Nebulizer System Research Articles

Radial line-scans as representative sampling strategy in dried-droplet laser ablation of liquid samples deposited on pre-cut filter paper disks

Nebulising liquid samples and using the aerosol thus obtained for further analysis is the standard method in many current analytical techniques, also with inductively coupled plasma (ICP)-based devices. With such a set-up, quantification via external calibration is usually straightforward for samples with aqueous or close-to-aqueous matrix composition. However, there is a variety of more complex samples. Such samples can be found in medical, biological, technological and industrial contexts and can range from body fluids, like blood or urine, to fuel additives or fermentation broths. Specialized nebulizer systems or careful digestion and dilution are required to tackle such demanding sample matrices. One alternative approach is to convert the liquid into a dried solid and to use laser ablation for sample introduction. Up to now, this approach required the application of internal standards or matrix-adjusted calibration due to matrix effects. In this contribution, we show a way to circumvent these matrix effects while using simple external calibration for quantification. The principle of representative sampling that we propose uses radial line-scans across the dried residue. This compensates for centro-symmetric inhomogeneities typically observed in dried spots. The effectiveness of the proposed sampling strategy is exemplified via the determination of phosphorus in biochemical fermentation media. However, the universal viability of the presented measurement protocol is postulated. Detection limits using laser ablation-ICP-optical emission spectrometry were in the order of 40μgmL−1 with a reproducibility of 10 % relative standard deviation (n=4, concentration=10 times the quantification limit). The reported sensitivity is fit-for-purpose in the biochemical context described here, but could be improved using ICP-mass spectrometry, if future analytical tasks would require it. Trueness of the proposed method was investigated by cross-validation with conventional liquid measurements, and by analyzing IAEA-153 reference material (Trace Elements in Milk Powder); a good agreement with the certified value for phosphorus was obtained.

Capturing the Efficiency of Vibrating Mesh Nebulizers: Minimizing Upper Airway Deposition

Vibrating mesh devices are portable nebulizer systems with reported high efficiency. Losses occur during expiration, and particle size distributions vary. We describe an aerosol chamber designed to capture and condition aerosols from a typical vibrating mesh nebulizer, the Omron U22. The goal was to improve inhaled mass (IM) and respirable fraction (RF) and shorten treatment time. With test solutions of radiolabeled saline, we characterized the Omron U22 (three examples) vibrating mesh nebulizer measuring aerosol output with different breathing patterns, with and without manual breath synchronization. Particle size distributions were measured by cascade impaction as a "standing cloud" and during ventilation with a piston respirator. IM (percentage of nebulizer charge), respirable mass (RM), particle size distribution, and breathing time were measured with and without use of the chamber. Breathing patterns were designed to simulate tidal breathing with a "COPD" (chronic obstructive pulmonary disease) pattern (450 mL, rate 15, duty cycle 0.35) and "slow and deep" breathing for maximal lung deposition (1,500 mL, rate 5, duty cycle 0.70). Patterns of deposition were confirmed in a human volunteer using a gamma camera. IM was significantly affected by breathing pattern and averaged 30.0±2.91% and 53.9±7.99% for COPD and slow and deep patterns, respectively. With the chamber, IM was less sensitive to breathing pattern (57.4±6.97%, 57.9±4.69%, respectively). Particle size distributions varied widely between devices and were markedly affected by both ventilating the device and addition of the chamber. With the chamber, RF and RM increased, and differences in particle size distributions between individual devices were minimized. Compared with breath synchronization, treatment time was reduced. Gamma camera images revealed reduced upper airway deposition consistent with predictions from in vitro cascade distributions. Our prototype chamber allowed for capture and conditioning of nebulized aerosol by mixing with room air and removal of large particles by impaction, providing better control of IM, RF, RM, and lung deposition, without the need for breath synchronization.

