sepa a ions
Re iew
Molecula ly Imp in ed Polyme s o Dispe si e (Mic o)Solid
Phase Ex ac ion: A Re iew
G. D. Thilini Madu angika Jayasinghe and An onio Mo eda-Piñei o *
Ci a ion: Jayasinghe, G.D.T.M.;
Mo eda-Piñei o, A. Molecula ly
Imp in ed Polyme s o Dispe si e
(Mic o)Solid Phase Ex ac ion: A
Re iew. Sepa a ions 2021,8, 99.
h ps://doi.o g/10.3390/
sepa a ions8070099
Academic Edi o : W. Rudol Sei z
Recei ed: 12 May 2021
Accep ed: 28 June 2021
Published: 6 July 2021
Publishe ’s No e: MDPI s ays neu al
wi h ega d o ju isdic ional claims in
published maps and ins i u ional a il-
ia ions.
Copy igh : © 2021 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
T ace Elemen , Spec oscopy and Specia ion G oup (GETEE), S a egic G ouping in Ma e ials (AEMAT),
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; [email p o ec ed]
*Co espondence: an onio.mo [email p o ec ed]
Abs ac :
The e iew desc ibes he de elopmen o ba ch solid phase ex ac ion p ocedu es based on
dispe si e (mic o)solid phase ex ac ion wi h molecula ly imp in ed polyme s (MIPs) and magne ic
MIPs (MMIPs). Ad an ages and disad an ages o he a ious MIPs o dispe si e solid phase
ex ac ion and dispe si e (mic o)solid phase ex ac ion a e discussed. In addi ion, an e o has also
been made o condense he in o ma ion ega ding MMIPs since he e a e a g ea a ie y o suppo s
(magne i e and magne i e composi es wi h ca bon nano ubes, g aphene oxide, o o ganic me al
amewo k) and magne i e su ace unc ionaliza ion mechanisms o enhancing MIP syn hesis, in-
cluding e e sible addi ion- agmen a ion chain- ans e (RAFT) polyme iza ion. Finally, d awbacks
and u u e p ospec s o imp o ing molecula ly imp in ed (mic o)solid phase ex ac ion (MIMSPE)
a e also app aised.
Keywo ds:
molecula ly imp in ed polyme s; magne ic molecula ly imp in ed polyme s; dispe si e
(mic o)solid phase ex ac ion
1. In oduc ion
Du ing he las wo decades he la ge de elopmen o analy ical ins umen a ion, mainly
he in oduc ion o mass spec ome y (MS) and andem mass spec ome y (MS/MS), has
acili a ed he de e mina ion o analy es in biological, ood, and en i onmen al samples a
ace concen a ions. Howe e , al hough he high sensi i i y p o ided by he ins umen a-
ion and he di ec injec ion/analysis o c ude samples/ex ac s a e no always possible,
new sample p epa a ion s a egies a e needed o po en ial in e e ences emo al and
analy e p e-concen a ion, o inc easing he obus ness and epea abili y o measu emen s,
o con e ing he analy e o a mo e sui able o m o sepa a ion/de ec ion, and also o
a oiding con en ional mul iple-s ep p e- ea men me hods [
1
]. Se e al ex ac ion/p e-
concen a ion echniques ha e been he e o e de eloped and among hose echniques,
solid phase ex ac ion (SPE) and solid phase mic oex ac ion (SPME) a e nowadays well
es ablished and comme cially a ailable me hodologies. Howe e , he main d awback
associa ed wi h hem is he mode a e selec i i y o so ben s, which can equi e u he
ex ac clean-up s ages [2].
