The material presented in this thesis falls into three main sections: 1) The measurement of nebulizer suction and its applications. Three methods of measurement of nebulizer suction were evaluated. The potential and limitations of each method was assessed. The most reliable and generally applicable method was measurement with a mercury manometer via a T-piece during aspiration, but after correction for suction drops along all the nebulizer capillaries and across connections. The measurement of suction was then applied to practical problems in AAS, i.e. the lack of dependence of signal on sample solution temperature, and to provide immediate warning of drift in aspiration rate. 2) Observations and causes of deposition in spray chambers. The deposition patterns of aerosol lost in the spray chamber was studied using a lithium tracer. Areas of high turbulence were identified and their positions related to the deposition patterns. The nebulizer/spray chamber system was considered to fulfill a sub-sampling role and the dual roles of pneumatic nebulizer as pumps and sub-samplers were critically discussed. 3) Observations on impactors in flame AAS. Five techniques for the evaluation of the effects of impact beads and other impactors were evaluated, i) aerosol droplet size distributions ii) aspiration of dye solutions iii) aerosol sizing with a second species introduced through the bead iv) effects on linear absorbance range v) effects on the extent of chemical interference The advantages and disadvantages of each technique were considered and the value of impactors critically appraised. An assessment was then made of the extent to which an impact cup or bead may be used to regulate sensitivity in flame AAS with a view to increasing the useful working ranges of calibration graphs.

Background: Aerosol therapy has been established as an efficient form of drug delivery to pediatric and adult patients with respiratory diseases; however, aerosol delivery to the pediatric population is quite challenging. While some studies compare jet nebulizer (JN), vibrating mesh nebulizer (VMN), or JN and pMDI, there is no study comparing these three devices in pediatric and young children. The aim of this study quantifies aerosol deposition using JN, VMN, and pMDI/VHC in a simulated pediatric with active and passive breathing patterns. Methods: Each aerosol generator was placed between manual resuscitator bag (Ambu SPUR II Disposable Resuscitator, Ambu Inc, Glen Burnie, MD) and infant facemask (Mercury Medical, Cleanwater, FL), which was held tightly against the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Active and passive breathing patterns were used in this study with aerosol device; active breathing pattern was created using a ventilator (Esprit Ventilator, Respironics/Philips Healthcare, Murrysville, PA) connected to a dual chamber test lung (Michigan Instruments, Grand Rapids, MI), which was attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc, Englewood, CO), to collect aerosolized drug, connected to the SAINT model. Pediatric resuscitator bag was run at 10 L/min of oxygen and attached to aerosol generator with facemask. In passive breathing pattern, SAINT model was attached to test lung and ventilated using the resuscitator bag with the same breathing parameters. Each aerosol device was tested three times (n=3) with each breathing patterns. Drug was eluted from the filter and analyzed using spectrophotometry. The amount of drug deposited on the filter was quantified and expressed as a percentage of the total drug dose. To measure the differences in the inhaled drug mass between JN, VMN, and pMDI/VHC in active or passive breathing, one-way analysis of variance (one-way ANOVA) was performed. To quantify the difference in aerosol depositions between the two breathing patterns, independent t-test was performed. A p < 0.05 was considered to be statistically significant. Results: Although the amount of aerosol deposition with the JN was the same in passive and active breathing without any significant difference, the VMN was more efficient in active breathing than the JN (p = 0.157 and p = 0.729, respectively). pMDI/VHC had the greatest deposition in the simulated spontaneous breathing (p=0.013) Conclusion: Aerosol treatment may be administered to young children using JN, VMN, or pMDI/VHC combined with resuscitator bag. Using pMDI/VHC with resuscitator bag is the best choice to deliver albuterol in spontaneously breathing children. Further studies are needed to determine the effectiveness of these aerosol generators with different type of resuscitator bag and different breathing parameters.

No / Aims To determine the bioavailability of gentamicin to the lung following inhalation from two jet nebulizers. Methods Serial urine samples were obtained from 10 volunteers after a 80 mg dose given orally, nebulized from a Pari LC + (PARI) and MicroNeb III (MN) devices, or after a 40 mg intravenous dose. In vitro aerodynamic characteristics of the nebulized doses were also determined. Results The mean (SD) absolute gentamicin lung bioavailalibility following delivery by PARI and MN devices was 1.4 (0.4) and 1.7 (0.5) %. The mass median aerodynamic diameter (MMAD) of the drug particles from the PARI and MN systems was 8.6 (0.6) and 6.7 (0.5) µm and the corresponding fine particle doses (FPD) were 10.2 (2.8) and 11.7 (1.5) mg. Conclusions The MMAD and FPD data reflect the poor lung deposition of gentamicin identified by urinary excretion.