Elemental speciation by capillary electrophoresis with inductively coupled plasma spectrometry: A new approach by Flow Focusing® nebulization

A novel system for Capillary Electrophoresis (CE) and Inductively Coupled Plasma (ICP) sample introduction that incorporates a dedicated Flow Focusing® based nebulizer as aerosol generation unit is presented, aiming to provide high signal sensitivity and low detection limits for element speciation at short analysis times. To prove its viability, the system prototype constructed has been coupled to an inductively coupled plasma-optical emission spectrometer (ICP-OES) and an inductively coupled plasma-mass spectrometer (ICP-MS) for Cr(III) and Cr(VI) speciation. Separation–nebulization system and operation parameters (i.e., capillary length, nebulizer geometry, carrier flow, carrier ionic strength, separation potential and sample injection volume) have been considered and studied, and the analytical figures of merit obtained for model samples in ICP-MS are presented. The results obtained show that the developed instrumental system permits Cr speciation in less than 2min with detection limits of 0.1, 0.2 and 0.03μg/L for Cr(III), Cr(VI) and total Cr, respectively.

Determination of 234U/238U, 235U/238U and 236U/238U isotope ratios in urine using sector field inductively coupled plasma mass spectrometry

Quantification of the isotopic composition of uranium in urine at low levels of concentration is important for assessing both military and civilian populations' exposures to uranium. However, until now there has been no convenient, precise method established for rapid determination of multiple uranium isotope ratios. Here, the authors report a new method to measure (234)U/(238)U, (235)U/(238)U and (236)U/(238)U. It uses solid-phase chelation extraction (via TRU columns) of actinides from the urine matrix, followed by measurement using a magnetic sector field inductively coupled plasma mass spectrometer (SF-ICP-MS-Thermo Element XR) equipped with a high-efficiency nebulizer (Apex PFA microflow) and coupled with a membrane desolvating nebulizer system (Aridus II™). This method provides rapid and reliable results and has been used successfully to analyse Certified Reference Materials.

Size effect on transfection and cytotoxicity of nanoscale plasmid DNA/polyethyleneimine complexes for aerosol gene delivery

Nanoscale plasmid DNA (pDNA)/polyethyleneimine (PEI) complexes were fabricated in the aerosol state using a nebulization system consisting of a collison atomizer and a cool-walled diffusion dryer. The aerosol fabricated nanoscale complexes were collected and employed to determine fundamental properties of the complexes, such as size, structure, surface charge, and in vitro gene transfection efficiency and cytotoxicity. The results showed that mass ratio between pDNA and PEI should be optimized to enhance gene transfection efficiency without a significant loss of cell viability. These findings may support practical advancements in the field of nonviral gene delivery.

Towards the use of ICP-OES for the elemental analysis of organic compounds such as glucosamine

Inductively coupled plasma optical emission spectrometry with a long demountable torch (whose outer tube is 2.5 cm longer than a standard torch) and a conventional pneumatic nebulisation system was applied to the determination of C, H and O concentrations from an organic compound dissolved in water. The sample solution was simply aspirated directly into the plasma without any sample pre-treatment (such as desolvation or degassing). The long torch was required to significantly decrease the background arising from entrained air. Good linearity was obtained for C, N, H and O upon calibration with standard solutions prepared from ultrapure tris(hydroxymethyl)aminomethane. A weighed blank correction was applied to compensate for the contribution from water, especially in the cases of H and O. Under these conditions, the detection limits for C, N, H and O were, respectively, 0.2, 50, 1000 and 2000 μmol of analyte per g of solution. Accurate concentrations, according to a Student's t test at the 95% confidence level, were measured for C, H and O in a solution of D-glucosamine hydrochloride. No internal standardisation was necessary. However, the N concentration was biased high, irrespectively of the N emission line used (from 149.262 to 593.178 nm), which rules out spectroscopic interference and will be further investigated. Nonetheless, the possibility of accurately determining C, H and O simultaneously with trace elements makes the approach quite promising. It is much simpler than alternate methods that require derivatisation of the compound prior to detection.