Molecula ly imp in ed polyme s (MIPs) a e e sa ile ma e ials ha mimic na u al
an igen–an ibody mechanisms and allow molecules/analy es ecogni ion [
2
,
3
]. These
ma e ials a e p epa ed by polyme izing monome s and c oss-linke s a ound he empla e
molecules, leading o a highly c oss-linked h ee-dimensional ne wo k polyme . A e
polyme iza ion, he empla e molecules a e emo ed, and he shape and size o he binding
si es a e es ablished complemen a y o he a ge analy e. Syn hesized MIPs a e s able
and show esis ance o wide ange o pH alues, empe a u es, and sol en s and in e -
ac wi h a ge molecule in a selec i e way. Due o hei p ac ical ea u es, MIPs ha e
been used as selec i e so ben s o (mic o)solid ex ac ion (
µ
-SPE) p ocedu es leading o
Sepa a ions 2021,8, 99. h ps://doi.o g/10.3390/sepa a ions8070099 h ps://www.mdpi.com/jou nal/sepa a ions
Sepa a ions 2021,8, 99 2 o 32
molecula ly imp in ed (mic o)solid ex ac ion (MIMSPE), which allows ad anced minia-
u ized sample p e- ea men s o g een p ocedu es in Analy ical Chemis y. This e iew
in ends o p o ide a snapsho o cu en s a e-o -a use o MIMSPE in sample p epa a ion,
desc ibing se e al ba ch MIMSPE app oaches such as memb ane-p o ec ed molecula ly
imp in ed polyme s and dispe si e (mic o)solid phase ex ac ion wi h magne ic MIPs and
non-magne ic MIPs. In addi ion o se e al e iews ega ding MIPs [
2
–
4
] and magne ic
MIPs [
5
] as selec i e adso ben s o SPE, some o he published e iews ha e ocused on he
applica ions o MIP-based adso ben s o d ug analysis [
6
], o assessing pollu an s, and
in ood [
7
] and en i onmen al samples [
7
,
8
]. Bene i s o dispe si e solid phase ex ac ion
(dSPE) and dispe si e mic osolid phase ex ac ion (D-
µ
-SPE) ha e led o se e al applica-
ions based on he use o qui e di e en adso ben s o p e-concen a ion and/o clean-up
pu poses, and some p ocedu es ha e consis ed o using MIPs as adso ben s [
9
–
11
]. This
e iew in ends o p o ide a snapsho o cu en s a e-o -a use o MIPs (magne ic and
non-magne ic composi es) o dSPE and D-
µ
-SPE. In o ma ion inhe en o he p epa a ion
o he MIP composi es, mainly he magne ic co e unc ionaliza ion, is shown and new
ends o su ace unc ionaliza ion, such as he use o bo onic acids, a e highligh ed.
2. Dispe si e (Mic o)Solid Phase Ex ac ion wi h MIPs
As shown in Figu e 1, dSPE and D-
µ
-SPE [
9
–
12
] p ocedu es consis o dispe sing
he adso ben (a ew millig ams o a e y ew millig ams) in o he sample/ex ac by
shaking (oscilla o s and o ex) and by applying ul asounds, and, o magne ic adso -
ben s, by magne ic s i ing [
4
]. Dispe sion enhances a ge adso p ion on he adso ben
(nano)mic opa icles, and he use o ul asound and mechanical shaking (mainly o ex)
a o s adso ben dis-agg ega ion and maximizes he su ace a ea o he adso ben pa icles.
Vo ex s i ing is a so and low-cos shaking echnique and dispe sion assis ance is mo e e-
pea able when compa ed wi h ul asounds because o he ul asound luency dependence
on he posi ion inside he wa e -ba h ank [
11
]. Vo ex assis ance also p e en s analy e
deg ada ion and adso ben agg ega ion, al hough he echnique o e s lowe ex ac ion
kine ics when compa ed o ul asounds dispe sion [
13
–
15
] (in ac , some epo s ha e
s a ed ha ul asounds change he abso p ion kine ics [16–18]).
Sepa a ions 2021, 8, x FOR PEER REVIEW 3 o 36
Sepa a ions 2021, 8, x. h ps://doi.o g/10.3390/xxxxx www.mdpi.com/jou nal/sepa a ions
Figu e 1. Schema ic ep esen a ion o dispe si e solid phase ex ac ion/dispe si e (mic o)solid phase dispe sion
(dSPE)/(D-µ-SPE) p ocedu es wi h magne ic and non-magne ic molecula ly imp in ed polyme (MIPs).
