the importance of atomic spectrometry in life and the ...plasma source spectrometry has...

ILASS-Americas 30th Annual Conference on Liquid Atomization and Spray Systems, Tempe, AZ, May 2019

The Importance of Atomic Spectrometry in Life and the Significance of Spray Quality

Akbar Montaser1* and John A. McLean2 1. Department of Chemistry

The George Washington University Washington, DC, 20052 USA

2. Department of Chemistry and Center for Innovative Technology Vanderbilt University

Nashville, TN 300235 USA

Abstract No one investigating atomic spectrometry one century ago could have conceived the amazing future journeys that are being traveled now in plasma spectrometry, expressly with inductively coupled plasmas (ICPs). It was G.E.F. Lundell in 1933 who settled how elemental analysis must be performed.1 He asserted that certain methods of chemical analysis "are about as helpful to the analyst as the method for catching a bird which the old folks used to recommend to children-namely, to sprinkle salt on its tail. To do that, one obviously must have the bird in hand, and in that case, there is no need for the salt." To highlight the absence of reliable and straightforward methods of chemical analysis, Lundell further advanced: "There is no dearth of methods that are entirely satisfactory for the determination of elements when they occur alone. The rub comes in because elements never occur alone, for nature and man both frown on celibacy. Methods of determination must, therefore, be judged by their selectiveness. It is in this respect that most methods are weak, and improvement must come". One wonders what to cherish most in Lundell, the psychological understanding for the advancement of ideas, the sureness of scientific argumentation, the deep-felt real intelligence, the capacity for precise, orderly display, the full treatment of the undertaking the subject, or the sureness of definitive assessment. It was an article by Lundell that guided me to the late Professor Velmer Fassel (Iowa State University and Ames Laboratory) who ultimately became my postdoctoral mentor. He had a profound impact on driving to the essential target. For this reason, he was nominated for Nobel Prize just before he passed away. At a major conference, Velmer spoke in recognition of Professor James Winefordner who had won a notable award. As was his standard practice, he critically appraised Professor Wineforder’s publications and asserted that Jim’s most influential article was a review article that he penned with his postdoc, Linda Cline. His deciding tone irritated the audience to the degree that only one person stayed in the hall to compliment Velmer, for what I defined as "an outstanding lecture." Perplexed, he stated: “No one liked my speech other than you!” Being thrilled by his lecture, I told him, "I would like to join your group for the sole purpose of investigating the ICP as an atomization source for atomic fluorescence spectrometry (AFS).2This was an unexpected proposal recognizing that Velmer had vigorously argued against the use of AFS! In puzzlement, he bought the idea! After publishing a single article, ICP-AFS was marketed by the Baird Corporation. This was before the first exploration on ICP-MS by Professor Sam Houk and coworkers, then and now at the Iowa States University and Ames Laboratory. Indeed, ICP-AFS is far more selective than ICP-atomic emission spectrometry and allows excellent detection limits for some, but not all elements. With the arrival of ICP-MS, Baird Corporation closed the destiny of ICP-AFS, my royalties, and consulting fees in relation to ICP-AFS. After the postdoctoral studies, I joined the faculty at the Sharif University of Technology, the so-called MIT of Iran, in Tehran Iran and worked there during 1975-79. Since 1975, our research has been centered on plasma spectrometry for trace, ultratrace, isotopic, and speciation analysis of materials, such as nuclear wastes and semiconductor materials. Here is the most vital subject: The quality of aerosol or spray controls sensitivity, selectivity, accuracy, precision, the amount of sample used for chemical analysis, the ease of conducting the measurements, the simplicity of the entire * Corresponding author: [email protected]


process, and the cost of chemical measurement. Excellent sprays offer excellent results at a low price. My lecture for the ILASS community intends to ask for help. We needed you yesterday and for many years to come! You are the key to our success! Since 1975, our expertise has been centered on fundamental studies, modeling, simulation of plasmas and aerosol systems, expansion of diagnostic systems for exploring plasmas and aerosol systems, investigations of intelligent plasmas and smart aerosols, instrument design, and the applications of aerospace, mechanical, electrical engineering, theoretical astronomy, and optics to the chemistry and the physics of novel plasmas, and cancer research, pharmacology, medical sciences, forensic science, and engineering. The techniques advanced by several groups, counting ours, have transformed the practice of analysis and guided to the advancement of new devices, such as cell phones, high-speed laptop computers, and other high-capacity storage devices. Preceding and current studies not only have marked difficult puzzles, but they have been declared indispensable for undertaking difficulties that could result in the future. These subjects will be discussed during my talk. Further, I will describe exciting potentialities in the development of new plasmas and sprays not being explored by research communities of atomic spectrometry and ILASS.

1. Introduction

Electrical flames, especially the argon inductively coupled plasma (Ar ICP), offer unique features for multielement analysis.3-7 Several traits make the Ar ICP the standard for atomizing, exciting, and ionizing samples of interest. These attributes comprise (a) high gas temperature (4500-8000 K) and electron temperature (8000-10000 K); (b) high electron number density (1-3 x 1015 /cm3); (c) an axial channel to surround the sample aerosol; (d) long residence time of the sample spray inside of the plasma (2-3 ms); (e) vaporization-atomization in a nearly chemically inert setting, (f) almost lack of all molecular species; and (a) a wide dynamic concentration range (up to ten orders of magnitude).

Figure 1. Comparison of atomic spectrometric systems detecting power and dynamic range using combustion flames, electrothermal atomizers, and Ar ICP for several techniques (ThermoFisher Scientific, with permission).

Plasma source spectrometry has revolutionized elemental, isotopic, and speciation analysis.3,4 Examples of

applications in ICP-atomic emission spectrometry (ICP-AES) and ICP mass spectrometry (ICP-MS) are shown in Table 1. For example, the semiconductor industry requires ever smaller electronic devices and more compact integrated circuits. These requirements demand extremely low trace metal impurity levels on the surface of silicon wafers, and high-purity chemicals and gases utilized in many steps of the semiconductor fabrication. Indeed, semiconductor applications constitute one of the most difficult applications areas for ICP-MS. To lessen costs and improve yield, chip producers are making larger diameter wafers with ever smaller chip parts. This trend is being driven by initiatives like the International Technology Roadmap for Semiconductors (ITRS).8 These requirements are establishing the path for the next generation of semiconductor devices. It has led to demands for lower and lower trace-element contamination levels in all semiconductor-related materials. Around 25 years ago the Semiconductor Equipment Manufacturers International (SEMI) organization believed that 10-ppb (µg/L) purity levels were sufficient for several of the process chemicals. Today, Tier C levels of 100 ppt (ng/L) are standard. Indeed, for some of the more critical process chemicals, detection limits of the 10-ppt (ng/L) levels are required.9


Tier C signifies third-generation guidelines generated by the SEMI North American Process Chemicals Committee and published in its Book of Semiconductor Standards (BOSS) (SEMI Book of Standards (BOSS): Process Chemicals.10 The guidelines are meant to define the attributes expected to manufacture integrated circuits whose critical dimensions extend in the range of 0.09–0.2 µm. Currently, hydrochloric acid (HCl) is in the BOSS at the Tier C guideline level, that is the highest contaminant level of 18 elemental impurities should each be less than 100 ppt (ng/L) in the process chemical. Upon completion and approval of the validated analytical method defined in the guideline, it will answer the SEMI Grade 4 Standard.11

Table 1. Highlights of Plasmas Spectrometry for Chemical Analysis of Everything

-----------------------------------------------------------------------------------------------------------------------------------

Semiconductor industry: detection limits of part per 1015 to1018

Isotope ratio analysis: geochemistry, nuclear weapons detection, nuclear wastes, WMD,…

Pharmaceutical analysis: heavy metal content of the drugs, …

Environmental analysis: water quality, speciation, …

Bio-medicine and metallomics Food, nutrition. Biological fluids. Agricultural materials.

