WO2010063338A1

WO2010063338A1 - Apparatus and method for treatment of gaseous material

Info

Publication number: WO2010063338A1
Application number: PCT/EP2009/006971
Authority: WO
Inventors: Bernd Van Ooy; Peter Schnell; Herbert Engels; Johannes Doll; Erwin Anskeit
Original assignee: Philip Morris Products S.A.
Priority date: 2008-12-05
Filing date: 2009-09-28
Publication date: 2010-06-10
Also published as: EP2373251A1; CA2743776A1

Abstract

There is provided apparatus for treatment of ambient air for supply to an individual small experimental animal. The apparatus comprises an inlet for the ambient air, an inner tube having a porous wall, an electric heater surrounding the inner tube and a cuff surrounding the electric heater and the inner tube. The cuff is arranged to deliver water to the electric heater. The cuff is connectable to a water supply. The apparatus further comprises an outlet for the treated air and an exposure tube for housing the individual small experimental animal. The exposure tube has an inlet for the treated air, connected to the outlet. There is also provided a method for treatment of ambient air, for supply to an individual small experimental animal.

Description

Apparatus and Method for Treatment of Gaseous Material

The present invention relates to an apparatus and method for treatment of ambient air. The apparatus and method are suitable to supply treated air to an individual small experimental animal. Particularly, but not exclusively, the invention relates to an apparatus and method for treating the temperature and humidity of air, for supply to an individual experimental rodent.

Individual exposure of experimental animals to gaseous material is known, particularly for small experimental animals, such as rodents. The experimental animals are usually confined individually and gaseous material for inhalation may be directed generally towards the nose of the animal. Alternatively, the gaseous material may be supplied intra-tracheally, that is, directly into the trachea of the experimental animal, optionally via a tracheal cannula. Exposure of experimental animals to gaseous material can be useful for toxicological evaluation of inhalable gaseous material.

For example, US patent US-A-4,721 ,060 describes an exposure system in which rodents are closely confined in exposure bottles, whose inner ends extend into fittings connected to a manifold and whose outer ends are closed. The manifold includes inner and outer sections. Aerosol or gas from the inner section of the manifold flows into each bottle via a tube.

Where experimental animals are being exposed to gaseous material on an individual basis, there is a need to be able to treat air in small volumes and at low flow rates so that it can be supplied individually to each small experimental animal. This is particularly important in intratracheal exposure, where the moisturising and heating functions of the nose of the experimental animal are missing.

According to a first aspect of the invention, there is provided apparatus for treatment of ambient air for supply to an individual small experimental animal, the apparatus comprising: an inlet for ambient air; an inner tube having a porous wall; an electric heater surrounding the inner tube; a cuff surrounding the electric heater and the inner tube, for delivering water to the electric heater, the cuff being connectable to a water supply; an outlet for treated air; and an exposure tube for housing the individual small experimental animal, the exposure tube having an inlet for the treated air, connected to the outlet.

Water is supplied to the electric heater, preferably, in a substantially uniform manner along its length. The electric heater vaporizes the water, and the resulting water vapour then diffuses through the porous wall, into the inner tube. The vapour mixes with the ambient air supplied at the inlet of the apparatus, and exits the apparatus with the air, through the outlet. Throughout the specification, the terms "untreated air" or "untreated ambient air" or simply "air" or "ambient air" and "treated air" are relative terms and refer to the relative state of air entering and exiting the apparatus respectively. The inlet may also be used for introducing an additional gaseous material. The cuff may also be used for delivery of an additional liquid to the electric heater. In that case, the cuff may be attached to an additional liquid supply.

The apparatus according to the invention is particularly useful to supply treated air to an individual small experimental animal, such as a rodent. The rodent may be a rat, a mouse or another suitable type of rodent. The apparatus according to the invention is particularly suitable for intra-tracheal exposure of small experimental animals, such as rodents. In one embodiment, the treated air is supplied to the trachea of the experimental animal via a tracheal cannula, for intra-tracheal inhalation. The treatment of the air in the apparatus substitutes for the heating and humidifying functions of the nose of the experimental animal. This means that the treated air is delivered to the lung of the experimental animal as if inhaled through the nose, but without the filtration function of the nose.