2.1. Dispe si e (Mic o)Solid Phase Ex ac ion wi h Magne ic Molecula ly Imp in ed Polyme s
(MMIPs)
MMIP beads we e i s in oduced by Ansell and Mosbach in 1998 as a co e–shell
s uc u e (magne ic i on oxide, magne i e, Fe
3
O
4
) o pe o ming d ug adioligand bind-
ing assays [19]. Then, MMIPs (magne ic nickel hexacyano e a e, NiHCF, nanopa icles
coa ed wi h a molecula ly imp in ed polyme o he he bicide chlo o olu on) we e p o-
posed o p epa ing selec i e modi ied elec odes [20]. MMIPs as selec i e adso ben s o
SPE p ocedu es o e ad an ages such as a oidance o d awbacks associa ed wi h con-
en ional ba ch SPE/µ-SPE p ocedu es, which need il a ion/cen i uga ion s eps o sep-
a a ing he adso ben om he bulk sample a e he loading s age and om he ex ac
a e analy e elu ion. In addi ion, losses o adso ben pa icles a e minimized since adso -
ben sepa a ion is easily and quickly achie ed by applying a magne [21]. As p e iously
men ioned, MMIP nanopa icles can be s i ed (dispe sed) in he sample/ex ac (loading
s ep) and in he elu ing solu ion (elu ion s ep), aking ad an age o hei magne ic p op-
e ies, bu s i ing can be also pe o med by o exing and by ul asound dispe sion.
The e a e se e al s a egies o p epa ing MMIPs, which lead o a g ea a ie yo
magne ic adso ben s. Mo eo e , despi e ee adical polyme iza ion mechanism(s), which
a e mainly used o p epa e MMIPs (and also MIPs), he he e ogenei y caused by he as
chain p opaga ion and i e e sible e mina ion eac ions has led o he use o con olled
adical polyme iza ion s a egies such as e e sible addi ion agmen a ion chain- ans e
Figu e 1. Con .
Sepa a ions 2021,8, 99 3 o 32
Sepa a ions 2021, 8, x FOR PEER REVIEW 3 o 36
Sepa a ions 2021, 8, x. h ps://doi.o g/10.3390/xxxxx www.mdpi.com/jou nal/sepa a ions
Figu e 1. Schema ic ep esen a ion o dispe si e solid phase ex ac ion/dispe si e (mic o)solid phase dispe sion
(dSPE)/(D-µ-SPE) p ocedu es wi h magne ic and non-magne ic molecula ly imp in ed polyme (MIPs).
2.1. Dispe si e (Mic o)Solid Phase Ex ac ion wi h Magne ic Molecula ly Imp in ed Polyme s
(MMIPs)
MMIP beads we e i s in oduced by Ansell and Mosbach in 1998 as a co e–shell
s uc u e (magne ic i on oxide, magne i e, Fe
3
O
4
) o pe o ming d ug adioligand bind-
ing assays [19]. Then, MMIPs (magne ic nickel hexacyano e a e, NiHCF, nanopa icles
coa ed wi h a molecula ly imp in ed polyme o he he bicide chlo o olu on) we e p o-
posed o p epa ing selec i e modi ied elec odes [20]. MMIPs as selec i e adso ben s o
SPE p ocedu es o e ad an ages such as a oidance o d awbacks associa ed wi h con-
en ional ba ch SPE/µ-SPE p ocedu es, which need il a ion/cen i uga ion s eps o sep-
a a ing he adso ben om he bulk sample a e he loading s age and om he ex ac
a e analy e elu ion. In addi ion, losses o adso ben pa icles a e minimized since adso -
ben sepa a ion is easily and quickly achie ed by applying a magne [21]. As p e iously
men ioned, MMIP nanopa icles can be s i ed (dispe sed) in he sample/ex ac (loading
s ep) and in he elu ing solu ion (elu ion s ep), aking ad an age o hei magne ic p op-
e ies, bu s i ing can be also pe o med by o exing and by ul asound dispe sion.
The e a e se e al s a egies o p epa ing MMIPs, which lead o a g ea a ie yo
magne ic adso ben s. Mo eo e , despi e ee adical polyme iza ion mechanism(s), which
a e mainly used o p epa e MMIPs (and also MIPs), he he e ogenei y caused by he as
chain p opaga ion and i e e sible e mina ion eac ions has led o he use o con olled
adical polyme iza ion s a egies such as e e sible addi ion agmen a ion chain- ans e
Figu e 1.
