficient manner.

(26) Typically, the operating temperatures of the device are no more than 200° C. Often the temperature required to aerosolize a product is between about 100 to 200° C. In some embodiments, the temperature required to aerosolize a product is about 150° C. Once the product within the device has been aerosolized, the aerosolized product is provided to a user through a mouthpiece. In many cases, a device of the invention is designed to emulate a smoking device, such as a cigarette, a pipe or a cigar holder.

(27) In FIG. 3, the device 300 comprises a heater assembly 322, which can be powered by any combustible fuel, and a series of bimetallic objects 332 to control the flow of the combustible fuel to heater assembly 322. Examples of combustible fuel include, but are not limited to, propane, butane, methane, and ethanol. As the device 300 heats up, or a portion of the device 300 heats up, the bimetallic objects 332 change their shape (for example, from flat to concave or convex) in order to regulate the amount of fuel entering the heater assembly 322. This can occur by variety of mechanisms, including pushing a rod 334 (pushrod 334 as referred to herein) against a variable flow valve 336 as shown in FIG. 3.

(28) A bimetallic object can be used to convert a temperature change into mechanical displacement. The object comprises two different metals which expand at different rates as they are heated, for example, steel and copper. The object can be an alloy or two metals that have been secured together. The bimetallic objects can be of any planar shape, such as a square, rectangle, or strip. Preferably, the bimetallic objects are bimetallic discs. The different expansions force the flat object to bend one way if heated, and to bend in the opposite direction if cooled. The bimetallic objects can be bimetallic discs such as the commercially available Truflex P675/700 discs.

(29) The mechanical displacement of a bimetallic object is much larger than the small lengthways expansion in either of the two metals. This effect is used in a range of mechanical and electrical devices. In most of the example devices of the invention, the bimetallic object is used in the planar form. In others, it can be wrapped into a coil for compactness.

(30) Nickel titanium (NiTi) is a shape memory alloy also commonly referred as Nitinol. Above its transformation temperature, Nitinol is superelastic and able to withstand a large amount of deformation when a load is applied and return to its original shape when the load is removed. Below its transformation temperature, it displays the shape memory effect. When it is deformed it will remain in that shape until heated above its transformation temperature, at which time it will return to its original shape. Nitinol is typically composed of approximately 55% Nickel by weight. Making small changes in the composition can change the transition temperature of the alloy significantly. These unique properties and tailorability of Nitinol to be used in a wide range of temperatures makes it suitable as substitute for the bimetallic object of the present invention. As will be appreciated by those skilled in the art other shape memory alloys can be used without departing from the scope of the invention.

(31) The use of alternately-stacked bimetallic discs in a device of the invention is not only a simple and cheap solution for fitting a thermal regulation scheme into a very small space, but also has some key advantages over other methods of thermal regulation. The discs are a modular solution, meaning that different numbers of discs can be used to tune the temperature sensitivity of a device. Using multiple discs instead of one disc allows longer overall travel for a given (small) diameter of disk. Thinner or thicker discs can also be used for the same purpose, or to add additional ability to exert force. Since the doming shape of the discs is particularly strong, the varying pressure of the fuel will have minimal effect on the regulation temperature. Also, since the bimetallic stack is a non-discrete, continuously acting system, the device can have a dampened regulation effect by using the roughened-seat design mentioned above, making the device much less likely to self-extinguish. The discs also respond to a temperature at a point nearest the oven of the device so that the oven is held at the most constant temperature possible.

(32) FIG. 4 demonstrates a detailed example of some components of a device 400 of the invention. In FIG. 4, fuel is supplied to the tank 426 through a filling valve 428 and compressed liquid fuel can be drawn for use by a wick 438. In the example in FIG. 5, the flow of gaseous fuel is then limited by a compressed foam flow restrictor 540 and may only leave through a valve orifice 542. There is a single elastomeric stopper 544 which prohibits the movement of gas. The use of a single stopper 544 for all gas flow regulation can increase the simplicity and reliability of the system significantly. The stopper 544 is also referred to herein as a variable flow valve 544. Also included can be a simple but separate means for regulating butane flow with temperature, dispensing an extremely low flow of gas to keep a portion of catalyst above its light-off temperature, and allowing the user to turn on and off the device 500. The variable flow valve 544 can allow all three of these needs to be handled by a single valve.

(33) The stopper 544 can be connected to a rigid jetting assembly terminating with an electrically insulating component 546. The jet assembly is normally held in a position that allows gas to exit the valve orifice 542 and to enter the jet assembly by a relatively low spring constant biasing spring 548. Gas is limited to only entering the jet assembly by a sliding seal 550. Alternately, a flexible diaphragm could be used. The user is able to defeat this normal flow of gas by sliding an activating slider so that the jetting assembly is held down such that the stopper 544 seals the valve orifice 542; this is the OFF state of the device 500. When the user allows the normal gas flow state by sliding an activating slider to the ON position a piezo-igniter is depressed so that a spark is generated between the jet rosette 552 and the oven heater 522, thereby igniting the flowing gas. As the oven heater 522 begins to reach its operating temperature a series of alternately stacked bimetal discs 532 change shape (transitioning from flat to domed) and act on a pushrod component 534 which in turn presses the jet assembly so that the stopper 544 limits or ceases the flow of gas.

