Spectrochimica Acta Part B 100 (2014) 14–37

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Spectrochimica Acta Part B

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Review

Liquid sample introduction in inductively coupled plasma atomic

emission and mass spectrometry — Critical review☆
N.H. Bings ⁎, J.O. Orlandini von Niessen, J.N. Schaper
Johannes Gutenberg-University Mainz, Institute for Inorganic and Analytical Chemistry, Laboratory for Trace Analysis and Plasma Spectrometry, Duesbergweg 10-14, 55128 Mainz, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Inductively coupled plasma optical emission spectroscopy (ICP-OES) and mass spectrometry (ICP-MS) can be
Received 1 June 2014 considered as the most important tools in inorganic analytical chemistry. Huge progress has been made since
Accepted 2 July 2014 the first analytical applications of the ICP. More stable RF generators, improved spectrometers and detection
systems were designed along with the achievements gained from advanced microelectronics, leading to overall
Keywords:
greatly improved analytical performance of such instruments.
Sample introduction
ICP-MS
In contrast, for the vast majority of cases liquid sample introduction is still based on the pneumatic principle as
Nebulization described in the late 19th century. High flow pneumatic nebulizers typically demand the use of spray chambers
Droplet generation as “aerosol filters” in order to match the prerequisites of an ICP. By this, only a small fraction of the nebulized
Single particles sample actually contributes to the measured signal. Hence, the development of micronebulizers was brought
forward. Those systems produce fine aerosols at low sample uptake rates, but they are even more prone for
blocking or clogging than conventional systems in the case of solutions containing a significant amount of total
dissolved solids (TDS).
Despite the high number of publications devoted to liquid sample introduction, it is still considered the Achilles'
heel of atomic spectrometry and it is well accepted, that the technology used for liquid sample introduction is still
far from ideal, even when applying state-of-the-art systems. Therefore, this review is devoted to offer an update
on developments in the field liquid sample introduction that had been reported until the year 2013. The most
recent and noteworthy contributions to this field are discussed, trends are highlighted and future directions
are outlined.
The first part of this review provides a brief overview on theoretical considerations regarding conventional
pneumatic nebulization, the fundamentals on aerosol generation and discusses characteristics of aerosols ideally
suited for introduction into the ICP. In the following chapters, novel developments and applications in the field of
low flow sample introduction are summarized with special focus on hyphenated techniques and multi-mode
sample introduction systems. Issues associated with continuous or pulsed non-pneumatic aerosol generation
systems, which has also been a major trend over the past couple of years, are also discussed in the final sections.
© 2014 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.1. Liquid sample introduction — general considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.2. Aerosol characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.3. Limitations of the pneumatic nebulization principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2. Conventional continuous aerosol generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.1. Concentric nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2. Babington-type, V-groove and cross-flow nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.3. Spray chambers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.4. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

☆ This paper is dedicated to Nicoló Omenetto, on the occasion of his 75th birthday, in recognition of his outstanding contributions to the field of laser spectrochemistry and as an editor of
Spectrochimica Acta Part B.
⁎ Corresponding author. Tel.: +49 6131 39 25882; fax: +49 6131 39 25082.
E-mail address: bings@uni-mainz.de (N.H. Bings).

http://dx.doi.org/10.1016/j.sab.2014.08.011
0584-8547/© 2014 Elsevier B.V. All rights reserved.
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37 15

3. Advancements in continuous aerosol generation and novel instrumentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.1. Micro-concentric nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
3.2. Torch-integrated/direct-injection nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.3. Parallel path nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.4. Cross-flow nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.5. Flow-focusing/flow-blurring nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.6. Ultrasonic nebulizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.7. Multi-mode nebulizer configurations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.8. Non-pneumatic aerosol generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.9. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4. Generation of discrete droplets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
4.1. Early studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
4.2. Novel approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
4.3. Single particle analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

1. Introduction
Liquid sample introduction is the most common way of introducing
samples into analytical flames and plasmas [1–6]. Numerous reviews,
monographs or other manuscripts have been published on this topic.
An early comprehensive overview on pneumatic sample introduction
systems in the field of atomic spectrometry was given by Sharp in
1988 [7,8]. In 2006, Todolí and Mermet presented a review with special
focus on micro flow sample introduction [3] and Montaser presented
his highly acknowledged collection on inductively coupled plasma
mass spectrometry in 1998 [9]. Within, a comprehensive and detailed
overview and the fundamental aspects of sample introduction systems
can be found [2,10]. In 2007 Sharp contributed an article to Hill's collec-
tion [11], and Todolí and Mermet presented a monograph in 2008, both
on liquid sample introduction [4].
This review intends to give an overview starting from the aforemen-
tioned work of Todolí and Mermet, providing a review of recent and
noteworthy studies. But for detailed information the cited literature
should be consulted. We trust that the readers of this article will under-
stand that the subject of liquid sample introduction can hardly be
completely covered and therefore a somewhat arbitrary selection of
references had to be made, which was done in view of citing work
from the prominent groups working in the field and in view of illustrat-
ing the trends discussed.
dependent filters [8]: aerosol properties can be improved but at the
expense of sample and analyte transmission [2,10].
Too large droplets may not be completely processed in the ICP even
if the liquid flow rate does not exceed the above mentioned limit. It is
assumed that there is a certain maximum diameter Dmax above which
incomplete vaporization/atomization of the droplets takes place and
finally sensitivity and signal noise are deteriorating [8,17,18]. This
limit, however, has not been accurately determined yet, but detrimental
effects of too large droplet sizes on signals corresponding to such
droplets or adjacent droplets in the ICP are well known [5,19].
The size of the droplet is not the exclusive criterion regarding its in/
complete desolvation followed by vaporization of the particulate resi-
due, the atomization and finally ionization of the analyte. The velocity
of the droplet is also of great importance, i.e. its residence time within
the hot zone of the ICP [20–22]. It can be assumed, that a single 30 μm
droplet of low velocity might be fully processed, while the same corre-
sponding total amount of liquid divided into 216 closely spaced droplets
of 5 μm diameter, traveling at significantly higher velocities might
rather not be completely processed. In addition, the abundance of poly-
atomic ions, secondary discharge and beam characteristics downstream
the interface of mass spectrometers is heavily dependent on e.g. the
liquid flow rate and ICP operation conditions [23]. This correlation was
already critically reviewed by Niu in 1996 [24].

1.1. Liquid sample introduction — general considerations

Table 1
All ICP-OES and -MS instruments are designed for liquid sample Comparison of characteristics of pneumatically generated aerosols vs. aerosols ideally suit-
introduction, as the vast majority of samples in daily routine are in the ed for atomic spectrometry as described by Todolí and Mermet.Reproduced from Ref. [4]
liquid form [10,12]. This is simply due to the ease of handling liquids, with permission of Elsevier
thus sample preparation steps like dilution, accurate portioning and
preparing calibration series are most conveniently done by using liquids Characteristics of aerosols ideally Characteristics of pneumatically
[2]. As a result huge efforts are being made to transfer solid samples into suited for atomic spectrometry generated aerosols
the liquid form either by digestion or dispersion [13]. As fine as possible (d b 10 μm) Too coarse (d even N100 μm)
In contrast, the ideal sample for an ICP would be in the gaseous Must be as slow as possible High velocity aerosols
phase. Thus, aerosols of suitable characteristics for introduction into Drop velocity similar to carrier gas Drop velocity up to 80 m s−1
this plasma have to be generated from the liquid sample [2]. This is con- velocity in the spray chamber
(2 m s−1 for a double-pass spray
ventionally achieved by pneumatic nebulizers, were the liquid passes a chamber)
fine orifice along with a gas stream of high velocity, forcing the liquid to All droplets with identical diameter Droplets with diameters ranging from
break up and form small droplets [10]. (monodisperse) several tens of nm up to hundreds of
Although the ICP is a very robust ionization source, there is a maxi- μm (very polydisperse)
Uniform droplet number density Very heterogeneous in terms of spatial
mum capacity for the introduction and processing of liquids [14]. It is
droplet number density
known that an ICP at typical operation conditions can process about Uniform spatial droplet diameters Coarse droplets are usually located at
20 μL min−1 of water accompanied by an equivalent vapor flux [8,15, preferential aerosol locations
16]. Any excess of aerosol generated has to be skimmed in order not Similar characteristics irrespective of Physical properties (e.g. surface tension
to alter plasma robustness or ultimately extinguish the ICP discharge. the sample composition and viscosity) affect the aerosol
characteristics
In this context spray chambers act as aerodynamic i.e. droplet-size
16 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
It has to be also considered that the focal plane (extraction zone) in
ICP-OES (ICP-MS) is defined by instrumental means and a homoge-
neous, narrow distribution of analyte atoms/ions within this volume is
of major importance as it influences the achievable sensitivity [23,25].
Not only the ICP operating conditions like the applied RF power and
the gas flow rates affect the point of the initial vaporization of the intro-
duced droplets and thus define the location and dimensions of the gen-
erated ion cloud, it is also influenced by the velocity and size of the
droplets. Therefore, the lateral and axial distributions of such ions
depend on the characteristics of the introduced aerosol [26,27]. The
broader the distribution regarding its droplet size, velocity and direction
of travel, the broader the ion distribution gets within the plasma. A large
number of studies stated the detrimental effects of aerosol polydispersi-
ty on e.g. signal precision, physical and chemical interferences and over-
all sensitivity [18,26,28–36].
An ideal aerosol should therefore be monodisperse concerning the
aforementioned parameters. Ideally, the properties of the primary gen-
erated aerosol would already match the prerequisites of the ICP, making
spray chambers dispensable. But additional and very important prereq-
uisites for ideal aerosols exist, which were summarized by Todolí and
Mermet [4] and are given in Table 1.
Droplet collision/coagulation promotes aerosol deterioration, as the
droplet size distribution shifts to more coarse droplets [8]. The probabil-
ity for droplet collision/coagulation is directly proportional to the drop-
let number density [3,8]. Therefore, not only a low droplet number
density is desired, but also a homogeneous distribution of the droplets
in time and space. Pronounced droplet coagulation will otherwise
occur in some regions, leading to compromised aerosol characteristics.
Droplet arrival time intermittence is also promoted for higher droplet
number densities and will therefore also lead to imprecision [36].
Lastly, most of the sample introduction systems are strongly affected
by matrix effects [37–39], but the ideal aerosol should neither change
with the analyte concentration, the amount of total dissolved solids
nor the physical properties of the respective solution. This is of special
importance for hyphenated techniques, e.g. when using solvent gradi-
ent flows in liquid chromatography in combination with ICP-MS.
The greater the degree of monodispersity and the smaller the drop-
lets of the respective aerosol the better it is suited for its introduction
into the ICP, since the efficiency of all subsequent processes, from
desolvation of the droplets to the ionization of the evaporated atoms,
depend on the droplet diameter. As Niemax demonstrated by introduc-
ing single droplets into an ICP, the initial point of atomization/ionization
determines the magnitude of lateral ion diffusion, i.e. the radius of the
ion cloud at the position of the sampler (ICP-MS) or focal plane (ICP-
OES) and finally the extraction/detection efficiency (cf. Fig. 1) [29].
Therefore, the dispersity of the aerosol defines the ICP-MS sampling
efficiency.
Fig. 1. Simplified schematics of the ion cloud generation depending on the position of atomization (left) and analyte diffusion (right) in the ICP for different cases.
Reproduced from Ref. [29] with permission of Elsevier.
Also the type and flow rate of the injector gas as well as the analyte
mass play an important role [29], which was also found by Dziewatkoski
et al. in 1996. Mass dependent diffusion coefficients were derived from
experiments using monodisperse single droplets [18]. The effect of in-
completely desolvated particles on the vaporization process of other
particles and their contribution to signal fluctuations was also outlined
[30,35]. Olesik et al. determined the desolvation rates of monodisperse
droplets within the ICP by means of Mie scattering [27] and simulations
of the solute-particle vaporization in an ICP were presented by Horner
et al. [40]. These simulations account for fundamental properties and
operation conditions such as the droplet diameter, its chemical compo-
sition and spatial location in the ICP. It was found that particle vaporiza-
tion shows nominally linear (for small particles) or approximately
quadratic (for very large particles) correlation with the particle size
and both heat- and mass-transfer limit the vaporization rate in the plas-
ma tail [40].
In the case of the detection of discrete droplets or particles additional
issues have to be considered, according to Olesik and Gray [41]. The sig-
nal corresponding to a single droplet or particle is typically of less than
1 ms of duration, thus optimum dwell times have to be chosen with
care. Due to the extreme transient nature of such signals, the detector
dead time in pulse counting mode becomes very important and the
resulting dynamic range is determined by the respective pulse duration.
For a given 5 ns pulse corresponding to a single ion impact, the counting
error, i.e. the probability of ions impacting on the detector during this
very pulse, reaches 1% at 2 Mcps. As the authors explained, the signal
duration of an isolated particle introduced into the ICP is in the range
of 100 μs (full width at half-maximum, fwhm). Even for a comparably
low count rate of e.g. 1000 cts for the entire integrated signal, this
would result in a corresponding count rate of 10 Mcps, considering
10% of the ions reaching the detector during the peak duration of
10 μs. Obviously, this would result in severe counting errors due to de-
tector dead time. A maximum count number of 200 within a 10 μs inter-
val constitutes the acceptable maximum and the dynamic range is no
longer 1 to 2,000,000 as for continuous signals and dwell times of sec-
onds, but 1 to 200 [41].
Since the dimensions of a single ion cloud determine the maximum
frequency at which particles can be introduced and individually detect-
ed, sample introduction systems capable of introducing single isolated
droplets at user-demanded frequencies are highly desired to overcome
the aforementioned drawbacks [41].
1.2. Aerosol characterization
To explore the capabilities of a certain sample introduction system
and to decide to what extent it will fit the prerequisites of the ICP men-
tioned above, suitable diagnostic tools for characterizing the aerosol
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
have to be selected [10]. Depending on the nature of the aerosol, its
droplet number and size range, different methods can be employed,
which are either based on mechanical, electrical or optical techniques.
The latter can be further divided into imaging and scattering methods.
Each method covers a different droplet size range while some provide
additional information on the droplets velocities. Not all methods
allow the detection of single droplets [10], while all mentioned methods
are capable of displaying the droplet size distribution of the respective
aerosol, as given schematically in Fig. 2 [42]. Those histograms can be ei-
ther given as count or volume based abundance (Fig. 2, left) or in the cu-
mulative form (Fig. 2, right). Since such graphs are not easily compared
for different liquid sample introduction systems, a number of figures are
derived to allow for direct and conclusive comparison (see also Fig. 5.4
and Table 5.1 of Ref. [10]). Among others, the median diameter (D50),
the Sauter mean diameter (D3,2) and the span of the distribution, de-
fined as (D90 − D10) / D50, can be given. The volume percentage of the
aerosol contained in droplets below a certain size (typically 10 μm)
also is a useful figure, as it most directly reflects the expectable transport
efficiency of the investigated sample introduction system, thus the
achievable transmission of a given aerodynamic filter i.e. the spray
chamber [8].
It is obvious that the analytical performance of the respective sample
introduction system directly correlates with the aerosol properties.
Resulting conclusions, fundamental aspects and implications for the de-
sign of sample introduction systems are reviewed and critically
discussed elsewhere [2–4,7,8,10,11,33,43].
The droplet size distribution of conventional pneumatic nebulizers
can be predicted by mathematical models. The most widely known
Nukiyama–Tanasawa equation correlates the Sauter mean diameter
D3,2 of the aerosol droplets with a) the physical properties of the liquid
and the gas used for operating the nebulizer, b) the operating conditions
of the nebulizer like the liquid and gas flow rates and c) the geometric
parameters of the nebulizer such as the diameter of its liquid outlet cap-
illary [44]. This model was confirmed in some studies, while others
imply erroneous prediction, most likely as it was not derived for condi-
tions typically used with ICP nebulizers [45,46]. Hence, the modified
model of Gras et al. [47] is usually employed instead of the original
equation. This model shows that numerous variables influence the aero-
sol characteristics, such as the liquid outlet diameter, the surface ten-
sion, the density and the viscosity of the liquid, as well as the gas and
liquid flow rates and their differences in velocity [11].
1.3. Limitations of the pneumatic nebulization principle
The characteristics of aerosols generated by conventional pneumatic
nebulizers significantly mismatch the aforementioned considerations
and prerequisites (cf. Table 1) [10], which can be explained by the aero-
sol generation processes relevant for e.g. a concentric nebulizer (cf.
Fig. 3). The liquid emerging from the sample capillary is accelerated
Fig. 2. Graphical overview of the key figures commonly used for aerosol characterization. Left: particle or droplet size distribution, right: cumulative distribution [42].
17
by the outer gas flow of high velocity and forced to build nodes of a cer-
tain wavelength [4,7]. As those waves grow, the interaction of the gas
and the liquid becomes more effective. If the kinetic energy of the gas
is now sufficiently high to overcome gravity and the surface tension of
the liquid, it will break up, leading to filaments and fine strings, which
further separate into several smaller droplets [2,5].
Aerosols formed this way show very broad droplet size distributions,
ranging from virtually zero to a few hundred μm in diameter. Due to the
droplet generation mechanism, the velocity of the droplets as well as
their direction of travel is rather undefined. Even droplets with impulses
towards the nebulizer tip can be found, leading to e.g. re-nebulization
[4,7,8,11,48]. Droplets can be initially accelerated to velocities of up to
80 m s−1, while the gas reaches the speed of sound at the nozzle tip.
The spray is contained in a comparably small cone downstream of the
nebulizer and droplet coagulation leads to aerosol deterioration, pro-
moting the abundance of larger droplets [3,4]. The existence of hot
spots within the spray chamber regarding droplet number density is
also disadvantageous. As both, the number and median diameter of pri-
mary pneumatic aerosols are too high for atomic spectrometric applica-
tion, they are filtered in suitable spray chambers. Droplets above a
certain diameter are then forced to impact onto the walls, while those
below the critical diameter will more likely pass the chamber [8]. This
so-called tertiary aerosol shows much finer and narrower droplet size
distributions. Along with gravitational settling other transport phenom-
ena like droplet coagulation and solvent evaporation take place (Fig. 4)
[4]. The final volume fraction contained in the removed droplets can be
as high as 98% [49]. It is imperative to optimize the sample utilization
and thus overall sensitivity of a given system by generating aerosols as
close as possible to the ideal characteristics instead of simply rejecting
droplets of improper size.
As the model of Gras et al. [47] suggests, finer aerosols might be pro-
duced through (i) low viscosity and low surface tension of the liquid, (ii)
a small liquid channel diameter, (iii) a small gas exit cross-sectional
area, and (iv) a high gas-to-liquid ratio [11]. However, adverse effects
can be found for all approaches. Shum et al. presented greatly improved
droplet size distributions for a direct injection nebulizer through an in-
creasing addition of methanol [50]. But this has to be done with care,
since the addition of any nebulization aid to the sample is principally a
source of errors and contaminations. The second approach, the reduc-
tion of the inner diameter of the sample capillary is common practice
and is realized in many micro-flow nebulizers [3]. Unfortunately, this
often promotes clogging or blocking of the nebulizer [7] and samples
with high amounts of total dissolved solids are rather not to be used,
while particles can even destruct the nebulizer. In contrast, the third ap-
proach is more easily realized, as adequate mass flow controllers may
compensate for the increasing back pressure due to the decreased gas
annulus area. Lastly, the gas-to-liquid ratio cannot be optimized by
higher gas flow rates, as it conflicts with the central channel flow limita-
tion of the ICP. As a result only the liquid flow rate can be reduced. This is
18 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37