Schema ic ep esen a ion o dispe si e solid phase ex ac ion/dispe si e (mic o)solid phase dispe sion (dSPE)/(
D-µ-SPE
)
p ocedu es wi h magne ic and non-magne ic molecula ly imp in ed polyme (MIPs).
2.1. Dispe si e (Mic o)Solid Phase Ex ac ion wi h Magne ic Molecula ly Imp in ed
Polyme s (MMIPs)
MMIP beads we e i s in oduced by Ansell and Mosbach in 1998 as a co e–shell
s uc u e (magne ic i on oxide, magne i e, Fe
3
O
4
) o pe o ming d ug adioligand binding
assays [
19
]. Then, MMIPs (magne ic nickel hexacyano e a e, NiHCF, nanopa icles coa ed
wi h a molecula ly imp in ed polyme o he he bicide chlo o olu on) we e p oposed
o p epa ing selec i e modi ied elec odes [
20
]. MMIPs as selec i e adso ben s o SPE
p ocedu es o e ad an ages such as a oidance o d awbacks associa ed wi h con en ional
ba ch SPE/
µ
-SPE p ocedu es, which need il a ion/cen i uga ion s eps o sepa a ing he
adso ben om he bulk sample a e he loading s age and om he ex ac a e analy e
elu ion. In addi ion, losses o adso ben pa icles a e minimized since adso ben sepa a ion
is easily and quickly achie ed by applying a magne [
21
]. As p e iously men ioned, MMIP
nanopa icles can be s i ed (dispe sed) in he sample/ex ac (loading s ep) and in he
elu ing solu ion (elu ion s ep), aking ad an age o hei magne ic p ope ies, bu s i ing
can be also pe o med by o exing and by ul asound dispe sion.
The e a e se e al s a egies o p epa ing MMIPs, which lead o a g ea a ie yo
magne ic adso ben s. Mo eo e , despi e ee adical polyme iza ion mechanism(s), which
a e mainly used o p epa e MMIPs (and also MIPs), he he e ogenei y caused by he as
chain p opaga ion and i e e sible e mina ion eac ions has led o he use o con olled
adical polyme iza ion s a egies such as e e sible addi ion agmen a ion chain- ans e
(RAFT) polyme iza ion o p epa ing MIPs [
22
] and also MIP coa ings o e magne ic and
non-magne ic suppo s [
23
–
26
]. RAFT polyme iza ion p o ides mo e accessible si es o
a ge adso p ion and as e mass ans e because o he mo e homogenous polyme ic
ne wo k [27].
2.1.1. Classi ica ion o MMIPs
Based on MMIP s uc u e, ou ypes o MMIPs can be es ablished: co e–shell MMIPs,
magne ic nano ube-suppo ed MIPs, magne ic nanoshee -suppo ed MIPs, and magne ic
hollow po ous MIPs [28].
A co e–shell s uc u e is he mos widely used, and i consis s o a co e magne ic phase
( ypically magne i e) and a polyme ic phase shell [
29
]. Magne ic nanopa icles (Fe
3
O
4
) in
he co e–shell-based s uc u es o e a high su ace a ea o MIP ancho age, and he su ace
can be also modi ied (ac i a ed/ unc ionalized) wi h hyd oxyl g oups and a SiO
2
laye o
p o ec he co e om oxida ion o dissolu ion [30].
Magne ic nano ube-suppo ed MIPs imply he p esence o ca bon nano ubes (CNTs)
o mul i-walled ca bon nano ubes (MWCNTs) in he eac ion medium du ing he co-
Sepa a ions 2021,8, 99 4 o 32
p ecipi a ion and sol o he mal syn hesis o Fe
3
O
4
o p epa e magne ic ca bon nano ubes
(MCNTs) in which he magne ic nanopa icles a e linked on o he CNTs’ su ace [
31
]. The
p epa ed MCNTs a e hen ea ed wi h a silica-based eagen o co e hem wi h a SiO
2
laye (MCNTs–SiO
2
) be o e MIP syn hesis. Because o he la ge su ace a ea o he CNTs,
he p epa ed MCNTs–SiO
2
s uc u es o e a highe speci ic su ace a ea o MIP ancho age
han ha ound in co e–shell MMIPs, leading o la ge binding/ ecogni ion si es o he
a ge . On o he occasions, MWCNTs, p e iously unc ionalized wi h ca boxylic acid
g oups (COOH), a e mixed wi h Fe
3
O
4
nanopa icles in he p e-polyme iza ion solu ion
o di ec MIP syn hesis [32].