(34) By using a bimetallic disc design, a device of the invention may be tuned to a specified temperature regulating range by simply changing the distance between the backstop of the discs and the valve seat. In FIGS. 4-5, by threading the oven heater component 422, 522 into the plastic body 420, 520 of the device 400, 500, the operating temperature can be changed by simply twisting the oven component 422, 522 externally using a tool that mates with the oven. The oven 424 can also be designed to be moved manually by a user. Features can also be incorporated onto the oven 424 for twisting the component.

(35) In FIG. 5, the pushrod component 534 can serve multiple functions. The pushrod 534 can act to transfer longitudinal motion of the bimetallic discs 532 to the jet assembly, which in turn transfers that motion to the valve stopper 544. The pushrod 534 can also hold the catalyst in an easily assembled manner, such as the catalyst being simply wound around the pushrod 534. The pushrod 534 designates a fixed space between the jet rosette 552 and the catalyst, so that initial combustion can easily occur. In an example, the pushrod 534 has roughly the shape of a dumbbell, with two flat, circular surfaces at opposing ends which are used to contact the bimetallic discs 532 at the top, and the insulating component 546 at the bottom. The lower end of the pushrod 534 has large cutouts which allow for gas flow to pass through and initial combustion to take place.

(36) Many devices of the invention use a temperature regulation scheme in that the temperature regulator (bimetallic discs) are located in close proximity to the area where temperature is most critical (at the oven). Related art has typically located the temperature-sensitive component at the flow valve, which can be easily influenced by the cool temperature of expanding fuel gas and has minimally intimate contact with the vaporizing chamber. Examples of related devices and methods are described in U.S. patent application Ser. No. 11/485,168, U.S. Pat. Nos. 4,819,665, 4,793,365, 5,027,836 and PCT Application WO 2006/082571. The regulation scheme of a device of the invention may be tuned to a specific temperature by a simple twist of the oven.

(37) In the exemplary devices of FIGS. 4-5, air enters the jet assembly through inlet apertures 454, 554 and mixes with the butane flow path at the venturi 556. Exhaust gas exits through outlet ports 458.

(38) The user is prevented from touching the hot internal elements by surrounding insulating features. A device of the invention can include insulation for keeping the user from contacting the necessarily hot portion of the device. While greater thermal insulating ability is preferable so that the device performs with the best efficiency possible, an important aspect for the user is to perceive a relatively cool surface temperature. Various strategies can be employed to address the perception of the user regarding the temperature of the device. The device may be wrapped in a thermal insulating material that has enough durability for external use. Materials for this purpose have low thermal conductivity and low thermal capacity (specific heat). The combination of these properties can allow little heat to be transferred to the fingers of the user. Examples of materials with low thermal conductivity and capacity include some polymers and ceramics. A separate strategy is to use standoff features that keep the user from touching the higher temperature area directly. This can also minimize the contact area of the user's fingers and the device to additionally reduce perceived heat. The thermal conductivity and specific heat of the standoff features should be as low as possible.

(39) A heater of a device of the invention can comprise a conductive shell and a catalyst, wherein the shell may be of one or more material formed by welding or pressing together. The catalyst within the heater can be chosen to provide an efficient flameless combustion of the fuel. In some cases, in order to provide a visual clue to the user, the catalyst or heater can emit a color, such as red, when the heater is heating to indicate that the device is activated.

(40) In some cases, the heater can exhaust directly to the surrounding atmosphere through a side aperture. However, as demonstrated in FIG. 1 a device 100 of the invention preferably incorporates a series of smaller apertures 158 around the heater assembly 122 which better transfer heat from the catalyzed gas to the oven 124. Also, as shown in FIG. 6, since the plastic body 620 exhaust apertures 662 are located above the heater exhaust apertures the escaping gas must pass along the heater body and exchange even more of its heat, improving efficiency of the device 600. The use of two barriers (heater wall and body wall), in conjunction with staggering the vent apertures, has the added benefit of improving wind-resistance (for example, ambient wind is less likely to disturb the internal flow of gases, or cool the catalyst to the point that it extinguishes.) The specific geometry of the exhaust path allows for these benefits without inhibiting the initial combustion of gas necessary to initiate catalytic activity. The gas flows smoothly through a continually expanding exhaust area, without torturous turns that could cause the initial burst of gas to extinguish itself.

(41) In the field of combustion catalysts, the light-off temperature is often used to describe the minimum temperature at which the catalyst must be maintained in order to catalyze the exothermic reaction of fuel and oxidant. Only a portion of the catalyst must remain at this temperature to prevent the reaction from extinguishing altogether. The targeted operating temperature of a heater of a device of the invention is close to the light-off temperature of most catalysts, and can make maintaining the catalyst difficult to achieve. The target operating of temperature of the heater can be 180° C. Examples of types of catalysts used in a device of the invention include, but are not limited to, platinum, palladium, and rhodium. The catalyst light-off temperature of a catalyst for use with the invention may be from about 100 to 200° C.

(42) To address the fine difference in temperature of the heater as compared to the light-off temperature a small trickle of gas can flow over the catalyst and/or the catalyst can be shielded from external factors, such as wind. A device of the invention can include a protected exhaust path, meaning that exhaust does not directly exit to the outside air but instead travels along a convoluted path so that the catalyst is difficult to extinguish by wind.