Fig. 3. Schematics of the fundamental processes of pneumatic aerosol generation, exemplarily shown for a conventional concentric nebulizer with focus on the liquid breakup mechanism
[42].

also advantageous for many other reasons: As mentioned before, the
probability of droplet coagulations and thus aerosol deterioration is a
function of the droplet number density, which in turn depends on the
liquid flow rate. The threshold for negligible probability of collisions
and droplet coagulation was defined by Porstendörfer et al. to be
1012 m−3 [43]. Todolí and Mermet calculated a droplet number density
of around 1013 m− 3 for an already reduced liquid flow rate of
50 μL min−1 [3]. A minimized liquid flow rate will also accommodate
for the solvent load limit of the ICP [8,15,16]. Furthermore, matrix
effects due to organic components were often found to be less pro-
nounced at lower liquid flow rates, while some studies imply the oppo-
site for inorganic concomitants [15,51–53]. A more detailed elaboration
on matrix effects in ICP can be found in the review of Agatemor and
Beauchemin [37].
However, a given sample introduction system usually has distinct
optimal operating conditions to produce fine aerosols [54]. Aerosol
characteristics and thus sensitivities and signal noise are altered by
variations in the liquid flow rate. Therefore, different circumstances,
matrix compositions and analytical applications demand individual
nebulization systems, as their flexibility is rather limited due to the
aforementioned reasons. This is accountable for the high number of
different sample introduction systems so far developed for application
in ICP-OES and ICP-MS.
In the case of hyphenated techniques, e.g. HPLC- or CE-ICP-MS, other
issues are becoming relevant for the selection and optimization of a po-
tential sample introduction system. In this field eluents are commonly
applied in gradients which in turn changes the viscosity and surface ten-
sion of the solution to be nebulized during the measurement. As pre-
dicted by the model of Gras et al. [47], primary and thus tertiary
aerosol droplet distributions are affected in either way, positively or
negatively, with respect to e.g. aerosol transport efficiency. Therefore,
internal standardization or gradient compensation via post-column
make-up flow addition using an inverse gradient is mandatory. How-
ever, both approaches come with their own drawbacks due to e.g.

Fig. 4. Illustration of aerosol transport/filtering processes within a Scott-type double-pass spray chamber.
Reproduced from Ref. [4] with permission of Elsevier.
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
spectral interferences or further issues associated with the additional
flow, as there are dilution, contamination errors and the risk of addi-
tional dead-volumes degrading chromatographic or electrophoretic
resolution.
2. Conventional continuous aerosol generation
As stated earlier, the basic concept of pneumatic nebulization was
first introduced for analytical purposes by Gouy in 1879 [55]. All nebu-
lizer types described so far are supposed to be driven in a continuous
fashion. Several geometric designs of pneumatic nebulizers are com-
pared in Fig. 5 [42]. Most of the nebulizer types can be divided into
(i) concentric and (ii) cross-flow i.e. orthogonal designs [4,7].
Besides a concentric nebulizer with and without a recessed sample
capillary (Fig. 5A and B), two orthogonal designs also exist, the cross-
flow and the V-groove nebulizer (Fig. 5D and E). The parallel path neb-
ulizer and the flow-focusing/blurring nebulizer are more recent addi-
tions to the field (Fig. 5C and F). A comprehensive historic overview of
pneumatic nebulizers and spray chambers and a thorough characteriza-
tion of such systems can be found elsewhere [2–4,7,8,10,11,56]. Some
nebulizers are demountable to allow for the exchange of e.g. the sample
capillary. This has to be done with great care, since the adjustment of
these capillaries is very critical and can diminish the reproducibility,
which is why most of such nebulizers are equipped with a fixed central
capillary.
2.1. Concentric nebulizers
The concentric nebulizer design is the oldest and most variant de-
sign [2–4,7,11]. It was customized for various purposes and was also
miniaturized for low flow applications. It can also be built using various
materials, like HF-resistant polymers instead of glass or quartz. The
more recent flow focusing/blurring nebulizer geometry is also evolved
from the concentric design [57,58,114]. The vast majority of ICP instru-
ments is originally equipped with some kind of concentric nebulizer
and a double pass spray chamber, because this combination is known
for its robustness and ease of use [3,4]. Low signal noise can be achieved
together with long-term reproducibility, although sample utilization
and achievable absolute sensitivity are limited. Those systems should
also only be applied to samples with medium salt and particle load
[12,19,59].
Fig. 5. Comparison of design principles of different pneumatic nebulizers. A: Conventional concentric nebulizer, B: concentric nebulizer with recessed capillary, C: parallel-path nebulizer,
D: cross-flow nebulizer, E: V-groove nebulizer and F: flow-focussing/blurring nebulizer [42].
19
2.2. Babington-type, V-groove and cross-flow nebulizers
The cross-flow, the V-groove as well as the Babington-type nebulizer
are specially designed for the nebulization of viscous samples or sam-
ples containing high amounts of total dissolved solids and even slurries
[4,7,60]. The parallel path geometry, which was recently introduced can
also be seen as special case of a cross-flow design [61]. All these types of
nebulizers have already been extensively described and characterized,
while the flow-focusing/blurring nebulizer is still a relatively recent
design. Therefore, Section 3.5 of this review article is dedicated to a
comprehensive characterization of this type of pneumatic nebulizer.
2.3. Spray chambers
Since the individual types of nebulizers generate aerosols of individ-
ual characteristics and properties, distinct and special spray chambers
have to be designed and combined with the respective nebulizer in
order to achieve optimum results. One criterion is the inner volume of
the spray chamber, which should be selected according to the nebulizer
liquid flow rate, while the geometry of a certain chamber will define its
D3,2 cutoff diameter [8,62]. Different spray chambers were originally de-
signed for higher liquid flow rates and others are more suitable for
micro-flow applications, where only little sample volume has to be
skimmed [3,4]. For special applications, e.g. isotope ratio measurements,
tandem spray chambers were proposed to offer improved signal stabil-
ity due to the more restrictive filter characteristics [63]. A comprehen-
sive overview of the various types of chambers and their analytical
characterization can be found by e.g. Todoli and Mermet [3,4].
2.4. Summary
Critically speaking, spray chambers can still be seen as an interim so-
lution or workaround to match the properties of the aerosol generated
by the nebulizer with the prerequisites of the ICP. Primary aerosols
should ideally offer characteristics and properties perfectly matching
the demands of the respective excitation/ionization source employed.
To minimize the waste of sample, spray chambers should be completely
omitted and only “aerosol transport chambers” without any aerosol fil-
tering effect should be used for mounting the nebulizer to the ICP. Also
because of solvent load limits of the respective excitation/ionization
sources micro-flow sample introduction is imperative, which also im-
proves the overall sample utilization. To achieve optimum sensitivity,
20 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37