A concentric pneumatic nebulizer (CPN) and a custom designed flow focusing nebulizer (FFN) are characterized. As will be shown, the classical Nukiyama-Tanasawa and Rizk-Lefebvre models lead to erroneous size prediction for the concentric nebulizer under typical operating conditions due to its specific design, geometry, dimension and different flow regimes. The models are then modified to improve the agreement with the experimental results. The size prediction of the modified models together with the spray velocity characterization are used to determine the overall nebulizer efficiency and also employed as input to a new Maximum Entropy Principle (MEP) based model to predict joint size-velocity distribution analytically. The new MEP model is exploited to study the local variation of size-velocity distribution in contrast to the classical models where MEP is applied globally to the entire spray cross section. As will be demonstrated, the velocity distribution of the classical MEP models shows poor agreement with experiments for the cases under study. Modifications to the original MEP modeling are proposed to overcome this deficiency. In addition, the new joint size-velocity distribution agrees better with our general understanding of the drag law and yields realistic results.

A concentric pneumatic nebulizer (CPN) and a custom designed flow focusing nebulizer (FFN) are characterized. As will be shown, the classical Nukiyama-Tanasawa and Rizk-Lefebvre models lead to erroneous size prediction for the concentric nebulizer under typical operating conditions due to its specific design, geometry, dimension and different flow regimes. The models are then modified to improve the agreement with the experimental results. The size prediction of the modified models together with the spray velocity characterization are used to determine the overall nebulizer efficiency and also employed as input to a new Maximum Entropy Principle (MEP) based model to predict joint size-velocity distribution analytically. The new MEP model is exploited to study the local variation of size-velocity distribution in contrast to the classical models where MEP is applied globally to the entire spray cross section. As will be demonstrated, the velocity distribution of the classical MEP models shows poor agreement with experiments for the cases under study. Modifications to the original MEP modeling are proposed to overcome this deficiency. In addition, the new joint size-velocity distribution agrees better with our general understanding of the drag law and yields realistic results.

BACKGROUND: Aerosol therapy using albuterol is one of the most prescribed asthma treatments. The most frequently used methods of aerosol delivery are pneumatic jet nebulizer (JN), pressurized metered-dose inhaler (pMDI), and breath-actuated nebulizer (BAN). Choosing among these devices is usually not based on thorough comparison of efficiency or cost. We compare the efficiency of these three devices using a spontaneously breathing adult model. METHODS: We connected each aerosol generator—JN, BAN, or pMDI with a valved holding chamber (VHC)—to the face of an adult teaching manikin. Below the bifurcation, an elbow adaptor was connected to a corrugated tube and was angled to be at a lower level than the collecting filter to prevent droplets from dripping directly into the collecting filter. From the collecting filter, another corrugated tube was connected to a prevention filter, which was then connected to an adult breathing simulator. Spontaneous breathing parameters were VT 450 mL, RR 20/min, and I: E ratio 1:2. First, we compared JN, BAN (2.5 mg/3 mL), and pMDI (4 puffs); second, we compared JN and BAN 2.5 mg/0.5 mL plus 0.5 mL normal saline. Data were analyzed using spectrophotometry (276 nm). One-way ANOVA and independent sample t-tests were used (p<0.05). RESULTS: There were no differences in inhaled mass percentage (p=0.172) JN, BAN, and pMDI in the first experiment. Treatment time with BAN was significantly longer (p=0.0001) than with JN or pMDI. In the second experiment, BAN delivered more medication (p=0.004) than jet nebulizer. Treatment time was significantly less with JN (p=0.010). There was no difference in residual volume among JN and BAN in both experiment (p=0.765, p=0.115). CONCLUSIONS: All the devices that were compared using a 3 ml or 4 pMDI puffs delivered comparable amount of medication with no significant difference. However, BAN using 1ml fill volume delivers more drug compared to JN. Additionally, treatment time was longest with BAN. Even with reduction of its filling volume, BAN delivers a higher amount of medication to that of pMDI but was not statistically significant.

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The present study was firstly aimed at producing the AM fungal inocula by using soil-based and soil-less culture techniques, including the in-vitro axenic technique, and secondly to assess the infectivity and effectiveness of the inocula so produced in glasshouse and field conditions. Indigenous AM fungi from 5 different sites of New South Wales were successfully propagated and multiplied using the pot-culture and atomizing disc aeroponic culture techniques, and their infectivity was measured using the MPN bioassay method. The coarse and fine sand mix was proven to be very effective for the production of AM fungal inocula. The findings indicated that aeroponic culture technique is far superior to that of conventional pot-culture technique, and could possibly substitute the most commonly used pot-culture technique of AM fungal inoculum production. The ultra-sonic nebulizer technology could possibly be an alternative to conventional aeroponic systems for producing AM fungal isolates in commercial quantities. The introduction of the sheared-root inoculum of Glomus intraradices, produced by the ultra-sonic nebulizer technique, into agricultural soils can substantially reduce the intake of P-fertilizers as much as 50% of the recommended level. The study also indicated that soil phosphorus is a critical factor in limiting mycorrhizal colonization, possibly limiting mycorrhizal responses.The research suggests that various commercially produced single or 'cocktail' inocula may work on mycorrhiza dependent plants in soils where the indigenous AM flora is either not abundant and/or efficient. Furthermore, ecophysiology of the same AM species have different effects on plant growth. / Doctor of Philosophy (PhD)