Forensics

Sky is the limit………………….

Another key application of ICP-MS, centered on mass cytometry (Figure 2), is the analysis of relative abundances of metal-labeled antibodies, bound to a single cell. It can provide cytometry studies at an unprecedented level of multiplexing, compared with conventional methods. Generally, flow cytometry is the measurement of cell features, including: determining cell characteristics and function, diagnosis of health disorders such as blood cancers, detecting microorganisms, cell counting, cell sorting, biomarker detection, and protein engineering detection. The technique allows investigators to obtain highly specific information about individual cells. To enhance specificity, Fluorescence In Situ Hybridization (FISH) is used. It is a molecular cytogenetic method that applies fluorescent probes that combines with just those parts of a nucleic acid sequence with a high degree of sequence complementarity. Biomedical investigators reported the method in the early 1980s.12 The investigators detected and located the presence or lack of particular DNA series on chromosomes. Usually, FISH is used for determining specific traits in DNA for aiding in genetic counseling, medicine, and species identification.13 Further, FISH can also be used to detect and localize particular RNA targets (mRNA, lncRNA, and miRNA) in cells, circulating tumor cells, and tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells and tissues.

Mass cytometry is a far more powerful technique than fluorescence cytometry. This method entails the simultaneous, high-speed detection allowed by ICP-time of flight mass spectrometry (TOFMS) to provide a multiplexed analysis on single cell level.14 The transient signal of an evaporating cell persists for several 100 µs (Figures 3 and 4). Thus, recording the transient signals at a rate >10 kHz is required to boost the signal/background ratio of the analyses and separate signals from unique cells. In addition, retrospective analysis of the pattern of the transient signals can offer new information on whether multiple and intact cells were sampled.15,16 In contrast to conventional fluorescence detection used in cytometry, the mass cytometry approach provides a dramatic increase in detection channels (effectively > 100). This level of multiplexing not only allows for a much greater depth of information per experiment


but also enables a “barcoding” approach which allows increasing sample throughput. Barcode identification is exceptionally advantageous for single cell genomics. Formation of an ICP. The plasma is formed at the open end of a plasma torch assembly made from three concentric tubes constructed from quartz. The torch is surrounded by a two- to four-turn coil or conductor. The plasma gas is typically argon. Figure 3 shows a picture of the plasma when an yttrium solution aerosol is injected.

Figure 2: Mass cytometry work flow and data processing scheme (with permission, Reference 17).


Figure 3. Time-of-Flight Mass Spectrometry of Nearly Simultaneous Analysis of Several

Elements by Injection of Liquid Sample Using a Direct Injection High Efficiency Nebulizer (DIHEN).14 The DIHEN is discussed later in the article).

Figure 4. Time-of-Flight Mass Spectrometry of Nearly Simultaneous Analysis of

Several Isotope of Chromium by Injection of suspension of Chromium treated human lung cells Using a DIHEN. 14

Sign

al in

tens

ity (c

ount

s/s)

0 10050 150 200 250Time (s)

4000

5000

0

1000

2000

3000

µFIA-DIHEN-ICP-TOFMS100 pg/injection

Anal. At. Spectrom. 17, 669-675 (2002)

6,7Li24,25,26Mg

59Co63,65Cu

64,66,67Zn75As

77,78,82Se85,87Rb

113,115In133Cs

136,137,138Ba140,142Ce

156CeO157CeOH

204,206,207,208Pb235,238U

254UO

Sign

al in

tens

ity (m

V)

28

34

33

32

31

30

36

35

Time (s)14.5 14.7 14.914.6 14.8

29

Transient Signal AnalysisSuspension of Cr treated human lung cells

Anal. At. Spectrom. 17, 669-675 (2002)

52Cr

54Cr53Cr

DIHEN-ICP-TOFMS

50Cr

(83.8 %)

(2.37 %)(9.5 %)

(4.35 %)

Sign

al in

tens

ity (m

V)

28

34

33

32

31

30

36

35

Time (s)14.5 14.7 14.914.6 14.8

29

Transient Signal AnalysisSuspension of Cr treated human lung cells

Anal. At. Spectrom. 17, 669-675 (2002)

52Cr

54Cr53Cr

DIHEN-ICP-TOFMS

50Cr

(83.8 %)

(2.37 %)(9.5 %)

(4.35 %)


Figure 5. The construction of Inductively Coupled Plasma torch. A plasma gas flow of argon is introduced tangentially in the outer tube of a torch made from three concentric quartz tubes. The intermediate gas flow primarily lifts the plasma to protect the central or injector tube. The injector gas transports sample aerosol in the center tube into the ICP. A two- to a four-turn coil or inductor is connected to a RF power supply operated at 1 to 2 kW at a frequency of 27 MHz to 40 MHz. The electrical power creates a strong magnetic field inside the torch. The magnetic field/electrical field form the plasma within the plasma torch. Yttrium aerosol is injected to the plasma with the blue color showing the normal emission zone and the red color showing the cooler tail plume (Perkin Elmer Corporation, with Permission).

Sample Introduction in Plasma Spectrometry. Despite many years of research, sample introduction remains the limiting factor in plasma source spectrometry. While a variety of sample introduction tools are available, no standard scheme exists for the everyday analysis of all samples.

In a perfect source, the sample spray, moving within a doughnut- or donut-shaped plasma, must not modify the fundamental attributes of the Ar ICP, the best sampling location of excited atoms and ions, or the operating characteristics of the spectrometer. In use, the characteristics of the sample spray does alter the original features of the cited properties. Variations in the plasma gas temperature, the electron temperature, the electron number density, or the shape of the plasma alters desolvation-vaporization-atomization-excitation-ionization processes. These shifts in sequence, impact the amount of chemical and spectral interferences presented by the sample, the plasma, and the ICP-AES and ICP-MS instruments. The critical factor for accurate and precise determinations is the generation and transport of a fine aerosol to the ICP. At one end, gaseous sample introduction allows advantages of increased transport efficiency, lessened matrix effects, and more effective atomization-excitation-ionization over the standard liquid sample introduction. This is because


the sample is in vapor form before entering the ICP. However, only a limited number of samples are readily converted to the gas phase.

Methods for solid sampling of materials are less reproducible, more expensive, and more complex, as opposed to liquid and gaseous sample introduction, for quantitative analysis. Moreover, appropriate standards are scarce. The characteristics of an ideal nebulizer for sample introduction are listed in Table 2. In liquid sample introduction, large droplets or particles must be separated to improve analytical performance criteria by using a spray chamber. Further, a desolvation system lessens the solvent mass. Still, any shift in the aerosol size distribution always changes analytical performance. In sum, a fundamental knowledge of the properties and limitations of the sample introduction system and the plasma is vital in conducting careful spectrochemical analyses by ICP-AES and ICP-MS. In this article, we discuss key sample introduction systems and the fundamental aspects of liquid sample introduction.