the aerosol characteristics of such an ideal nebulizer have to fit the re-
quirements of the given instrumentation regarding e.g. maximum drop-
let diameter, speed and frequency of the droplets. However, if such
“total consumption systems” are considered for a respective application
employing micro- or nano-flow nebulizers, one has to be aware of more
pronounced matrix effects caused by inorganic concomitants in com-
parison to conventional pneumatic nebulizer/spray chamber systems.
3. Advancements in continuous aerosol generation and
novel instrumentation
In this chapter, novel as well as recently advanced sample introduc-
tion systems are summarized and compared. Examples for interesting
applications are given with respect to the nebulization principle. The
properties and characteristics of a broad selection of sample introduc-
tion systems as well as noteworthy applications are summarized in
Tables 2 and 3 to allow for easier comparison.
In their review on sample introduction Todolí and Mermet give a
comprehensive overview on relevant systems and the corresponding
fundamental processes [3]. They also outline the need of systems for
micro- and nanosample analysis and highlight respective applications,
since sample material is often limited due to availability as for forensic
studies or due to security concerns as in e.g. nuclear chemistry or toxi-
cology. Analytical methodologies offering highest sensitivity and sam-
ple utilization are becoming increasingly important also because of the
growing number of applications of nanoscale material, e.g. the treat-
ment of single cells with nanoparticles. According to a recent keyword
lookup in PubMed (NCBI, US National Library of Medicine), roughly
8000 publications can be found for ‘nanoparticles + cell, −cancer and
−tumor’ while only 1565 articles were published on these topics in
2006. Therefore, powerful analytical procedures for the investigation
of samples of single μL volume or even less are of increasing demand.
Another growing field over the last couple of years is represented by
the hyphenation of low flow separation techniques to ICP-MS/OES. In
this case the sample introduction system is of major importance as
not only maximum sensitivity but also sufficient chromatographic or
electrophoretic resolution is mandatory for optimum results. Several
studies can be found focusing on instrumental development and meth-
od optimization. In the following section a number of interesting exam-
ples of such studies are classified according to the sample introduction
system employed.
3.1. Micro-concentric nebulizers
The concentric geometry is still the most common principle in use
[4]. Accordingly, a high number of reports on modifications or even
novel micro-concentric systems have been presented in the period cov-
ered by this review article. One such system is the high performance
concentric nebulizer (HPCN), of which several types were introduced
by Inagaki et al. and Groombridge et al. [64–66]. The original HPCN
was designed for micro-flow applications from 1 to 10 μL min−1,
while the latter model was explicitly modified with a large-bore capil-
lary (LB-HPCN) to improve TDS tolerance at liquid flow rates from
0.25 to 0.8 mL min−1. Both systems are based on the triple concentric
design, although some distinct deviations can be found. The outer part
of the nebulizer was taken from a commercial 6 mm concentric nebuliz-
er, while for the low flow type the inner diameter of the original liquid
path was 250 μm [65], in which a liquid capillary of 50 μm inner diam-
eter was inserted. This was tapered in the lab by mechanical tension
during the exposure to an arc discharge. The reproducibility of this pro-
cess is proposed to be high, although no specific data e.g. yield or rejec-
tion rates were given. In contrast, the large-bore type has a 200 μm
liquid path and a tapered sample capillary of 100 μm inner diameter
[64]. Optimum sample capillary recess was found to be between 25
and 50 μm. Both HPCN systems were compared with commercially
available nebulizers regarding the resulting droplet size distributions
of the generated primary aerosols. Sauter mean diameters and cumula-
tive volume fractions of D b 10 μm were determined for the HPCN, a
HEN-120-A.01, a HEN-90-A.01, the CEI-100 and the AriMist-HP at
5 μL min−1 [65]. Only the HEN-120-A.01 offered values comparable to
the presented HPCN prototype (D3,2: 2.6 vs 2.4 μm; D b 10 μm: 90 vs
94%) [65]. However, the gas back pressure of the HPCN was only
60 psi, thus half of the HEN-120. The observed sensitivity in ICP-MS
analysis was linear in the range of 2–10 μL min− 1, while a 35% drop
was found for 1 μL min−1. In addition, the HPCN was proven to nebulize
a 1% NaCl solution for 8 h without clogging [65]. The system was also ap-
plied to speciation analysis of arsenic by using capillary-LC-ICP-MS.
With this, eight compounds were separated within 9 min employing a
liquid flow rate of 2.0 μL min−1 [65].
For the LB-HPCN aerosol data was gained and compared with data
achieved with the MiraMist, the SeaSpray, a Conikal-, a Meinhard and
a slurry nebulizer [64], which is also shown in Fig. 6. All systems selected
for comparison produced coarser primary aerosols with Sauter mean
diameters in the range of 5.8–26.5 μm in contrast to 3.1 μm in the case

Table 2
Comparison of different types of sample introduction systems for discrete or continuous sample introduction in atomic spectrometry.

Sample introduction system Liquid flow rate/μL min−1 Primary aerosol Ref.

Name Principle Droplet generation mode Commercially available I.d. cap./μm Lower limit Upper limit Droplet diameter/μm

DOD Thermal inkjet Discrete n 28 0.005 12.5 17a [101]

MicroDrop Piezo-electric Discrete y 50 0.01 50 65b [185]
nDS-200e MicroConcentric Continuous n 20 0.05 4 – [76]
EnyaMist Parallel path Continuous y 60 0.2 50 – [98]
HPCN Flow-focusing Continuous n 50 1 10 2.4a [64,65]
OCN Mechanical Continuous n 40–50 1 400 – [158]
Ar–ESI Electrospray Continuous n 30 1 4 – [164]
DIHEN MicroConcentric Continuous y 104 1 100 12.6a [86]
AriMist HP Parallel path Continuous y 150 5 1000 6.3a [64,65]
OneNeb Flow-blurring Continuous y 500 5 2000 – [115]
MDMI Piezo-electric Discrete n 30 6 35 65b [34]
HEN MicroConcentric Continuous y 75–100 10 300 2.6a [64,65]
MicroMist MicroConcentric Continuous y 140 40 120 32.5b [110]
FFPN Flow-focusing Continuous n 50–200 50 100 3.1b [58,110]
Thermospray Thermal Continuous n 127 50 500 2b [163]
FBPN Flow-blurring Continuous n 100–700 250 500 – [58]
MWTN Thermal Continuous n 150–200 500 2000 – [161]
USN Piezo-electric Continuous n – 500 2500 5.5b [36]
a
Median diameter.
b
Sauter mean diameter.
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37 21

Table 3
Fields of application of novel and enhanced sample introduction systems. Comparison of employed nebulization techniques and achievable LODs, wherever respective data was provided
in the corresponding literature (last column).

Nebulizer/spray chamber Application and nebulization technique Analytes Range of LODs Comments Ref.

V-groove, concentric ICP-OES multielement analysis of Ti, Al, Zn, Mg, Fe, 0.2–0.5 mg/kg Slurry introduction was inefficient [105]
sunscreens; comparison of wet digestion Mn, Cu, Cr, Pb, B due to insolubility and viscosity.
prior to introduction with direct
emulsified slurry introduction.
V-groove/cyclonic ICP-OES slurry introduction of powdered Al, Ca, Cu, Fe, Mg, 0.04–0.48 mg/kg Trition X100 as surfactant; Cross-Flow/ [104]
Cross-flow/Scott-type antibiotics Mn, Zn Scott-type chamber less tolerable to
introduction of slurries.
MiraMist CE-ICP-MS for quantifications of cobalamin Co, Rh, Mg, Pb Not determined Different spray chamber designs with [98]
species; use of methanol make-up solution. and without additional gas outlets were
evaluated; addition of methanol
improved signal intensity.
MiraMist Characterization of CE-ICP-MS for the Co not determined Addition of 15 mL/min methanol as [99]
separation of cobalamin. make-up liquid.
MSIS/dual conical Simultaneous detection of hydride and As, Bi, Co, Cr, Fe, 0.1–30 μg/L Simultaneous determination is [144]
nonhydride-forming elements by ICP-OES in Mn, Mo, Ni, Sb, Se, hampered by spectral interferences.
high alloy steel samples and nickel alloys. Sn, Ti, V, W
CN, MCN Evaluation of a shortened demountable torch Li, Mg, V, Mn, Co, 0.3–104 ng/L Figures of merit at low solution uptake [87]
for direct introduction nebulizers and Ni, Cu, As, Se, Rh, (HEN); rates are improved for HEN compared to
comparison to DIHEN; application to the In, Cs, Pb, Th, U 0.3–47 ng/L DIHEN.
analysis of CR-DNA by ICP-MS. (DIHEN)
MCN Multielement detection by ICP-MS in As, Ba, Cd, Co, Cu, 0.0005–0.22 mg/ External calibration with formic acid. [71]
biological samples after sample Fe, Ga, Mn, Mo, Ni, kg
solubilization with formic acid. Pb, Rb, Se, Sr, TI, U,
V, Zn
MCN Determination of trace elements in fuel V, Mn, Fe, Co, Ni, 0.01–0.6 μg/L Solutions containing up to 70% v/v [70]
ethanol by ICP-MS. Cu, Zn, Ga, As, Se, ethanol
Rb, Sr, Mo, Cd, Sn, were introduced into the ICP.
Sb, Tl, Pb, Bi
DIHEN/single pass Effect of the chemical form of silicon in Si Not determined Effect of organic solvent on aerosol [95]
MCN/cyclonic petroleum samples in ICP-OES. characteristics is mitigated by both
investigated systems.
DIHEN/single pass Detection of silicon in fuel products by ICP- Si Not determined TISIS allows for improved sensitivity to [94]
TISIS/single pass OES, comparison of DIHEN with TISIS. the expense of longer wash out times.
USN Multielement analysis of fuel ethanol using Ag, Cd, Co, Cu, Cu, 0.02–0.10 μg/L Formation of carbon deposits caused by [122]
FIA-ICP-MS. Fe, Mn, Ni, Pb direct introduction of 10% v/v of ethanol.
USN Determination of Cu and Fe in fuel ethanol by Cu, Fe 0.11–5.0 μg/kg [123]
ICP-OES.
DIHEN CN/cyclonic Comparison of DIHEN with conventional CN As, Cd, Pb, Hg 0.01–0.5 μg/L Slightly weaker figures of merit through [81]
for the analysis of urine by ICP-MS. (DIHEN); the application of the DIHEN.
0.003–0.2 μg/L
(CN)
Triple-mode USN Determination of iodine in biological samples I 1.6 μg/L In-chamber mixing of reactants. [139]
by vapor generation ICP-OES.
MSIS Multielement detection of hydride forming As, Bi, Ge, Sb, Se, 0.02–0.42 mg/kg Slurry concentrations of up to 4% m/v; [138]
and non-hydride forming Sn, Hg, Ca, Fe, Mg, addition decanol; standard addition
elements in slurries of biological and Mn, Zn calibration.
environmental samples through MIP-OES.
Dual-mode/cyclonic Evaluation of a dual-mode nebulization system As, Ba, Cd, Mg, Mn, 0.6–5.4 μg/L Comparison of HEN and dual-mode neb- [151]
HEN/cyclonic for hydride generation and direct introduction Sb, Sc, Sr, Zn (dual-mode); ulizer; slightly weaker precision for dual-
into ICP-OES; on-line 0.4–3.8 μg/L mode design.
standard addition. (HEN)
DIHEN Boron isotope ratio measurements in sea B Not determined Achievable sensitivities 2–5 times higher [82]
water by MC-ICP-MS. compared to systems employing double
pass Scott-type chamber or cylonic
chamber.
CN, cross-flow, Burgener T2100 Multielement detection in biological slurry Al, B, Ba, Ca, Cu, Fe, Not determined Similar behavior of the investigated [107]
samples by ICP-OES. Mg, Mn, P, Pb, S, Sr, nebulizers; slurry introduction (5%
Ti, Zn, Cd, K (w/v)); accurate determination of 7 out
of 9 (bovine liver) and
14 out of 16 elements (whole blood
reference material).
MCN, TISIS Determination of ultra-trace elements in snow Cr, V, Fe, Mn, Pb, 0.02–4.5 ng/L Sample uptake rate of 20 μL/min, spray [96]
by ICP-MS. Zn, Cd, Co, Cu chamber temperature of 70 °C.
Cross-flow/Scott-type Comparison of different sample introduction Se Not determined Lowest achievable mass bias through [154]
MSIS systems for precise Se isotope ratio hydride generation.
Hydride generation determination by
Aerosol desolvation MC-ICP-MS.
Demountable capillary microflow Microfluidic sub-microliter flow injection Cd, Pb Not determined Injected sample volumes: 0.4 μL or [68]
nenulizer/heated spray sample introduction; application to direct 0.8 μL; carrier flow rate: 20 μL/min.
chamber analysis of Chinese rice wine by ICP-MS.
MCN/heated total consumption Analysis of light petroleum samples by Ti, V, Cr, Fe, Ag, Cd, 0.04–20 μg/kg Achievable LODs depend on type of [73]
spray chamber ICP-MS; investigation of signal suppression. Sn, Hg, Pb petroleum; μFIA method (5 μL sample
volume, 20 μL/min carrier flow);
standard addition calibration.

