Talan a 242 (2022) 123286
A ailable online 4 Feb ua y 2022
0039-9140/© 2022 The Au ho s. Published by Else ie B.V. This is an open access a icle unde he CC BY license (h p://c ea i ecommons.o g/licenses/by/4.0/).
Single-pa icle induc i ely coupled plasma mass spec ome y using
ammonia eac ion gas as a eliable and ee-in e e ence de e mina ion o
me allic nanopa icles
C is ian Su´
a ez-Oubi˜
na, Paloma He bello-He melo, Pila Be mejo-Ba e a,
An onio Mo eda-Pi˜
nei o
*
T ace Elemen , Spec oscopy and Specia ion G oup (GETEE), Ins i u e o Ma e ials iMATUS, Depa men o Analy ical Chemis y, Nu i ion and B oma ology. Facul y o
Chemis y, Uni e sidade de San iago de Compos ela, A enida das Ciencias, s/n, 15782, San iago de Compos ela, Spain
ARTICLE INFO
Keywo ds:
Dynamic- eac ion-cell
Single-pa icle-ICP-MS
In e e ences
On-mass app oach
Mass-shi app oach
Me allic nanopa icles
ABSTRACT
In ensi e p oduc ion o nanoma e ials, especially me allic nanopa icles (MNPs), and hei elease in o he
en i onmen pose se e al isks o humans and ecosys em heal h. Consequen ly, high-e iciency analy ical
me hodologies a e equi ed o con ol and cha ac e iza ion o hese eme ging pollu an s. Single-pa icle
induc i ely coupled plasma – mass spec ome y (SP-ICP-MS) is a p omising echnique which allows he
de e mina ion and cha ac e iza ion o MNPs. Howe e , se e al elemen s o iso opes a e hampe ed by spec al
in e e ences, and dynamic- eac ion cell (DRC) echnology is becoming a use ul ool o ee in e e ence
de e mina ion by ICP-MS. DRC-based SP-ICP-MS me hods using ammonia as a eac ion gas (ei he on-mass
app oach o mass-shi app oaches) ha e been de eloped o de e mining i anium dioxide nanopa icles
(TiO
2
NPs), coppe oxide nanopa icles (CuO NPs), coppe nanopa icles (Cu NPs), and zinc oxide nanopa icles
(ZnO NPs). The e ec s o pa ame e s such as ammonia low a e and dwell ime on he peak wid h (NP ansien
signal in SP-ICP-MS) we e comp ehensi ely s udied. In luence o NP size and na u e we e also in es iga ed.
1. In oduc ion
A wide a ie y o nanoma e ials (NMs), me allic nanopa icles (NPs)
included, a e playing an inc easing ole in medicine and in many in-
dus ial sec o s such as cons uc ion, cosme ics and ood [1–5]. The
in e es in hese nanome e -scale ma e ials is due o hei unique
p ope ies, which di e om hose o he chemically iden ical bulk
ma e ials. Mo eo e , he ou s anding p ope ies o NMs a e highly
dependen on he NM na u e and size dis ibu ion [6,7]. The inc easing
use o NMs, and hence hei elease in o he en i onmen and he po-
en ial isk o humans and ecosys em heal h, conce ns he scien i ic
communi y. Se e al go e nmen al egula o y agencies ha e b ough
abou egula ions such as hose in he cosme ic and ood indus ies
[8–10]. Undoub edly, he de elopmen and use o NMs mus be sus-
ainable, and analy ical me hodologies a e equi ed o an accu a e
de e mina ion/cha ac e iza ion and moni o ing.
The de e mina ion and cha ac e iza ion o NPs, mainly in complex
ma ices, is a di icul ask, and mos common analy ical echniques do
no p o ide enough selec i i y and sensi i i y. In addi ion, a comple e
cha ac e iza ion o NPs equi es he assessmen o se e al physical-
chemical p ope ies, such as su ace po osi y and unc ionali y, be-
sides he na u e (chemical composi ion), numbe o NPs and size dis-
ibu ion. In addi ion o he well-es ablished ansmission and scanning
elec on mic oscopy (TEM and SEM) and sepa a ion echniques, mainly
based on low ield ac iona ion (FFF), induc i ely coupled plasma mass
spec ome y (ICP-MS) in ime esol ed analysis mode, e e ed o as
single pa icle ICP-MS (SP-ICPMS), has gained popula i y o me allic
NPs de ec ion and cha ac e iza ion [11–15]. SP-ICP-MS is able o p o-
ide in o ma ion abou he nanopa icle numbe concen a ion, size,
and numbe size dis ibu ion by moni o ing a mass- o-cha ge a io o a
ce ain me al con ained in he nanopa icle. Mo eo e , dissol ed and
pa icula e analy es can be p ope ly dis inguished by measu ing he
disc e e pa icles (pulses) o e a con inuous backg ound (dissol ed
species). The numbe o pa icle e en s is p opo ional o he pa icle
numbe concen a ion in he suspension; whe eas, he in ensi y o each
e en is p opo ional o he mass o elemen pe pa icle. The g ea
coun ing and sizing capabili ies a e y low concen a ions makes
SP-ICP-MS an appealing echnique o he assessmen o me allic
* Co esponding au ho .
E-mail add ess: [email p o ec ed] (A. Mo eda-Pi˜
nei o).
Con en s lis s a ailable a ScienceDi ec
Talan a
jou nal homepage: www.else ie .com/loca e/ alan a
h ps://doi.o g/10.1016/j. alan a.2022.123286
Recei ed 22 No embe 2021; Recei ed in e ised o m 1 Feb ua y 2022; Accep ed 2 Feb ua y 2022
Talan a 242 (2022) 123286
2
nanopa icles (MNPs) in biological and en i onmen al samples [12,13].
Howe e , SP-ICP-MS measu emen s assume ha all measu ed NPs
exhibi a sphe ical shape, which is no always ue when coping wi h
MNPs in en i onmen al, ood and clinical ma ices. In addi ion,
SP-ICP-MS equi es imp o emen s o measu ing small MNP sizes [12,
15].
The e a e se e al analy es (elemen s o iso opes) in which de e mi-
na ion by ICP-MS is hampe ed by spec al in e e ences caused by
isoba ic iso opes o polya omic species. These in e e ences can be
o e come by selec ing o he ee-in e e ence iso opes (i a ailable) o
by using ma hema ical co ec ions agains he in e e ing species. In
addi ion, in e e ence a oidance can be also achie ed by imp o ed mass
analyse s, such as sec o ield ICP-MS (SF-ICP-MS), and success ul ap-
plica ions ha e been epo ed o ICP-MS measu emen s [16–20].
Spec al in e e ences in ICP-MS can also be o e come by using a
quad upole (a cell) in which he polya omic in e e ences collide wi h a
collision gas ( ypically He in combina ion wi h kine ic ene gy disc im-
ina ion, KED) o eac wi h a eac ion gas such as H
2
, NH
3
and O
2
(dy-
namic eac ion cell, DRC). The use o KED and DRC echnologies mus be
p ope ly op imized o emo ing spec al in e e ences in SP-ICP-MS, a
ask which is no as s aigh o wa d as in ICP-MS since po en ial addi-
ional in e e ences can be de i ed om pollu an s, impu i ies o colloid
s abilize s included in he NPs.
Since SP-ICP-MS is an eme ging echnique o NPs assessmen , he e
a e no many applica ions o DRC echnology o in e e ences emo al.
The NPs beha iou in he cell is qui e di e en om hose exhibi ed by
dissol ed analy es. DRC echnology leads o ion bu s enhancemen in
he cell, and he ion bu s om MNPs is much la ge han ha obse ed
o dissol ed analy es. The expe imen al e idence leads o he need o
lowe eac ion gas (ammonia) low a es o MNPs han o dissol ed
me allic ions [21].
In addi ion o he eac ion gas low a e, ICP-MS ins umen a ion
wi h quad upole ion de lec o equi es he ca e ul op imiza ion o he
Ma hieu o Rejec ion Pa ame e s (RPa and RPq) in he eac ion cell,
pa ame e s which co espond o he high-mass and low-mass cu -o ,
espec i ely. Mo eo e , NPs de e mina ion by SP-ICP-MS wi h DRC e-
qui es he e alua ion o he e ec o he dwell ime and he wid h peak
on he numbe o pa icle and pa icle size in o de o a oid unde - o
o e -es ima ions. Resea ch li e a u es men ion he use o O
2
o SP-ICP-
MS assessmen o SiO
2
NPs [22], TiO
2
NPs [23], and Au, Ag, P and
Fe
3
O
4
NPs [24]. In addi ion, s udies based on he use o H
2
, NH
3
and
CH
3
F as eac ion gases o SiO
2
NPs de e mina ion [22], H
2
o Au, Ag,
P and Fe
3
O
4
NPs [24], and NH
3
o SP-ICP-MS de e mina ion o TiO
2
NPs [25], ha e also been epo ed. High eac i i y, and hence high
sensi i i y, and he gene a ion o p edic able adduc s (mass shi
app oach), has been epo ed o O
2
; whe eas, H
2
has been ound use ul
o o e coming A in e e ences [22,25]. Howe e , an unp edic able
eac i i y has been epo ed o NH
3
and CH
3
F eac ion gases, o e ing
he ad an age o gene a ing se e al adduc s o ion-p oduc s, and hence
highe selec i i y in ICP-MS/MS o in e e ences emo al by using
ei he on-mass and mass-shi app oaches [26,27].