Table 2. Characteristic of an Ideal Nebulizer

1. Provides 100% analyte transport efficiency. 2. Consumes small quantities of sample, nanoliter or less. 3. Generates monodisperse droplets. 4. Produces uniform droplet velocity. 5. Droplets are below the critical droplet diameter and velocity. 6. Minimal fluctuations to reduce noise and drift. 7. Aerosol properties can be predicted by simple models. 8. Contains no dead volume. 9. Contributes no adverse solvent load effects. 10. Tolerates solutions containing high solids. 11. Operates without clogging or premature failure. 12. Simple to use, rugged and demountable. 13. Tunable. 14. Inexpensive. 15. Intelligent, but not smart.

Pneumatic Nebulizers (PNs) and Ultrasonic Nebulizers (USNs). Examples of nebulizers used in ICP spectrometry are shown in Table 3. These devices are the most generally used sample introduction devices for ICP spectrometry. The evolution of PNs in the manner generally practiced now in analytical spectroscopy is based on the first work of Gouy.18 Aerosol generation by ultrasonic nebulization was first outlined by Wood and Loomis.19 One shortcoming of pneumatic nebulization is the clogging of nebulizer solution orifice. In ultrasonic nebulization, the liquid sample is delivered to the surface of a piezoelectric transducer actuated by an ultrasonic generator at for excluding excess solvent to avoid plasma cooling. Analyte transport efficiencies nearing 20% are reached for regular commercial ultrasonic nebulizers using 1 mL/min sample.20,21 Greater analyte transport efficiency may be realized if the spray chamber is heated or if the solution uptake rate is lessened to a few microliters. For instance, analyte transport efficiencies close to 100% are attained with a microflow USN at liquid uptake rates of 5 µL/min.22 The microflow USN does not require an aerosol desolvation device. Still, a conventional USN needs a desolvation system consisting of a heated chamber (typically 150 oC) succeeded by a condenser chilled to nearly zero degree centigrade. The limits of detection with USNs is measured by any type of spectrometer are ten times better than with pneumatic nebulizers if the matrix is not complex.23-25 For example, samples made in aqueous solutions of 10% sulfuric acid are too viscous for USNs, and no meaningful increases in the limits of detection are achieved by ultrasonic versus pneumatic nebulization. Chemical and spectral interferences and the clogging of plasma torch injector are enhanced with solutions having elevated salt concentrations. Solvent-related spectral interferences can be diminished with USN. Further, an increase in "aerosol ionic redistribution interferences" may happen.26 Because of the presence of strong Coulombic forces during ion extraction and transfer in ICP-MS, similar effects are observed in the ion optics which affects accuracy. In contrast, those chemical interferences that are particle-size dependent are likely to be diminished because the bulk of droplets generated by a 1-MHz USN with desolvation are less than those from pneumatic devices.


27,28 For example, a high-speed photographic examination of the mass spectrometer interface has shown emission from whole particles using concentric and crossflow pneumatic nebulizers, but no such particles were seen when the USN is coupled with a desolvation system.22

Figure 4. Fate of droplets and solid particles in ICP.

The drawbacks of USNs compared with PNs include lower precision (2-3% vs. 1% RSD), more significant sample sizes (2-3 mL/min vs. 0.5-1 mL/min), delayed washout times (60-90 s vs. 30 s), and a much higher cost ($15,000 vs. $250 to $300). Ultrasonic devices for injecting microliter quantities of solutions have been adapted for liquid chromatographic purposes. With one such tool, 10 to 200 µL samples can be sprayed, but this method is not broadly used. 29 Thus, the commercial USNs, notwithstanding their high price, became standard devices in the 1990s, and their applications to ICP spectrometry have increased due to low detection limits and corresponding freedom from clogging because the desolvation device removes the solvent nearly completely, primarily when cryogenic desolvation is applied. 30-32 Because nearly ten times more sample is injected into the plasma with USNs, vaporization-type interferences are foreseen to start at lower concomitant concentration than encountered with pneumatic nebulization.

Thermospray nebulizers are generally used for the interfacing of liquid chromatography instruments (LC)

with mass spectrometers. The approach has also been explored for transporting liquid samples into the ICP. Thermospray nebulization is achieved by injecting the liquid into a heated capillary.33 The liquid begins to bubble near the exit of the capillary and is turned to an aerosol by the swelling solution vapor. Such devices render aerosols with smaller droplets, 34 but are more costly, intricate, and give greater solvent vapor loading than PNs. Accordingly, desolvation of the aerosol is essentially like USNs when primarily samples in organic solvents are presented into the ICP.35,36 Desolvation is performed by heating the aerosol enough to volatilize the solvent from the aerosol droplets. Both the short-term (minutes) and long-term (hours) stability is 2%.37

Table 3. Examples of Methods for the Introduction of Liquid Samples into ICPs.3

_______________________________________________________________________________________________ Pneumatic nebulizers

1. Crossflow and concentric pneumatic nebulizers such as Meinhard TR+ Glass Nebulizer with PFA Quick Connects

2. GemCone High Dissolved Solids Nebulizer (Perkin Elmer Corporation) 3. Hydraulic high-pressure nebulizers

Analytical Signal from Droplets

Incomplete desolvation of the droplets contributes to noise, interferences, and lowered sensitivity in ICP-MS and ICP-AES

Excitat

ion

Ionization

Atomiza

tion

Relaxation (Emission)

Desolva

tion

Evapora

tion


4. Babington-type nebulizers for samples having high dissolved solids and/or particulates:

a) V-groove nebulizers b) Hildebrand dual-platinum grid nebulizers c) Conespray nebulizers

Ultrasonic nebulizers (USN, by Teledyne CETAC Technologies) Thermospray nebulizers Low-sample consumption nebulizers:

1. High efficiency Nebulizer (HEN by J. E. Meinhard Associates) 2. Direct injection nebulizers (DIN by Teledyne CETAC Technologies) 3. Direct injection high efficiency nebulizer (DIHEN by J. E. Meinhard Associates) 4. Large bore DIHEN (LB-DIHEN by J. E. Meinhard Associates) 5. Droplet direct injection nebulizer (D-DIN) 6. Parallel path nebulizer 7. Microconcentric nebulizers 8. Examples of marketed nebulizers for Aqueous and Organics Analyses

(a) SeaSpray - the high dissolved solids nebulizer (b) MicroMist - the low uptake nebulizer for all ICPs (c) Conikal - an industry standard (d) Slurry - for slurries or suspensions (e) Ceramic VeeSpray - handles high particle and TDS loads best

9. Examples of marketed nebulizers for HF analyses (Glass Expansion)

(a) DuraMist - for routine high precision HF analyses (b) PolyCon - for routine high precision HF analyses (c) OpalMist - high purity PFA, ideal for ICP-MS (d) Ceramic VeeSpray for high particle density and TDS loads best

Piezoelectrically driven nebulizer (Under investigation by Perkin Elmer Corporation) The monodisperse dried microparticulate injector Micro ultrasonic nebulizers

Oscillating capillary nebulizers

Jet impact nebulizers

Glass frit nebulizers

Electrospray nebulizers Electrothermal vaporizers Rotating disk nebulizers _____________________________________________________________________________________

A thermospray nebulization system consisting of a thermospray nebulizer, a spray chamber, and a PTFE membrane separator (MS) was examined for aqueous samples.38 It improved detection 20- to 6-fold using ICP-MS, over a PN used with and without a desolvation system, respectively. Still, the USN presented detection limits that are


generally two- to five-fold better than those attained with the thermospray system coupled to membrane separator. When cryogenic desolvation is adopted with the USN, detection limits are improved by a factor of two to three. Low ion kinetic energies and zero or minimal oxide levels are required for accurate ICP-MS analysis. The smallest ion kinetic energies (5.0 - 7.7 eV) were obtained when USN-cryogenic desolvation or the TN-membrane separator was applied. The lowest oxide levels are measured when either the TN-membrane separator method was used, or if the desolvated aerosol is further cryogenically cooled.