(continued on next page)

22 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
Table 3 (continued)
Nebulizer/spray chamber Application and nebulization technique
MCN/single pass Hg detection in gas condensates with
FIA-ICP-MS; high sample throughput.
DS-5/total consumption Determination of trace elements in oil by
spray chamber isotope dilution ICP-MS.
of the LB-HPCN at a liquid flow rate of 0.25 mL min−1 [64]. All nebu-
lizers were applied to ICP-OES and the sensitivity achieved with the
HPCN was higher compared to all other systems and a correlation
with the excitation energy of the respective spectroscopic transition
was found. While the sensitivity improvement factor was in the range
of 1.7–2.2 for low energy transitions (Cr I, 3.47 eV), a factor of roughly
1.8–3.3 was observed for transitions of higher energies (Zn II,
15.41 eV) [64]. The modifications compared to the former type led to
a higher TDS tolerance, as now 20% NaCl solutions can be aspirated.
The system was successfully validated via the analysis of certified refer-
ence material (white rice flour, NMIJ CRM 7502-a) [64].
Another lab-built micro-nebulizer designed for hyphenation with
low flow separation techniques was presented by Cheng et al. [67].
This demountable capillary microflow nebulizer has a self-aspiration
rate of less than 5 μL min−1 and offers analytical characteristics compa-
rable to a MicroMist nebulizer at 200 μL min−1. Signal precision in ICP-
MS was found to be good, with RSDs in the range of 3–4% and 0.75–2%
for 10 and 100 μL min−1, respectively. Detection limits for several
elements at different liquid flow rates range from 1 to 100 μL min−1
and are degrading with decreasing liquid flow rate. In addition, iodine
speciation analysis was successful through the hyphenation of CE with
ICP-MS via this nebulizer, using a make-up liquid of 10 μL min−1.
This device was also attached to a lab-built microfluidic system [68]
for the determination of Cd and Pb in 0.4 μL portions of Chinese rice
wine samples of varying glucose content. Due to the minute sample
amount, carbon built-up on the sample cones of the ICP-MS as well as
a deterioration of the plasma characteristics were avoided. In addition,
matrix effects were minimized, which usually complicate external
calibration with aqueous standards.
Another lab built concentric system based on the modification of a
commercially available slurry nebulizer (AR30-1-FS6E) into which
capillaries with different diameters were inserted was presented by
Geertsen et al. [69]. The position of such capillaries with respect to the
Fig. 6. Droplet size distributions of primary aerosols for five different concentric nebulizers
including the modified HPCN. Data was obtained at a gas (Qg) and liquid (Ql) flow rate of
Qg = 1 L min−1 and Ql = 0.8 mL min−1.
Reproduced from Ref. [64] with permission of the Royal Society of Chemistry.
Analytes Range of LODs Comments Ref.
Hg 0.5 μg/kg 30 μL/min flow rate; addition of [74]
70 mL/min O2.
Ni, Mo, Sn, Pb 0.09–0.8 ng/g μFIA method (2 μL sample volume, [75]
20 μL/min toluene carrier flow).
nebulizer front as well as their tip geometry (tapered or flat-end) was
also optimized. The ICP-MS signal for 238U was monitored at a flow
rate of 1.0 μL min−1 while the position of different capillaries with
20–100 μm i.d. was changed ranging from recessed to a protruding noz-
zle. Optimum results were found for a flat-end 100 μm capillary in co-
planar or slightly protruding configuration (+0.5 mm). The gained sig-
nal was twice as high as the one resulting from a flow-rate-corrected
MicroMist nebulizer. However, poor signal stability of 9% RSD for opti-
mum conditions was found. Efforts were made to measure and compare
droplet velocity profiles for the different setups, but no conclusive cor-
relation of the aerosol characteristics with the observed ICP-MS perfor-
mance was found. To summarize, the introduction of capillaries into
large-bore concentric nebulizers makes flow rates in the μL min− 1
range accessible. However, handling of such devices is still difficult
and signal precision has to be further optimized.
Tormen et al. [70] presented a study on the analysis of fuel ethanol by
using ICP-MS and a MCN-100. A sensitivity gain of 15–25% was found for
solutions containing ethanol of up to 70% (v/v). However, signal RSDs of
about 9% were somewhat degraded. A high nebulizer gas flow rate along
with low RF power showed optimum performance within that study,
which is in contrast to what is commonly referred to as robust
conditions [20]. The concentrations of Cu, Cd, Ni, Pb, Tl and Sn deter-
mined via external calibration with internal standardization were in
good agreement with those determined via isotope dilution, demon-
strating low matrix effects for the presented application. In a subsequent
study, the matrix effects stemming from up to 50% (v/v) formic acid
were also investigated by the same group [71].
The DS-5 nebulizer, as presented by Schaumlöffel and coworkers
[72] was further applied to the analysis of light petroleum, oils or
other carbon-rich sample matrices [73–75]. This nebulizer type provid-
ed about 3–4 times improved sensitivity in the case of sample matrices
mentioned above compared with conventional systems [73] together
with improved wash-out times [74] at liquid flow rates in the range of
some tens of μL min−1.
An improved version of the aforementioned system, the nDS-200e
was introduced by Rappel and Schaumlöffel in 2010 [76]. The various
prototypes of the system were capable of producing fine aerosols from
a delivered volume flow of roughly 50 nL min−1 although the resulting
RSDs were found to be 20%. The deviation is reduced at higher flow rates
(5% RSD at 0.2–2.0 μL min−1) and further improves with increasing
sample uptake rate. The study on the effect of a sheath gas flow to one
of the employed single pass spray chambers is also presented. A
make-up gas addition of 11% was claimed to be optimum, but the
total gas flow rate was not maintained at a constant value while the
make-up/nebulizer gas flow ratio was changed. The observed effect of
signal enhancement might therefore be due to the applied total flow
rate, which coincides with the observed ICP-MS signal. Accordingly,
the comparison of the different combinations of the nebulizer and
spray chamber prototypes lead to the conclusion, that the combination
of a shorter nebulizer with a larger spray chamber generates maximum
ICP-MS signal. The application of such a nebulizer system to hyphenate
a sheath-flow nanoHPLC to ICP-MS was also successfully demonstrated.
A Lu-labeled peptide was separated from excess of the labeling reagent
and a by-product. The post-column addition of the internal standard
had no visible effect on the chromatographic resolution. Although the
addition of a sheath flow should reduce solvent effects, the solvent
gradient was still noticeable through the time-resolved signal of the
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
internal standard. Nevertheless, the novel system shows improved
characteristics regarding back-pressure and is less prone to clogging
while providing an extended liquid flow range compared to its
predecessor.
A number of studies were recently presented focusing on method
development rather than instrumental improvements in the field of hy-
phenated techniques, of which a selected number will be presented
here. Paredes et al. hyphenated HPLC with ICP-OES through six diffe-
rent nebulizer spray chamber combinations: a HEN and a PFA micro-
nebulizer in combination with a conventional cyclonic, a Cinnabar and
a Scott double-pass spray chamber, respectively. It turned out that
differences regarding analytical performance are small, but the HEN/
cyclonic setup was chosen for further HPLC analysis of tomato cultivars
[77]. With the presented method, it was possible to differentiate sam-
ples of native tomato cultivars.
Another comparison of sample introduction systems was carried out
by Lokits et al. [78]. Two HEN and the DS-5 were applied to capLC-ICP-
MS studies using four different spray chamber designs. Again, differ-
ences regarding distinct properties like signal RSD, oxide or doubly-
charged ion ratios were reported. But none of the investigated designs
can be rated superior. One most important parameter with respect to
hyphenation is peak width dispersion, and it is suggested to therefore
choose the 170A.01-HEN, as the FWHM of the chromatographic signal
is minimal using this nebulizer in combination with two out of three
of the investigated spray chambers [78].
In a different field of application Balcaen et al. reported on the sensi-
tive determination of bromine-containing drugs via HPLC-ICP-MS [79].
They demonstrated the application and evaluation of a PFA nebulizer
attached to a PC3 system.
3.2. Torch-integrated/direct-injection nebulizers
Several articles on direct-injection or torch-integrated sample intro-
duction systems were published over the past years. Those systems
were initially introduced a while ago [80] and recent studies provide
information on modifications and further developments which are
proposed to lead to optimized figures of merit or improved applicability
in atomic spectrometry [81–86].
Goitom et al. presented two studies on a Vulkan-DIN compared to a
DIHEN in combination with ICP-MS [85,86]. Noise characteristics of
both systems were recorded and discussed. It was found that signal
RSD for the Vulkan-DIN is a virtually linear function of the chosen inte-
gration time in contrast to the DIHEN [85]. In addition, noise power
spectra revealed a higher white noise level for the Vulkan DIN with
low 1/f contribution and vice versa for the DIHEN [85]. Also the aerosol
characteristics showed significant differences: the Vulkan-DIN gave
coarser aerosols with lower velocities and narrower size distribution
[86]. 95% of the aerosol of this nebulizer was contained in droplets larger
than 10 μm (D3,2: 30.1 and 10.9 μm for the Vulkan-DIN and DIHEN, re-
spectively). It was concluded that this is the main reason for the ob-
served poorer signal precision due to the elevated white noise level.
However, the detrimental effect of peristaltic pump noise was virtually
absent in contrast to the DIHEN. A similar conclusion was drawn by
Maldonado et al. in a comparative study of the performance of a de-
mountable DIHEN and a HEN combined with a cyclonic spray chamber
for ICP-OES [84]. A significant improvement in sensitivity together with
reduced signal noise was found for the DIHEN compared to the HEN. No
differences were found regarding limits of detection and neither system
was valued to be superior.
A thorough investigation of the torch integrated direct injection
systems was presented by Louvit et al. in comparative studies on sample
introduction systems for isotope ratio determination of boron via multi-
collector ICP-MS [82,83]. The d-DIHEN was proven to be more suitable
for the application of interest compared to both, conventional sample
introduction using a double-pass Scott-type spray chamber and pneu-
matic nebulization including aerosol desolvation (APEX). The ICP-MS
23
sensitivity in case of the d-DIHEN was comparable with such achieved
by the APEX, while both offered about 2–4 times higher sensitivity com-
pared to the conventional system [82]. But the oxide ratios (NdO+/
Nd+) were found to be poorer for the DIHEN (up to 30%) compared to
the other systems (typically 9 and 3% for the conventional and the
APEX system, respectively). In contrast, doubly charged ion intensities
for (e.g. U2+ vs. U+) were reduced for the DIHEN (0.5–1%) compared
to the conventional (1.5%) and the APEX system (3%) [82]. Wash-out
times, very critical in the field of boron analysis due to severe memory
effects, were drastically reduced in the case of the d-DIHEN. A rinsing
period of 15–20 min with 0.5 mol L− 1 HNO3 was needed to reach a
blank below 1% of the previous signal when applying the conventional
system, while for the d-DIHEN 100 s were sufficient to reduce the back-
ground signal to 0.1% using the same rinsing solution [82], which is most
likely due to the absence of wetted glass surfaces in the case of the
DIHEN. No comparative data was presented for the APEX system. Accu-
rate and precise isotope ratio determination was achieved by the au-
thors using the d-DIHEN system and no significant deviations were
found compared to data achieved with TIMS.
Minnich et al. applied a large-bore DIHEN to ICP-MS determination
of trace metals in urine [81] and despite slightly poorer analytical
figures of merit (sensitivity, LODs and precision) in comparison with a
conventional pneumatic reference system no difference with clinical
relevance was reported. The key benefit of the LB-DIHEN was found to
be its greatly reduced sample consumption.
Since DIHEN systems are usually more expensive compared to
conventional or high-efficiency nebulizers, Westphal et al. presented a
short ICP torch which allows us to reduce the length of the nebulizer
to typical dimensions of conventional systems [87]. With this torch
common micronebulizers can be used which significantly reduces the
costs of such direct introduction system. In this study a conventional
HEN was operated at a flow rate of 5–85 μL min−1 thus a typical range
for a DIHEN. At the lowest applied liquid flow rate of 5 μL min−1 higher
sensitivity and better signal RSDs (3.5–6.0%) compared to a regular
DIHEN system (4.7–9.1%) were achieved, whereas at high flow rates
signal precision was found to be slightly degraded while sensitivity was
still improved, still leading to comparable LODs.
DIHEN systems were also successfully hyphenated to different
separation techniques [88–90]. Matusiewicz et al. compared several
micronebulizers for speciation analysis of copper via CE-MIP-OES [88].
The d-DIHEN offered better detection limits and lower RSDs compared
to a DS-5, a MicroMist and the MiraMist CE. In a study by Chang et al.
the DIHEN was successfully applied to the analysis of Pb and Hg species
using HPLC-ICP-MS [90] while Montaser and coworkers employed a d-
DIHEN for speciation analysis of arsenic [89]. In the latter study signal
precision with RSDs in the range of 3.7–7.1% was found to be somewhat
degraded due to the low liquid flow rate applied (0.9 μL min−1). Five
arsenic compounds were effectively separated within 12 min using
50 nL injections. Both, sensitivities and chromatographic resolution
were comparable to those results achieved when using much higher
flow rates.
An alternative approach is the application of a torch-integrated sam-
ple introduction system (TISIS), originally presented by Todolí, Mermet
and coworkers in 2002 [91,92]. A torch of regular length is used with
an integrated single pass spray chamber to which common micro-
nebulizers can be attached. The aerosol is then introduced into the plas-
ma through a shortened injector tube. For a better understanding of the
aforementioned different approaches and designs, the DIHEN, the short
DIN with the short torch and the TISIS are compared schematically in
Fig. 7. Paredes et al. investigated the effect caused by heating the
integrated spray chamber of the TISIS (h-TISIS) and the analytical per-
formance was compared to a regular and a demountable DIHEN,
although the data of the reference system were not corrected for its
higher sample uptake rate [93]. Heating the spray chamber to 105 °C
was found to lead to improved ICP-OES sensitivities as long as the liquid
flow rate was kept below 40 μL min−1. The plasma remained robust due
24 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