As p e iously commen ed, li e a u e ega ding DRC echnology o
spec al in e e ences emo al is mainly ocused on con en ional ICP-
MS [21], al hough he e a e some de elopmen s o sedimen a ion
ield- low ac iona ion (SdFFF) coupled o ICP-MS/MS [28] and mo e
ecen ly o SP-ICP-MS [22–25]. The aim o he cu en esea ch has
been o es he easibili y o DRC-SP-ICP-MS using NH
3
as a eac ion gas
o a ee-in e e ence de e mina ion o TiO
2
NPs, Cu NPs, CuO NPs, and
ZnO NPs. In addi ion o he NPs’ na u e (chemical composi ion), he
e ec o he NPs size, as well as he dwell ime and NH
3
low a e, was
also in es iga ed in on-mass and mass-shi measu emen modes. Find-
ings om his esea ch will be use ul o imp o e he use o eac ion gases
in SP-ICP-MS analysis and he applica ion o challenging complex ma ix
analysis.
2. Expe imen al
2.1. Ins umen a ion
A NexION 2000 induc i ely coupled plasma mass spec ome e
(Pe kinElme , Wal ham, MA, USA) equipped wi h dynamic eac ion cell
(DRC) echnology and Single Cell Mic o DX au osample (Pe kinElme )
was used o de e mina ions. The ins umen is equipped wi h nickel
sample /skimme /hype skimme cones. The nebulize was a concen ic
Meinha d™ ype coupled o a cyclonic sp ay chambe (Glass Expansion,
Inc., Melbou ne, Aus alia) and a ached o a qua z o ch wi h a qua z
injec o ube (2.5 mm i.d.). Da a acquisi ion and managemen was
pe o med wi h he Syngis ix™ Nano Applica ion 2.5 e sion so wa e
(Pe kinElme ), which allows da a isualiza ion as i is being acqui ed in
eal- ime and displays backg ound-co ec ed in ensi y his og am which
con inuously upda es du ing da a acquisi ion [29]. The so wa e uses
he same o mula ega ding he basic p inciples o SP-ICP-MS [12] o
assessing he numbe o NPs and NPs sizes. An USC-TH ul asound wa e
ba h (45 Hz, 80 W) om VWR In e na ional Eu olab S.L (Ba celona,
Spain) was used o dispe sing NPs be o e analysis.
2.2. Reagen s and s anda ds
All solu ions we e p epa ed wi h ul apu e wa e (18.2 MΩ cm o
esis i i y) ob ained om a Milli-Q® IQ 7003 pu i ica ion de ice sys em
(Millipo e, Bed o d, MA, USA). Mono-elemen al 1000 mg L
−1
s anda ds
o i anium [(NH
4
)
2
TiF
6
] and coppe [Cu(NO
3
)
2
] we e pu chased om
Pe kinElme ; whe eas, mono-elemen al s anda d o zinc [Zn(NO
3
)
2
] was
om Me ck (Da ms ad , Ge many). Gold NPs solu ions we e p epa ed
om a N8151035 (49.6 nm by TEM, 12.4 ng mL
−1
, 9.89 ×10
6
NPs
mL
−1
, in aqueous 1 mM ci a e) ce i ied e e ence ma e ial om nano
Composix (San Diego, CA, USA). Ti anium dioxide nanopa icles s ock
suspensions (100 mg L
−1
as TiO
2
in ul apu e wa e ) we e p epa ed om
TiO
2
nanopowde ( u ile, 99.9%) o 30, 50 and 100 nm ae odynamic
pa icle size (APS) pu chased om US Resea ch Nanoma e ials (Hous-
on, TX, USA), and TiO
2
suspension (mix u e o u ile and ana ase,
99.5%, size <150 nm, 40 w % in wa e ) pu chased om Sigma-Ald ich.
Zinc oxide NPs suspensions (100 mg L
−1
as ZnO in ul apu e wa e ) we e
p epa ed om 35 o 45 and 80–200 nm ZnO nanopowde om US
Resea ch Nanoma e ials, and ZnO dispe sion (size <100 nm, 20 w % in
wa e ) pu chased om Sigma-Ald ich. Coppe NPs suspensions we e
p epa ed om 40 o 60 and 60–80 nm Cu nanopowde (99.5%) and Cu O
nanopowde (size <50 nm) om Sigma-Ald ich (s ock suspensions a
100 mg L
−1
as Cu and CuO in ul apu e wa e , espec i ely). S ock
suspensions, as well as u he dilu ed suspension we e p epa ed
wi hou adding s abilizing agen s and homogeniza ion be o e sampling
was pe o med by ul asound s i ing (excep o Au NPs). NexION Se up
Solu ion, 10
μ
g L
−1
Be, In, U, and Ce, was om Pe kinElme . Hype pu e
ni ic acid 69% (w/ ) was om Pan eac (Ba celona, Spain). A gon
(99.998%) and ammonia (99,999%) we e om Nippon Gases (Mad id,
Spain).
Glasswa e and plas ic wa e was decon amina ed by soaking in 10%
( / ) ni ic acid o a leas 48 h. The ma e ial was hen insed wi h
ul a–pu e wa e se e al imes.
2.3. SP-ICP-MS measu emen s
SP-ICP-MS se ings a e lis ed in Table 1. Since an exac mass- o-
cha ge a io is no isola ed wi h he quad upole ion de lec o (axial
ield ol age, AFT a 350 V), RPa (high-mass cu -o ) and RPq (low-mass
cu -o ) ejec ion pa ame e s ha e o be ixed a he op imum alues o
a be e ocusing o he mass- o-cha ge a io o in e es (adduc in mass
shi app oach, and he analy e in on-mass app oach). RPa was ound o
be less signi ican o bo h on-mass and mass shi app oaches, and his
pa ame e was ixed a 0 o all NPs and bo h measu emen modes.
Howe e , RPq was ound o be qui e impo an [21], and he op imized
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
3
alues o on-mass and mass shi measu emen modes a e displayed in
Table 2.
Daily pe o mance was assessed by moni o ing Be, In, U, Ce (Ce++/
Ce and CeO/Ce a ios) and backg ound (mass- o-cha ge a io o 202),
and e i ying in ensi ies highe han he alues es ablished as op imum
by he manu ac u e . T anspo e iciency (TE%) was assessed by he
pa icle equency me hod, which implies he assessmen o he sample
low a e, an aqueous ionic Au calib a ion, and he measu emen o an
Au NPs ce i ied e e ence ma e ial. The e o e, sample low a e was
es ablished by aspi a ing ul apu e wa e and weighing he solu ion
a e and be o e aspi a ion a he selec ed pump condi ions (sample low
a es we e be ween 0.19 and 0.21 mL min
−1
). Ionic Au calib a ion was
pe o med wi hin he 0–3.5
μ
g L
−1
ange, and a suspension a 1.0 ×10
5
pa icles mL
−1
, p epa ed in ul apu e wa e om a 49.6 nm Au NPs
ce i ied e e ence ma e ial, was inally measu ed. T anspo e iciency
(TE%) alues (close o 8.0%) we e au oma ically calcula ed by Syngis-
ix™ Nano Applica ion.
Ma ched 1.0% ( / ) ni ic acid calib a ions co e ing ionic Ti, Zn,
and Cu concen a ions wi hin he 0.1–10
μ
g L
−1
ange ( i e le el con-
cen a ions) we e p epa ed o he assessmen o NPs size dis ibu ion
[11]). Reagen blanks (1.0% ( / ) ni ic acid) we e also analysed
h oughou he wo k.