Simila o CNTs, he use o g aphene oxide (GO) du ing he sol o he mal syn he-
sis o Fe
3
O
4
leads o a GO–Fe
3
O
4
composi e in which he magne i e nanopa icles a e
linked o he GO nanoshee [
33
,
34
]. MIP syn hesis can be hen pe o med a e g a ing
he Fe
3
O
4
@GO su ace wi h ac ylic acid, and he esul ing magne ic nanoshee -suppo ed
MIP p o ides high speci ic su ace a ea and high a ini y o he a ge molecule, as well
as an ex emely as abso p ion a e [
33
]. On o he occasions, he magne ic Fe
3
O
4
@GO
composi e can be unc ionalized wi h silica and inyled eagen s be o e MIP syn hesis [
34
].
O he app oaches a e based on ac i a ed CNTs (p esence o ca boxyl g oups abso bed
on o he su ace o GO h ough
π
–
π
a ac ions a e acidic ea men ) which, a e hy-
d o he mal ea men o syn hesizing Fe
3
O
4
nanopa icles, lead o 3D magne ic GO-CNT
composi es [35].
Finally, well-designed magne ic hollow po ous MIPs (magne ic HPMIPs) ha e been
in oduced as a sac i icial suppo in he molecula imp in ing p ocess. As epo ed, MIP
syn hesis is pe o med on he in e nal su ace o mesopo ous silica sphe es ( e e ed as
MCM-48) ollowed by silica and empla e emo al ( ypically hyd o luo ic acid/e hanol
mix u es) [
36
–
39
]. P e ious o magne i e syn hesis o e he HPMIPs (co-p ecipi a ion
me hod), a ea men wi h dilu ed pe chlo ic acid was equi ed o ob ain 1,2-diol g oups
o e he HPMIPs s uc u es [37].
In addi ion o mesopo ous silica, mesopo ous ca bon has also been ound o be an
excellen suppo o p epa ing hollow po ous MIPs, wi h he ad an age ha ca bon
suppo is no emo ed (sac i iced) o ob ain he equi ed po osi y o he ma e ial. D-
glucose [
40
] and aw Pe ica pium G ana i (a medicinal plan ) [
41
] ha e been used as
sou ces o ca bon o he syn hesis o he magne ic mesopo ous ca bon (MMC) pa icles by
hyd o he mal me hods (high empe a u es as well as long syn hesis imes) in he p esence
o e ic and e ous ions. Bene i s o he hollow composi es a e he p esence o high dense
accessible ecogni ion si es o molecula imp in ing, and a high abso p ion capaci y, which
leads o highe en ichmen ac o s when compa ed wi h adi ional MIPs.
Hollow po ous MIPs ha e been also designed by Fe
3
O
4
nanopa icle su ace modi i-
ca ion by a sol–gel ou e wi h silica-based eagen s such as e ae hyl o hosilica e (TEOS),
which p omo es hyd oxyl g oups on he su ace o he magne ic nanopa icles, ollowed
by MIP syn hesis, and empla e and silica laye emo al [42–44].
O he magne ic HPMIPs ha e been syn hesized by using hollow Fe
3
O
4
mic osphe es
ins ead o con en ional magne i e [
45
] (hollow Fe
3
O
4
mic osphe es a e ob ained by one-
po hyd o he mal me hods [
46
]). In addi ion, o he au ho s ha e p epa ed magne ic
nano ings wi h abundan epoxy g oups on he su ace o imp in ing pu poses in ol -
ing ing-opening eac ions. The p epa ed ma e ial, named co e–shell nano ing amino-
unc ionalized magne ic molecula ly imp in ed polyme (CS-NR-Mag-MIP), was ound o
o e high abso p ion capaci ies o bisphenol A [47] and sul onamides [48].