Fig. 7. Comparison of the principle designs of a DIHEN in a standard ICP torch (top), the
torch-integrated sample introduction system (TISIS, middle) and the short DIN in a
modified short torch (bottom).
Redrawn based on figures in Refs. [93,3,87].
to the introduction of the solvent as vapor instead of droplets. LODs of
the non-heated TISIS were weaker compared to both DIHEN configura-
tions while its heated version yielded an improvement of about 6 times
although a four times elevated background level. The heated TISIS was
proven to be an efficient sample introduction system offering superior
analyte transport rates at lower costs compared to the DIHEN.
Two subsequent studies on the determination of Si in petroleum
products via ICP-OES were outlined by Sanchez et al. [94,95]. In the
first study, a h-TISIS was compared to a d-DIHEN system for character-
ization of six different Si compound in xylene solutions [94]. It was
Fig. 8. Schematics of the tip of the enhanced parallel-path Nebulizer. Side-view (left) and comparison of parallel-path vs. microconcentric nebulizers (end-on view, right).
Courtesy of J. Burgener, Burgener Research, Missisauga, Canada [97].
shown, that the h-TISIS offered higher sensitivities while the d-DIHEN
provided shorter wash-out times. Observed effects caused by the chem-
ical form of the Si were minimized for the TISIS and the DIHEN com-
pared to a conventional system and the latter was successfully applied
to the analysis of kerosene [95]. Grotti et al. compared the analytical ca-
pabilities of a TISIS and a PFA/Cinnabar system in the field of trace metal
determination in Antarctic snow samples using ICP-MS equipped with a
dynamic reaction cell [96]. It was shown that the TISIS offered signifi-
cant improvements in both sensitivity and limits of detection compared
to the PFA/Cinnabar system.
3.3. Parallel path nebulizers
Presented and patented by John Burgener, several types of parallel-
path nebulizers have been introduced over the past years, e.g. the
AriMist and MiraMist [97]. Recently, the original design was optimized,
now applying the so-called enhanced parallel-path method. One prom-
inent addition to this field is the EnyaMist which is designed to operate
at liquid flow rates of 0.2–50 μL min−1. Due to its narrow liquid trans-
port capillary the EnyaMist does not tolerate particles within the sample
solution, which is why a filter should be permanently attached to the
sample uptake capillary. As can be seen from Fig. 8, the sample and
gas orifice are rather in parallel instead of concentric [97]. Therefore,
the aerosol cone might not exit the nebulizer on-axis but rather under
a certain off-axis angle. The angle of operation of this type of nebulizer
with respect to the spray chamber might therefore be of importance.
In this context, Yanes et al. report on issues regarding the orientation
of a MiraMist CE nebulizer within the used cyclonic spray chamber
[98]. Placing the gas exit to the 11 o'clock position in end-on view
yielded maximum ICP-MS sensitivity. Elemental speciation analysis of
cobalt in different vitamin B12 compounds was then performed via CE/
μHPLC-ICP-MS and a thorough investigation of the type and flow rate
of the nebulizer make-up liquid was carried out [99]. Interestingly, ef-
fects of the applied MeOH gradients were observed, showing different
behavior for increasing gradients compared to decreasing gradients.
But the observed effect was negligible at optimum flow rates of both
the make-up solvent and the eluent and at the selected flow ratios
(45-time excess of the make-up flow over the eluent flow rate).
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
The design of spray chambers more suitable for nebulizers generat-
ing an aerosol cloud slightly off-axis the nebulizer axis might even im-
prove the analytical performance of such systems. But this might not
be that relevant for the EnyaMist nebulizer. In the case of liquid flow
rates of single μL min− 1 or even less, rates at which such so-called
total consumption systems are being operated, very small drain-less
single pass spray chambers are sufficient. In the lab of the authors of
this review preliminary studies were carried out with an EnyaMist
using different configurations concerning gas and liquid flow rates and
spray chamber designs [100]. This nebulizer was adapted to a lab-built
single pass spray chamber of minimum inner volume for fundamental
characterization. Since this nebulizer has to be driven by a syringe
pump for stable aerosol production, conventional analysis of discrete
samples becomes a bit cumbersome as changing the sample in the sy-
ringe requires proper and tedious rinsing procedures. But it has to be
pointed out, that this type of nebulizer was originally designed for han-
dling transient sample introduction either by coupling ICP-MS with
flow injection analysis or separation techniques of ultra-low flow rates
such as CE or capLC [97].
We noticed the aforementioned issues regarding the orientation of
the EnyaMist inside the spray chamber, too, as also found by Yanes
et al. [98] in the case of the MiraMist. In our case, the signal noise was
significantly more affected than the measured sensitivity. Optimum re-
sults were achieved with the nebulizer spray angle oriented upwards,
while the nebulizer was not fully inserted into the fitting of the lab-
built single pass spray chamber but rather recessed around 10–
15 mm. When using this configuration, the EnyaMist showed superior
performance compared to a MicroMist-based system. The absolute
ICP-MS sensitivity (i.e. corrected for different liquid flow rates) for
115
In was found to be about 4 times higher while the signal noise was
only slightly elevated [101]. Extensive studies were carried out on the
signal noise generated by this type of nebulizer as well as its suitability
for hyphenation with FIA and ion-pair chromatography using cap-LC
instrumentation [42,102].
3.4. Cross-flow nebulizers
Jankowksi et al. presented a study on a commercial cross-flow neb-
ulizer with a micro-capillary array [103]. The nebulizer is demountable
and consists of an array of several thousand nozzles through which the
nebulizer gas stream is supplied. Aerosol generation efficiency should
be improved and was found to be up to 50%, since positioning the sam-
ple capillary with respect to the nebulizer gas outlet is not as critical as
Fig. 9. Schematics of the flow-blurring/flow-focusing nebulizer with geometric descriptors (left). A liquid flow l is passing a sample tube T, with the outer and inner diameter Do and Di
forming a meniscus M in the direction of t towards j. The capillary is placed at distance H to the orifice plate with the orifice diameter D and thickness S. θt and θ represent the angle of
the tapered capillary and the orifice and Po and Pa represents the plenum pressure and the ambient pressure, respectively. Right: Transition from continuous flow-focusing (CFF) to
flow-bluring (FB) operation is determined by the Weber number We and the ratio of the tube-to-plate distance H to the orifice diameter D. A H/D-value of 0.5 represents the transition
from CFF to FB. Turbulent flow focusing (TFF) is dominant at We numbers greater than 20.
Reproduced from Ref. [58] with permission of the American Physical Society.
25
for single orifice designs. This device may be used for liquid flow rates of
20–500 μL min− 1. The ICP-OES sensitivity, signal precision and de-
tection limits were improved for a number of elements compared to
the concentric reference system. In different studies performed by
Zachariadis et al. the direct introduction of slurries of diverse types of
samples were evaluated for their applicability in ICP-OES [104–106].
Different sample introduction systems were considered for undigested
and digested antibiotics, infant milk powders and sunscreens. It was
found that the Babington-type nebulizer/cyclonic spray chamber com-
bination allows for higher concentrated slurries to be introduced with-
out detrimental effects compared to the “gem tip cross-flow”/Scott-
type double pass system. The former provided LODs in the μg g− 1
range for 21 elements. Fairly high sample introduction rates of up to
3 mL min−1 were used within those studies. Impressively, the present-
ed method was capable of introducing slurries of up to 2.5% (m/v).
A comparative approach was presented by Kollander et al. [107]. The
presented method was applied to the analysis of whole blood and
bovine liver via ICP-OES using three sample introduction systems: a
conventional concentric nebulizer, a Burgener T2100 and a cross-flow
nebulizer. The results were found to be comparable, while only for
liver samples the cross-flow nebulizer showed irreproducible behavior.
Although 100% (v/v) whole blood could be introduced without clogging
the nebulizer or extinguishing the plasma, recovery rates decreased for
increasing volume fractions of whole blood if no internal standardiza-
tion was applied. A number of 14 out of 16 elements were quantified
with a maximum deviation of 10% for a 70% (v/v) diluted whole blood
CRM, while 7 of 9 elements were quantified in bovine liver slurries
with similar accuracy.
3.5. Flow-focusing/flow-blurring nebulizers
In the view of the authors, the most interesting pneumatic nebuliza-
tion principle presented lately is the flow-focusing/blurring method. It
was originally described by Gañán-Calvo in 1998 [57]. The schematic
design of such device is shown in Fig. 9 [58]. The critical dimensions
for its mode of operation are the capillary to plate distance H, the orifice
diameter D and the jet diameter Dj. But the capillary wall and plate
thickness as well as their shape are also of importance. The flow-
focusing effect, as described in the original work, offers the possibility
to overcome the drawbacks that all pneumatic nebulizers share so far,
which is the need for a reduction in sample capillary diameter to
achieve fine sprays at microliter flow rates. This leads to a strongly
reduced tolerance of TDS and/or particle load with an increased risk
26 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
for clogging/blocking of the nebulizer tip in combination with higher
liquid back-pressures [7]. For concentric designs, the mean diameter
of the produced droplets depends in a complex way on the diameter
of the liquid outlet: smaller diameters usually led to finer aerosols. But
this does not apply to the flow focusing principle. Due to its special
geometry, the liquid emerging from the capillary builds a meniscus
which is then tapered by the pressure drop from inside the inner cham-
ber through an orifice of smaller diameter than the sample capillary to
the area outside the chamber. This pressure drop results in the for-
mation of a liquid jet with about a third of the orifice diameter and
the generation of nearly monodisperse droplets [2]. Originally, a sample
capillary of 200 μm in diameter was placed in front of a 150 μm orifice
[57]. Through the applied pressure drop, a jet of 46 μm diameter was
formed which subsequently built well-defined droplets of approx.
75 μm in diameter with less than 7% standard deviation. As an additional
advantage, the gas flow surrounding the liquid jet prevents the liquid
from any contact with the orifice wall, thus preventing nebulizer block-
age. Rosell-Llompart and Gañán-Calvo presented a very detailed funda-
mental study on this nebulizer geometry [58]. A mathematical model
for droplet generation was discussed with respect to physical properties
of the sample solution and geometrical parameters of the instrument.
Interestingly, according to Eq. 12 of Ref. [58], the diameter of the jet is
not a function of the diameter of the sample capillary at all. The authors
point out that careful variations of the operation conditions allows to in-
fluence the aerosol characteristic due to changing the droplet genera-
tion mechanisms [58]. Three different operating modes can therefore
be achieved with the same device: (i) the capillary flow-focus mode,
(ii) the turbulent flow-focusing mode and (iii) the flow-blurring
mode. According to Fig. 9, the different flow regimes are defined by
two parameters, the Weber number We, and the ratio of the capillary
to plate distance to the plate orifice diameter H/D. The Weber number
is defined deviant from common equations (see Eq. 5 of Ref. [58]) de-
pending again on the surface tension, the density and flow rate of the
liquid as well as the pressure drop across the orifice. Within that
study, a high number of prototypes for both, flow-focusing and flow-
Fig. 10. Flow focusing pneumatic nebulizer: (left, A) schematics (see Fig. 9 for explanation); (left, B) photograph; (right, A) comparison of primary droplet size distributions obtained with
the FFPN at different sample uptake rates; (right, B) comparison of primary droplet size distributions obtained with five different micronebulizers.
Reproduced from Refs. [109,110] with permission of the Royal Society of Chemistry.
blurring with varying geometries, were tested. In conclusion, capillary
flow-focusing dominates at orifice diameter D between 50 and
200 μm and a plate thickness S in the range of 50–75 μm [58]. It offers
very narrow droplet volume distributions as stated earlier by Gañán-
Calvo [57]. Turbulent flow-focus is somewhat a transition stage. The
formed jet still remains for some distance outside the nozzle, but turbu-
lent disturbances come to the fore, leading to a less robust droplet pro-
duction and more polydisperse aerosol [58]. The flow-blurring regime is
known to be obtained in the case of a large orifice in thick plates
(100 b D b 700 μm; 75 b S b 400 μm). This breakup mechanism leads
to a finer and less monodisperse spray. For fixed liquid and gas flow
rates, the median droplet diameter in flow-blurring mode is about 2–4
times lower than for both, capillary flow-focusing and turbulent flow-
focusing modes. With this principle a tunable pneumatic nebulizer is
presented which combines large bore sample feed with the generation
of fine primary aerosols [58].
A study performed by Vega et al. offered a closer look on the stability
of the different flow regimes [108], mainly focusing on the minimum
liquid flow rate Qmin, which is necessary to reach the stability regime
for jet formation. It was shown that the capillary to orifice distance H
had a strong effect on the value of Qmin. Minimum values of around
33 μL min−1 were achieved for 100 b H b 150 μm and a pressure drop
of 150 and 250 mbar. The capillary diameter also plays an important
role. In general, lower minimum flow rates were reached by finer capil-
laries, which in turn demands for a shorter capillary to orifice distance
(const H/D). Below the above given range of Hopt, the values for Qmin
are strongly increasing which was interpreted as transition to the
flow-blurring regime [108]. An optimum value for Qmin of approx.
26 μL min−1 was reached for 100 μm capillaries combined with a capil-
lary to orifice distance of 90 μm. These findings led to the conclusion,
that neither of both geometrical parameters can be optimized individu-
ally. It was also pointed out that for stable jet formation a certain angle
of the meniscus of the liquid has to be reached [108].
The first analytical characterization of a flow-focusing pneumatic
nebulizer (FFPN) was carried out by Almagro et al. [109] and relevant
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
schematics are shown in Fig. 10 (left A + B). Primary aerosol character-
istics were determined for different liquid and gas flow rates. It was
shown that for low liquid and high gas flows virtually 100% of the aero-