Study of a direct current atmospheric pressure glow discharge in helium with wet aerosol sample introduction systems

In this study a He DC atmospheric pressure glow discharge (APGD) is characterized under dry conditions and with the introduction of wet aerosols. The aerosols are generated by a conventional pneumatic nebulization system using a MicroMist nebulizer placed in a double pass spray chamber according to Scott or alternatively by a custom-built drop-on-demand (DOD) system based on printer cartridges. The experiments are performed at a He gas flow of 500 mL min−1 and 40 mA current. The influences of the H2O load on the discharge rotational temperature (Trot), excitation temperature (Texc) and the electron number density (ne) are determined. Temperature reductions when comparing dry and wet conditions are found to be around 500 K for the Trot and 240–400 K for the Texc. Detection limits for the elements Cd, Cu, Mg, Mn and Na are presented for pneumatic nebulization coupled to a continuous flow injection system. They are found to be between 10 μg L−1 for Na and 140 μg L−1 for Cu. In the case of the drop-on-demand system a value of 16 μg L−1 for Na was obtained. The applicability of the discharge to the determination of Na in a tap water sample at concentration levels of 20 mg L−1 is shown for both introduction systems and the accuracy of the results is found to be within 1.3 mg L−1 as compared to the result of inductively coupled plasma optical emission spectrometry (ICP-OES).

Nebulizing poractant alfa versus conventional instillation: Ultrastructural appearance and preservation of surface activity

Nebulized surfactant therapy has been proposed as an alternative method of surfactant administration. The use of a perforated vibrating membrane nebulizer provides a variety of advantages over conventional nebulizers. We investigated the molecular structure and integrity of poractant alfa pre- and post-nebulization. Curosurf® was nebulized using an Investigational eFlow® Nebulizer System. Non-nebulized surfactant ("NN"), recollected surfactant droplets from nebulization through an endotracheal tube ("NT") and nebulization of surfactant directly onto a surface ("ND") were investigated by transmission electron microscopy. Biophysical characteristics were assessed by the Langmuir-Wilhelmy balance and the Captive Bubble Surfactometer. Volume densities of lamellar body-like forms (LBL) and multi-lamellar forms (ML) were high for "NN" and "NT" samples (38.8% vs. 47.7% for LBL and 58.2% vs. 47.8% for ML). In the "ND" sample, we found virtually no LBL's, ML's (72.6%) as well as uni-lamellar forms (16.4%) and a new structure, the "garland-like" forms (9.4%). Surface tension for "NN" and "NT" was 23.33 ± 0.29 and 25.77 ± 1.12 mN/m, respectively. Dynamic compression-expansion cycling minimum surface tensions were between 0.91 and 1.77 mN/m. The similarity of surfactant characteristics of nebulized surfactant via a tube and the non-nebulized surfactant suggests that vibrating membrane nebulizers are suitable for surfactant nebulization. Alterations in surfactant morphology and characteristics after nebulization were transient. A new structural subtype of surfactant was identified.

Nebuliser systems for drug delivery in cystic fibrosis

Nebuliser systems for drug delivery in cystic fibrosis

In Vitro Delivery of Aerosolized Treprostinil via Modern Mechanical Ventilation

The Tyvaso Inhalation System is a hand-held nebulizer system used to administer treprostinil, an approved therapy for pulmonary arterial hypertension. Our goal was to establish an in vitro method for delivering a standard dose of treprostinil through a ventilator circuit and artificial airway. An AeroTech II jet nebulizer (continuous air flow at 10 L/min; Biodex Medical Systems) was placed in the ventilator circuit with a test lung. Two ventilators were tested, the Dräger Evita 2 Dura (Dräger Medical GmbH) and Avea (CareFusion), without humidity. Delivered dose was defined by capturing radiolabeled particles exiting the endotracheal tube with a filter (Pari) and measuring radioactivity. Particle distributions were measured distal to the endotracheal tube by cascade impaction. We hypothesized that drug delivery would be determined by the number of breaths needed, such that the complete time of inspiration totaled 29 sec (e.g., number of breaths needed=29 sec/TI, where TI is the inspiratory time of an average breath read from the ventilator display). Nebulizer output was linear for 6 min, and the standard prescribed target dose of 54 μg (3.1% of full ampule) was delivered in 29 sec. Using our TI algorithm to control delivery, the mean inhaled dose±SD was 72.2±16.5 μg (range 47.2-98.6; n=23). Dräger delivered higher doses than Avea. Effects of mode, breathing pattern, and positive-end expiratory pressures were not significant. The mass median aerodynamic diameter and fine particle fraction were 0.71±0.015 and 0.997±0.0006, respectively. Using the algorithm, it was possible to deliver aerosolized treprostinil, at controlled doses, via mechanical ventilation over a wide range of controlled breathing patterns. The conditions of nebulization must be precisely followed (one full ampule per treatment, use of the AeroTech II nebulizer, continuous nebulization using an external flow of 10 L/min, bypass of the humidifier or removal of in-line heat and moisture exchanger, and treatment completed in 6 min or less).