2.1.2. Magne i e Su ace Func ionaliza ion o Co e–Shell MMIPs
The e a e some p ocedu es o MMIP p epa a ion in which Fe
3
O
4
nanopa icles a e
p esen in he polyme iza ion mix u e du ing MIP syn hesis [
49
–
51
]. Al hough ansmis-
sion elec on mic oscopy (TEM) images show ha he sphe ical Fe
3
O
4
nanopa icles a e
well enw apped by he MIP shell [
51
], on o he occasions he used o un- unc ionalized
Fe
3
O
4
nanopa icles du ing MIP syn hesis leads o uni o m polyme ic laye composi es [
50
].
Sepa a ions 2021,8, 99 5 o 32
Dispe sed sphe ical (nano)pa icles a e p e e ed as adso ben s in SPE, and he sphe ical
shape o a magne i e-based composi e is gua an eed by pe o ming MIP syn hesis o e
su ace unc ionalized magne i e. In addi ion, once Fe
3
O
4
nanopa icles a e syn hesized
(magne i e is also comme cially a ailable), unc ionaliza ion o he nanopa icles’ su ace
makes i a o able o MIP adhesion, and also p omo es a high speci ic su ace a ea and
imp o es pola i y [
52
]. Al hough magne i e su ace unc ionaliza ion can be pe o med
a e Fe
3
O
4
syn hesis o di ec ly o e comme cial nanopa icles, one-s ep Fe
3
O
4
syn hesis
and su ace unc ionaliza ion p ocedu es ha e been also desc ibed. A e su ace modi-
ica ion, polyme iza ion can be pe o med by se e al polyme iza ion me hods using he
adequa e empla e molecule, monome , c oss-linke , ini ia o , and po ogen. The esul ing
composi e adso ben will o e good selec i i y/ ecogni ion o he a ge molecule as well
as good magne ic p ope ies [52].
Magne i e su ace unc ionaliza ion can be pe o med mainly by using silica-based,
diol-based, and inyled compounds (Table 1). Howe e , he e a e o he unc ionaliza-
ion mechanisms as well as se e al combina ions o su ace modi ie eagen s o Fe
3
O
4
nanopa icle su ace unc ionaliza ion.
Table 1. Func ionaliza ion eagen s o magne i e co e–shell magne ic molecula ly imp in ed polyme s (MMIPs).
Fe3O4@OH Func ionaliza ion
Diol-based eagen s Re .
Polye hylene glycol (PEG) [53–58]
Poly( inyl alcohol) [59]
Ac ylic acid [60]
Me hac ylic acid (MAA) [61]
Bo onic acids:
2,4-Di luo o-3- o myl-phenylbo onic acid (DFFPBA) a,b [62,63]
4-Fo mylphenylbo onic acid (FPBA) plus sodium cyanobo ohyd ide (NaBH
3
CN)
[64,65]
4-Vinylphenbo onic acid (VPBA) c[66]
3-Aminophenylbo onic acid (APBA) d[67]
Silica-based eagen s
Te ae hyl o hosilica e (TEOS) [52,58,68–90]
Fe3O4@CH=C2H4 unc ionaliza ion
Oleic acid (OA) [91–102]
Silica-based eagen s:
3-(T ime hoxysilyl) p opyl me hac yla e (TMSMA) [103]
3-Me hac yloxyp opyl ime hoxysilane (MPS o KH-570) [27,71,72,75–77,80–84,90,104–114]
Vinyl ime hoxy silane (VTMOS) [72]
Vinyl ie hoxy silane (VTEO o VTES) [115–118]
Fe3O4@NH2 unc ionaliza ion
Silica-based eagen s:
(3-Aminop opyl) ie hoxysilane (APTES) [78,105,119–124]
Me hac yloyl chlo ide [125]
Fe3O4@COOH unc ionaliza ion
Silica-based eagen s
Poly(e hylene glycol)bis(ca boxyme hyl) e he e[123]
Fe3O4@X, X= Cl o B unc ionaliza ion
Silica-based eagen s
4-Chlo ome hyl phenyl ichlo osilane (4-CPS) [74,77,126–131]
3-B omop opyl ime hoxy silane (BPTS) [132]
(
a
) Fe
3
O
4
unc ionalized wi h 1,6-hexanediamine o gi e Fe
3
O
4
@NH
2
; (
b
) Fe
3
O
4
unc ionalized wi h TEOS and APTES o gi e Fe
3
O
4
@SiO
2
;
(
c
) Fe
3
O
4
@pTiO
2
unc ionalized wi h
γ
-me cap op opyl ime hoxysilane (
γ
-MPTS) o gi e Fe
3
O
4
@pTiO
2
@SH; (
d
) Fe
3
O
4
@MCM-48 (meso-
po ous silica sphe es) composi e; (
e
) Fe
3
O
4
unc ionalized wi h TEOS and APTES o gi e Fe
3
O
4
@NH
2
; (
) Fe
3
O
4
unc ionalized wi h TEOS
o gi e Fe3O4@OH.