sol volume was contained in droplets of less than 10 μm in diameter
(Qg N 0.7 L min−1; Ql b 0.2 mL min−1). ICP-OES sensitivity was investi-
gated for a number of elements with different ionization potentials.
While for elements of low energies the sensitivity was quite comparable
to such achieved with a Conikal nebulizer (Glass Expansion), up to 5
times improvement was observed for high-energy elements. However,
the sensitivity was not corrected for the different liquid flow rates of
0.2 and 2.0 mL min−1 for the flow-focusing and the Conikal nebulizer,
respectively. The subsequent study of this research group presented a
more comparative report on nebulizer performance [110]. Five com-
mercial micronebulizers were compared to the FFPN: a PFA micro-
nebulizers, the MicroMist (MM), a HEN, the AriMist (AM) and the
MiraMist (MiM). In this study the applied liquid flow rates were identical
for all systems. Primary aerosol characterization at 0.2 mL min−1 liquid
and 0.7 L min−1 gas flow showed decreasing median diameters from
31.75 μm down to 3.25 μm for the MicroMist, PFA, AriMist, MiraMist
and FFPN (cf. Fig. 10, right A + B). Analyte transport values Wtot were
found in the order of FFPN ≫ HEN ≫ MM ≥ AM ≥ PFA ≥ MiM. However,
signal precision of the FFPN was slightly worse than the HEN, although
better than or comparable to all other devices. Another study of Almagro
et al. dealt with the introduction of samples with high salt content into
ICP-OES using the FFPN and a SeaSpray nebulizer as reference system
[111]. After the nebulization of a 3% (w/v) NaCl solution for 2 h a micro-
scopic inspection of the nebulizer tip showed neither blockage nor salt
deposition. Detection limits in both, axial and radial ICP-OES analysis
were determined for the FFPN and the SeaSpray nebulizer using solutions
of 2% (w/v) NaCl in 0.5 M nitric acid. For every investigated element the
FFPN allowed for at least comparable, in the majority of cases superior
detection limits. This is remarkable as for most other systems presented
above only comparable detection limits were gained due to elevated sig-
nal noise (cf. Sections 3.1–3.4). Additionally, using the axial viewing
mode the analyte signals were found to be more stable, resulting in
lower detection limits for both sample introduction systems.
A comparison of micronebulizers as tools for sample introduction
into microwave induced plasmas was carried out by Matusiewicz et al.
[112]. The FFPN, a micro3 nebulizer, the NAR-1 (microcapillary array
nebulizer, see above) and a conventional Meinhard concentric nebulizer
were considered for this study. All systems were applied to the analysis
of four certified reference materials: lobster hepatopancreas, human
hair, lichen and soy flour. It was found that each of the nebulizer
systems allowed for results being in good agreement with data of the re-
spective reference material. The FFPN offered slightly improved preci-
sion and the corresponding detection limits were superior in most of
the presented studies while the RSD values were similar for all four sys-
tems. The authors repeated the study now comparing a flow-blurring
pneumatic nebulizer (FBPN) with six additional types of micro-
nebulizers: a HEN, a dDIHEN, an AriMist, a MiraMist CE, an ultrasonic
nebulizer (NOVA-1) and the conventional concentric pneumatic nebu-
lizer [113]. The application of the FBPN yielded highest MIP-OES sensi-
tivity and slightly lower LODs compared to the other systems [113].
A commercially available nebulizer based on the flow blurring
principle was finally introduced as “OneNeb” and was recently ap-
plied to the analysis of metals and phosphorus in biodiesel from dif-
ferent feedstocks using ICP-OES [114]. It was brought to the market
as all-purpose sample introduction system covering a wide liquid
flow range of 0.005–2.0 mL min− 1. Due to its large bore liquid feed-
ing tube of 0.5 mm its tolerance to particles and high salt contents is
denoted as very good.
Flow-blurring nebulizers were also successfully applied as fuel injec-
tion systems. Simmons et al. and Sadasivuni et al. presented studies on
the influence of the operating conditions of such a nebulizer on the
flame- and emission profiles of vegetable oil, biodiesel and conventional
diesel for clean combustion [115–117].
27
3.6. Ultrasonic nebulizers
Since its initial presentation [118] and its significant impact on the
introduction of liquid samples in atomic spectrometry the ultrasonic
nebulizer (USN) lost some of its importance over the last past years
due to the ongoing development of a number of diverse low-flow and
high-efficiency nebulization systems. Only a few studies were undertak-
en on the further development and improvement of such a system and
its application in ICP-MS/OES.
Kahen et al. reported on the loss of bromine as HBr within the
aerosol desolvation system of such USN [119] and proposed the addi-
tion of 1 mg L NaCl as suppressing agent preserving linearity of bromine
calibration curves in ICP-MS. A more sophisticated approach was pre-
sented by Asfaw et al. [120,121]. In the first study, the authors investi-
gated the effect of the replacement of the heater/condenser unit by a
pre-evaporation tube (PET) which is heated to 400 °C [121]. Multivari-
ate optimization lead to operation conditions providing better sensitiv-
ity, improved limits of detection and plasma robustness in ICP-OES. The
novel approach also allows for the determination of Hg, which would
otherwise be lost within the desolvation unit. External calibration with-
out matrix matching was possible for the analysis of certified soil refer-
ence material using internal standardization by an Ar emission line. The
authors suggest that slightly degraded signal RSDs might be due to the
fact that the liquid flow rate applied was reduced to 0.3 mL min−1 in
contrast to 2.5 and 2.0 mL min−1 for the conventional USN and pneu-
matic system, respectively. In the more recent study, sensitivities were
improved by an average factor of 2 by heating the PET via infrared radi-
ation instead of applying a heating tape [121]. Plasma robustness was
further improved and memory effects were reduced. Measured ICP-
OES signal intensities for B and Hg were found to be even higher com-
pared to the approach using the heating tape, while both analytes expe-
rience severe losses within the conventional membrane desolvation
system.
Additional studies employing USN systems dealt with the ICP-MS
analysis of fuel ethanol [122,123] and focused on matrix effects caused
by carbon built-up on sample cones stemming from organic com-
pounds. The impact of the amount of water content of the organic sam-
ple solvent on the decrease in sensitivity and the selection of an
appropriate calibration technique were also investigated. Ultrasonic
nebulizers were combined with various types of other excitation
sources, too, such as an RF microstrip He plasma [124], flames used for
flame atomic absorption spectrometry [125] and miniature microwave
plasma torches [126].
3.7. Multi-mode nebulizer configurations
For the past couple of years, an increasing number of studies was
published presenting the application of dual-, triple-mode or an even
higher number of sample introduction systems being operated in
parallel [127–145]. In these studies different nebulization techniques
were investigated based on concentric nebulizers, parallel-path, flow-
blurring and flow-focusing nebulizers as well as (micro)ultrasonic neb-
ulizers. These multi-mode nebulizer configurations were applied to the
determination of volatile species using online matrix matching calibra-
tion techniques or online hydride generation. Different strategies for the
optimization of the respective method are presented, from univariate to
complex multivariate chemometric methods like simplex or composite
design.
A quadruple flow-focusing nebulizer was presented by Kovachev
et al. [145]. It consists of four separate sample feeds sharing a common
gas supply. The system was characterized regarding the respective
droplet size distribution and droplet velocities of the primary aerosols
and the combined tertiary aerosol. It was found that the four nozzles
produce different aerosols regarding both, Sauter mean diameter and
mean velocity and each of the four nozzles does not equally contribute
to the total aerosol composition. Highest share of about 60% was
28 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
found for one individual nozzle, which coincides with the smallest
Sauter mean diameter and fastest mean velocity compared to the
remaining nozzles. The analytical performance was determined via
ICP-OES analysis of synthetic samples and the results were compared
to those values achieved with an ICP-OES equipped with a standard
nebulization system. The relative sensitivities were compared for differ-
ent liquid flow rates of the standard system using the axial and the radi-
al viewing mode of the spectrometer. For the majority of investigated
elements and operating conditions no significant differences in relative
sensitivities were found except for some easily ionized elements (K, Li,
Ba). The LODs for most of the respective elements were overall im-
proved in the case of the flow-focusing multi-mode nebulizer in axial
viewing mode of the ICP-OES due to slightly lower signal RSDs. The sys-
tem was applied to the analysis of certified reference materials, using
both external calibration and “online in chamber” standard addition.
It was shown that the latter gave rise to more accurate yet less precise
results.
The study by Angel Aguirre et al. focused on the effect of different
geometries (parallel to 30° convergent) of a dual flow-blurring system
on the achievable accuracy and precision for online standard addition
[146]. Three different designs of the dual flow-blurring system as well
as a standard nebulizer as a reference system were applied to the anal-
ysis of certified estuarine water samples through ICP-OES. The reference
system was exclusively applied to external calibration whereas the
determined accuracy and precision were compared to those values
achieved with the novel system using standard addition calibration
only, which makes it difficult to evaluate the results and the conclusion
given by the authors. It was found that a 30° convergent setup of both
nebulizers showed the best achievable accuracy while precision was
somewhat degraded for all geometries compared to the reference
system.
A dual-mode cross-flow nebulizer for the analysis of organic solu-
tions using calibration through aqueous standard solutions in ICP-OES
was presented by Bauer et al. [130,147]. The achievable detection limits
were still slightly better when using a conventional cross-flow nebulizer
combined with sequential aspiration of organic sample and aqueous
standard solutions rather than the simultaneous introduction of both
types of solvents employing the proposed dual-mode nebulization
unit. But relative errors of less than 4% were found for the analysis of
oil standards using the novel nebulizer system.
Fig. 11. Setup of a multimode sample introduction system (MSIS) employing a pre-evaporation tube (PET) for ICP-OES. Liquid samples can be introduced either via a pneumatic (A) or
ultrasonic (B) nebulizer while gaseous samples may be introduced in parallel through the vapor generation (VG) line.
Reproduced from Ref. [127] with permission of the Royal Society of Chemistry.
A proposed dosing frequency-based calibration strategy also makes
use of a simultaneous dual-mode sample introduction system,
employing the so called “dual drop-on-demand aerosol generator”
recently introduced by Bings and coworkers [148]. Since this aerosol
generator is considered a non-pneumatic system it will be further
described in the corresponding following chapter.
The largest number of publications focusing on multi-mode sample
introduction systems was devoted to online hydride generation. An ex-
cellent overview on this topic was already given by Pohl and Sturgeon
[142] which is why only selected work will be presented here in closer
detail. Multi-mode sample introduction units used for this application
contain a dual or a triple nebulizer arrangement, usually attached to a
common spray chamber. Studies show improvements in sensitivity by
factors ranging from 20 to 100 [128,140,143] compared to the applica-
tion of conventional nebulizers. In general it has proven to be quite
difficult to establish compromise conditions for the simultaneous
detection of volatile hydrides and analytes introduced through the
liquid phase of the aerosol even when multivariate optimization proce-
dures were considered e.g. based on the Simplex algorithm, Plackett–
Burman or composite designs [120,128,129,132,136,138–140,144,
149–151]. Benzo et al. reported on the design of a suitable spray cham-
ber for hosting multi-mode nebulizer systems [132]. The entrance
angles of a cyclonic spray chamber were varied from 0, 45, 90 to 180°
and it was found, that signal precision for most analytes was best
when using the 45° geometry but signal-to-background ratios (SBR)
varied extremely without trend [132].
A more complex multi-mode sample introduction system was pre-
sented by Asfaw et al. [120,127] and can be seen in Fig. 11. It consists
of a vapor generation line, a pneumatic nebulizer for the introduction
of the reductive reagent and a third inlet for either a MiraMist
parallel-path or USN nebulizer all combined with a cyclonic spray/
aerosol mixing chamber. The USN was attached through its heater/
condenser segment while the whole system was connected to the ICP
through a pre-evaporation tube. In multi-mode operation using the
pneumatic nebulizers, improvements of the achievable sensitivities in
ICP-OES were in the range of 35–83 for As, Bi, Ge, Hg, Sb and Sn, while
no significant effect compared to the use of conventional pneumatic
nebulizers was reported for all other investigated elements. In the
case of the USN, the multi-mode operation yielded sensitivity improve-
ment factors in the range of 4.2–18.6 for the aforementioned elements if
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
compared to conventional USN operation. Mg II/I ratios as indicator for
plasma robustness were found to be as high as 12 for both systems con-
taining the pre-evaporation tube while values of roughly 4–8 were
found for the configuration without the PET.
The application of multi-mode sample introduction systems
(MSIS) is not limited to the detection of As or Se, as in focus of
most of the presented studies. Matusiewicz et al. contributed several
articles on different applications of ultrasonic-based MSIS [139,149,
150,152]. A dual-capillary USN was used for simultaneous intro-
duction of the acidified sample and the reductant at low uptake
rates of 15 μL min− 1 . By this, volatile species of transition and
noble metals (Au, Ag, Cd, Cu, Mn, Ni, Pb, Zn, Pd, Pt, Rh) were formed
and transported into an MIP-OES by means of an Ar carrier gas flow.
Simplex optimization procedures led to improved detection limits
compared to conventional sample introduction. Although signal
precision was degraded, ranging from 8 to 12% RSD, the proposed
method was successfully validated through the analysis of standard
reference materials [149,150]. The system was further improved by
adding a third capillary, providing separate supply of the sample
and the solutions containing the acid and the reductant. Lower
RSDs (7–8%) and improved detection limits were achieved [152].
This configuration was also used for direct iodine vapor generation