(43) A concern for the reliability of the device of the invention is to maintain catalyst operation at the low target temperatures of the device. A discrete on/off valve alone can have difficulty in this regard because the cycle time between butane bursts can sometimes allow the catalyst to cool to too low of a temperature, and a rapid burst of expanding butane can actually serve to extinguish the catalyst since the butane temperature will be cool. A simple solution that can be incorporated into a device of the invention is to slightly roughen the valve seat surface, or to use a textured stopper surface so that the device can achieve a low-flow of butane just before it closes the flow completely during regulation. This is similar in operation to a needle valve, but much cheaper and easier to implement. A needle valve can also be used in a device of the invention to regulate fuel flow. Some prior art uses a thermal mass so that the light-off temperature can be maintained between regulation intervals. When gas flow resumes between regulation intervals only the area in contact with the thermal mass will initially catalyze the gas, exhausting a reasonable amount of unused fuel. A device of the invention does not require such a thermal mass since the valve seat can act as an analog valve and allow the device to dampen regulation intervals and intensity. A device of the invention can trickle an amount of butane needed to keep the catalyst above light-off temperature, in other words, not overwhelming the catalyst.

(44) As demonstrated in FIG. 3, a device 300 of the invention can be used aerosolize a material contained within a cartridge 370 that can be inserted into the oven chamber 324 of the device 300. With the spark of an igniter (immediately following the start of gas flow), the gas ignites and heat starts conducting throughout the heater assembly 322. Heat transfers to the cartridge 370 by conduction, convection, and/or radiation. The cartridge 370 can be shaped to fill the chamber 324 so as to maximize surface contact for thermal conduction. As the cartridge 370 heats, vapor generates within the cartridge 370 and in the space immediately above it. When a user draws on the device 300, fresh air enters through an air inlet, mixes with the vapor, and the mixture is delivered to the user via the inhalation passage. The air inlet or inlets can be directed downward, so as to improve the extraction of vapor from the cartridge 370. The air inlet can also be directed along a diagonal through the mouthpiece 310, or laterally through the case itself, above the cartridge 370. The air inlet or inlets can have a diameter and direction sized to admit ambient air into the chamber 324 to stir up vapor while not affecting the operating temperature. The air inlet apertures can also regulate the velocity of ambient air entering and mixing with the vapor generated in the oven chamber 424 at either a set rate or a rate chosen by the user. For example, the rate of air entering the device 300 can provide a perception to the user as if the smoke is drawn through a cigarette. Once the cartridge 370 is used, the device 300 can be turned off and the cartridge 370 is removed by opening the oven chamber 324 of the device 300. The cartridge 370 can be removed by hand or by a mechanism that can quickly and easily remove the cartridge 370. This mechanism can include the use of a pin or slide part to eject the cartridge 370 as another part of the device 300 is moved or removed. The removal mechanism could also involve introduction of a foreign object.

(45) A device as shown in FIG. 7 can incorporate a mouthpiece 710 that is connected to the body 720 of the device 700. The mouthpiece 710 can be a hinged component. The mouthpiece 710 can also be manufactured such that it securely fits into place when it is closed onto the device body 720. The device 700 can be intended for use with a cartridge 770 of the invention as is described herein. A cartridge 770 can be inserted into the oven chamber 724 of a device 700 of the invention. As demonstrated in FIG. 7, the mouthpiece 710 can be removed, or hinged open, to provide access to the oven chamber 724 and wherein a cartridge 770 containing a material to be aerosolized can be inserted. The mouthpiece 710 of the device 700 can also be removable or removable and configured for one time use. In this way, multiple users could use the same device 700 but have interchangeable mouthpieces 710. Or if a mouthpiece 710 was soiled, another mouthpiece 710 could easily replace it to prevent having to dispose of the entire device 700. When the device 700 incorporates a mouthpiece 710 that is connected to the body of the device, such as a hinged mouthpiece 710, the device 700 can be operated by a single hand of a user.

(46) A mouthpiece can be made of a high-temperature and food-safe material such as ceramic, glass, or various high-temperature plastics such as polyimide thermoplastic resins, polyetherimide (PEI) resin (brand name Ultem®). Design is simplified by use of high temperature materials, but standard plastics or wood, could also be used with the addition of an insulating component that prevents excessive heat from reaching the user, e.g., the user's lips. Additionally, a mouthpiece can be extended in length, such that the temperature at the mouth of the user is substantially lower than the end of the mouthpiece close to the source of heat.

(47) The mouthpiece 710 of a device 700 of the invention, such as the example in FIG. 7 can include a puncturer 712 for piercing a sealed cartridge containing a material for use with the device 700. For example, a hinged mouthpiece 710 can be opened, a cartridge 770 inserted into the device 700, and the mouthpiece 710 can then be closed, which punctures the cartridge 770 for use with the device 710. The puncturer 712 can be any object as would be obvious to one skilled in the art. Preferably the puncturer 712 is a small protuberance 712 that is molded into a mouthpiece 710 and which terminates in a point or edge 714 for puncturing the cartridge 770 when a small amount of force is applied.