S ock NPs suspensions we e p ope ly dilu ed in ul apu e wa e and
sonica ed jus be o e SP-ICP-MS measu emen s o a oid agglome a ion
and agg ega ion phenomena. NPs s anda ds concen a ions a ied om
0.5 o 5.0
μ
g L
−1
depending on he analy e and mainly on he mea-
su emen mode. The e o e, he s anda d mode and he on-mass
app oach equi e simila concen a ions o achie ing an adequa e
numbe o peaks in he ime window de ec ion o 100 s and size dis i-
bu ion close o a Gaussian dis ibu ion. Howe e , mass-shi measu e-
men s equi e highe concen a ions.
2.4. Da a ea men
O igin8 P o so wa e (O iginLab Co po a ion, No hamp on, MA,
USA) was used o peak in eg a ion. Raw da a om Syngis ix ICP-MS
so wa e (1.0 million measu emen s) we e i s expo ed o Excel and
ea ed ( il e ed) o emo e low in ense peaks ( ew cps, as well as 0 cps)
and educed he da a se . Fil e ed da a we e hen expo ed o O igin8 o
peak in eg a ion by a semi-au oma ic p ocedu e. Fi s , he baseline was
es ablished by ixing he a ea wi hou peaks and hen he peaks we e
selec ed o au oma ic in eg a ion by he so wa e. A leas 10 peaks
we e in eg a ed o assess mean peak wid hs unde each condi ion, and
he selec ed peaks we e hose o in e media e heigh (in ensi y) o
a oiding he selec ion o peaks loca ed in he wings o he dis ibu ion.
In eg a ion was ca ied ou and he peak wid h a he baseline (whole
peak) and a di e en heigh s (5, 15 and 50% o peak heigh ) was ob-
ained. The da a gene a ed was manually checked and lis ed, and, he
mean and he s anda d de ia ion o peak wid hs a e in eg a ion we e
calcula ed o in e p e a ion and/o plo ing.
3. Resul s and discussion
The e ec o he ammonia low a e, dwell ime and wo k-modes
using ammonia as a eac ion gas ha e been e alua ed o bo h on-
mass and mass-shi app oaches, and compa ed wi h en ed mode in
each speci ic condi ions. In addi ion, he e ec o hese expe imen al
pa ame e s on peak shape, peak in ensi y, and peak s abili y was also
e alua ed by measu ing he peak wid h a di e en heigh s (baseline,
5%, 15% and 50%). The s udies we e ocused on TiO
2
NPs, Cu NPs, CuO
NPs, and ZnO NPs o se e al size dis ibu ions.
3.1. Selec ion o he ammonia-based adduc s
A e ixing op imum RPq Ma hieu pa ame e and ammonia low a e
[21], mass scanning expe imen s we e pe o med o ob ain he se e al
ammonia ion p oduc s o each elemen using ionic Ti, Cu, and Zn
s anda ds a 5
μ
g L
−1
(solu ions p epa ed in 1.0%( / ) ni ic acid) and
he ICP-MS ope a ing condi ions lis ed in Table 1. The mos in ense
signals o Ti we e obse ed a m/z a ios o 63, 114 and 131, which
co espond o
48
Ti(NH), Ti(NH)(NH
3
)
3
and Ti(NH)(NH
3
)
4
clus e s,
espec i ely (Fig. 1A). O he in ense signals ha e been obse ed o m/z
49 and 46 (Fig. 1A), bu hey do no come om Ti (lack o Ti iso opic
pa e n in he signals). I has been epo ed in he li e a u e ha
48
Ti
(NH
3
)
6
(m/z 150) is a sui able ammonia ion p oduc o Ti assessmen by
ICP-MS [26,30,31] and SdFFF-ICP-MS/MS [28]. O he epo ed
ammonia-based adduc s o Ti ha e been
48
TiNH
2
(NH
3
)
4+
(m/z 132) in
ICP-MS measu emen s [32], and
48
Ti(NH) (m/z 63) in SP-ICP-MS anal-
ysis [25]. The m/z 114 and 131 ha e been inally selec ed o u he
mass shi s udies. Howe e , m/z 63 was no u he used since he
NexIon 2000 is equipped wi h a quad upole ion de lec o which is no a
eal quad upole, and low m/z a ios could be no excluded and be p e-
sen in he eac ion cell (
63
Cu and
63
Zn could be po en ial in e e ences).
Fig. 1B and C shows he mass spec a o Cu (ammonium low a e o
1.5 mL min
−1
) and Zn (ammonium low a e o 2.0 mL min
−1
),
espec i ely (RPq o 0.20). The highes signals we e ob ained a m/z
a ios o 97 and 115 o Cu and Zn, espec i ely, which co espond o
63
Cu(NH
3
)
2+
and
64
Zn(NH
3
)
3+
ion p oduc s (mass shi app oach).
Findings ega ding Cu ag ee wi h hose ob ained by Fu e al. [32] when
using an ammonia/helium mix u e o DRC-ICP-MS. Howe e , he m/z
115 adduc o Zn is di e en om ha p e iously p oposed (m/z o 100,
66
Zn(NH
3
)
2+
) [32]. O he compa isons we e no possible because,
al hough ammonia has been used as a eac ion gas in DRC-ICP-MS, he
measu emen me hods we e based on on-mass app oaches [33–37]. I
mus be no ed ha he o ma ion o adduc s om he m/z o in e es is
less e icien when using ammonia as a eac ion gas han when using
o he eac ion gases such as oxygen and hyd ogen [26]. Howe e ,
ammonia as a eac ion gas is appealing in DRC because he high
Table 1
Ope a ing condi ions o SP-ICP-MS measu emen s.
Pa ame e (uni s)
Ins umen Nex Ion 2000
Sp ay chambe Qua zCyclonic
PC
3x
Pel ie Coole Sys em 4 ֯C
Nebulize ype Concen ic Meinha d™
RF powe (W) 1600
Plasma gas low a e (L min
−1
) 15
Auxilia y gas low a e (L min
−1
) 1.2
Nebulize gas low a e (L min
−1
) 1.14
Sample low a e (mL min
−1
) ≈0.21
Quad upole ion de lec o (V) Se o maximum ion ansmission
T anspo e iciency (%) ≈8%
Scan ime (s) 100
Table 2
Op imized SP-ICP-MS condi ions o mass-shi and on-mass app oaches.
Analy e Moni o ed
ion/adduc
Moni o ed
m/z
Mode NH
3
low
a e (mL
min
−1
)
Dwell
ime
(
μ
s)
RPq
Ti Ti(NH)
(NH
3
)
3
114 Mass-
shi
0.5–0.75 100 0.2
Ti(NH)
(NH
3
)
4
131 Mass-
shi
0.75–1.0 100 0.2
Cu Cu 63 On-
mass
0.5 50 0.5
Cu(NH
3
)
2
97 Mass-
shi
1.25 100 0.2
Zn Zn 64 On-
mass
0.25 50 0.35
Zn(NH
3
)
3
115 Mass-
shi
1.75 200 0.2
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
4
selec i i y achie ed (adduc s o high m/z a ios a e o med and mass
shi measu emen s can be ca y ou a a la ge and ee-in e e ence
egion o he mass spec a).
3.2. E ec o ammonia low a e
The e ec o ammonia low a e (mass shi and on-mass measu e-
men s) has been s udied o TiO
2
, Cu, CuO, and ZnO NPs o se e al size
dis ibu ions. The e ec on he o ma ion o me al-ammonia adduc s
(mass shi app oach) was pe o med o TiO
2
, Cu, and CuO NPs;
whe eas, he on-mass app oach was ocused on he speci ic elemen al
masses
63
Cu and
64
Zn. On-mass measu emen s o Ti and mass shi
measu emen s o Zn we e no pe o med due o he low sensi i i y and/
o ine icien o ma ion o ammonia-based adduc s. The axial ield
ol age (AFT) was se a 350 V (de aul alue) o all measu emen s.
Simila ly, he ejec ion pa ame e RPa was se a 0 (on mass and mass-
shi app oaches) o all cases since he in luence o his pa ame e was
sca ce. Rega ding RPq pa ame e , p e ious op imized alues o each
analy e and measu emen mode [21] we e ixed (Table 2); whe eas, he
de lec o ol age was daily se a he speci ic elemen mass o achie e
maximum ion ansmission in he eac ion cell.