applied to the analysis of biological samples through ICP-OES [139].
Achievable RSDs were in the range of 2–4% and thus superior to
data gained with the aforementioned “two-capillary” configuration
presented by the same group. The method was optimized by means
of simplex procedures and was successfully validated through the
analysis of two different certified reference materials.
An MSIS was applied by Al-Assaf et al. to species specific determina-
tion of four arsenic containing compounds in slit loam soil using ICP-
OES after high performance ion exchange chromatography [153]
whereas Elwaer et al. employed a multi-mode system for isotope ratio
determinations of As and Se [135,154]. Although the detection limits
were improved [135] and lowest mass bias was observed in the case
of hydride generation [154], the system's applicability for isotope ratio
measurements was found to be limited due to degraded long-term sig-
nal stability [135].
In conclusion, most of the presented studies involving MSIS em-
phasize improved LODs for the investigated elements, even non-
hydride forming ones. In that case the improvement is attributed
to the introduction of hydrogen into the ICP as by-product of the
chemical vapor generation process which promotes excitation/
ionization processes [120]. This was also systematically investigat-
ed by Wiltsche et al. [144]. The authors were able to prove that the
intensity enhancements for a number of hydride and non-hydride
forming elements were virtually identical for both, the operation
of the MSIS under the addition of NaBH 4 and without NaBH 4 but
with 10 mL min − 1 of H 2 being added to the carrier gas. It was
found that intensities also improve with increasing first ionization
potential of the investigated elements and higher Mg II/I ratios
were observed when higher excitation temperatures of the plasma
were reached.
The reported improvements may therefore not only be explained by
the superior analyte transport efficiency of gaseous samples into the ICP
compared to wet aerosols. They might also be due to the beneficial
effects of hydrogen on the excitation/ionization processes within the
plasma [144]. In a report on the analysis of waste water samples, Se
was proven to be transferred into its volatile hydride with an efficiency
of 99.9% [135]. But that is not generally the case, neither for Se nor for
other elements. Furthermore, hydride generation yields are not always
explicitly investigated and especially for precious metals quantitative
conversion may not be reached [149,150]. It can therefore be concluded
that an unknown yet reasonable part of the aforementioned sensitivity
enhancements in the case of multi-mode sample introduction systems
can be attributed to the beneficial effect of hydrogen added to the Ar
carrier gas of the ICP.
29
3.8. Non-pneumatic aerosol generation
The formation of droplets from liquid samples and thus the genera-
tion of corresponding aerosols can also be accomplished by non-
pneumatic means, i.e. without applying kinetic energy transfer from a
high velocity gas stream onto the liquid phase. Instead, mechanical,
thermal and electrostatic interactions are being utilized for the genera-
tion of droplets. Mechanical droplet generation and its application to
analytical atomic spectrometry were thoroughly studied by Hieftje
and coworkers [155–157]. Herein, the investigated droplet generators
are based on active movement of the sample capillary by e.g. a bimorph
transducer, whereas the more recent oscillating capillary nebulizer pre-
sented by Wang et al. [158] makes use of the passive movement of a
long slackly capillary caused by gas-induced transverse and longitudinal
vibrations within a flowing carrier gas stream. The advantage of an ac-
tive capillary movement is the generation of monodisperse droplets at
a frequency equal to the oscillating frequency of the capillary, compared
to a more polydisperse aerosol in the case of the passive design [2]. Al-
though the proposed passive system suffered from poorer signal preci-
sion and the lack of long-term stability Wang et al. successfully applied
it to the determination of five organic Se compounds through HPLC-ICP-
MS [158]. A similar commercial system, a vibrating orifice aerosol gen-
erator, was recently applied by Su et al. for the in situ generation and
introduction of monodisperse Tb nanoparticles into an ICP-MS for cali-
bration purposes in the field of airborne radioactive particle analyses
[159]. Miyahara et al. proposed a liquid sample introduction system
which employs a magnetic valve for switching the hydrostatic pressure
stemming from a reservoir as the driving force for droplet formation at
the tip of a sample capillary [160]. This “droplet direct injection nebuliz-
er (D-DIN)” was used to directly inject a single droplet or a series of
small droplets of nanoliter samples into different (micro)plasmas.
Thermal droplet formation can be achieved through electrothermal
spray, i.e. conventional thermospray and microwave-assisted nebuliza-
tion [161–163]. Amirav et al. presented the application of thermospray
for the in situ generation of highly monodisperse nanoparticles [163].
The characterization of the aerosol revealed an extremely narrow drop-
let size distribution and decreasing droplet diameters (9.5–4.5 μm) with
increasing liquid flow rates (50–500 μL min−1). This device was origi-
nally designed for the generation of high quality semiconductor
nanocrystals rather than for sample introduction in atomic spectrome-
try. An analytical characterization of this promising system was there-
fore not carried out.
In contrast, the microwave-assisted liquid sample introduction sys-
tem (MASIS) as presented by Grindlay et al. was explicitly designed
for ICP spectrometry [161,162]. For a selection of nine elements the pre-
sented systems offer at least a 15-time improvement of the achievable
LODs in ICP-OES over conventional pneumatic nebulization in combina-
tion with a cyclonic spray chamber. Drawbacks such as significant salt
deposition at the nebulizer tip and potential carbon built-up in IPC-
OES/MS might become limiting factors due to the fairly high liquid
flow rate of 0.9–1.8 mL min−1 in combination with excessive solvent
evaporation and analyte and/or matrix crystallization. To provide the
suitable heat transfer from the microwave radiation into the liquid
phase, sample matrix composition with respect to inorganic salt content
and organic solvents has to meet certain requirements. Early investiga-
tions of this type of nebulizer revealed a minimum amount of 40% (v/v)
of organic solvents necessary for stable aerosol production together
with at least 0.25% (w/v) of inorganic matrix components [162]. In a
more recent study it was pointed out that organic solvents are dispens-
able as long as the aqueous sample matrix provides a certain ion con-
centration and thus electrical conductivity [161].
Electrospray ionization (ESI) is a well-known technique for sample
introduction/ionization in molecular mass spectrometry. Brennan
et al. adopted, modified and characterized a heat-assisted argon
electrospray interface for application in ICP-OES and ICP-MS [164].
The schematic design of that device is shown in Fig. 12. The long-term
30 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
Fig. 12. Schematics of an electrospray interface for ICP spectrometry. The solution is supplied to a tapered stainless steel rod which is positioned in the center of a heated laminar Ar gas
flow. The droplets produced are accelerated towards a ring electrode and directed to the ICP.
Reproduced from Ref. [164] with permission of the American Chemical Society.
stability of the Ar–ESI interface was found to be rather poor but internal
standardization helped to improve the RSD from 12% to less than 0.5%.
An addition of 5% (v/v) methanol to the aqueous solutions is mandatory
to achieve stable droplet generation. The proposed Ar–ESI interface rep-
resents a convenient approach for the generation of droplets without
the aid of a high-velocity and high-volume nebulizer gas flow. Low liq-
uid flow rates in the range of 2–4 μL min−1 become accessible, which is
of particular importance when hyphenating liquid sample introduction
to miniaturized excitation/ionization sources.
3.9. Summary
When reviewing recent contributions to the field of sample intro-
duction into atomic and mass spectrometry it can be concluded that
the miniaturization of systems utilized for sample introduction has be-
come a major trend [3]. The reason for this might be the increasing
need to cope with minute amounts of sample material to be analyzed
without dilution and to establish the hyphenation of low flow separa-
tion techniques without the need for the addition of make-up liquids.
But as outlined in the above Sections 3.1–3.8, most approaches pro-
posed for micro- or even nano-flow liquid sample introduction into ICP-
MS or ICP-OES still suffer from the fact that signal noise and long-term
precision are deteriorating with the reduction of the liquid-flow rate.
It can also be concluded that the minority of the presented studies
focuses on the development and characterization of novel pneumatic
nebulization techniques, rather than on the advancements and further
development of common and traditional instrumentation for liquid
sample introduction. But even such modified conventional systems de-
mand smaller diameters of the sample outlet capillary to form fine aero-
sols at lower liquid flow rates. Down-scaling of such instrumentation
was therefore commonly applied to achieve lower flow rates at the ex-
pense of reduced tolerance of particles and higher amounts of total dis-
solved solids. The novel and recently commercialized flow-focusing
pneumatic nebulizer does not show the same dependence of the droplet
size on the sample capillary diameter. Here the capillary to plate dis-
tance is rather important (cf. Section 3.5) leading to droplets with diam-
eters smaller than such of the sample capillary. Finer aerosols can be
generated without the aforementioned drawbacks associated with
small-bore capillaries.
Increased signal noise, usually also observed with lower liquid flow
rates, can be explained by the distinct decrease of the droplet number
density. The reduced amount of sample contributing to the signal within
a given period of time (detector dwell time) is based on a reduced num-
ber of droplets. For example, the system with the lowest accessible flow
rate of 0.05 μL/min and a monodisperse droplet size of 5 μm in diameter,
the nDS-200e (cf. Table 2), would produce approx. 1270 droplets within
a dwell time of 0.1 s, compared to 2.5 × 107 droplets at a flow rate of
1 mL/min. In this context it is also important to consider that the
lower the liquid flow rate, the stronger the necessity to introduce mono-
disperse aerosols into the ICP. This is because the mass fraction of a sin-
gle droplet relative to the total aerosol mass increases with decreasing
number density of droplets of the same volume. Therefore, the relative
contribution of a single droplet to the measured signal also increases
with decreasing droplet number density. As a result signal fluctuations
and therefore RSDs increase with the degree of polydispersity of the
aerosol and with decreasing droplet number densities.
This becomes even more important when analyzing nanoparticles,
i.e. detecting discrete signals stemming from individual particles,
which is still a major challenge for ICP-MS and ICP-OES in general and
for sample introduction systems in particular [29,41]. The introduction
of discrete particles dispersed in the respective liquid phase into the
ICP often demands for extreme dilution of the sample to ensure a max-
imum number of one particle per droplet generated by the nebulizer.
This requirement can also be met if sample introduction devices are
being used which allow the generation of individual droplets from liq-
uid samples which contain a suitable concentration of the nanoparticles.
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
Different techniques to achieve both the generation of individual drop-
lets on demand and at desired frequencies together with applications of
these approaches will be reviewed in the following section.
4. Generation of discrete droplets
4.1. Early studies
The monodisperse dried-microparticulate injector (MDMI) as pre-
sented by French et al. in 1994 first allowed the variation the droplet
generation frequency within a certain range [34], while the previously
introduced devices had to be operated at a fixed frequency. However,
as the MDMI is driven by a piezo-actuator, a minimum operating fre-
quency is mandatory to ensure stable droplet generation. In even earlier
studies Olesik et al. focused on the effect and fate of individual droplets
in the ICP [30,32] and had a closer look on the measured signal caused
by isolated droplets on a μs time scale [31,165]. The MDMI was found
to be a valuable diagnostic tool for elucidating fundamental processes
within the ICP, but it was not applied to the introduction and analysis
of real samples [2].
First applications of the alternative thermal-inkjet principle in atom-
ic spectrometry were introduced in 2006 [166,167]. Original thermal-
inkjet printers were used for the deposition of pL-volume droplets
onto solid targets for calibration purposes in total reflexion X-ray fluo-
rescence spectrometry (TXRF) and laser ablation ICP-MS (LA-ICP-MS).
In later studies Fittschen et al. investigated a prototype of a pL pipette
system provided by Hewlett-Packard [168]. This automated dispenser
permits the transfer of variable droplet volumes but it suffers from sig-
nificant evaporation of the used solvent through the dosing nozzles.
This was found to result in analyte enrichment within the channel
leading to the dosing nozzle, which can only be compensated by rinsing
the respective nozzle through discarding the first droplets of a series of
droplets being ejected during each dosing sequence. As a result, a lower
Fig. 13. Schematics of the DOD aerosol generator. A: Original ink cartridge, type HP45; B: modified ink cartridge for analytical applications; C: cross-section of the dosing device showing
both liquid channels integrated into the silicon chip; D: close-up bottom-view of a single dosing nozzle; E: combination of the modified dosing cartridge with the aerosol transport
chamber via a mounting plate; F: principle of thermal inkjet droplet generation process [42].
31
number of droplets dispensed by this device leads to higher errors in av-
erage mass, most significantly when dosing single droplets [169]. The
use of a humidified sheathing gas combined with a mechanical shutter
to reject a certain number of undesired droplets was recognized by
Petersen et al. to greatly improve the achievable precision especially
when transferring a single droplet onto a LA-target [170].
4.2. Novel approach
The application of a modified thermal inkjet printer cartridge com-
monly used for commercial inkjet printers as aerosol generator for sam-
ple introduction in atomic and mass spectrometry was recently
introduced by Bings and coworkers [101,148,171,181]. In contrast to
former inkjet systems used as dispensers (see above) this so-called
“drop-on-demand” aerosol generator (DOD) is driven by a lab-built
micro-controller to gain full access to all electronic parameters impor-
tant to influence and optimize the thermal inkjet process. Additional
support through any printer hard- and software is no longer necessary.
The dosing device, a modified HP45 cartridge containing 300 nozzles of