Background: HFNC system is a novel device used with aerosol therapy and seems to be rapidly accepted. Although there are some studies conducted on HFNC and vibrating mesh nebulizer, the effect of HFNC on aerosol delivery using jet nebulizer or pressurized metered-dose inhaler (pMDI) has not been reported. In an effort to examine the effect of HFNC on aerosol deposition, this study was conducted to quantify aerosol drug delivery with or without a HFNC using either pMDI or jet nebulizer. Methodology: The SAINT model, attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc., Englewood, CO, USA) for aerosol collection, was connected to a pediatric breathing simulator (Harvard Apparatus, Model 613, South Natick, MA, USA). To keep the filter and the SAINT model in upright position to collect aerosolized drug, an elbow adapter was connected between the absolute filter and the breathing simulator. An infant HFNC (Optiflow, Fisher & Paykel Healthcare LTD., Auckland, New Zealand) ran at 3 l/min O2 was attached to the nares of the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Aerosol drug was administered using: 1) Misty-neb jet nebulizer (Allegiance Healthcare, McGaw Park, Illinois, USA) powered by air at 8 l/min using pediatric aerosol facemask (B&F Medical, Allied Healthcare Products, Saint Louis, MO, USA) to deliver albuterol sulfate (2.5 mg/3 mL NS), and 2) Four actuations of Ventolin HFA pMDI (90 μg/puff) (GlaxoSmithKline, Research Triangle Park, NC, USA) combined with VHC (AeroChamber plus with Flow-Vu, Monaghan Medical, Plattsburgh, NY, USA). Aerosol was administered to the model with and without the HFNC and another without (n=3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. Independent t tests were performed for data analysis. Statistical significance was determined with a p value of <0.05. Results: The mean inhaled mass percent was greatest for pMDI with (p = 0.0001) or without HFNC (p = 0.003). Removing HFNC from the nares before aerosol treatment trended to increase drug delivery with the jet nebulizer (p = 0.024), and increased drug delivery by 6 fold with pMDI (p = 0.003). Conclusions: Aerosol drug may be administered in pediatrics receiving HFNC therapy using either jet nebulizer or pMDI. However, using pMDI, either with or without HFNC, is the best option. When delivering medical aerosol by mask, whether by jet nebulizer or pMDI, removing HFNC led to an increase in inhaled mass percent. However, the benefit of increased aerosol delivery must be weighed against the risk of lung derecruitment when nasal prongs are removed.

Accompanied with the improvements of instrument, design, mass spectrometer can provide rapid detection speed, accurate molecular weight of the analyte, and analyte structure, which was identified by tandem mass spectrometry (MS / MS). Because of rapid detection speed of mass spectrometer not only can be applied for real-time detection of the signals of the reactants and products in chemical reactions, but also was validated to detect the intermediates, which have existed in a very short time. For real-time monitoring of liquid phase chemical reactions, it not only must has an the rapid detection speed of mass spectrometer, but also have a suitable ionization source, which can assist that neutral analytes in the liquid directly fused into gas phase and be ionized to form analyte ion. In this study, ion spray ionization source was applied to explore the drolpet-synthesis reaction in the gas phase. In the experimental process, pneumatic nebulizer was validated for producing neutral droplets. The atomization effect is mainly caused by validating high-speed air flow through the liquid surface to shatter the liquid solution into population of droplets. In this experiment, two pneumatic atomizer set at a particular angle for spraying neutral droplets; some of neutral droplets with different analytes would fused into larger one in the gas phase. At the same time, reactant A and reactant B in the fused droplet would process chemical reaction in just a few hundred microseconds. End of the chemical reaction, fused droplets was sent near the entrance of MS inlet by the transmission of gas flow, dry air eluted from mass entrance outflow (dry gas) was validated for the desolvation. Based on the field ionization mechanism, induced electrospray ionization was occurred when MS inlet applied with 4.5 kV. Then, analyte ions via induced electrospray ionization were transferred to the inner of MS inlet and detected by mass spectrometer. In this experiment, several experimental parameters have been discussed and optimized including the angle of nebulizer (15 degrees - 90 degrees), the flow rate of nebulizing gas (3 psi -15 psi), the flow rate of sample solution (100 £gL/hr. - 500 £gL/hr), the flow rate of dry gas (3 L/min - 12 L/min) and the temperature of dry gas (50 oC-300 oC) for improvement of the reaction process and ionization efficiency. Finally, the droplet-synthesis reaction was performed under the optimal experimental parameters. The derivatives of aniline as reagent A, consisting a phenyl group attached to the different functional groups including hydroxyl group (-OH), nitric group (NO2), varied the different functional groups to change the reaction rate of reactant A in the chemical reaction. Then, benzaldehyde and acetic anhydride as reagent B was separately reacted with reagent A via droplet synthesis process to perform addition-elimination reaction. Beside, all of the tested chemical reactions through droplet-synthesis device were also re-verified by the liquid phase chemical reaction. Through the observation of mass spectra, The comparison of the differences (i.e. intermediate and product) between droplets synthesis reaction and liquid phase chemical reaction can also be obtained.