Small-volume nebulizer

The key to a successful HPLC-ICP-MS coupling is the interface. In the simplest case the outlet of an HPLC column (4.6 D10 mm) is connected to a conventional pneumatic or crossBow nebulizer. The use of capillary or megabore (0.32D1.0mm) HPLC systems that are becoming popular, especially for RPC, requires the use of micronebulizers, either direct injection nebulizers (DIN) or micronebulizers (e.g., Micromist, DS-5) bttcd with a small-volume nebulization chamber. 

P3). The average mass median aerodynamic diameter was 3.55 0.07 pm with the geometric standard deviation of 2.55. The test was also conducted to compare the device performance with other small-volume nebulizers,and found to be more efficient in the delivery rate (mass out per minute) than that of other SVNs. 

Blacker, R. Morton, R.W. Mitchell, J.P. Nagel, M.W. Hess, D.R. The Effect of Small Volume Nebulizer (SVN) Design on Fine Particle Mass Delivery of a Bronchodilator, Present at Drug Delivery to the Lungs, London, UK, Dec., 1999. 

Clinical complications related to the use of nebulizers have been observed. Facial dermatitis with superimposed bacterial infections have been described and are caused by the prolonged use of a face mask [145]. Contamination of the small-volume nebulizers has been linked with oropharyngeal colonization [146,147]. In one report, infections were seen four times more frequently in patients receiving inhalation therapy for respiratory diseases than in those who are not. At least one example of death resulting from contamination has been reported. 

Mitchell JP, Scarrot PM, Nagel MW, Wiersema KJ, Bates SA, Lusty ME. An in vitro investigation of common nebuhzer dosing protocols, comparing a breath-actuated with a conventional pneumatic small volume nebulizer. In Respiratory Drug Delivery V Dalby RN, Byron PR, Farr SJ, eds. Interpharm Press Tucson, AZ, 2002 627-630. 

Gutierrez CJ, Nelson R. Short-term bronchodilation in mechanically ventilated patients receiving metaproterenol via small volume nebulizer (SVN) or metered-dose inhaler (MDI). Respir Care 1988 33 910-913. 

In cases of severe acute asthmatic attacks, bronchodilators and steroids for direct dehveiy to the lungs may be needed in large doses. This is achieved by direct inhalation via a nebulizer device this converts a liquid into a mist or fine spray. The dmg is diluted in small volumes of Water for Injections BP before loading into the reservoir of the machine. This vehicle must be sterile and preservative-fiee and is therefore prepared as a terminally sterilized unit dose in polyethylene nebules. 

The sample solution is drawn first into a nebulizer by the flow of support gas where it forms a mist or aerosol. Fuel gas is introduced and the mixture passed to a spray chamber where large droplets condense and run to waste. Alternatively a small volume of solution (10-100 pi) may be injected directly into the orifice of the nebulizer using a micropipette. 

In ICP-MS mostly liquids are analyzed. The aqueous solution is nebulized using an effective pneumatic nebulizer (e.g., Meinhard or MicroMist nebulizer with cyclonic spray chamber, ultrasonic nebulizer (USN), microconcentric nebulizer with desolvator (e.g., Aridus or APEX), the latter for the introduction of small volumes of solution)3 as described in Section 5.1.6. 

Figure 21-24 compares detection limits for flame, furnace, and inductively coupled plasma analyses on instruments from one manufacturer. The detection limit for furnaces is typically two orders of magnitude lower than that observed with a flame because the sample is confined in the small volume of the furnace for a relatively long time. For instruments in Figure 21-24, detection limits for the inductively coupled plasma are intermediate between the flame and the furnace. With ultrasonic nebulization and axial plasma viewing, the sensitivity of the inductively coupled plasma is close to that of the graphite furnace. 