Suspensions o TiO
2
NPs o 30, 50 and 100 nm (1.25
μ
g L
−1
o TiO
2
),
and <150 nm (2.5
μ
g L
−1
o TiO
2
) we e analysed unde ammonia low
a es wi hin he 0.25–1.0 mL min
−1
(adduc
48
Ti(NH)(NH
3
)
3
, m/z o
114), and om 0.5 o 1.25 mL min
−1
when moni o ing he
48
Ti(NH)
(NH
3
)
4
adduc (m/z o 131). RPq alue was se a 0.20 (Table 2) and
measu emen s we e pe o med wi h a dwell ime o 50
μ
s o moni o ing
bo h ammonia-based adduc s. As expec ed [23,24], b oad signals
(highe peak wid h a baseline, and also a 5%, 15% and 50% heigh )
we e measu ed when using eac ion gas (ammonia) espec o he en-
ed mode (no eac ion gas), and he peak wid h was ound o be
inc eased wi h highe ammonia low a es (Fig. 2). Fo Ti, na owe
peaks we e ob ained when moni o ing he
48
Ti(NH)(NH
3
)
3
adduc (m/z
o 114) han hose obse ed o he
48
Ti(NH)(NH
3
)
4
adduc (m/z o 131),
and he e o e
48
Ti(NH)(NH
3
)
3
moni o ing appea s o be mo e appealing
since he na ow peaks ob ained (less ailing). Howe e , since he
quad upole ion de lec o in he ins umen does no selec a speci ic m/z
a io, he adduc o m/z o 114 could be in e e ed om
114
Cd, and om
o he polya omic adduc s o med om he ma ix sample such as
98
Mo
16
O,
98
Ru
16
O, and also om p oduc s o med wi h ammonia (
63
Zn
(NH
3
)
3
). The e o e, al hough b oade peaks (la ge ailings) a e ob ained
o
48
Ti(NH)(NH
3
)
4
, he peak weigh is lowe han 6.0 ms o all
ammonia low a es (Fig. 2), and his adduc is p e e able since he
measu emen is mo ed o a egion o la ge m/z a ios (m/z o 131) which
is po en ially ee o in e e ences.
F om Fig. 2 (peak wid hs), and also by analysing he numbe o peaks
and peak in ensi ies (Table S1, elec onic supplemen a y in o ma ion,
ESI), and peak shape om aw spec a (Fig. S1 and S2, ESI), he mos
sui ed ammonia low a es we e 0.50 and 0.75 mL min
−1
when moni-
o ing he Ti(NH)(NH
3
)
3
adduc s, and highe a es, wi hin he 0.75–1.0
mL min
−1
ange, o Ti(NH)(NH
3
)
4
adduc measu emen . Low ammonia
low a e ha e led o low peak in ensi ies and a low numbe o peaks
eco ded, bu high ammonia low a e also educe he peak in ensi ies as
well as he numbe o peaks because a dilu ion e ec . The e o e, in e -
media e ammonia low a es, which exhibi low peak wid hs, high
numbe o peaks and mode a e peak in ensi ies, ha e been selec ed o
Ti-based ammonia adduc s. Compa ison wi h ICP-MS based on DRC
wi h ammonia as a eac ion gas led o lowe ammonia low a es in SP-
ICP-MS han in ICP-MS. This inding is a ibu ed o he hund eds o
a oms inside he NPs which inc ease he ammonia eac i i y in he cell
due o a igo ous ion-bu s compa ed o single a oms one-by-one [24].
As shown in Fig. 2 o TiO
2
NPs, and also o o he NPs ( igu es in he
ESI sec ion), he NP size ha e a small in luence on he peak wid h, and
b oade peaks a e no ela ed o TiO
2
NPs o highe sizes (Fig. 2A–C). In
he case o TiO
2
NPs <150 nm (Fig. 2D), he na ow peaks mus be
a ibu ed o a high p opo ion o TiO
2
NPs o small size in he suspen-
sion p epa ed om his s anda d ( he manu ac u e s a es ha he ma-
e ial con ains TiO
2
NPs <150 nm). In addi ion, NPs agglome a ion also
in luences he peak wid hs since la ge ion bu s s a e p oduced om he
agglome a e han hose p oduced om dispe se NPs. Finally, peak
Fig. 1. Mass spec a illus a ing adduc s ha a e o med wi h ammonia: (A) Ti,
1.0 mL min
−1
, (B) Cu, 1.5 mL min
−1
and (C) Zn, 2.0 mL min
−1
.
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
5
wid hs a e s ongly dependen on he ion-p oduc selec ed (Ti-131
agains Ti-114) o he same condi ions and NPs size (and also o Cu-63
and Cu-97, and o Zn-64 and Zn-115). Thus, boa de peaks a e ob ained
om o he la ges ion-p oduc (Ti-131 agains Ti-114).
Rega ding Cu and CuO NPs, on-mass and mass-shi app oaches
using se e al ammonia low a es we e compa ed using a dwell ime o
50
μ
s, and RPq alues o 0.2 o mass-shi app oach and 0.5 o on-mass
app oach. Suspensions o 40–60 nm and 60–80 nm Cu NPs (2.5
μ
g L
−1
o
Cu), and <50 nm CuO (2.5
μ
g L
−1
o CuO) we e es ed a low a es om
0.25 o 0.75 mL min
−1
and om 0.75 o 2.0 mL min
−1
o he on-mass
app oach and mass-shi app oach, espec i ely. Simila ly o TiO
2
NPs,
esul s showed a clea co ela ion be ween he ammonia low added and
he peak wid h (Fig. S3, ESI); whe eas, “noisy” spec a a e obse ed
when ammonia low was added, especially a 1.5 mL min
−1
ammonia
(mass-shi mode), as shown in Fig. S4 (ESI). Taking in o accoun pa-
ame e s such as he numbe o peaks and peak in ensi ies (Table S1,
ESI) and peak wid hs in Fig. S3 (ESI), he mos sui able low a es we e
0.4–0.5 mL min
−1
(on-mass app oach) and 1.25–1.5 mL min
−1
(mass
shi mode), sligh ly lowe han hose equi ed o Cu de e mina ion in
ICP-MS wi h ammonia-based DRC (1.5 mL min
−1
in p e ious expe i-
men s) [21]. As shown in Fig. S3 (ESI), CuO and Cu NPs measu emen s
based on he on-mass app oach we e also possible using low ammonia
low a es.
The e ec o he ammonia low a e on ZnO NPs measu emen s
(dwell ime o 50
μ
s and RPq o 0.2) we e pe o med wi h suspensions o
ZnO NPs o 35–45 nm (1.25
μ
g L
−1
), 80–200 nm (2.5
μ
g L
−1
), and <150
nm (2.5
μ
g L
−1
). As shown in Fig. S5B (ESI) he mass shi app oach (RPq
o 0.2) was only possible when using he ZnO NPs o la ges size
(80–200 nm), which shows spec a wi h enough in ense peaks o peak
heigh measu emen a high ammonia low a es (1.5–2.25 mL min
−1
).
Howe e , e y ew and small signals we e obse ed o ZnO NPs s an-
da ds o lowe size dis ibu ion (Table S1, ESI), and imp o emen s we e
no ob ained when using he highes ammonia low a es (dilu ion e -
ec ). These indings a e qui e simila o hose ob ained o o he NPs,
such as Fe
3
O
4
NPs [24,37], and a p ope measu emen o he adduc s
was epo ed o equi e he use o highe dwell imes ( he e ec o he
dwell ime will be discussed in he ollowing sec ions). An ammonia low
a e o 1.75 mL min
−1
when analysing 80–200 nm ZnO NPs was he e-
o e selec ed o u he s udies.
Rega ding on-mass mode measu emen o ZnO NPs (RPq o 0.35),
Fig. S5(A-C) and Table S1 (ESI) shows ha low ammonia low a es
( om 0.1 o 0.5 mL min
−1
) allow he measu emen o in ense
64
Zn
signals o all ZnO suspensions (low and high sizes), being he numbe o
peak qui e cons an wi hin he 0.1–0.5 mL min
−1
ammonia low a e.
On-mass measu emen mode seems he e o e o be an e icien app oach
o in e e ences emo al in ZnO NPs assessmen . In addi ion, a dwell
ime o 50
μ
s is adequa e o ZnO NPs on-mass measu emen s. An
assessmen be ween s anda d mode and se e al ammonia low a es o
on-mass app oach was pe o med as well (Fig. S6).
Finally, i mus be no ed ha he mass shi app oach wi h high
ammonia low a e, case o he measu emen s o
48
Ti(NH)(NH
3
)
4
(m/z
131) adduc , may ha e an e ec o he NPs size dis ibu ion since he
b oade peaks ob ained.
3.3. In luence o dwell ime
A sui able dwell ime mus be selec ed ega ding possible mul i-peak
coincidence, high backg ounds o unde /o e es ima ion in NP concen-
a ion o size [12,13,36]. The e o e, dwell imes o 20, 50, 100 and 200
μ
s we e s udied. As an example, Fig. 3 shows TiO
2
NPs peak shapes
ob ained o low (20 and 50
μ
s, Fig. 3A and B, espec i ely), in e me-
dia e (100
μ
s, Fig. 3C), and high (200
μ
s, Fig. 3D) dwell imes. The use o
low dwell imes gi es noisy peaks (Fig. 3A and B), which a e a ibu ed
o ion-bu s wi h nanopa icles in eac ion cell; whe eas, measu emen s
Fig. 2. E ec o he ammonia low a e on he peak wid h eco ded by using mass-shi app oach om TiO
2
NPs o (A) 30 nm, (B) 50 nm, (C) 100 nm, and (D) <
150 nm.