(48) Some related art devices require two hands for ignition, leading to a clumsy user experience. Preferably a method of ignition using a device of the invention allows for single-handed ignition. As shown in FIGS. 8A-8B, the user can press a button 802 on the device 800 to turn it on, and then press the button 802 again to turn it off. In other embodiments, the user can slide a strip of material towards the mouthpiece end 810 of the device 800 to turn it on, and then slide the strip back towards the fill port to turn it off. Other components can be incorporated into a device of the invention as would be obvious to one skilled in the art, such as a switch. A mechanical advantage may be provided to the user in order to activate an igniter without undue force from the user. Examples of a mechanical advantage include, but are not limited to, levers, four-bar linkages, and other devices as would be obvious to those skilled in the art.

(49) A device of the invention may also provide additional user friendly advantages. For example, the bimetallic object temperature regulator allows for the device to be of a slim, compact, and thus appealing form. Thermal insulating methods prohibit the user from being startled by high heat. A simple on/off mechanism allows for the user to begin and end the use session using a single hand.

(50) II. Cartridge

(51) FIG. 9 demonstrates a cartridge 970 that can contains a moist vaporizable product 972 (also referred to sometimes herein as a viscous vaporizable material, a fluidic vaporizable material, a moist smokable material, a fluidic smokable material, or moist vaporizable content) for use with a device capable of vaporizing the product 970. In the figure, the cartridge 970 contains a shell 974 that is sealed with a lid 976. In this example, the shell 974 comprises a flange 978 for adhering the lid 976 to the shell 974. The shell 974 of the cartridge 970 or the entire cartridge 970 can be made from a variety of materials including, but not limited to, metals, rigid plastics, flexible plastics, paper, paperboard, cardboard, and wax paper. The shell 974 of the cartridge 970 typically comprises a food-safe material, as in most cases, the cartridge 970 is to be used with a device for inhalation of a substance by a subject. Examples of some food-safe materials include aluminum, stainless steel, polyethylene terephthalate (PET), amorphous polyethylene terephthalate (APET), high density polyethylene (HDPE), polyvinyl chloride (PVC), low density polyethylene (LDPE), polypropylene, polystyrene, polycarbonate, and many varieties of paper products. In some cases, especially when the material is paper, the shell 974 can be lined with a material or a food-safe material to prevent both drying of the moist vaporizable content 972 and to protect the moist vaporizable content 972.

(52) Preferably a cartridge formed and shaped for easier insertion into an oven chamber of a device of the invention and to snugly fit into the cavity of the oven chamber for improved thermal conduction and vaporization. Cartridges can be formed and wrapped in a process that does not produce significant amount of harmful gases.

(53) A shell of a cartridge can be lidded with, for example a heat-sealable lidding film, to make a fully enclosed and airtight cartridge. A sealed cartridge of the invention can have the advantage of preserving freshness of the contents, and preventing spill of the materials within the cartridge during shipment or handling by the user.

(54) The lid of a cartridge can also be made by a variety of materials. Typically, the lid comprises a food-safe material. The lid can be sealed onto the cartridge after the moist vaporizable content is inserted into a cartridge of the invention. Many methods of sealing the lid upon the shell of a cartridge are known to those with skill in the art. One example of a method of sealing the lid on a shell of a cartridge comprising a flange is heat sealing. Preferably, the lid of the cartridge is considered food-safe to at least about 400° F. The lid can be a commercially-available film for use with foods cooked in a conventional oven, and are often referred to as dual-ovenable (for microwave and conventional oven use). The dual-ovenable films typically comprise of a PET (polyethylene terephthalate) base layer and an APET (amorphous polyethylene terephthalate) heat-sealing layer. Such lidding films can readily be metallized, or foilized in advance, preferably with aluminum to improve the barrier performance of the film regarding moisture, oxygen and other gases. Metallized films can be produced by common converting processes known to those skilled in the art.

(55) For illustration, FIG. 10 shows a basic heat-sealable film 1076 with PET base layer 1080 and APET heat-sealing layer 1082. FIG. 11 shows a composite film 1176 with a similar PET base layer 1180 and APET heat-sealing layer 1182, but with additional metal layer 1184 and metal adhesion layer 1186. In both cases, the APET heat-sealing layer 1182 is what comes in contact with a flange of a shell of a cartridge of the invention.

(56) The material of a cartridge of the invention and the shell can serve to preserve the freshness of the fill material, and increase shelf life of the cartridges. A metallized cartridge or lid or shell can also improve the visual appeal and perceived value of the cartridges. The material of the cartridge can also allow for improved printing and visibility of product information such as brand and indication of flavor.

(57) A cartridge 1270 of the invention that contains a moist vaporizable product can have apertures or vents 1288 in the cartridge 1270, as demonstrated by the example cartridge 1270 in FIG. 12. These apertures 1288 can allow for the content within the cartridge 1270 to have access to the environment. Some types of contents may need or find the access to the environment advantageous.

(58) The exemplary cartridge 1270 in FIG. 12 may also be composed of a material that can be punctured or opened when put into a device capable of vaporizing the contents of the cartridge 1270. For example, if a cartridge 1270 is heated to a certain temperature, the contents vaporize, and the aperture or apertures or openings 1288 created by the device allow the vapor content from the heated cartridge 1270 to escape. In a different manner, the cartridge 1270 may comprise a lid or a seal 1276 that can be opened immediately prior to the cartridge 1270 being inserted within a device.