Determination of trace level cadmium in SRM 3280 Multivitamin/Multielement Tablets via isotope dilution inductively coupled plasma mass spectrometry

Cadmium was quantified at 80.15±0.86ng/g (mean±95% expanded uncertainty) in NIST SRM 3280 Multivitamin/Multielement Tablets, using isotope dilution mass spectrometry. The method described utilized various precipitation and solid-phase extraction separation methodologies to isolate Cd from Sn and Mo, present respectively, at 11.1±0.9mg/kg and 70.7±4.5mg/kg in the tablet matrix. This allowed for measurement of 111Cd/113Cd and 111Cd/114Cd isotope ratios using both quadrupole collision cell technology inductively coupled plasma mass spectrometry (Q-CCT-ICP-MS) and sector field (SF)-ICP-MS equipped with a desolvating nebulizer system to mitigate the MoO+ and MoOH+ molecular ion interferences that typically affect the envelope of Cd isotopes.

Nebuliser systems for drug delivery in cystic fibrosis

Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.

Nebuliser systems for drug delivery in cystic fibrosis

Nebuliser systems for drug delivery in cystic fibrosis

Small-airways deposition of dornase alfa in children with asthma and persistent airway obstruction

Small-airways deposition of dornase alfa in children with asthma and persistent airway obstruction

In vitro efficiency of Amikacin Inhale, a novel drug-device delivery system

Amikacin Inhale (NKTR-061, BAY41-6551) is a drug-device combination in clinical development for adjunctive treatment of intubated and mechanically ventilated patients with Gram-negative pneumonia. The product uses a proprietary vibrating mesh nebulizer system (PDDS Clinical) with amikacin sulfate formulated for inhalation (3.2 ml of 125 mg/ml amikacin solution) for a 10-day twice-daily course of therapy. It is designed for use with two delivery systems: one system for intubated patients (On-vent; Figure ​Figure1),1), and a second Handheld (HH) system for patients who are extubated before completing the course of therapy (Figure ​(Figure2).2). We investigated in vitro the amikacin lung dose delivered by PDDS Clinical. Open in a separate window Figure 1 On-vent system with brown blinder shell for clinical trials.

Nanoparticle generation by intensified solution crystallization using cold plasma

In this study, atmospheric pressure cold plasma (surface dielectric barrier discharge) was used as an alternative energy form to intensify solution crystallization and produce nano-sized organic crystals. Nano-sized particles can have beneficial product properties such as improved internal quality and dissolution rate, compared to conventionally sized crystalline products. In cold plasma intensified crystallization a nebulizer system sprays the solution aerosol into the plasma with the help of a carrier gas. The plasma simultaneously heats and charges the droplets causing fast solvent evaporation and Coulomb-fission to occur, after which nucleation and crystal growth commence within the small, confined volume offered by the small droplets. In this manner, nano-sized crystals of the energetic material RDX and the pharmaceutical niflumic acid were produced.