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
6
a 200
μ
s could lead o mul i-peak coincidence p obabili y (b oad peaks
in Fig. 3D and high in ensi ies and low numbe o peaks as lis ed in
Table S1, ESI) and hence high backg ound (dissol ed analy e) and low
pa icle concen a ions (low numbe o peaks) as lis ed in Table S1 (ESI).
Howe e , a dwell ime o 100
μ
s (Fig. 3C) implies enough ime o
de ec ion o disc e e TiO
2
NPs wi h se e al measu ed poin s ha can
de ine he peaks p ope ly wi hou any ac iona ion.
The e ec o he dwell ime on egis e ed peak weigh o TiO
2
NPs o
se e al size dis ibu ions [suspensions o TiO
2
NPs o 30, 50 and 100 nm
(1.25
μ
g L
−1
o TiO
2
), and <150 nm (2.5
μ
g L
−1
o TiO
2
)] is shown in
Fig. S7 (ESI). This e ec was illus a ed wi h TiO
2
NPs o 50 nm egis-
e ing
48
Ti(NH)(NH
3
)
4
ion p oduc as i can be obse ed in Fig. S8.
Ammonia low a es we e ixed a 0.75 mL min
−1
when eco ding he
48
Ti(NH)(NH
3
)
3
adduc , and 1.0 mL min
−1
o
48
Ti(NH)(NH
3
)
4
mea-
su emen . The e ec o he dwell ime unde s anda d condi ions ( en-
ed mode) is also shown in Fig. S7 (ESI). In gene al, he peak wid h
ollows a clea co ela ion wi h he dwell ime, and high dwell imes lead
o he b oades peaks. Howe e , aking in o accoun he peak shape in
he spec a (Fig. 3), as well as he peak wid hs, he numbe o peaks and
he peak in ensi ies (Table S2, ESI), de ec ed signals wi h a dwell ime o
100
μ
s seem o be mo e eliable han peaks eco ded wi h lowe dwell
imes such as 20 and 50
μ
s Peak ac iona ion (mainly when using a
dwell ime o 20
μ
s) can occu (low peak in ensi ies as lis ed in Table S2,
ESI); whe eas, a dwell ime o 200
μ
s led o a lowe numbe o peaks
(peak coincidence e en s) and a highe amoun o ionic Ti concen a ion
(Table S2, ESI), ob aining biased measu emen s.
Expe imen s o Cu and CuO NPs [suspensions o 40–60 nm and
60–80 nm Cu NPs (2.5
μ
g L
−1
o Cu), and <50 nm CuO (2.5
μ
g L
−1
o
CuO)] we e pe o med by se ing an ammonia low a e o 0.5 mL min
−1
o on-mass measu emen s (
63
Cu) and 1.5 mL min
−1
when using he
mass shi app oach (
63
Cu(NH
3
)
2
). The e ec o he dwell ime on Cu and
CuO NPs peak weigh s (Fig. 4) was simila o hose obse ed o TiO
2
NPs, and mode a e peak weigh s, as well as a la ge numbe o in ense
peaks (Table S2, ESI), we e obse ed a in e media e dwell imes (50
and 100
μ
s). La ge dwell imes could lead o mul i-peak coincidence
(Fig. S9 and S10, ESI) which ag ees wi h he lowe numbe o peaks
de ec ed when using a dwell ime o 200
μ
s (Table S2, ESI). Reco ding a
low dwell imes such as 50
μ
s gi es adequa e (clean) peaks and 50
μ
s is
enough o egis e well-de ined peaks and signal s abili y when using on-
mass measu emen s. Rega ding mass shi mode, despi e peak ailing is
obse ed a a low dwell ime o 50 as well as 100
μ
s, he ion-bu s ex-
plosion o med in hese condi ions due o ammonia clus e s sugges s no-
p oblema ic and accu a e acquisi ion, and ollowing explana ions
men ioned abo e simila o he Ti discussion, a dwell ime o 100
μ
s was
he bes choice (Fig. S9 and S10, ESI).
Rega ding ZnO NPs, he e ec o he dwell ime when using he mass
shi app oach was pe o med wi h ZnO NPs suspensions o 80–200 nm
(2.5
μ
g L
−1
) and eco ding he
64
Zn(NH
3
)
3
adduc a an ammonia low
a e o 1.75 mL min
−1
; whe eas, on-mass measu emen (
64
Zn) we e
pe o med wi h ZnO NPs suspensions o 35–45 nm(1.25
μ
g L
−1
),
80–200 nm (2.5
μ
g L
−1
), and <150 nm (2.5
μ
g L
−1
) a an ammonia low
a e o 0.5 mL min
−1
. Simila peak weigh s we e obse ed
64
Zn(NH
3
)
3
adduc (mass shi app oach) as shown in Fig. S11 (ESI). The s udy o he
peak spec a when using he mass shi app oach has shown ha sho
dwell imes (50
μ
s) a e no enough o a well-de ined peak egis a ion
due o poo peak in ensi y and low numbe o peaks (Table S2, ESI).
Simila ly, be e esul s (peak-shape, peak in ensi y and numbe o
peaks) we e also ob ained when using highe dwell imes o mass shi
moni o ing (Fig. S12 and Table S2, ESI). The e o e, he eco ding o he
64
Zn(NH
3
)
3
adduc equi es high dwell imes, and a alue o 200
μ
s gi es
he bes pe o mance in con as o he ob ained in Ti and Cu expe i-
men s. Howe e , since he b oade peaks ob ained when using he mass-
shi mode o Zn (Fig. S12, ESI), on-mass measu emen s a low
ammonia low a es a e p e e able o ZnO NPs, and a epea able
acquisi ion (good peak-shapes and high numbe o coun ed peaks) a e
ob ained a low dwell imes such as 50
μ
s (Fig. S11, ESI).
Fig. 3. Raw da a peaks ob ained om SP-ICP-MS measu emen s o TiO
2
NPs o 100 nm. (m/z 131) a 1.0 mL min
−1
ammonia and dwell imes o (A) 20
μ
s, (B) 50
μ
s,
(C) 100
μ
s, and (D) 200
μ
s
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
7
3.4. In luence o NP size and NP ype
A e ixing he ammonia low a e and dwell ime o each NP ype
and measu emen mode (on-mass and/o mass shi ), he in luence o
he NP size on he peak wid h and peak shape was in es iga ed. The
expe imen s we e pe o med wi h suspensions o TiO
2
NPs o 30, 50 and
100 nm (1.25
μ
g L
−1
o TiO
2
), and <150 nm (2.5
μ
g L
−1
o TiO
2
); sus-
pensions o 40–60 nm and 60–80 nm Cu NPs (2.5
μ
g L
−1
o Cu), and <50
nm CuO (2.5
μ
g L
−1
o CuO); and suspensions o ZnO NPs o 35–45 nm
(2.5
μ
g L
−1
), 80–200 nm (2.5
μ
g L
−1
), and <150 nm (2.5
μ
g L
−1
). Fig. 5A
shows esul s ega ding he peak wid h o TiO
2
NPs measu emen s
when eco ding he Ti(NH)(NH
3
)
3
(m/z o 114) and he Ti(NH)
(NH
3
)
4
(m/z o 131) adduc s (mass shi mode). Low in luence o he
TiO
2
NPs size on he peak wid h was obse ed o Ti(NH)(NH
3
)
3
(m/z o
114) measu emen s ( o ins ance, he baseline peak wid h a ies be-
ween 1.5 and 2.0 ms, whe eas Ti(NH)(NH
3
)
4
(m/z o 131) adduc
eco ding implies a a ia ion be ween 5.0 and 7.0 ms). Simila ly, he
size o Cu NPs (ei he mass shi and on mass app oaches) and he size o
ZnO NPs (on-mass app oach using 0.25 mL min
−1
o ammonia) do no
a ec he peak wid h (Fig. 5B and C). Howe e , an inc ease on he peak
wid h was obse ed o ZnO NPs when using an ammonia low a e o
0.5 mL min
−1
(g adual inc ease om 1.9 o 3.0 ms o ZnO NPs sizes o
35–45 nm, <150 nm, and 80–200 nm, Fig. 5C). Resul s o on-mass
measu emen s o ZnO NPs (ammonia low a e o 0.5 mL min
−1
)
ag ee wi h he li e a u e ega ding SiO
2
NPs [22], and Fe
3
O
4
NPs, Au
NPs, Ag NPs and P NPs [24], o which high NPs sizes ha e been e-
po ed o lead b oad peaks. Howe e , esul s o on-mass measu emen s
o Cu/CuO NPs, and o mass shi de e mina ions ha e shown a
di e en end.