(59) The portions of a cartridge can be of FIG. 13A, a cartridge 1370 with two portions 1390, 1392 can be fit together, or have a mechanism for sealing the two portions 1390, 1392 together. FIG. 13B demonstrates a cartridge 1370 that is put together, with each portion containing apertures or vents 1388 for releasing a vapor from the contents of the cartridge 1370 when the cartridge 1370 is heated.

(60) In many cases, a cartridge of the invention is intended for a single use and to be disposable. However, some types of cartridges, such as those that have methods for sealing two portions together, could be used multiple times as a reusable cartridge.

(61) A cartridge can be provided or sold to an end user containing a single use of a moist vaporizable product. The type of product contained within the cartridge can be stamped or written on the cartridge, or indicated by the color, size, or shape of the cartridge. However, a cartridge can be filled by an end used with a moist vaporizable product.

(62) As intended for use by the end consumer, a sealed cartridge of the invention can be inserted into the oven chamber of the device of the invention. The mouthpiece of the device is then returned to the closed position, at which point it can puncture the film on the top of the cartridge. Vapor generated by the heating process is then allowed to exit the cartridge and be inhaled by the user through the mouthpiece.

(63) III. Aerosolized Materials

(64) Any material that is capable of being aerosolized and inhaled by a user may be incorporated into a device or cartridge of the invention as would be obvious to one skilled in the art. It is of particular interest that the material provides an experience to the user either in terms of tactile response in the respiratory tract, or in terms of visual feedback regarding the exhalation of the inhaled material. For example, many materials have be contemplated for use with the present invention including, but not limited to, those containing tobacco, natural or artificial flavorants, coffee grounds or coffee beans, mint, chamomile, lemon, honey, tea leaves, cocoa, and other non-tobacco alternatives based on other botanicals. A device or cartridge of the invention can also be compatible for use with pharmaceutical compounds or synthetic compounds, either for pharmaceutical or pleasurable use. Any such compound which can be vaporized (or volatized) at a relatively low temperature and without harmful degradation products can be suitable for use with a cartridge or device of the invention. Examples of compounds include, but are not limited to, menthol, caffeine, taurine, and nicotine.

(65) Active elements contained in botanicals vaporize at different temperatures. The device can be calibrated to establish a single stable temperature, intended for vaporizing specific products, for example. A controller can also be used to select a variety of temperature settings. The user would choose which setting based on the type of cartridge used. The controller can also affect a desired temperature mechanically, such as by changing flow rate of the valve, or electronically, such as by electromechanical valve and micro-controller intermediary. For example, to change the operating temperature of a device of the invention, the oven chamber can be moved in respect to the temperature regulator, such as bimetallic discs.

(66) Here, tobacco or tobacco material is defined as any combination of natural and synthetic material that can be vaporized for pleasure or medicinal use. In one embodiment of the present invention, a cartridge can be prepared using cured tobacco, glycerin, and flavorings. Those skilled in the art of tobacco product manufacture are familiar with these and other ingredients used for cigarettes, cigars, and the like. The cartridge can be produced by chopping tobacco into fine pieces (for example, less than 2 mm diameter, preferably less than 1 mm), adding the other ingredients, and mixing until even consistency was achieved. In another embodiment, a cartridge can be prepared by processing the fill material into an even paste-like consistency (for example, particle size less than 1 mm), which facilitates the processing of filling the cartridge, for example, by use of an auger filler, peristaltic pump or a piston pump.

(67) Preferably the material for use with a device of the invention or contained within a cartridge of the invention comprises at least one of a vapor-forming medium and a medium for providing a tactile response in a respiratory tract of a user. The aerosolized product from the material inserted into a device can be a combination of vapor phase gases as well as small droplets which have condensed out of vapor phase and remain suspended in the gas/air mixture (the latter constitutes the visible portion of the inhaled substance).

(68) Propylene glycol (PG), glycerin, or a combination of both can be used as vapor-forming medium. Other vapor-forming media can be used with a cartridge and device of the invention. The vapor-forming medium serves to produce a visual vapor, such as a smoke-like vapor, when heated. This vapor can be visualized both before inhalation and during exhalation of the medium. PG has some advantages as compared to glycerin alone, as it exhibits a much higher vapor pressure at equivalent temperature and allows the device to operate at a lower temperature. Reducing the operating temperature conserves energy, and potentially can further improve the health benefits of using this system.

(69) In some cases, vapor resulting from PG that is inhaled by the user can partially absorb in the respiratory tract. If this occurs, it can appear as though the user is expelling primarily air. This differs from the conventional smoking experience in that in the case of smoking, users can typically see and play with expelled smoke as they exhale. Because the visual vapor created by heating glycerin can be seen upon exhale, some preparation of fill material for this invention can comprise a combination of both glycerin and PG. In these embodiments, the PG allows for high densities of visual vapor which the user can see/experience prior to inhaling as well as a tactile response in the respiratory tract, and the addition of glycerin allows for increased amounts of vapor to be seen or otherwise experienced upon exhale.

(70) One method of manufacturing the material for use in a device or cartridge of the invention is to combine cured tobacco leaves with the other ingredients at low heat, and then allow the mixture to incorporate or marinate at room temperature for an extended period of time, from one day to as long as three weeks (depending on the particular recipe and flavors used). The material can then processed by chopping into even consistency with particles 1-2 mm in diameter and inserted into the cartridge, or directly into the device. Alternatively, the material can be processed into a more even, paste-like consistency for improved handling in conventional pump equipment, as described herein.