For solutions holding high dissolved solids, sensitivities diminish more rapidly for the USN than for thermospray nebulization. These investigations were conducted at comparatively high solution uptake rates (1.3-10 mL/min).39-42 At an uptake rate of 80 - 120 (µL/min and an optimized thermospray tip temperature, the ICP-AES detection limits were better by a factor of 3 - 25 than those achieved by PN, and matrix effects were insignificant in the presence of a 1% solution of potassium. The same trend is expected when measurement is conducted by ICP-MS. In some respects, the analytical performance of the thermospray nebulizer is comparable to the USN. Due to improved sample transport rates, non-spectroscopic interferences are worsened, so the method cannot be easily used to sample solutions holding high salt content. Table 4. Analyte Transport Efficiency and Sauter Mean Diameter for a Microflow USN. (From Reference 22, with permission.) _______________________________________________________________________________________________ Flow rate (µL/min) Transport efficiency (%) D3,2 (µm) _______________________________________________________________________________________________ 5 99 ± 6 1.85 10 80 ± 8 2.02 20 83 ± 4 2.12 _______________________________________________________________________________________________

2. Micronebulization The low sample consumption micronebulizers shown in Table 3 have reduced sample consumption, create fewer chemical wastes, and produce diminished spectral and matrix interferences, minimum memory effects, less analysis time, and improved accuracy and precision. While the combination of PN-spray chamber is essentially practiced in ICP spectrometries because of its simplicity and low price, the method suffers from low analyte transport efficiency (typically 1 - 2%), large sample consumption (typically 1 – 2 mL/min), and large memory effects. Vittaly, a simple, low- consumption, consumption, highly efficient nebulizer is usually needed for chromatographic and electrophoresis purposes when coupled to ICP spectrometers or for the direct introduction of samples such as semiconductor, biological, forensic, or toxic substances without a spray chamber. In these and other instances, the sample is limited, costly, or dangerous, and it may include a significant portion of organic solvents that can considerably change the plasma characteristics.

Table 4. Nominal Critical Dimensions and Parameters for the Conventional and HEN. 43 Parameters TR-50-A4 HEN-170-AA Annulus area (mm2) ~0.02 ~0.007 Capillary I.D. (mm) ~0.4 ~0.09 Capillary wall thickness (mm) ~0.05 ~0.03 Solution uptake rate used (µL/min) 10-2000 10-1200 Operating pressure (psi) 50 170 Injector gas flow rate (L/min)a 1 1


One of the most efficient nebulizers is the high-efficiency nebulizer (HEN, J. E. Meinhard Associates) which is typically used with a spray chamber and works at a solution uptake rate as low as 10 µL/min (Table 4) but demands a higher operating gas pressure (~170 psi) for 1 L/min argon injector gas flow rate.

The HEN displays excellent long-term stability, but because of the small capillary inner diameters (75 - 100

µm), it is subject to blockage by particles in the solution and by solutions having large solute concentrations. 44,45 Related with a conventional PN (capillary i.d. ~ 400 µm), the HEN is novel as it works more efficiently at solution uptake rates down to 10 µL/min and creates a very fine aerosol with a narrower size distribution. Importantly, ICP-AES detection limits measured with the HEN at a solution uptake rate of 80 µL/min are similar to those achieved with a standard concentric nebulizer using 1 - 2 mL/min.45 Simplicity and low price are further benefits of the HEN. The HEN also offers considerably smaller tertiary aerosol droplets than a conventional PN when both nebulizers are operated at almost the same nebulizer gas and liquid uptake flow rates.45 The aerosol feature from the HEN is not significantly changed at low uptake rates by the viscosity or surface tension of the liquid sample, or the injector gas flow rate. For example, a solution uptake rate of 100 µL/min or less, about 85 - 95% of the tertiary aerosol volume from the high-efficiency nebulizer consists of droplets with diameters less than 8 µm. 45 46,47 Thus, operation of the HEN at a solution uptake rate less than 100 µL/min gives detection limits similar to a conventional PN operated at 1 - 2 mL/min, both for ICP-AES 44 48,49 and ICP-MS. 50-53

The standard HEN is used with a spray chamber. Any nebulizer used with a spray chamber suffers from a several drawbacks. Montaser and coworkers described a direct injection high-efficiency nebulizer (DIHEN) not requiring a spray chamber.54,55 As shown in Figure 6, a HEN was designed to replace the regular injector tubing of a demountable torch. At a solution uptake rate of 85 µm L/min, the DIHEN affords optimal sensitivity and limits of detection comparable to, or somewhat better than those achieved with a standard crossflow nebulizer (1 mL/min). Note that this renders a 12-fold increase in the absolute detection limits. Further, precision is enhanced as opposed to standard PNs. Optimal signal intensities are acquired at meager injector gas flow rates and high radio frequency powers, typically 0.25 L/min and 1.5 kW, respectively. Nevertheless, because 100% of the solvent is carried into the plasma, oxide ion levels are high, much like those observed for the earlier direct injection nebulizer (DIN)56 which is more complex and expensive (ca. $20,000) compared to the DIHEN which cost less ($2,000) and is far simpler.

Figure 5. High Speed Photography of Standard Nebulizer and HEN57

0.5 mm

High-Speed Photography1 µs Exposure

Meinhard TR-50Solution flow rate = 1.17 mL/minNebulizer gas flow rate = 0.99 L/min

0.5 mm

Meinhard HENSolution flow rate = 85 µL/minNebulizer gas flow rate = 0.96 L/min


One of the critical limitations of the DIHEN is solution capillary blockage. A large bore-DIHEN (LB-DIHEN) is less subject to capillary obstruction and optimally runs at low nebulizer gas pressures compared to the conventional DIHEN.58

The aerosol droplets measured utilizing a two-dimensional phase Doppler particle analyzer (2D PDPA)

produces larger droplets, but the velocity patterns and mean droplet velocities are smaller and lower, respectively, affording longer residence times for the droplets in the plasma (Figures 8 and 9). High RF power (1500 W), low nebulizer gas flow rates (0.25 - 0.35 L/min), and low solution uptake rates (80 - 110 mL/min) are needed to operate the LB-DIHEN at best conditions for ICP-MS. Detection limits and sensitivities estimated with the LB-DIHEN are better than those of a traditional nebulizer-spray chamber combination, but precision is poorer.

Figure 6. Direct and Indirect Sample Introduction Methods into the ICP.