The small experimental animal preferably has a mass less than about 2000 g. Even more preferably, the small experimental animal has a mass less than about 1500 g. Even more preferably, the small experimental animal has a mass less than about 1000 g. Even more preferably, the small experimental animal has a mass less than about 500 g. In one example, the small experimental animal has a mass between about 250 g and about 550 g. The small experimental animal preferably has a lung capacity of less than about 5 ml. Even more preferably, the small experimental animal has a lung capacity of less than about 2 ml. Even more preferably, the small experimental animal has a lung capacity of less than about 0.3 ml. In one example, the small experimental animal has a lung capacity of between about 0.1 ml and 0.3 ml. Preferably, the apparatus is sized for a small experimental animal with a lung capacity of between about 0.1 ml and about 5 ml.

Preferably, the treatment of the air comprises at least one of: increasing the temperature of the air, and increasing the vapour content of the air. The vapour content is a measure of the amount of liquid vapour in a given volume of gaseous material, and may be indicated as a percentage or as a temperature below which liquid will begin to condense out of the gaseous material. Preferably, the apparatus according to the invention increases the humidity of the air passing through the apparatus to between about 80 % and about 99 %, more preferably to between about 90 % and about 99 %, most preferably to between about 93 % and about 98 %. Preferably, the treatment comprises at least one of: increasing the temperature of the air to a temperature higher than ambient temperature, and increasing the humidity of the air to a humidity higher than ambient humidity. The humidity is a measure of the amount of water vapour in a given volume of gaseous material, and may be indicated as a percentage or as a temperature (the dew point) below which water will begin to condense out of the gaseous material.

In one embodiment, the apparatus further comprises a temperature sensor for sensing the temperature of treated air. The temperature sensor may be near to the outlet. Preferably, the temperature sensor comprises a thermocouple. Preferably, the temperature of the treated air is controllable, by controlling the electric current through the electric heater and hence the temperature of the electric heater. Preferably, the temperature sensor is coupled to the electric heater for control of the temperature of the treated air. In one embodiment, the apparatus further comprises control means for controlling the temperature of the electric heater in response to a signal from the temperature sensor.

Preferably, the water vapour content of the treated air is controllable, by controlling the amount of water vapour diffusing through the porous wall of the inner tube. Alternatively, the humidity may be controlled manually, by adjustment of the water supply, for example with an infusion pump. Preferably the relative humidity is determined before connection with a tracheal cannula of an experimental animal.

Preferably, the water vapour content is controlled by controlling the dimensions of the inner tube, including the thickness of the porous wall, or by controlling the dimensions of the electric heater, including the length and thickness and, if the electric heater comprises an electric heating coil, the number of turns. The water vapour content may be further controlled by the dimensions of the cuff, including the length and thickness, or by the flow rate of air into the inlet. In addition, the water vapour content may be controlled by the electric current through the electric heater or by the supply of water to the cuff. Furthermore, the water vapour content may be controlled by any combinations of the above.

In one embodiment, the internal volume of the inner tube is between about 0.05 ml and about 0.5 ml. More preferably, the internal volume of the inner tube is between about 0.1 ml and about 0.3 ml. Most preferably, the internal volume of the inner tube is about 0.2 ml. This is advantageous because the volume of the inner tube is comparable to or smaller than the lung volume of a small experimental animal. In addition, such a small volume means that, if the apparatus is used with an aerosol, there is only a low level of particle deposition on the inner surface of the inner tube.

Preferably, the internal diameter of the inner tube is between about 1 mm and about 2 mm. In one embodiment, the internal diameter of the inner tube is about 1.5 mm. Preferably, the inner tube comprises a ceramic tube. Preferably, the porosity of the ceramic is known. Preferably, the pore diameter of the ceramic tube is between about 2 μm and about 10 μm. Even more preferably, the pore diameter of the ceramic tube is about 3 μm. Preferably, the tube comprises alpha-aluminium oxide.