(71) Example methods of filling a material into a cartridge included an auger fill method and a piston pump method. Both of these are common fill processes used in the packing industry for food and pharmaceutical goods. Either method allows for loading a repeatedly controlled volume of fill material (for example, about 0.25 cubic centimeters) into the shell. The filled shell can then be lidded using the heat-sealable lidding film. The fill and seal operations can be combined on an indexing machine known to those skilled in the art of food and pharmaceutical packaging.

(72) IV. Uses

(73) The device can emulate smoking by providing many of the desirable effects of smoking required by a user. An example of a method of use of a device and/or cartridge of the invention is demonstrated in FIG. 14. A vapor-forming medium as described herein can be combined with a tobacco material and inserted into a device 1400 of the invention either directly or using a cartridge of the invention. The tobacco material provides to the user the inhalation of substances 1494, such as nicotine, but not many of the tar-type substances, such as many of the Hoffmann analytes (see below), that accompany burning the tobacco material. A device 1400 of the invention can be used in a similar manner to a cigarette or other smoking article by placing the mouthpiece of the device 1400 into contact with the mouth 12 of a user 10. However, without the smoke or the feel of smoke, the user may not be satisfied with the experience. In order to provide a tactile response to the inhalation of the tobacco material, the vapor-forming medium 1494 can be added, such as propylene glycol, that can be absorbed in the respiratory tract 14.

(74) Also, when smoking a tobacco material, the smoke may provide a visual aide and/or visual recognition to the user. In order to provide a similar visual aide, the vapor-forming medium may contain a substance, such as glycerin, that can be visualized before and during inhalation, as well as during exhalation. In an exemplary method of use demonstrated in FIG. 15, the user 10 has received inhaled tobacco substances from a device 1500 of the invention in a manner that has reduced the Hoffman analyte intake of the user 10 by at least 70%. After the intake of the substance, the user may exhale a visible vapor 1596 from the vapor-forming medium through the mouth 12. The visible vapor 1596 can provide a similar visual aide to that of exhaled smoke in the act of smoking.

(75) V. Hoffman Analytes

(76) Cigarette smoke is a complex mixture of thousands of chemical constituents. Many of these have been linked to smoking-related illnesses. A standard reference on the more harmful compounds found in cigarette smoke is the Hoffmann analytes list recognizing about 44 different analytes that may be present in mainstream smoke. It is named in honor of Dietrich Hoffmann, a biochemist and leading authority on tobacco carcinogenesis. This list contains chemicals commonly associated with the health risks of smoking. These analytes and chemicals include, for instance, ammonia, aminonaphthalenes, benzopyrene, formaldehyde, acetaldehyde, acetone, methyl ethyl ketone, butyraldehyde, hydrogen cyanide, nitrous oxides, tobacco-specific nitrosamines (TSNAs), pyridine, quinoline, hydroquinone, phenol, cresols, tar, nicotine, carbon monoxide, 1,3-butadiene, isoprene, acrylonitrile, benzene, toluene, styrene, and various others. It has been determined that some Hoffmann analytes may be unwanted in the mainstream smoke from a smoking article. As such, extensive research has been conducted on reducing Hoffmann analytes. The Hoffmann analytes may also be carcinogenic and a device for smoking or emulating smoking would be desirable.

(77) Using a device of the invention, a tobacco material can be aerosolized without burning the material. By aerosolizing the tobacco, many of the unwanted chemicals and Hoffmann analytes are not inhaled by the user. For example, a device of the invention can reduce the inhalation of Hoffmann analytes by about 70% or more. In some embodiments, a device of the invention can reduce the inhalation of Hoffmann analytes by about 50% or more. In some embodiments, a device of the invention can reduce the inhalation of Hoffmann analytes by about 60% or more. In some embodiments, a device of the invention can reduce the inhalation of Hoffmann analytes by about 70% or more. In some embodiments, a device of the invention can reduce the inhalation of Hoffmann analytes by about 80% or more. In some embodiments, a device of the invention can reduce the inhalation of Hoffmann analytes by about 90% or more.

(78) VI. Ames Assay

(79) The bacterial reverse mutation test was originally developed by Ames et al. The Ames assay serves as a predictor for compounds that might cause carcinogenesis in humans. The method has been widely adopted, and the FDA incorporates it as part of a more comprehensive study of toxicity for new food additives and drugs. The same test has been widely used to study the toxicity of tobacco products and tobacco smoke. The Ames test is a biological assay to assess the mutagenic potential of chemical compounds. As cancer is often linked to DNA damage, the test also serves as a quick assay to estimate the carcinogenic potential of a compound. In comparison, the standard tests for carcinogenicity done on rodents take years to complete and are expensive. The Ames test uses several strains of the bacterium Salmonella typhimurium that carry mutations in genes involved in histidine synthesis, so that they require histidine for growth. The variable being tested is the mutagen's ability to cause a reversion to growth on a histidine-free medium. The tester strains are specially constructed to have both frameshift and point mutations in the genes required to synthesize histidine, which allows for the detection of mutagens acting via different mechanisms. Some compounds are quite specific, causing reversions in just one or two strains. The tester strains also carry mutations in the genes responsible for lipopolysaccharide synthesis, making the cell wall of the bacteria more permeable, and in the excision repair system to make the test more sensitive. Rat liver extract is added to simulate the effect of metabolism, as some compounds, like benzopyrene, are not mutagenic themselves but their metabolic products are. In order to perform an assay, the bacteria are spread on an agar plate with a small amount of histidine. This small amount of histidine in the growth medium allows the bacteria to grow for an initial time and have the opportunity to mutate. When the histidine is depleted, only bacteria that have mutated to gain the ability to produce histidine will survive. The plate is incubated for 48 hours. The mutagenicity of a substance is proportional to the number of colonies observed.