Recognizing and overcoming analytical error in the use of ICP-MS for the determination of cadmium in breakfast cereal and dietary supplements

The potential effect of spectral interference on the accurate measurement of the cadmium (Cd) mass fraction in fortified breakfast cereal and a variety of dietary supplement materials using inductively coupled plasma quadrupole mass spectrometry was studied. The materials were two new standard reference materials (SRMs)--SRM 3233 Fortified Breakfast Cereal and SRM 3532 Calcium Dietary Supplement--as well as several existing materials--SRM 3258 Bitter Orange Fruit, SRM 3259 Bitter Orange Extract, SRM 3260 Bitter Orange-containing Solid Oral Dosage Form, and SRM 3280 Multivitamin/Multielement Tablets. Samples were prepared for analysis using the method of isotope dilution and measured using various operating and sample introduction configurations including standard mode, collision cell with kinetic energy discrimination mode, and standard mode with sample introduction via a desolvating nebulizer system. Three isotope pairs, (112)Cd/(111)Cd, (113)Cd/(111)Cd, and (114)Cd/(111)Cd, were measured. Cadmium mass fraction results for the unseparated samples of each material, measured using the three instrument configurations and isotope pairs, were compared to the results obtained after the matrix was removed via chemical separation using anion exchange chromatography. In four of the six materials studied, measurements using the standard mode with sample introduction via the desolvating nebulizer gave results for the unseparated samples quantified with the (112)Cd/(111)Cd isotope pair that showed a positive bias relative to the matrix-separated samples, which indicated a persistent inference at m/z112 with this configuration. Use of the standard mode, without the desolvating nebulizer, also gave results that showed a positive bias for the unseparated samples quantified with the (112)Cd/(111)Cd isotope pair in three of the materials studied. Collision cell/kinetic energy discrimination mode, however, was very effective for reducing spectral interference for Cd in all of the materials and isotope pairs studied, except in the multivitamin/multielement matrix (SRM 3280) where the large corrections for known isobaric interferences or unidentified interferences compromised the accuracy. For SRM 3280, matrix separation provided the best method to achieve accurate measurement of Cd.

Cold plasma synthesis of high quality organic nanoparticles at atmospheric pressure

Atmospheric pressure cold surface dielectric barrier discharge (SDBD) plasma was used for the first time to produce nano-sized organic crystals. Nano-sized particles can have beneficial product properties, such as improved internal quality and dissolution rate, compared to conventionally sized crystalline products. In cold plasma crystallization a nebulizer system sprays the solution aerosol into the plasma with the help of a carrier gas. The plasma heats and charges the droplets causing solvent evaporation and coulomb fission to occur, after which nucleation and crystal growth commence within the small, confined volume offered by the small droplets. As a result nano-sized crystals are produced. The operation conditions of SDBD plasma to produce nano-sized crystals of the energetic material RDX were determined by scanning electron microscopy, and the product was investigated with X-ray powder diffraction and sensitivity tests. The sensitivity tests indicated that the nano-sized product had reduced sensitivity for friction, indicating a higher internal quality of the crystalline product.

Targeted versus chrono-targeted chemotherapy for inhaled chemotherapy in non-small cell lung cancer.

Lung cancer long term survival still remains poor and early detection is still the best methodology to treatment. Therefore several novel approaches have been investigated for anticancer drug administration. Inhaled therapies for lung diseases are used since the ancient times. Inhaled anticancer treatment administration was firstly investigated almost 30 years ago. Since then the inclusion and exclusion criteria have been investigated in correlation with the safety and efficacy of cisplatin, 5-fluoracil, carboplatin, paclitaxel, docetaxel, 9-nitro camptothecine, gemcitabine, cetuximab, granulocyte-colony stimulating factor, interleukins and recently with bevasizumab. Along with the anticancer drug formulations administered, other aspects of this local treatment have been also investigated to improve the efficiency and safety, such as; proper nebulization system, drug formulation delivery system, setting of administration, aerosol protection measures, inhalation techniques and safety issues follow up. During the last years with the use of actigraphy wrist watches, an extended investigation of the circadian rhythm of animals and humans has been performed and new insights are included in lung cancer chemotherapy administration. The "personalized" therapy administration should not be considered only as a molecular pathway inhibition, but also as a chrono-targeted anticancer treatment.

Aerosol Delivery to the Lung Is More Efficient Using an Extension with a Standard Jet Nebulizer than an Open-Vent Jet Nebulizer

Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2). In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2). In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p<0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p<0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p<0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p<0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.