In one embodiment, in use, the apparatus is used with a pump for pumping the untreated ambient air into the inlet. Preferably, the flow rate of the untreated air into the inlet is controlled to match the lung volume of the experimental animal. Preferably, the stroke volume of the pump is adjustable between about 0.1 ml and about 5 ml. Preferably, the stroke frequency can be adjusted to match the breathing behaviour of the experimental animal. For example, where the experimental animal is a rat, the stroke volume of the pump is about 1.5 ml and the frequency of the pump is about 100/min.

Preferably, the electric heater comprises an electric heating coil. Preferably, the electric heating coil comprises a metal wire. In one embodiment, the electric heating coil is a metal alloy wire. In one preferred embodiment, the electric heating coil is a constantan wire.

Preferably, the cuff comprises a glass fibre delivery cuff. Preferably, the cuff has a length substantially equal to the length of the electric heater, so as to provide a uniform delivery of water to the heater. In addition, preferably, the cuff has a circumference substantially equal to the circumference of the electric heater, so as to provide a uniform delivery of water to the heater. Preferably, the water supply is arranged to supply water to the cuff along its length, so as to assist with a uniform delivery of water from the cuff to the heater. Preferably, the water supply is arranged to supply water to the cuff around its circumference, so as to assist with a uniform delivery of water from the cuff to the heater.

The apparatus may further comprise an outer tube surrounding the inner tube, electric heater and cuff. In one embodiment, the outer tube is a glass outer tube. Preferably, the outer tube is sealed at both ends with end caps. The apparatus may further comprise an insulating cover surrounding the outer tube.

According to the second aspect of the invention, there is also provided a method for treatment of ambient air for supply to an individual small experimental animal, the method comprising the steps of: delivering water to an electric heater, the electric heater surrounding an inner tube having a porous wall; pumping ambient air into an inlet of the inner tube; the electric heater heating the air in the inner tube and vaporizing the water; the water vapour diffusing through the porous wall into the tube, thereby increasing the water vapour content of the air; and delivering the treated air into an inlet of an exposure tube for housing an individual small experimental animal.

The method may further comprise delivering an additional liquid to the electric heater. The method may further comprise pumping an additional gaseous material into the inlet.

According to the invention, there is also provided a method of supplying air to a small experimental animal including the step of treating ambient air according to the method of the second aspect of the invention.

Throughout the specification, the term "gaseous material", wherever used, is used to refer to any gas or vapour or aerosol or combination thereof. Aerosols comprise small solid particles dispersed in a gas. One example of an aerosol is smoke, in which solid smoke particles are dispersed in air. The term "flow of gaseous material" is therefore flow of the gas or vapour or aerosol or combination thereof.

Features described in relation to one aspect of the invention may also be applicable to another aspect of the invention.

The invention will be further described, by way of example only, with reference to the accompanying Figure 1 , which shows a partially cut away view of one embodiment of the apparatus of the invention.

Figure 1 shows one exemplary embodiment of the apparatus of the invention. The apparatus 101 comprises an inner tube in the form of porous ceramic tube 103. Surrounding the porous ceramic tube 103 is an electric heater in the form of electric heating coil 105, having electrical connections 107a and 107b. The porous ceramic tube 103 and heating coil 105 are covered with a cuff for liquid delivery, in the form of glass fibre wadding 109. The glass fibre wadding 109 is fed with a constant flow of water via water inlet 111. The porous ceramic tube 103, heating coil 105 and wadding 109 are surrounded by an outer tube in the form of tubing 1 13, sealed at each end with an end cap, 115a and 115b. The tubing 113 is covered with an insulating cover 1 17. A temperature sensor in the form of thermocouple 119 is also provided to determine the air temperature of the treated air exiting the apparatus. During operation, air enters the apparatus at input 201 via a pump (not shown). Treated air exits the apparatus at outlet 205. Exhaled air exits at outlet 203.

The porous ceramic tube 103 preferably has a small pore size. In one example, the pore diameter is about 3 μm, although the pores may have any suitable diameter, according to the volume of treated air required. The internal diameter of the inner tube is preferably between about 1 mm and about 2 mm. In one embodiment, the porous ceramic tube has an internal diameter of about 1.5 mm. In one embodiment, the porous tube comprises alpha-aluminium oxide (σ-aluminium oxide, σ-AI₂O₃). Such a tube may be obtained from inocermic GmbH of Hermsdorf, Germany

In one embodiment, the electric heating coil 105 comprises a constantan wire. Constantan is a copper-nickel alloy usually including 60% copper and 40% nickel. Other metals and alloys may also be suitable. In one embodiment, the wire is 28 cm long and has a diameter of 0.25 mm. The resistance provided by such a heating coil is 10 Ω/m.