approx. 28 μm in diameter can be fitted to an ICP-MS via a lab-built
aerosol transport chamber. A schematic overview of such device and
the operation principle is provided in Fig. 13. With this DOD used for
sample introduction in ICP-MS, sensitivities can be improved for a
large number of investigated elements by a factor of 8–18 compared
to a MicroMist-based reference system [171]. Signal noise was found
to be slightly elevated as it is also the case for merely all micro-flow
systems discussed above. It was also found to be different to such
generated by other pneumatic low-flow nebulizers, e.g. the MicroMist
and the EnyaMist [42,172]. Both produce distinct frequency-specific
noise, while the DOD generates more white noise at higher frequencies.
The amplitude of this noise was found to correlate with the span of
the distribution of the drop-to-drop time intervals. The divergence of
the respective droplet travel time from the dosing nozzle to the ICP,
32 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
commonly known as jitter, was identified as the main source of the sig-
nal noise. Identical detrimental effects of varying divergences of the
droplet travel times on the signal noise were also identified by Chan
et al. [173,174]. In addition to an outstanding calculated aerosol trans-
port efficiency of up to 94 vol.% [42,172] the DOD allows to indepen-
dently optimize the carrier gas and liquid flow rates. The latter can be
varied from 0.04 to 6.3 μL min−1 for a single nozzle without changing
the aerosol characteristics [171]. This range was further expanded to
0.005–12.5 μL min−1 by modifications of the controller electronics of
the DOD [101]. Full control of the aerosol characteristics can thus be
gained simply through the respective electrical operation conditions of
the dosing device and without the attachment of e.g. a heating chamber
for aerosol modification, as it is the case for the MDMI.
Orlandini et al. presented a dual-DOD device and applied it to the
analysis of urine reference material [148]. With this system, novel cali-
bration techniques based on the dosing frequency were introduced
and successfully validated, similar to the approach which was formerly
described as “null-point technique” by Bastiaans and Hieftje [175]. It
was shown, that the DOD device is less susceptible to effects caused
by the urine matrix compared to the employed MicroMist reference sys-
tem, which is indicated by narrower spatial ion distributions within the
ICP. Despite this high matrix load five certified trace elements were ac-
curately determined based on dosing frequency-based external calibra-
tion without matrix matching, while values for only two out of five
elements were in agreement with the reference data in the case of the
MicroMist system using conventional non-matrix matching external
calibration [148]. The dosing frequency-based calibration was also
found to significantly reduce sample consumption to less than 12 μL of
reference material for both, the external calibration and the standard
addition method. All investigated approaches, i.e. both calibration tech-
niques employing the dual-DOD and the application of the reference
sample introduction system lead to similar accuracies, while the ob-
served precision is weaker in comparison to the data gained with the
reference system.
Due to its extraordinary low sample uptake rate, the DOD is
predestined for the use with low-temperature plasma sources. In the
past couple of years, the field of ambient desorption/ionization (ADI)
Fig. 14. Schematic diagram of the FAPA ion source in combination with DOD liquid sample introduction. A suitable glass interface supports droplet introduction directly into the afterglow
of a pin-to-plate FAPA.
Reproduced from Ref. [181] with permission of the American Chemical Society.
mass spectrometry has drawn lots of attention. Numerous new ion
sources were introduced, e.g. the low-temperature plasma probe
(LTP), the direct analysis in real-time system (DART) and the flowing
atmospheric-pressure afterglow (FAPA) source [176–178]. For further
details the interested reader might consult one of the excellent reviews
devoted to this field [179].
The beam of reactive ions generated by each of those sources is usu-
ally directed onto the sample surface to desorb and ionize the analyte of
interest which is then sampled into the mass spectrometer. Dissolved
samples are preferably analyzed through residues stemming from
dried volumes of the corresponding liquid spotted onto targets or by
directing the plasma source directly onto the liquid surface [180]. Due
to the very low energy of the plasma, the direct introduction of liquids
into these ADI sources was so far hardly possible, until Schaper et al.
presented the hyphenation of the DOD to the FAPA for direct mass spec-
trometric identification and quantification of drugs of abuse and their
corresponding metabolites in urine samples [181]. The achievable limits
of detection were greatly improved compared to data gained with both,
alternative liquid sampling methods for FAPA-MS and other ion sources
for molecular MS. The schematics of the corresponding DOD-FAPA-MS-
setup is shown in Fig. 14.
4.3. Single particle analysis
A major field of modern instrumental analytical chemistry is the de-
velopment of methods and instrumentation for the detection and anal-
ysis of individual droplets and particles, especially nanoparticles. High
sensitivity of the employed detection technique combined with high-
speed data acquisition are needed to achieve this goal, as well as the
sampling system has to be capable of introducing droplets at low
frequencies.
First applications of ICP-OES for size characterization of airborne
aerosols were carried out in 1986 by Kawaguchi et al. [183] and Bochert
and Danneker [182]. The method was adapted to ICP-MS by Degueldre
et al. and was then applied to the analysis of zirconia particles [184].
Since then this approach is referred to as “single-particle (SP) ICP-MS”.
In general, two approaches for the detection of individual events are
 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
possible. Firstly, using a fast detector offering high time-resolution for
data acquisition with a repetition rate of a multiple of the particle intro-
duction frequency which allows the detection of each individual tran-
sient event, i.e. each droplet or particle introduced. In contrast, the
detector dwell time can be suitably extended in combination with
very low droplet introduction frequencies that each measured signal
represents an average of only one droplet or particle [41]. The latter
can be easily accomplished and does not require significant modifications
of existing ICP-MS instrumentation other than synchronizing droplet/
particle generation and data acquisition to avoid erroneous particle size
values due to improperly selected dwell times. However, background/
noise correction is more difficult compared to the first approach.
Olesik and Gray also focused on the correlation of the quality of the
achieved SP-ICP-MS data with the detector dead-time, the dynamic
range in pulse counting or analog mode and the integration time [41].
For instance, even a data repetition rate of 500 s− 1 in combination
with the introduction of only 10 particles per second will still result in
a probability of 1% that the detected signal is caused by more than one
particle.
The final treatment of the collected data is identical for both ap-
proaches: Suitable thresholds have to be considered first, to distinguish
between signals stemming from either the background or the particles
and to differentiate between signals caused by a single and multiple
particles. Then the detected events have to be categorized to obtain a
Gaussian distribution of the number of detected events vs. the mea-
sured intensity. After appropriate calibration using reference particles
of known size the intensity distribution yields the size distribution of
the respective particles to be characterized. This data processing strate-
gy as well as its capabilities to distinguish between Ag nanoparticles and
dissolved Ag was outlined by Franze et al. [185] and is illustrated in
Fig. 15.
Single particle ICP-MS was already applied to the characterization
and quantitative analysis of nanoparticles [185–188] and to the devel-
opment of novel immunoassays [189]. In this context, the MicroDrop
dispenser was used for the generation of individual droplets and was
further characterized and applied by Niemax and coworkers [186–
188,190]. It is based on a setup similar to the previously described
MDMI [34] and consists of a piezo-actuator which pressurizes a capillary
to form monodisperse droplets of certain diameters (i.e. 65 μm accord-
ing to [185]). In contrast to the MDMI, no heating/evaporation unit but
rather a relatively long vertical tube is attached to the dispenser to
achieve complete evaporation of the droplets together with improved
sampling efficiency. As a disadvantage of such a piezo-based system,
the droplet generation frequency cannot be varied over a wide range.
For example, only 5 or 100 s−1 were applicable in the case of the system
employed by Gschwind et al. [187].
Franze et al. [185] compared three different sample introduction sys-
tems, the PC3, the APEX Q and a MicroDrop dispenser and employed
them in studies for the characterization of Ag nanoparticles of different
Fig. 15. Application of single-particle ICP-MS for the simultaneous detection of Ag nanoparticles and Ag+ ions. Application of the MicroDrop dispenser for introduction of individual
droplets (A). Resulting histograms for 60 nm Ag nanoparticles in a solution containing 3 mg L−1 of Ag(I) (B) and without dissolved Ag(I) (C).
Reproduced from Ref. [185] with permission of the Royal Society of Chemistry.
33
sizes with ICP-MS. The latter system represents the only discontinuous
sample introduction system and was found to be optimum for this
kind of application. The achievable ICP-MS sensitivity was superior for
the MicroDrop dispenser, allowing the determination of nanoparticles
down to 20 nm in diameter.
Niemax and coworkers also proposed an atomic spectrometric
method for size classification of nanoparticles using monodisperse
droplets of known volume and solutions of known concentrations
[186,188]. The reported LODs in terms of nanoparticle size of approx.
200 and 470 nm for Au and SiO2, respectively, are rather high as the
work was based on ICP-OES detection. In a following study ICP-MS de-
tection using the high-speed data-acquisition approach (see above)
was applied and size-related LODs of 33 and 21 nm were reported for
Ag and Au nanoparticles, respectively [187]. However, the proposed
method based on manual data acquisition suffered from severe analog
background noise of roughly 180 mV. In contrast, when using the
pulse-counting approach as in the case of studies by Franze et al., Ag
nanoparticles of 20 nm were readily detected, although no size-
related LOD was reported [185].
The performance of SP-ICP-MS might be even further improved
through synchronizing the introduction of the droplet into the plasma
and the ICP-MS data acquisition, i.e. the first event acts as a trigger for
initializing the measurement procedure [173,174]. As mentioned be-
fore, significant deviations in travel time appear during the transport
of the droplets towards the ICP, which hampers the use of such trigger
pulse. In an alternative approach Chan et al. successfully developed a
method for using either a distinct change in plasma impedance or the
Hα-emission line of the plasma as a trigger signal, both associated
with the introduction of a droplet [173,174].
It can be concluded that the principle of discontinuous sample intro-
duction offers several advantages: size-related LODs can be significantly
improved, mostly due to the superior transport efficiency but also due
to the reduced background noise in ICP-MS [185]. Additionally, sample
preparation can be simplified and associated errors can be reduced, as
less extreme dilution of the liquid sample containing the nanoparticles
is required to ensure a maximum number of one particle per droplet.
Droplet dispensers can also be used for the synthesis of nanoparticles
through the generation of monodisperse pL-droplets from highly dilut-
ed solutions containing the desired, dissolved material. The subsequent
evaporation of the solvent is than followed by the formation of the pre-
ferred nm-sized residues [190].
5. Conclusions
Liquid sample introduction is commonly referred to as the Achilles'
heel of atomic emission and mass spectrometry, e.g. in view of the
achievable aerosol transport efficiency, the robustness and matrix sensi-
tivity of the nebulizer, its ease-of-use and its applicable ranges of gas
and liquid flow rates, just to name a few of the parameters critical for
34 N.H. Bings et al. / Spectrochimica Acta Part B 100 (2014) 14–37
ICP-OES and ICP-MS. Novel nebulizers in combination with suitable
spray chambers were introduced in the recent past, based on different
approaches and techniques, such as the parallel-path nebulizer, the
Microwave-assisted thermal nebulizer or multi-mode sample introduc-
tion systems. An even larger number was presented based on classical
but further developed and improved approaches for liquid sample
nebulization, e.g. the micro-concentric and direct injection designs.
Most of the proposed systems expand the liquid flow regime to the
single digit μL min− 1–nL min− 1 and offer improved characteristics
and great potential for novel and future applications.
The innovative flow-focusing/blurring nebulizer, which produces
comparably finer aerosols and allows flexible sample flow rates in the
μL min−1 range was recently introduced for pneumatic continuous
aerosol generation, whereas the drop-on-demand aerosol generator
(DOD) was proposed for non-pneumatic discontinuous droplet intro-
duction into the ICP. However, a strong demand still exists for additional
even more sophisticated liquid sample introduction techniques.
Especially for the hyphenation of low-flow separation techniques
such as capLC or CE to ICP-MS suitable sample introduction systems
are currently rather limited, which perfectly match the eluent or elec-
trolyte flow rate of the separation device. Instead, an additional make-
up liquid has to be supplied with the risks of e.g. deteriorated chromato-
graphic resolution due to possible dead-volumes, increased background
signal levels and higher matrix/solvent load of the ICP. But also the
rapidly growing field of novel ambient plasma sources of comparably
low energy and temperature demands for liquid sample introduction
systems with extremely low uptake rates. For both areas of application,
non-pneumatic aerosol generators like the monodisperse dried-
microparticulate injector and the DOD should be advantageous as the
droplet generation process and thus the achievable aerosol characteris-
tic is independent of the carrier gas flow. This allows for an easier opti-
mization of the carrier gas flow rate used for aerosol transportation to
achieve maximum performance of the low-temperature plasma source,
preferably at low gas flow rates.
The relatively new field of nanoparticle analysis also benefits
considerably from the advantages of this kind of discontinuous sample
introduction systems. Smallest detectable particle sizes could be signif-
icantly reduced due to superior transport efficiencies of the generated
aerosol and further decreased background noise in ICP-MS.
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