Vapor phase dissolution (VPD) is commonly used for surface and contamination analysis of semiconductor wafers [374-379]. HF vapor is used to remove a silicon oxide or native silicon layer. A drop of hydrofluoric acid or deionized water (with a volume of 50 to 200 jxL) is placed on the surface and rolled around the surface to dissolve the metals. The small drop is then analyzed by ICP-MS by using either a direct injection nebulizer, a micronebulizer, or ETV. The ability of ICP-MS to measure several elements rapidly in a small volume of solution is essential. 

Over the years many analytical spectroscopists have attempted to improve upon this situation, but the only reliable way to improve transport efficiency with pneumatic nebulizers is apparently to restrict the aspiration rate.17,18 Reduced aspiration rate means that the nebulizer energy is distributed to less aerosol per unit time, resulting in a finer droplet size distribution finer droplets (e.g. < 2 pm in diameter) are more likely to be transported through the spray chamber. Alternatively, the determinant may be introduced to the flame in gaseous form, or in a small cup. Such approaches are discussed in Chapter 6. However often the approach taken is to use electrothermal atomization rather than a flame,6,19 but this is outwith the scope of the present small volume. 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

Flow injection procedures are very useful for performing trace analyses in highly concentrated salt solutions. Fang and Welz [270] showed that the flow rate of the carrier solution can be significantly lower than the aspiration rate of the nebulizer. This allows even higher sensitivities than with normal sample delivery can be obtained. Despite the small volumes of sample solution, the precision and the detection limits are practically identical with the values obtained with continuous sample nebulization. The volume, the form of the loop (single loop, knotted reactor, etc.) and the type and length of the transfer line between the flow injection system and the nebulizer considerably influence the precision and detection limits that are attainable. 

Jet nebulizer (small volume) Volume fill (3-6 mL) Gas flow (6-12 L/min) Dead-space volume Open versus closed system Thumb-activating valve Mouthpiece versus facemask Inspiratory flow (slow, deep) Breath-holding Tapping nebulizer... 

Wildhaber JH, Devadason SG, Hayden Ml, Eber E, Summers QA, LeSouef PN. Aerosol delivery to wheezy infants a comparison between a nebulizer and two small volume spacers. Pediatr Puhnonol 1997, 23 212-216. 

The power consumption of the vibrating membrane is low allowing small batteries to power the device. Because the additional components (fluid reservoir, electronics, mouthpiece, and valves) do not require large volumes, it should be feasible to develop a small, portable nebulizer with a self-contained battery... 

The combination of nebulizing and desolvation gases (probe parameters) described above is suited to liquid flows of -0.2 ml/min. Because mass spectrometry is a concentration-dependent technique, reducing solvent flow will increase the residence time of the analyte in the source. The consequent enhancement of absolnte sensitivity can reach 1,000-fold. The potential for snch inCTeases in sensitivity led to the development of instrumentation and techniqnes for LC where solvent flows are 0.3-1.0 til/min, nano-LC. At such flow rates fused silica and stainless steel lines (with tips tapered to 10-20 ti) can be used as the ESI source. The flow rates in nano-LC also permit the reduction of the nebulization gas pressure to -250 Torr (<1 bar), sometimes even to zero. Furthermore, a drying gas is no longer required. When there is no need to separate the components of the sample, small volumes of material (-1 al) can be loaded into a capillary and placed in the ESI housing. In this case no gases are needed and the potential difference between the liquid in the capillary and that in the instrument chamber is sufficient to create an electro-osmotic flow of nebulized droplets from the tip of the capillary. 

Concentric nebulizers date back more than a century, to Gouy [75], and in principle are selfaspirating. They can be made of metal, plastic, or glass. In atomic absorption spectrometry. Pt-lr capillaries are often used to allow the aspiration of highly acid solutions. In plasma atomic spectrometry, concentric glass nebulizers (Meinhard) 74] are well known. They use a rather lower gas flow (1-2 L/min) than atomic absorption types (up to 5 L/min). In both cases, aspiration rates are 1-2 mL/min and aerosol efficiencies 2-5%. Direct injection nebulizers are a useful alternative for the introduction of small-volume samples [76]. 

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