(80) As demonstrated in Example 2 below, device of the invention for use with a tobacco containing material can show significant improvement in Ames assay results as compared to many types of smoking tobacco. Thus, a device of the invention can provide many of the substances of the tobacco, such as nicotine, to a user while not providing some key carcinogenic components that are associated with the burning or smoke of tobacco.

Example 1

(81) Cigarette smoke is a complex mixture of thousands of chemical constituents. Many of these have been linked to smoking-related illnesses. The Hoffman analytes list is a standard reference on the more harmful compounds found in cigarette smoke. A set of 52 target compounds will be selected based on the Hoffman list. It is expected that the vapor produced by a device of the invention will reduce the levels of these target compounds by a significant amount (70% reduction or greater).

(82) Constituent testing of a prototype device of the invention and a reference cigarette (KY2R4F) will be conducted in a laboratory. Samples from both types of devices will be acquired onsite, in automated smoking machines and under the Canadian Intense regime (55 cubic centimeter (cc) puffs every 30 seconds). It is believed that this method approximates actual smoking conditions better than the FTC regime (35 cc puffs every 60 seconds). Arista has developed extensive protocols for the analysis of the target compounds, based on literature. These protocols will be employed for testing. Methods of collection and extraction for each group of analyte are summarized in TABLE 1.

(83) TABLE-US-00001 TABLE 1 Hoffman Analyte Analysis Analyte Collection method Extraction Method Analysis Method Ammonia Five cigarettes through a The pad is extracted with Ion chromatography (IC) 44-mm Cambridge filter the impinger solutions. with a Dionex IonPac CS14 pad with two impingers cation exchange analytical containing 20 ml of 0.01N column. MSA. Aromatic Amines Five cigarettes through a Extract pad with 5% HCl Gas chromatography-mass 2-Aminonaphthalene 44-mm Cambridge filter and internal standards. spectrometry selective ion 3-Aminobiphenyl pad. Liquid-liquid extraction monitoring (GC/MS SIM) 4-Aminobiphenyl with dichloromethane. The with a J&W DB5MS, 30-m × (3 total) eluent is collected and then 0.25-mm × 0.25-μm film concentrated. thickness. Trimethylamine is added and the extract is derivatized with pentafluoropropionic anhydride. The resultant solution is eluted through a florisil column and then concentrated before analysis. Polynuclear Aromatic Five cigarettes through a Add internal standard and GC/MS SIM with a J&W Hydrocarbons 44-mm Cambridge filter then extract pad with DB5MS, 30-m × 0.25-mm × Benz(a)anthracene pad. mixture of cyclohexane and 0.25-μm film thickness. Benzo(b)fluoranthene benzene. Filter through a Benzo(j)fluoranthene silica solid phase extraction Benzo(k)fluoranthene (SPE) cartridge and Benzo(a)pyrene concentrate. Add a mixture Chrysene of 33% methanol in water Dibenz(a,h)anthracene and put through a C18 SPE Dibenzo(a,i)pyrene cartridge. Wash with 30% Dibenzo(a,l)pyrene methanol in water and Indeno(1,2,3-c,d)pyrene extract with 1.5 mL of 5-Methylchrysene benzene for analysis. (11 total) Carbonyls One cigarette through two The impinger solutions are High-pressure liquid Formaldehyde impingers containing combined. An aliquot is chromatography with UV Acetaldehyde 25 mL of 2,4- removed, pyridine is added detector (HPLC-UV) with a Acetone dinitrophenylhydrazine and to the aliquot and the reversed phase, C18, 250-mm × Acrolein perchloric acid in solution is analyzed. 4.6-mm column. Propionaldehyde acetonitrile. Crotonaldehyde Butyraldehyde Methylethylketone (8 total) Hydrogen Cyanide Mainstream smoke is The Cambridge filter pad is The gas and particulate collected from one to three extracted with 0.1N sodium phases are analyzed cigarettes through a 44-mm hydroxide. The impinger separately by continuous Cambridge filter pad solution is shaken by hand. flow analysis. followed by one impinger containing 0.1N sodium hydroxide. Carbon Monoxide The gas phase smoke is Not Applicable The concentration of CO is collected in a gas-sampling determined using a non- bag. dispersive infrared spectrometer (NDIR spectrometer). Nitric Oxide Puff-by-puff on-line Not Applicable The gaseous phase smoke is analysis. passed through a NO chemiluminescence detector. Mercury Hg is trapped in impingers The samples are microwave Flow injection, cold vapor containing potassium digested. atomic absorption permanganate. spectrometry (cold vapor AA) Metals The smoke is trapped in an The CSC is first extracted Analysis by inductively Nickel electrostatic precipitation using methanol and then the coupled plasma mass Lead unit. solvent is evaporated before spectrometry (ICP-MS). Cadmium digestion with heat and Chromium nitric acid. Arsenic Selenium (6 total) Nitrosamines Five cigarettes through a Extraction of filter with Liquid chromatography NNN 44-mm Cambridge filter 0.1N ammonium acetate. tandem mass spectrometry NNK pad. (LC-MS/MS) with NAT electrospray ionization NAB (ESI) using a 2.0 × 50 mm (4 total) C18 column. Semi-Volatiles Three to five cigarettes The filter pad and impinger Gas chromatography-mass Pyridine through a 44-mm solution are combined. spectrometry (GC/MS) with 3-Vinylpyridine Cambridge filter pad Internal standards are added a J&W DB-Wax, 30-m × Quinoline followed by an impinger with orbital agitation. The 0.25-mm × 0.25-μm film (3 total) containing methanol and resultant solution is thickness. triethanolamine (TEA). decanted and analyzed. Phenols Five cigarettes through a Extraction using a 1% HPLC/Fluorescence with a Catechol 44-mm Cambridge filter acetic acid in 30% methanol reversed-phase column. Phenol pad. with agitation for 60 Hydroquinone minutes. Filter an aliquot of Resorcinol the extract and then m- & p-Cresol analyze. o-Cresol (6 total) Volatiles Three to five cigarettes The filter pad and cold GC/MS with a J&W 1,3-Butadiene through a 44-mm impinger solution are DB5MS, 60-m × 0.25-mm × Isoprene Cambridge filter pad combined. Internal 1.0-μm film thickness Acrylonitrile followed by an impinger standards are added and the column. Benzene containing methonal solution is vortexed briefly. Toluene maintained at sub-ambient The resultant solution is Styrene temperature. decanted and analyzed. (6 total)