The normalized volume distributions depicted in Figure 10 show that the bigger droplets generated by the LB-DIHEN compose an important part of the sample aerosol. The portion of small droplets (smaller than 8 µm) is significantly lessened for the aerosol of the LB-DIHEN compared to the DIHEN. Based on annular gas areas (Table 5), the gas velocity developing from the LB-DIHEN outlet at a given nebulizer gas flow rate is almost four times smaller than that attained by the DIHEN, leading to reduced gas-liquid interplay, and thus, bigger droplets. The

Liquid Sample IntroductionArgon gas inlets

Aluminainjector tube

Nebulizer

Spray Chamber

Analytical zone

RF coil

DIHENAkbar Montaser et. al. US Patent # 6166379, Dec. 2000


patterns seen in D3,2 for low nebulizer gas flow rates are supported by the Nukiyama and Tanasawa equation which provides an empirical relation between the aerosol droplet diameter and the nebulizer parameters. 59

Figure 7. Dimensions and Operating Conditions of the LB-DIHEN and DIHEN and ICP.

Table 5. Critical Dimensions and Parameters for the LB-DIHEN and DIHEN

LB-DIHEN (DIHEN-30-AA)

DIHEN (DIHEN-170-AA)

Solution capillary i.d., µm 318 104

Capillary wall thickness, µm

16 20

Gas orifice i.d., µm 412 173

Capillary annulus area, mm2 0.0794 0.0085

Gas annulus area, mm2 0.0371 0.0094

Gas operating pressure (at 1 L/min Ar), psig

36 155

Large Bore-DIHEN vs. DIHENB. W. Acon, J. A. McLean, and A. Montaser, Anal. Chem. 72, 1885-1893 (2000)

Nebulizer gas

Sample solution

LB-DIHEN

Solutioncapillary

Nozzleend surface

DIHEN

200-350 µm i.d. 70-110 µm i.d.

Nebulizer gas

Typical Quadrupole ICP-MS Operating Conditions

RF power, kW

Nebulizer gas flow rate, L/min

Solution flow rate, µL/min

LB-DIHEN DIHEN1.5-1.71.5-1.7

0.1-0.250.2-0.4

50-130 1-120

ConventionalNebulizer

1.1-1.3

0.7-1.1

1000-2000


Figure 8. Droplet Size Distributions for DIHEN and LB-DIHEN

Figure 9. Axial and Radial Velocity Distributions of Droplet for DIHEN and LB-DIHEN

Based on the cumulative count percent, about 50 % and 80 % of the number of droplets generated by the LB-

DIHEN and DIHEN, respectively, at a nebulizer gas flow rate of 0.2 L/min are below 8 µm at a point of 15 mm from the top of the nebulizer with no plasma torch. Generally, droplets below 8 to 10 µm in diameter give favorably to the signal intensity in ICP spectrometries because they are more readily desolvated-vaporized-atomized in the argon plasma.5,6 Still, it is the volume or mass of the aerosol which corresponds well with the analytical signal. At a nebulizer

Count DistributionNebulizer gas flow rate = 0.2 L/min

LB-DIHEN D3,2 = 20.1 µmDIHEN D3,2 = 9.0 µm

0.6 L/min8.4 µm6.3 µm

0.8 L/min6.4 µm5.9 µm

Diameter (µm)0 10 20 30 40 50

Nor

mal

ized

cou

nt p

erce

nt

00.2

0.4

0.6

0.81.0

Velocity Distributions

Axial Velocity (m/s) Radial velocity (m/s)

Cou

nts

0

200

400

600

800

0

500

1000

1500

0 20 40 60 80 -20 0 20

Nebulizer gas flow rate = 0.2 L/minLB-DIHEN axial mean = 7.5 m/s

DIHEN axial mean = 13.8 m/sradial RMS = 2.0 m/s

radial RMS = 1.4 m/s

0.6 L/min29.5 m/s

36.1 m/s3.9 m/s

3.4 m/s

1.0 L/min42.9 m/s

41.7 m/s5.0 m/s

4.7 m/s


gas flow rate of 0.2 L/min, only 3% and 35% of the volume of the aerosol for the LB-DIHEN and DIHEN, respectively, are comprised of droplets less than 8 µm (Figure 10).

While smaller droplets are beneficial, low droplet velocities and narrow droplet velocity patterns are needed

to improve desolvation-atomization-ionization processes, lessen signal variations and improve sensitivity.4,6 The data in Figure 9 display axial and radial droplet velocity distributions. As the nebulizer gas flow rate is raised, both the axial and radial velocity distributions become wider, and the mean axial velocity is improved. Note that the LB-DIHEN presents a lower mean axial velocity and a tighter velocity distribution at low nebulizer gas flow rates compared to the DIHEN. For instance, the mean axial velocities at 0.2 L/min are nearly 8 and 14 m/s for the LB-DIHEN and the DIHEN, respectively. Thus, although D3,2 of the aerosol from the LB-DIHEN is almost two times higher than that for the DIHEN, the mean axial velocity is nearly a factor of two lower. The lower mean droplet velocities achieved with the LB-DIHEN allows a longer residence time in the plasma for desolvation and vaporization of larger droplets.

Figure 10. Cumulative Volume Distribution of Aerosol for DIHEN and LB-DIHENDetection Limits, Sensitivity, and Precision. Sensitivity, relative detection limits (3s), and short-term

precision (4 min) for the LB-DIHEN and DIHEN using the natural aspiration mode are shown in Table 5 for several elements over the mass range at the best condition for each nebulizer. The applicability of this mode to a broad range of sample types is limited, though, because of the solution flow rate changes with solution viscosity, length, and radius of the capillary, and barometric pressure. Generally, the LB-DIHEN offers sensitivities which are about 0.5 times that produced by the DIHEN over the mass range. The reduced sensitivity for the LB-DIHEN is obviously reflected in the relative detection limits achieved.

Short-term precision is also degraded by a factor of 1.1 (24Mg) to 3.0 (169Tm) which is likely connected to

the poorer quality of the aerosol and the introduction of some droplets which possibly cannot fully desolvate-vaporize-ionize in the ICP. For example, long-term stability estimated over 3 hours (not shown here) is 1.4 %, 1.1 %, and 1.2 %RSD for 24Mg, 59Co, and 238U, respectively. Due to the sequential nature of the quadrupole analyzer, increased stability results are achieved when just a few isotopes are observed in the peak hopping mode.

Cumulative Volume Percent

0

0.2

0.4

0.6

0.8

1.0

0 10 20 30 40 50Diameter (µm)

Cum

ulat

ive

volu

me

perc

ent

0.2 L/min1.0 L/minDIHENLB-DIHEN


Table 6. Typical Sensitivity in ICP-MS Obtained with the LB-DIHEN and DIHEN

The data in Table 6 show precision for the LB-DIHEN run at several solution uptake rates. At lower uptake rates, sensitivity and precision degrade, especially < 42 µL/min (Table 6). A syringe pump was utilized to obtain all data at solution uptake rates less than 85 µL/min. The decrease in solution uptake rate from 85 µL/min to 5.6 µL/min denotes a 15-fold reduction in the absolute amount of sample injected in the ICP. Certainly, with the LB-DIHEN sensitivity is lessened when the solution flow rate is diminished from 85 µL/min to 5.6 µL/min. Also, precision is seriously diminished at 5.6 µL/min. These precision data are worse than the results achieved for the standard DIHEN (5 to 9 %RSD) run at the same solution uptake rate. Therefore, while the use of a large bore solution capillary reduces clogging, solution-gas interplay is reduced, particularly at very low uptake rates, whereby resulting in larger droplets that further flicker noise and diminish precision. In short, for very low sample consumption rates (1-10 µL/min) it is beneficial to use a DIHEN rather than an LB-DIHEN for the direct injection of the test sample to the plasma.