The tubing 113 is preferably glass. In one embodiment, the tubing 113 is Duran® tubing manufactured by Schott AG of Mainz, Germany. The end caps 115a and 1 15b are preferably made from Teflon® and provide a watertight and gastight seal. In this embodiment, the electrical connection 107a passes through end cap 115a and through tubing 113, and the electrical connection 107b passes through end cap 115b and through tubing 113. The insulating cover is preferably made from Teflon®.

The thermocouple 1 19 is preferably centrally located at the outlet 205 of the apparatus. The thermocouple may be located in a LuerLock® connector made by OzoneLab Instruments of Burton, Canada.

During operation, air is pumped into the apparatus at input 201. Where the experimental animal is for example a rat, the stroke volume of the pump may be about 1.5 ml and the frequency of the pump may be about 100/min. Water is injected into inlet 111 by an infusion pump, through a stainless steel tube (not shown) that is tightly mounted onto the tubing 1 13. The glass fibre wadding achieves a uniform delivery of water to the heating coil 105. Because the water is evaporated outside the porous ceramic tube and subsequently diffuses through the porous wall into the inner tube, a uniform humidification can be achieved. In one embodiment, the air is treated to a temperature of around 35° C and a humidity of around 85 to 95%.

Figure 1 shows an embodiment of the apparatus in which the gaseous material pumped into the apparatus is ambient air, and liquid supplied to the glass fibre wadding, and hence to the heating coil, is water. However, additional gaseous material may be supplied to the apparatus, for example, any other type of gas, vapour, aerosol or combination thereof, for example a pharmaceutical aerosol or cigarette smoke. In addition, additional liquid may be vaporized by the heating coil, for example, any type of evaporable liquid, for example, flavours or pharmaceuticals.

Claims

1. Apparatus for treatment of ambient air for supply to an individual small experimental animal, the apparatus comprising: an inlet for ambient air; an inner tube having a porous wall; an electric heater surrounding the inner tube; a cuff surrounding the electric heater and the inner tube, for delivering water to the electric heater, the cuff being connectable to a water supply; an outlet for treated air; and an exposure tube for housing the individual small experimental animal, the exposure tube having an inlet for the treated air, connected to the outlet.

2. Apparatus according to claim 1 , wherein the treated air is supplied to the trachea of the experimental animal via a tracheal cannula, for intra-tracheal inhalation.

3. Apparatus according to claim 1 or claim 2, wherein the apparatus is sized for a small experimental animal with a lung capacity of between about 0.1 ml and about 5 ml.

4. Apparatus according to any preceding claim, further comprising a temperature sensor for sensing the temperature of the treated air.

5. Apparatus according to claim 4, further comprising control means for controlling the temperature of the electric heater in response to a signal from the temperature sensor.

6. Apparatus according to any preceding claim, wherein the internal volume of the inner tube is between about 0.05 ml and about 0.5 ml.

7. Apparatus according to any preceding claim, wherein the internal diameter of the inner tube is between about 1 mm and about 2 mm.

8. Apparatus according to any preceding claim, further comprising an outer tube surrounding the inner tube, electric heater and cuff.

9. Apparatus according to claim 8, further comprising an insulating cover surrounding the outer tube.

10. A method for treatment of ambient air for supply to an individual small experimental animal, the method comprising the steps of: delivering water to an electric heater, the electric heater surrounding an inner tube having a porous wall; pumping ambient air into an inlet of the inner tube; the electric heater heating the air in the inner tube and vaporizing the water; the water vapour diffusing through the porous wall into the tube, thereby increasing the water vapour content of the air; and delivering the treated air into an inlet of an exposure tube for housing an individual small experimental animal.

11. A method of supplying air to a small experimental animal including the step of treating ambient air according to the method of claim 10.