Finally, om Fig. 5B i can be seen ha CuO NPs (size <50 nm) show
na owe peaks han hose measu ed o Cu NPs (sizes 40–60, 60–80
nm), bu hese indings canno be exclusi ely a ibu ed o he NP size
since he composi ion o he NPs is di e en (Cu mass ac ion o 79.89%
o CuO NPs, and 100% o Cu NPs). The in luence o he NP chemical
na u e is he e o e impo an and na owe peak wid hs (on-mass and
mass shi app oaches) ha e been ob ained o CuO NPs when
compa ing wi h Cu NPs o simila size (Fig. 5B). In addi ion, on mass
measu emen s o CuO NPs show b oade peak wid hs han ZnO NPs
(Fig. 5B and C); whe eas, peak wid hs when using he mass shi
app oach inc ease in he o de o TiO
2
NPs (
48
Ti(NH)(NH
3
)
3
) >CuO NPs
(
63
Cu(NH
3
)
2+
) >TiO
2
NPs (
48
Ti(NH)(NH
3
)
4
) >Cu NPs (
63
Cu(NH
3
)
2+
)
>ZnO NPs (
64
Zn(NH
3
)
3+
), as shown in Fig. S13 (ESI). Ti-ammonia
clus e s (m/z 114 and 131) exhibi a well-de ined peak-shape
(Fig. S13, ESI) wi h high in ensi ies and a high numbe o de ec ed peaks
(Table S1 and S2, ESI), being na owe han Cu- and Zn-ammonia
clus e s. As p e iously men ioned, Cu-ammonia clus e s exhibi be e
Fig. 4. E ec o he dwell ime in luence on peak wid h eco ded by on-mass
and mass shi app oaches (ammonia low a e o 0.5 mL min
−1
o m/z 63
and 1.5 mL min
−1
o m/z 97) o (A) Cu NPs o 40–60 nm, (B) Cu NPs o 60–80
nm, and (C) CuO NPs o <50 nm.
Fig. 5. E ec o he NPs size on he peak wid h o (A) TiO
2
NPs, (B) Cu NPs
and CuO NPs, and ZnO NPs.
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
8
pe o mance in hei oxide na u e (lowe peak wid hs de i ed om CuO
NPs han om Cu NPs), and b oad peaks a e obse ed o Zn-ammonia
clus e s (peak wid h close o 10 ms).
3.5. On-mass and mass shi app oaches: selec ed condi ions
On-mass measu emen s o e na owe peaks han hose ob ained
when using he mass-shi mode, making i an appealing me hodology
mainly o assessing ZnO NPs. Howe e , on-mass measu emen s we e
no ound use ul o assessing TiO
2
NPs due o he g ea eac i i y o Ti
wi h ammonia (and also he high-s abili y o Ti-ammonia clus e s),
which leads o a low
48
Ti mass abundance. Peak wid h ela ed o Ti-
ammonia clus e m/z 131 (
48
Ti(NH)(NH
3
)
4
) is 3–4 imes highe han
Ti-ammonia clus e m/z 114 (
48
Ti(NH)(NH
3
)
3
). This beha iou is
s ongly in luenced by ammonia low a e. High amoun s o ammonia in
he eac ion cell esul in a s onge ion-bu s in he eac ion cell.
Mo eo e , Ti-ammonia clus e m/z 131 con ains mo e molecules,
esul ing again in a s onge ion explosion and, consequen ly, a highe
peak ime measu emen . Despi e he peak wid h o Ti-ammonia clus e
m/z 131(
48
Ti(NH)(NH
3
)
4
) being la ge (highe measu emen ime), he
m/z 131 alls in a ee-in e e ence egion as shown in he mass spec um
gi en in Fig. S14.
Cu NPs and CuO NPs can be measu ed by ei he on-mass and mass
shi app oaches, bu , as p e iously men ioned, na owe peaks a e
ob ained o on-mass measu emen s. The selec ion o one mode o o he
will be depend on he p esence o po en ial in e e ences close o m/
z
63
Cu o m/z
63
Cu(NH
3
)
2+
. Howe e , on-mass app oach leads o be e
esul s when de e mining ZnO NPs (0.25 mL min
−1
).
Taking in o accoun he peak wid h as well as he numbe o peaks
and peak in ensi ies (Table S1 and S2, ESI), selec ed condi ions o bo h
on-mass and mass shi modes a e lis ed in Table 2. As p e iously
men ioned, he ammonia low a e equi ed o NPs assessmen is
sligh ly lowe han hose equi ed/ epo ed o de e mining dissol ed
analy es [21], and i can be explained by he successi e eac ion among
hund eds o a oms included in he nanopa icles. Finally, o illus a e a
compa ison be ween h ee di e en modes, Fig. S15 (Cu and CuO NPs)
and Fig. S16 (ZnO NPs) we e shown a hei op imized condi ions.
3.6. Sensi i i y
The assessmen o he limi o de ec ion (LOD) and he limi o
quan i ica ion (LOQ) was based on he 3 SD/m and 10 SD/m c i e ion,
whe e SD is he s anda d de ia ion o ele en measu emen s o a blank;
and m is he slope o a calib a ion g aph. Ionic aqueous calib a ion o
TiO
2
NPs assessmen we e up 2.0
μ
g L
−1
(s anda d and mass shi mode
wi h m/z 131,
48
Ti(NH)(NH
3
)
4
) and up o 4.0
μ
g L
−1
o mass shi mode
wi h m/z 114,
48
Ti(NH)(NH
3
)
3
). Simila ly, ionic aqueous calib a ions up
o 1.0
μ
g L
−1
(s anda d and on-mass mode, m/z 63) and up o 2.0
μ
g L
−1
(mass shi mode wi h
63
Cu(NH
3
)
2
, m/z 97) we e pe o med o Cu NPs
de e mina ion; whe eas, calib a ion up o 2.0
μ
g L
−1
(s anda d and on-
mass mode, m/z 64) and up o 3.0
μ
g L
−1
(mass shi mode wi h
64
Zn
(NH
3
)
3
, m/z 115) we e used o ZnO NPs assessmen . Fo all cases,
calib a ion g aphs we e ound o exhibi
2
>0.999, and he RSD% o he
blank measu emen s we e always below 7%.
The limi o de ec ion in size (lowes size measu ed by SP-ICP-MS)
was ob ained om he Syngis ix™ Nano Applica ion so wa e. These
alues (LOD in size) and he LOD/LOQ alues o numbe concen a ions
a e lis ed in Table 3. The imp o ed sensi i i y ob ained o he s anda d
mode is expec ed since he use o eac ion/collision gases implies a
educ ion o sensi i i y because he inhe en dilu ion in he eac ion/
collision cell. Rega ding DRC echnology o TiO
2
NPs assessmen ,
sensi i i y is qui e be e when using he
48
Ti(NH)(NH
3
)
4
(m/z 131)
adduc han o
48
Ti(NH)(NH
3
)
3
(m/z 114) adduc (Table 3). Mass shi
measu emen s o Cu NPs (
63
Cu(NH
3
)
2
, m/z 97) showed simila sensi-
i i y han ha ob ained when wo king wi h he s anda d mode, bu on-
mass measu emen s we e mo e sensi i e in numbe concen a ion and
size. These indings can be a ibu ed o a p ope in e e ences emo al
and a minimum dilu ion in he eac ion cell since on–mass measu e-
men s equi e a low ammonia low a e. Simila conclusions can be
a ained o Zn NPs, and he on-mass app oach also showed he highes
sensi i i y (Table 3).
