Use of Capillary Aerosol Generator in Continuous Production of Controlled Aerosol for Non-Clinical Studies

The CAG is useful for continuous and repeatable thermal generation of aerosols in large volumes, such as for in vivo inhalation toxicology studies, where the use of consumer products or inhalation devices is not feasible. Using the CAG allows experimentalists to precisely control the factors that influence aerosol particles'chemistry and physical characteristics, such as temperature, liquid composition, liquid flow rates, and air flows. The liquid in the CAG is evaporated, producing supersaturated vapors that immediately cool in contact with airflow, triggering homogeneous nucleation, and subsequently, condensation processes forming the aerosol particles.

The presented protocol gives an insight into the assembly and complexity of CAG use for the general purpose of aerosol generation. As a working example, testing a typical liquid composition present in electronic cigarette mixtures is used. Start by placing the capillary in the capillary groove of the aluminum heating blocks with the output end protruding by about five millimeters.

Lightly tighten the screws of the two halves of the aluminum heating blocks. Next, assemble the heating elements and thermocouple in the aluminum heating blocks with the wires protruding through the aluminum rear cap. Install the push-in fittings, ensuring that the 2-by-4-millimeters push-in fittings are tightly secured onto the outer SS tube.

Place O-rings on the two grooves of the inner peak tube and insert the inner peak tube into the outer SS tube from the front end. Slide the inner peak/outer SS tube assembly over the assembled aluminum heating elements through to fit tight with the SS rear backing. Next, place the aluminum front cap over the aluminum heating body inside the inner peak tube.

Ensure that the capillary is slightly protruding from the aluminum front cap. Place the peak adapter over the inner peak tube front. Ensure that the peak adapter fits on the front groove of the inner peak tube.

Place the coupling over the peak adapter. Hand tighten the nuts over the coupling, such that the peak adapter is tight. Connect the heating elements to the temperature controller, temperature controller thermocouple to the CAG, and the tubing from the peristaltic pump to the CAG.

Connect the compressed air for heated airflow to the capillary aerosol generator via the 2-by-4-millimeter push-in fittings. Assemble the capillary aerosol generator to the glass piece and supply dilution airflow to preset values. Based on the theoretical calculations described in the text manuscript, perform the initial engineering runs to quantify the actual aerosol constituent concentration and obtain the actual yield of the capillary aerosol generator.

Perform further fine tuning of aerosol concentration by using the same calculations for adjustment of total dilution airflow or liquid flow rate. Using a solution containing 2%nicotine and a liquid flow rate of 0.35 grams per minute with a measured nicotine aerosol concentration of 15 micrograms per liter at a total dilution airflow of 320 liters per minute will result in 68.57%nicotine actual yield. Weigh and record the value of the test liquid, magnetic stirrer, and bottle to the nearest 0.01 grams.

Liquid stock formulations are prepared with components described in the text manuscript. Set the temperature control set point on the digital temperature controller to 250 degrees Celsius and begin heating of the capillary aerosol generator. Place the liquid stock solution with a magnetic stir bar on a magnetic stirrer.

Place the inlet tube from the peristaltic pump in the test solution. Turn on the peristaltic pump and set the liquid flow rate to 5%When the temperature reaches 250 degrees, begin aerosol generation by starting the peristaltic pump to deliver test liquid to the capillary aerosol generator. Check that the aerosol is generated near the capillary tip and record the time as necessary to calculate the mass flow rate.

Place a filter in the filter holder and place the filter caps. Weigh the filter holder to nearest 0.0001 gram with the filter before sample collection and document the weight. Connect the filter holder containing the filter to the aerosol flow and start sample collection.

After sample collection, weigh the filter with the filter holder and caps and document the end weight. Calculate the aerosol-collected mass using the formula stated in text manuscript. Now, remove the filter pad from the filter holder and deposit it into a glass vial containing five milliliters of ethanol.

Extract the aerosol-collected mass by shaking the filter pad on a laboratory shaker for 30 minutes at 400 rotations per minute. Chemical characterization of CAG-generated aerosols confirmed high degree of reproducibility under same heating, cooling, dilution air flows, sampling conditions, with a relative standard deviation of 2.48%for aerosol-collected mass, 3.28%for nicotine, 3.43%for glycerol, and 3.34%for propylene glycol. The greatest influence on particle size was observed when changing the cooling flow from 10 to 20 liters per minute and the first dilution flow from 160 to 150 liters per minute.

The mass-median aerodynamic diameter of aerosol particles increased in size with the increasing cooling flow rates. The distribution of the aerodynamic diameter of the aerosol particles was clearly shifted towards larger diameters when comparing aerosols generated at 10 liters per minute cooling flow with those generated at 20 to 50 liters per minute. An intended target aerosol concentration, along with including airflow rate and liquid flow rate values, allow operators to experimentally account for the yields from the CAG setup.

Following this procedure, other liquid mixtures can be tested under similar or altered conditions that allow investigators to better experimentally understand physical and chemical property changes that occur through heated aerosolization.