(84) For each target compound, five replicate tests will be run, both for a device of the invention and the reference cigarette. The differences in mean yield between the two articles will be determined as a percentage. It is expected that a device of the invention will reduce the level of Hoffman analytes by about 70% or more as compared to the reference cigarette.

Example 2

(85) The bacterial reverse mutation test, or “Ames assay,” serves as a predictor for compounds that might cause carcinogenesis in humans. This test has been widely used to study the toxicity of tobacco products and tobacco smoke. The objective of this study described here was to screen the smoke condensate of the present invention for mutagenicity in the TA 98 strain of the bacterium Salmonella typhimurium using the Ames assay. Strain TA 98 was chosen because it is among the most sensitive strains of Salmonella typhimurium, and can detect a wide variety of mutagens. If a dose-dependent response is detected, the smoke condensate is considered to be mutagenic for that strain.

(86) Testing Facility.

(87) Test article preparation (i.e., “smoking” and extraction), chemical constituent analysis and genotoxicity were conducted at Arista Laboratories, 1941 Reymet Road, Richmond, Va. 23237.

(88) Preparation of Extracts of Test Articles.

(89) Three cartridges were “smoked” per each replicate using a smoking device of the present invention connected to an automated rotary smoking machine (Borgwaldt RM-20 CSR) using the following parameters: 1) puff volume of 55 ml; and 2) puff duration of 30 seconds and an air flow according to ISO standards. Total Particulate Matter (TPM) phase was collected onto a 44 mm Cambridge filter pad and extracted into dimethyl sulfoxide (DMSO). Immediately following extraction, TPM samples were aliquoted into individual amber vials and stored at less than or equal to −70° C. for greater than or equal to 48 h prior to testing by the Ames assay. Once thawed and used for testing, TPM extracts were not reused or refrozen.

(90) Mutagenicity Testing (Ames Assay).

(91) The Ames assay was conducted on TPM extracts generated during three independent “smoking” sessions. The assay was performed according to according to Arista Standard Operating Procedure #TOX 001. TPM samples were tested in triplicate with the addition of an exogenous metabolic activation system (S9). For each replicate sample, ten concentrations of particulate phase ranging from 0-2000 μg TPM per plate were tested in a minimum of three plates per concentration. Concurrent testing of strain-specific positive controls (with and without S9) and a single concentration (i.e., 100 μg) of the KY2R4F reference cigarette condensate were conducted. The assay was conducted according to Health Canada Official Method 501, second edition, 2004-11-01, Arista Standard Operating Procedure #TOX 001. Results of the Ames assay are shown in FIG. 16. Vehicle and positive controls, KY2R4F and spontaneous revertant concurrently run with each test and pertinent to bacteria strains and incubation conditions were within the expected laboratory control limits or deemed scientifically acceptable by the study director.

(92) Results.

(93) As shown in FIG. 16, the study found no dose-dependent effect of the Total Particulate Matter (TPM) generated by “smoking” the device of the present invention. Moreover, all TPM samples showed a reversion rate less than half that of the control. In contrast, published data for the “1R4F” Kentucky reference cigarette, a cigarette of common tobacco and filter composition, produce a positive-sloping trend for the TA 98 tester strain. See D. W. Bombick et al., “Chemical and Biological Studies of a New Cigarette that Primarily Heats Tobacco. Part 3. In vitro toxicity of whole smoke,” Food and Chemical Toxicology, 36:183-190 (1997).

(94) Although preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein can be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.