3.7. In e e ences s udy
Ti anium and Zn measu emen s a e in e e ed in ICP-MS by la ge
amoun s o Ca and P, majo me als p esen in many ma ices such as
biological/ ood ma e ials. The e o e, he de e mina ion o 100 nm TiO
2
NPs (2.5
μ
g L
−1
), 60–80 nm Cu NPs (5.0
μ
g L
−1
), and 80–200 nm ZnO
NPs (5.0
μ
g L
−1
) unde s anda d condi ions ( en ed mode, no DRC
echnology) wi h he mos abundan iso opes (
63
Cu,
64
Zn, and
48
Ti), and
unde he op imized DRC on-mass (
63
Cu and
64
Zn) and mass shi (
63
Cu
(NH
3
)
2
, m/z 97;
64
Zn(NH
3
)
3
, m/z 115;
48
Ti(NH)(NH
3
)
3
, m/z 114; and
48
Ti(NH)(NH
3
)
4
, m/z 131) condi ions was pe o med in he p esence o
inc easing concen a ions o Ca and P (up o 50 mg L
−1
o Ti mea-
su emen s and up o 10 mg L
−1
o Cu and Zn measu emen s). Resul s in
iplica e o ionic backg ound (ionic me al concen a ion) and NPs
concen a ion a e gi en in Fig. S17. The
48
Ti(NH)(NH
3
)
4
(m/z 131)
adduc was ound o allow a ee in e e ence de e mina ion o TiO
2
NPs
e en in he p esence o 10 mg L
−1
plus 10 mg L
−1
o Ca and P. De-
e mina ions based on moni o ing he
64
Zn(NH
3
)
3
(m/z 115) adduc a e
no in e e ed up Ca plus P concen a ions o 5.0 plus 5.0 mg L
−1
:
whe eas, in e e ences we e ound o be impo an o Ca plus P con-
cen a ions o 1.0 plus 1.0 mg L
−1
unde s anda d condi ions (Fig. S17A-
B). Rega ding Cu NPs, simila esul s we e obse ed o on-mass (
63
Cu)
and mass shi (
63
Cu(NH
3
)
2
, m/z 97) condi ions, and in e e ence ee
de e mina ions we e possible e en in he p esence o 2.0 mg L
−1
plus
2.0 mg L
−1
o Ca plus P (Fig. S17C-D). Calcium and P in e e ence on Cu
NPs s a o be impo an up o 0.5 mg L
−1
plus 0.5 mg L
−1
o Ca plus P
unde he s anda d mode measu emen (Fig. S17C-D). Finally,
Fig. S16E-F shows ha Ca plus P a e se ious in e e ences on he ZnO
NPs assessmen a 0.5 mg L
−1
plus 0.5 mg L
−1
o Ca plus P unde he
s anda d mode measu emen and also by using he on-mass and mass
shi app oaches. Howe e , on-mass measu emen s appea o con ol
be e he Ca plus P in e e ence.
4. Conclusions
Condi ions o DRC in ICP-MS wo king in single-pa icle mode mus
be ca e ully es ablished because condi ions, mainly eac ion gas
(ammonia) low a e, a e di e en om hose equi ed o dissol ed
analy es in con en ional ICP-MS. Op imized condi ions can be depen-
den on he size and he NPs ype. On-mass and mass-shi app oaches
Table 3
Limi o de ec ion in size and limi o de ec ion and quan i ica ion (numbe
concen a ion) o he s anda d mode and on-mass and mass shi app oaches.
Wo k-
mode (m/
z)
LOD
size
(nm)
LOD
numbe
concen a ion
(pa icles
L
−1
)
LOQ
numbe
concen a ion
(pa icles
L
−1
)
TiO
2
NPs
STD (48) 16 2.42 ×10
5
8.07 ×10
5
Mass-shi
(114)
41 9.10 ×10
5
3.03 ×10
6
Mass-shi
(131)
23 4.51 ×10
5
1.50 ×10
6
ZnO
NPs
STD (64) 19 1.06 ×10
6
3.53 ×10
6
On-mass
(64)
13 8.40 ×10
4
2.80 ×10
5
Mass-shi
(115)
31 3.58 ×10
6
1.19 ×10
7
Cu
NPs
STD (63) 13 3.57 ×10
5
1.19 ×10
6
On-mass
(63)
7 3.50 ×10
4
1.17 ×10
5
Mass-shi
(97)
16 4.53 ×10
5
1.51 ×10
6
C. Su´
a ez-Oubi˜
na e al.
Talan a 242 (2022) 123286
9
ha e been ound use ul o Cu NPs and CuO NPs; whe eas on-mass mode
was p e e ed o ZnO NPs assessmen . In addi ion, he mass shi
app oach is he bes op ion o acing Ti in e e ences in TiO
2
NPs de-
e mina ions. Rega ding mass-shi mode, he eco ding me al-ammonia
adduc s gene a ed om he second mos abundan iso opes can also be
appealing al e na i es o o e coming complex in e e ences. This is he
case o Cu NPs, CuO NPs and ZnO NPs because he abundance o he
second mos abundan iso opes (
65
Cu and
66
Zn) a e 31% and 28%,
espec i ely. Finally, ca e ul op imiza ion has o be pe o med o NPs in
complex samples (ex ac s) which can inc ease he backg ound signal
and can lead o o he condi ions o eac ion gas (ammonia), low a e
and dwell ime.
C edi au ho s s a emen
C is ian Su´
a ez-Oubi˜
na: Fo mal analysis, In es iga ion, Valida ion,
Visualiza ion, W i ing – o iginal d a p epa a ion. Paloma He bello-
He melo: Da a cu a ion, Supe ision, Valida ion. An onio Mo eda-
Pi˜
nei o: So wa e, Valida ion, W i ing- Re iewing and Edi ing, Supe -
ision, W i ing- Re iewing and Edi ing. Pila Be mejo-Ba e a: Re-
sou ces, P ojec adminis a ion, Funding acquisi ion.
Decla a ion o compe ing in e es
The au ho s decla e ha hey ha e no known compe ing inancial
in e es s o pe sonal ela ionships ha could ha e appea ed o in luence
he wo k epo ed in his pape .
Acknowledgemen s
The au ho s wish o acknowledge he inancial suppo o he Min-
is e io de Economía y Compe i i idad (INNOVANANO p ojec s, e e ence
RT2018-099222-B-100), and he Xun a de Galicia (G upo de Re e encia
Compe i i a, g an numbe ED431C2018/19).
Appendix A. Supplemen a y da a
Supplemen a y da a o his a icle can be ound online a h ps://doi.
o g/10.1016/j. alan a.2022.123286.
Re e ences
[[1]] V. Sogne, F. Meie , T. Klein, C. Con ado, In es iga ion o zinc oxide pa icles in
cosme ic p oduc s by means o cen i ugal and asymme ical low ield- low
ac iona ion, J. Ch oma og ., A 1515 (2017) 196–208, h ps://doi.o g/10.1016/
j.ch oma.2017.07.098.
[2] J. A hina ayanan, V.S. Pe iasamy, M.A. Alsai , A.A. Al-Wa han, A.A. Alsha wi,
P esence o nanosilica (E551) in comme cial ood p oduc s: TNF-media ed
oxida i e s ess and al e ed cell cycle p og ession in human lung ib oblas cells,
Cell Biol. Toxicol. 30 (2014) 89–100, h ps://doi.o g/10.1007/s10565-014-9271-
8.
[3] A. Wei , P. Wes e ho , L. Fab icius, K. H is o ski, N. Von Goe z, Ti anium dioxide
nanopa icles in ood and pe sonal ca e p oduc s, En i on. Sci. Technol. 46 (2012)
2242–2250, h ps://doi.o g/10.1021/es204168d.
[4] P. Van B oekhuizen, F. Van B oekhuizen, R. Co nelissen, L. Reijnde s, Use o
nanoma e ials in he Eu opean cons uc ion indus y and some occupa ional heal h
aspec s he eo , J. Nanopa icle Res. 13 (2011) 447–462, h ps://doi.o g/10.1007/
s11051-010-0195-9.
[5] A.M. Alkilany, L.B. Thompson, S.P. Boulos, P.N. Sisco, C.J. Mu phy, Gold nano ods:
hei po en ial o pho o he mal he apeu ics and d ug deli e y, empe ed by he
complexi y o hei biological in e ac ions, Ad . D ug Deli . Re . 64 (2012)
190–199, h ps://doi.o g/10.1016/j.add .2011.03.005.
[6] B. Jo ano i´
c, G. Bezi ci, A.S. Ça˘
gan, J. Coppens, E.E. Le i, Z. Oluz, E. Tuncel,
H. Du an, M. Beklio˘
glu, Food web e ec s o i anium dioxide nanopa icles in an
ou doo eshwa e mesocosm expe imen , Nano oxicology 10 (2016) 902–912,
h ps://doi.o g/10.3109/17435390.2016.1140242.
[7] J.J. Faus , K. Doud ick, Y. Yang, P. Wes e ho , D.G. Capco, Food g ade i anium
dioxide dis up s in es inal b ush bo de mic o illi in i o independen o
sedimen a ion, Cell Biol. Toxicol. 30 (2014) 169–188, h ps://doi.o g/10.1007/
s10565-014-9278-1.