In an early report,7 we presented 2D elastic light scattering images of the aerosol spray structure produced

by the DIHEN using optical patternation.60 These investigations showed that a notable portion of aerosol at low solution flow rates (namely 5.6 and 11 µL/min) remains within the coil, off from optimal sampling area of the ICP-MS instrument. Note that similar sensitivities are obtained for both the LB-DIHEN and DIHEN at solution flow rates below 42 µL/min, that is, analytes from both nebulizers are sampled from a non-optimal zone in the plasma. Accordingly, to obtain maximal sensitivity at low solution flow rates, the sampling depth must be lessened and preferably moved within the torch. This condition grows more severe as the solution flow rate is further reduced, where changes in the spray structure become more pronounced.

It is likewise reasonable to examine analytical figures of merit for the LB-DIHEN to those of a standard

nebulizer utilized with a spray chamber. In general, the results achieved in this work for the LB-DIHEN are equivalent to or better to those detailed before using a common crossflow nebulizer with a spray chamber.

Sensitivity (MHz/ppm) Obtainedwith the LB-DIHEN and DIHEN ( )

Solution Uptake Rate (µL/min)5.6 11 42 85

Isotope24Mg55Mn59Co75As

103Rh208Pb238U

4

14

11

2

23

16

33

(9)

(25)

(18)

(4)

(50)

(37)

(80)

9

33

26

5

53

36

67

(20)

(47)

(36)

(6)

(76)

(54)

(91)

1

4

3

0.5

6

5

11

(2)

(4)

(3)

(0.6)

(8)

(7)

(11)

0.5

2

1

0.3

3

2

5

(0.6)

(2)

(1)

(0.3)

(3)

(3)

(6)

RF power = 1500 WNebulizer gas flow rate = 0.25 L/min


Table 6. Typical Sensitivity in ICP-MS Obtained with the LB-DIHEN and DIHEN

Diagnostic and Modeling Studies of The Nebulization System and Plasmas. In atomic spectrometry, it is desirable to estimate the optimum values of the ten properties of the spray (Table 7) in the plasma to obtain the best analytical conditions. Several parameters are measured for identifying suitable aerosol characteristics. Some of these parameters have been discussed above. We shall review new diagnostics, fundamental, and modeling studies in this talk.

Table 7. Defining Aerosol Portrait for ICP Spectrometry ____________________________________________________________________________

1. Droplet-size distribution and mean diameter. 2. Spatial distribution. 3. Span of a distribution. 4. Cumulative percent volume of aerosol under certain size. 5. Volume flux. 6. Axial and radial droplet velocities. 7. Droplet size-droplet velocity correlation. 8. Droplet time of arrival. 9. Droplet clustering. 10. Droplet number density.

____________________________________________________________________________

The ultimate aims of elemental analysis are to realize the attributes listed in Table 8. These goals may not be realized without fundamental studies of the sample introductions systems and the plasmas. It is in these respects that new diagnostics instrumentations must be developed to test the viability of the models. The studies we conducted in the cited area must wait for the next ILASS conference.

Precision (%RSD) Obtained with the LB-DIHEN and DIHEN ( )

Solution Uptake Rate (µL/min)5.6 11 42 85

Isotope24Mg55Mn59Co75As

103Rh208Pb238U

3.5

3.6

2.9

3.2

2.6

2.6

2.0

(1.6)

(1.2)

(1.2)

(1.3)

(1.6)

(0.9)

(0.9)

2.5

1.7

1.3

1.1

1.2

1.2

1.0

(0.6)

(0.7)

(0.8)

(1.3)

(0.9)

(0.5)

(0.8)

12.3

13.4

13.6

13.6

12.8

11.8

12.3

(5.7)

(5.3)

(5.4)

(4.7)

(5.2)

(5.7)

(5.6)

15.7

16.8

16.4

15.0

17.2

15.1

13.6

(5.5)

(5.8)

(6.7)

(6.2)

(7.1)

(7.6)

(6.8)

RF power = 1500 WNebulizer gas flow rate = 0.25 L/min


Table 8. Ultimate Goal Ideal Elemental Analysis Method

_______________________________________________________________________

1. Capable of speciation and mapping. 2. Sample atomized in a controlled event. 3. Each atom extracted individually. 4. Position, oxidation state, and nearest neighbors recorded. 5. Atoms sorted by size and isotope and counted. 6. Detection limits at single atom level. 7. Absence of matrix effects. 8. Dynamic range extends over full composition of sample. _______________________________________________________________________

In science and engineering, the most fascinating question we can encounter is the yarn of mysterious. It is the root of science, philosophy, music, dance, literature, language, and everything. Oscar Wills Wilde (16 October 1854 – 30 November 1900), the famed Irish poet and playwright said, "Success is a science; if you have the conditions, you get the result." In this relation, Stephen Hawking, stated “Science is beautiful when it makes simple explanations of phenomena or connections between different observations. Examples include the double helix in biology and the fundamental equations of physics.” Our journey to reach the ultimate aims of the chemical analysis is tied to the understanding and betterment of the sample introduction into plasma, and it is in this respect that we seek your assistance.

Acknowledgments This work was sponsored by The Department of Energy, The National Science Foundation, Perkin-Elmer Corporation and J E Meinhard Associates Inc. We thank Dr. Kaveh Kahen (Sigma Analytical Services), a former member of our group, for examining this article.

References 1. G.E.F. Lundell, The Chemical Analysis of Things as They Are, Ind. Eng. Chem., Anal. Ed. 5, 221-225

(1993). 2. A. Montaser and V. A. Fassel, "Inductively Coupled Plasmas as Atomization Cells for Atomic Fluorescence

Spectroscopy"; Anal. Chem. 48, 1490-1499 (1976). 3. A. Montaser, Editor, Inductively Coupled Plasma Mass Spectrometry, Wiley/VCH, New York, 1998. 4. A, Montaser and D. W. Golightly, Editors, Inductively Coupled Plasmas in Analytical Atomic Spectrometry,

2nd Ed., A. Montaser and D. W. Golightly, Eds., VCH, New York, 1992. 5. A. Montaser, M. G. Minnich, H. Liu, A. G. T. Gustavsson, and R. F. Browner, Fundamentals Aspects of

Sample Introduction in ICP Spectrometry. In Inductively Coupled Plasma Mass Spectrometry; A. Montaser, Editor, Wiley-VCH, New York, 1998, pages 335-420.

6. A. Montaser, M. G. Minnich, J. A. McLean, H. Liu, J. A. Caruso, and C. W. McLeod, Sample Introduction in ICPMS. In Inductively Coupled Plasma Mass Spectrometry, A. Montaser, Editor, Wiley-VCH, New York, 1998, pages 83-264.

7. A. McLean, M. G. Minnich, A. Montaser, J. Su, and W. Lai, Optical Patternation: A Novel Technique for Three Dimensional Aerosol Diagnostics, Anal. Chem. 72, 4796-4804 (2000); (b) M. G. Minnich, J. A. McLean, and A. Montaser, Elucidation of Spatial Aerosol Characteristics of a Direct Injection High Efficiency Nebulizer via Optical Patternation, Spectrochim. Acta, Part B, 56, 1113-1126 (2001).