[8] Eu opean Commission, Regula ion (EC) No 1223/2009 o he Eu opean pa liamen
and o he council o 30 no embe 2009 on cosme ic p oduc s, O . J. Eu . Union 22
(2009) 12 (2009) L342/59–L342/209.
[9] Eu opean commission, Regula ion (EC) No 450/2009 o 29 May2009 on ac i e and
in elligen ma e ials and a icles in ended o come in o con ac wi h ood, O . J.
Eu . Union 30 (2009) 5, 2009) L135/3–L135/11.
[10] Eu opean Commission, Regula ion (EU) No 10/2011 o 14 Janua y 2011 on plas ic
ma e ials and a icles in ended o come in o con ac wi h ood, O . J. Eu . Union
15 (2011) 1 (2011) L12/1–L12/89.
[11] H.E. Pace, N.J. Roge s, C. Ja olimek, V.A. Coleman, C.P. Higgins, J.F. Ran ille,
De e mining anspo e iciency o he pu pose o coun ing and sizing
nanopa icles ia single pa icle induc i ely coupled plasma mass spec ome y,
Anal. Chem. 83 (2011) 9361–9369.
[12] F. Labo da, E. Bolea, J. Jim´
enez-Lamana, Single pa icle induc i ely coupled
plasma mass spec ome y: a powe ul ool o nanoanalysis, Anal. Chem. 86
(2014) 2270–2278, h ps://doi.o g/10.1021/ac402980q.
[13] F. Labo da, E. Bolea, J. Jim´
enez-Lamana, Single pa icle induc i ely coupled
plasma mass spec ome y o he analysis o ino ganic enginee ed nanopa icles in
en i onmen al samples, T ends En i on. Anal. Chem. 9 (2016) 15–23, h ps://doi.
o g/10.1016/j. eac.2016.02.001.
[14] M.D. Mon a˜
no, J.W. Olesik, A.G. Ba be , K. Challis, J.F. Ran ille, Single Pa icle
ICP-MS: ad ances owa d ou ine analysis o nanoma e ials, Anal. Bioanal. Chem.
408 (2016) 5053–5074, h ps://doi.o g/10.1007/s00216-016-9676-8.
[15] D. Mozhaye a, C. Engelha d, A c i ical e iew o single pa icle induc i ely
coupled plasma mass spec ome y-A s ep owa ds an ideal me hod o
nanoma e ial cha ac e iza ion, J. Anal. A . Spec om. 35 (2020) 1740–1783,
h ps://doi.o g/10.1039/c9ja00206e.
[16] N. Jakubowski, L. Moens, F. Vanhaecke, Sec o ield mass spec ome e s in ICP-MS,
Spec ochim. Ac a Pa B A . Spec osc. 53 (1998) 1739–1763, h ps://doi.o g/
10.1016/S0584-8547(98)00222-5.
[17] N. Jakubowski, T. P ohaska, L. Ro mann, F. Vanhaecke, Induc i ely coupled
plasma- and glow discha ge plasma-sec o ield mass spec ome y: Pa I. Tu o ial:
undamen als and ins umen a ion, J. Anal. A . Spec om. 26 (2011) 693–726,
h ps://doi.o g/10.1039/c0ja00161a.
[18] I. Rodushkin, E. Engs ¨
om, A. S enbe g, D.C. Bax e , De e mina ion o low-
abundance elemen s a ul a- ace le els in u ine and se um by induc i ely coupled
plasma-sec o ield mass spec ome y, Anal. Bioanal. Chem. 380 (2004) 247–257,
h ps://doi.o g/10.1007/s00216-004-2742-7.
[19] J.M. Ha ing on, D.J. Young, A.S. Essade , S.J. Sumne , K.E. Le ine, Analysis o
human se um and whole blood o mine al con en by ICP-MS and ICP-OES:
de elopmen o a mine alomics me hod, Biol. T ace Elem. Res. 160 (2014)
132–142, h ps://doi.o g/10.1007/s12011-014-0033-5.
[20] K. Saka a, K. Kawaba a, Reduc ion o undamen al polya omic ions in induc i ely
coupled plasma mass spec ome y, Spec ochim. Ac a Pa B A . Spec osc. 49
(1994) 1027–1038, h ps://doi.o g/10.1016/0584-8547(94)80088-X.
[21] C. Su´
a ez-Oubi˜
na, P. He bello-He melo, P. Be mejo-Ba e a, A. Mo eda-Pi˜
nei o,
Exploi ing dynamic eac ion cell echnology o emo al o spec al in e e ences in
he assessmen o Ag, Cu, Ti, and Zn by induc i ely coupled plasma mass
spec ome y, Spec ochim. Ac a B. 187 (2022) 106330, h ps://doi.o g/10.1016/
j.sab.2021.106330.
[22] E. Bolea-Fe nandez, D. Lei e, A. Rua-Iba z, L. Balcaen, M. A amendía, M. Resano,
F. Vanhaecke, Cha ac e iza ion o SiO
2
nanopa icles by single pa icle-induc i ely
coupled plasma- andem mass spec ome y (SP-ICP-MS/MS), J. Anal. A .
Spec om. 32 (2017) 2140–2152, h ps://doi.o g/10.1039/c7ja00138j.
[23] S. Cand´
as-Zapico, D.J. Ku sche , M. Mon es-Bay´
on, J. Be me , Single pa icle
analysis o TiO
2
in candy p oduc s using iple quad upole ICP-MS, Talan a 180
(2018) 309–315, h ps://doi.o g/10.1016/j. alan a.2017.12.041.
[24] E. Bolea-Fe nandez, D. Lei e, A. Rua-Iba z, T. Liu, G. Woods, M. A amendia,
M. Resano, F. Vanhaecke, On he e ec o using collision/ eac ion cell (CRC)
echnology in single-pa icle ICP-mass spec ome y (SP-ICP-MS), Anal. Chim. Ac a
1077 (2019) 95–106, h ps://doi.o g/10.1016/j.aca.2019.05.077.
[25] M. Tha aud, A.P. Gondikas, M.F. Benede i, F. Von De Kamme , T. Ho mann,
G. Co nelis, TiO
2
nanoma e ial de ec ion in calcium ich ma ices by spICPMS. A
ma e o esolu ion and ea men , J. Anal. A . Spec om. 32 (2017) 1400–1411,
h ps://doi.o g/10.1039/c7ja00060j.
[26] L. Balcaen, E. Bolea-Fe nandez, M. Resano, F. Vanhaecke, Induc i ely coupled
plasma - andem mass spec ome y (ICP-MS/MS): a powe ul and uni e sal ool
o he in e e ence- ee de e mina ion o (ul a) ace elemen s - a u o ial e iew,
Anal. Chim. Ac a 894 (2015) 7–19, h ps://doi.o g/10.1016/j.aca.2015.08.053.
[27] E. Bolea-Fe nandez, L. Balcaen, M. Resano, F. Vanhaecke, Tandem ICP-mass
spec ome y o S iso opic analysis wi hou p io Rb/S sepa a ion, J. Anal. A .
Spec om. 31 (2016) 303–310, h ps://doi.o g/10.1039/c5ja00157a.
[28] J. So o-Al a edo, F. Du schke, J. Be me , M. Mon es-Bay´
on, D. P ¨
o ock,
A. P ange, Ini ial esul s on he coupling o sedimen a ion ield- low ac iona ion
(SdFFF) o induc i ely coupled plasma- andem mass spec ome y (ICP-MS/MS)
o he de ec ion and cha ac e iza ion o TiO2 nanopa icles, J. Anal. A . Spec om.
31 (2016) 1549–1555, h ps://doi.o g/10.1039/c6ja00079g.
[29] Syngis ix Nano Applica ion So wa e Module o Single Pa icle ICP-MS. h ps
:// esou ces.pe kinelme .com/lab-solu ions/ esou ces/docs/PRD_Syngis ix-Nano-
So wa e-Module_011657_01.pd (accessed Janua y 18
h
2022).
[30] L. Balcaen, E. Bolea-Fe nandez, M. Resano, F. Vanhaecke, Accu a e de e mina ion
o ul a- ace le els o Ti in blood se um using ICP-MS/MS, Anal. Chim. Ac a 809
(2014) 1–8, h ps://doi.o g/10.1016/j.aca.2013.10.017.
[31] L. Fu, S.Y. Shi, J.C. Ma, Accu a e De e mina ion o ha m ul and doping elemen s in
so magne ic e i e powde s using induc i ely coupled plasma andem mass
spec ome y, Chin. J. Anal. Chem. 47 (2019) 1382–1389, h ps://doi.o g/
10.1016/S1872-2040(19)61189-8 [31] E.
C. Su´
a ez-Oubi˜
na e al.