8. International Technology Roadmap for Semiconductors (ITRS) Published on Friday, 2015 by Semiconductor Industry Association.


https://www.semiconductors.org/resources/2015-international-technology-roadmap-for-semiconductors-

itrs/ 9. Semiconductor Equipment and Materials International (SEMI) (Organization, Milpitas, California,

(http://www.semi.org/en/). 10. Updated periodically, http://ams.semi.org/ebusiness/standards/semistandard.aspx?volumeid=13 11. SEMI C27-0708 - Specifications and Guidelines for Hydrochloric Acid,

http://ams.semi.org/ebusiness/standards/SEMIStandardDetail.aspx?ProductID=211&DownloadID=30.. 12. P. R. Langer-Safer, M. Levine, and D. C. Ward, Immunological Method for Mapping Genes on Drosophila

Polytene Chromosomes, Proc Natl Acad Sci U S A. 79(14): 4381–4385 (1982). 13. R. Amann and B. M. Fuchs, Single-Cell Identification in Microbial Communities by Improved Fluorescence

in Situ Hybridization Techniques, Nature Reviews Microbiology, 339–348 (2008). 14. C. S. Westphal, J. A. McLean, B. W. Acon, L. Allen, and A. Montaser, Axial Inductively Coupled Plasma

Time-of-Flight Mass Spectrometry Using Direct Liquid Sample Introduction, J. Anal. At. Spectrom. 17, 669-675 (2002).

15. S. D. Tanner, O. Ornatsky, D. Bandura and V. I. Baranov, Multiplex Bio-Assay with Inductively Coupled Plasma Mass Spectrometry: Towards a Massively Multivariate Single-Cell Technology, Spectrochim. Acta B 62, 188-195 (2007).

16. B. Bodenmiller, E. R. Zunder, R. Finck, T. J. Chen, E. S. Savig, R. V. Bruggner, E. F. Simonds, S. C. Bendall, K. Sachs, P. O. Krutzik and G. P. Nolan, Multiplexed Mass Cytometry Profiling of Cellular States Perturbed by Small-Molecule Regulators, Nat. Biotechnol. 30 (9), 858-U889 (2012).

17. P. Jitaru, M. Tanner, O. Borovinskaya, M. Gonin, B. Hattendorf, A. Gundlach-Graham, and D. Günther, Time of Flight Mass Spectrometry Inductively Coupled Plasma-Time of Flight Mass, Spectrometry: Principle, Instrumentation and Applications, in Inductively Coupled Plasma Mass Spectrometry: Instrumentation and Application, A. Montaser, Ed, Wiley/VCH, 2019.

18. C. L. Gouy, Photometric Research on Colored Flames, Ann. Chim. et Phys. 18, 5-101 (1879). 19. W. R. Wood and A. L. Loomis, The Physical and Biological Effects of High Frequency Sound-waves of

Great Intensity, Phil. Mag. Ser. VII 4, 417-436 (1927). 20. K. W. Olson, W. J. Haas, Jr., and V. A. Fassel, Multielement Detection Limits and Sample Nebulization

Efficiencies of an Improved Ultrasonic Nebulizer and a Conventional Pneumatic Nebulizer in Inductively Coupled Plasma-Atomic Emission Spectrometry, Anal. Chem. 49, 632-637 (1977).

21. M. A. Tarr, G. Zhu, and R. F. Browner, Transport Effects with Dribble and Jet Ultrasonic Nebulizers, J. Anal. At. Spectrom. 7, 813-817 (1992).

22. M. A. Tarr, G. Zhu, and R. F. Browner, Microflow Ultrasonic Nebulizer for Inductively Coupled Plasma Atomic Emission Spectrometry, Anal. Chem. 65, 1689-1695 (1993).

23. V. A. Fassel and B. R. Bear, Ultrasonic Nebulization of Liquid Samples for Analytical Inductively Coupled Plasma-Atomic Spectroscopy: An Update, Spectrochim. Acta 41B, 1089-1113 (1986).

24. R. H. Clifford, P. Sohal, H. Liu, and A. Montaser, Diagnostic Studies on Desolvated Aerosols from Ultrasonic Nebulizers, Spectrochim. Acta 47B, 1107-1122 (1992).

25. A. Montaser, R. H. Clifford, S. A. Sinex, and S. G. Capar, Atomic Emission Spectrometric Detection Limits and Noise Power Spectra of Argon Inductively Coupled Plasma Discharges Sustained in Laminar- and Tangential-flow Torches, J. Anal. At. Spectrom. 4, 499-503 (1989).

26. R. F. Browner, M. S. Black, and A. W. Boorn, “Recent Studies with Sample Introduction into the RFICP.” In Developments in Atomic Plasma Spectrochemical Analysis, R. M. Barnes, Ed., London, Heyden, 1981.

27. (a) J. M. Mermet and C. Trassy, “Design of a New Ultrasonic Nebulizer for Routine Analysis in ICP-AES.” In Developments in Atomic Plasma Spectrochemical Analysis, R. M. Barnes, Ed., London, Heyden, 1981; (b) A. Montaser, H. Tan, I. Ishii, S-H. Nam, and M. Cai, Argon Inductively Coupled Plasma Mass Spectrometry with Thermospray, Ultrasonic, and Pneumatic Nebulization, Anal. Chem. 63, 2660-2665 (1991).

28. R. K. Winge, J. S. Crain, and R. S. Houk, High Speed Photographic Study of Plasma Fluctuations and Intact Aerosol Particles or Droplets in Inductively Coupled Plasma Mass Spectrometry, J. Anal. At. Spectrom. 6, 601-604 (1991).

29. J. F. Karnicky and L. T. Zitelli, Nebulizer Particularly Adopted for Analytical Purposes, U.S. Patent 4,582,654 (1986).

30. A. Montaser, H. Tan, I. Ishii, S-H. Nam, and M. Cai, Argon Inductively Coupled Plasma Mass Spectrometry with Thermospray, Ultrasonic, and Pneumatic Nebulization, Anal. Chem. 63, 2660-2665 (1991).


31. R. K. Winge, J. S. Crain, and R. S. Houk, High Speed Photographic Study of Plasma Fluctuations and Intact

Aerosol Particles or Droplets in Inductively Coupled Plasma Mass Spectrometry, J. Anal. At. Spectrom. 6, 601-604 (1991).

32. D. R. Wiederin, R. S. Houk, R. K. Winge, and A. P. D'Silva, Introduction of Organic Solvents into Inductively Coupled Plasmas by Ultrasonic Nebulization with Cryogenic Desolvation, Anal. Chem. 62, 1155-1160 (1990).

33. G. A. Meyer, J. S. Roeck, and M. L. Vestal, Thermospray Nebulizer for Inductively Coupled Plasma Spectrochemical Analysis, ICP Inf. Newsl. 10, 955-963 (1985).

34. J. A. Koropchak and H. Aryamanya-Mugisha, Aerosol Particle Size Effects on Plasma Spectrometric Analysis, J. Anal. At. Spectrom. 4, 291-294 (1989).

35. D. R. Wiederin, R. S. Houk, R. K. Winge, and A. P. D'Silva, Introduction of Organic Solvents into Inductively Coupled Plasmas by Ultrasonic Nebulization with Cryogenic Desolvation, Anal. Chem. 62, 1155-1160 (1990).

36. J. W. Elgersma, J. Balke, and F. J. M. J. Maessen, The Performance of a Low Consumption Thermospray Nebulizer for Specific Use in Micro-HPLC and General Use in FI with ICP-AES Detection, Spectrochim. Acta 46B, 1073-1088 (1991).

37. K. A. Vermeiren, P. D. P. Taylor, and R. Dams, Optimisation and Evaluation of a Sample Introduction Device for Inductively Coupled Plasma Atomic Emission Spectrometry Using Thermospray Nebulisation, J. Anal. At. Spectrom. 3, 571-577 (1988).

38. A. Montaser, H. Tan, I. Ishii, S-H. Nam, and M. Cai, Argon Inductively Coupled Plasma Mass Spectrometry with Thermospray, Ultrasonic, and Pneumatic Nebulization, Anal. Chem. 63, 2660-2665 (1991).

39. J. A. Koropchak, M. Veber, and J. Herries, Fused Silica Aperture Thermospray Sample Introduction to Inductively Coupled Plasma Atomic Emission Spectrometry, Spectrochim. Acta 47B, 825-834 (1992).

40. M. Veber, J. A. Koropchak, T. S. Conver, and J. Herries, Matrix Effects Studies with Fused Silica Aperture Thermospray Sample Introduction to ICP-AES, Appl. Spectrosc. 46, 1525-1531 (1992).

41. J. A. Koropchak and T. S. Conver, Development of a High Liquid Flow Thermospray Sample Introduction System for Inductively Coupled Plasma Atomic Emission Spectrometry: Invited Lecture, J. Anal. At. Spectrom. 9, 899-903 (1994).

42. T. S. Conver, and J. A. Koropchak, Comparison of Ultrasonic and Thermospray Systems for High Performance Sample Introduction to Inductively Coupled Plasma Atomic Emission Spectrometry, Spectrochim. Acta 50B, 341-354 (1995).

43. A. Montaser, M. G. Minnich, J. A. McLean, and H. Liu, “Sample Introduction in ICPMS “In Inductively Coupled Plasma Mass Spectrometry; A. Montaser, Ed. Wiley: New York, 1998.

44. H. Tan, B. A. Meinhard, J. E. Meinhard, Recent Investigations of Meinhard Concentric Nebulizers, presented at the 19th Annual Meeting of the Federation of Analytical Chemistry and Spectroscopy Societies, Philadelphia, Pennsylvania, USA (September 1992).

45. H. Liu and A. Montaser, Phase-Doppler Diagnostic Studies of Primary and Tertiary Aerosols Produced by a New High-Efficiency Nebulizer, Anal. Chem. 66, 3233-3242 (1994).

46. R. H. Clifford, H. Tan, and I. Ishii, and A. Montaser, Phase Doppler Technique for Simultaneous Measurements of Drop Size and Velocity Distributions of Aerosols Produced by ICP Nebulizers, FACSS Meeting, Chicago, IL, October 1989.

47. R. H. Clifford, I. Ishii, A. Montaser, and G. A. Meyer, Dual-Beam, Laser-Scattering Interferometry for Simultaneous Measurements of Drop-Size and Velocity Distributions of Aerosols From Commonly Used Nebulizers, Anal. Chem. 62, 390-394 (1990).

48. J. W. Olesik, J. A. Kinzer, and B. Harkleroad, Inductively Coupled Plasma Optical Emission Spectrometry Using Nebulizers with Widely Different Sample Consumption Rates, Anal. Chem. 66, 2022-2030 (1994).

49. H. Liu, R. H. Clifford, S. P. Dolan, and A. Montaser, Investigation of the High-Efficiency Nebulizer and the Thimble Glass Frit Nebulizer for Elemental Analysis of Biological Materials by Inductively Coupled Plasma-Atomic Emission Spectrometry, Spectrochim. Acta 51B, 27-40 (1996).

50. S-H. Nam, J-S. Lim, and A. Montaser, High Efficiency Nebulizer for Argon Inductively Coupled Plasma Mass Spectrometry, J. Anal. At. Spectrom. 9, 1357-1362 (1994).

51. H. Liu, A. Montaser, S. P. Dolan, and R. S. Schwartz, Evaluation of a Low Sample Consumption, High-Efficiency Nebulizer for Elemental Analysis of Biological Samples Using Inductively Coupled Plasma Mass Spectrometry, J. Anal. At. Spectrom. 11, 307-311 (1996).


52. S. A. Pergantis, E. M. Heithmar, and T. A. Hinners, Microscale Flow Injection and Microbore High-

Performance Liquid Chromatography Coupled with Inductively Coupled Plasma Mass Spectrometry Via a High-Efficiency nebulizer, Anal. Chem. 67, 4530-4535 (1995).

53. J. A. Kinzer, J. W. Olesik, and S. V. Olesik, Effect of Laminar Flow in Capillary Electrophoresis: Model and Experimental Results on Controlling Analysis Time and Resolution with Inductively Coupled Plasma Mass Spectrometry, Anal. Chem. 68, 3250-3257 (1996).

54. J. A. McLean, H. Zhang, S. R. Dubow, M. G. Minnich, R. A. Huff, D. A. Haydar, and A. Montaser, A Direct Injection High-Efficiency Nebulizer for Inductively Coupled Plasma Mass Spectrometries, presented at the Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, Atlanta, Georgia, USA (March 1997).

55. See for example: (a) (J. A. McLean, H. Zhang, and A. Montaser, “A Simple, Low-Cost Direct Injection High Efficiency Nebulizer for Inductively Coupled Plasma Mass Spectrometry”, Anal. Chem. 70, 1012-1020 (1998); (b) (b) . Singh, D. E. Pritchard, D. L. Carlisle, J. A. McLean, A. Montaser, J. M. Orenstein, and S. R. Patierno, Internalization of Carcinogenic Lead Chromate Particles by Cultured Normal Human Lung Epithelial Cells: Formation of Intracellular Lead Inclusion Bodies and Induction of Apoptosis, Toxicology and Applied Pharmacology, 161, 240-248 (1999).

56. D. R. Wiederin, F. G. Smith, and R. S. Houk, Direct Injection Nebulization for Inductively Coupled Plasma Mass Spectrometry, Anal. Chem. 63, 219-225 (1991).

57. J. A. McLean, M. G. Minnich, L. A. Iacone, H. Liu, and A. Montaser, "Nebulizer Diagnostics: Fundamental Parameters, Challenges, and Techniques on the Horizon "; J. Anal. At. Spectrom. 13, 829-842 (1998).

58. See for example: (a) B. W. Acon, J. A. McLean, and A. Montaser, A Large Bore-Direct Injection High Efficiency Nebulizer for Inductively Coupled Plasma Spectrometry, Anal. Chem. 72, 1885-1893 (2000); (b) J. A. McLean, B. W. Acon, A. Montaser, J. Singh, D. L. Pritchard, and S. R. Patierno, The Determination of Cr in Human Lung Fibroblast Cells Using a Large Bore-Direct Injection High Efficiency Nebulizer with Inductively Coupled Plasma Mass Spectrometry, Appl. Spectrosc. 54, 659-663 (2000).

59. Nukiyama, S.; Tanasawa, Y. Experiments on the Atomization of Liquids in Air Stream, Trans. Soc. Mech. Eng. (Japan), 4, 5, and 6, (1938-1940), E. Hope, transl., Defense Research Board, Department of National Defense, Ottawa, Canada 1950.

the importance of atomic spectrometry in life and the ...plasma source spectrometry has...

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