Sepa a ions 2021,8, 99 6 o 32
Su ace Func ionaliza ion wi h Hyd oxyl (Diol) and Vinyl-Based Reagen s
Diol-based eagen s such as polye hylene glycol (PEG) [
53
–
57
] in e ac wi h he
nanopa icle su ace h ough one o he hyd oxyl g oups, allowing he emaining hy-
d oxyl g oups o be a ailable o eac wi h he componen s o he p e-polyme iza ion
mix u e (Figu e 2). A simila mechanism is ob ained o oleic acid [
91
–
102
], which in e ac s
wi h he nanopa icle’s su ace h ough he hyd oxyl g oups bu p omo es he p esence o
inyl g oups in he modi ica ion laye . Simila ly, poly ( inyl alcohol) [
59
] is also a sou ce
o hyd oxyl and inyl g oups o eac ing wi h he p e-polyme iza ion componen s. A
magne ic co e su ace ich in inyl g oups can be also ob ained by ea ing he p epa ed
Fe
3
O
4
nanopa icles wi h ac ylic acid [
60
] o by one-s ep co-p ecipi a ion o Fe
3
O
4
in he
p esence o me hac ylic acid [61].
Sepa a ions 2021, 8, x FOR PEER REVIEW 7 o 36
Sepa a ions 2021, 8, x. h ps://doi.o g/10.3390/xxxxx www.mdpi.com/jou nal/sepa a ions
Figu e 2. Schema ic ep esen a ion o binding mechanism be ween magne i e nanopa icles and polye hylene glycol (PEG)
(a) and MMIP p epa a ion (b), Adap ed wi h pe mission om Re . [55]. Copy igh 2016 Else ie .
The main ad an age o using hese eagen s o magne i e su ace modi ica ion is he
simplici y o he p ocedu e and he mode a e ope a ing condi ions ( oom empe a u e o
ice-ba h). In addi ion, su ace unc ionaliza ion wi h hese eagen s a oids he elec os a ic
agglome a ion o magne i e, which ensu es he uni o mi y o magne ic nanopa icles in
he p e-polyme iza ion solu ion and a u he MIP homogeneous embedding. Howe e ,
d as ic condi ions, such as ex eme pHs, when emo ing he empla e a e MMIP syn he-
sis can damage he link be ween he nanopa icle and he unc ionaliza ion laye , which
leads o a sepa a ion o he MIP laye (shell) om he magne i e nanopa icles (co e).
Simila ly, he p esence o hyd oxyl g oups on he nanopa icle su ace can also be
achie ed by using bo onic acids ha bind cis-diol-con aining compounds and esul as
adequa e o imp in ing la ge biomolecules, such as p o eins, and achie ing o ien ed su -
ace imp in ing, depending on he a ini y be ween he empla e molecule and he bo o-
na e esidues [62–67] (Table 1). The bo onic acid 2,4-di luo o-3- o myl-phenylbo onic acid
(DFFPBA) has been p oposed o p epa ing MMIPs, which equi es amino- unc ionalized
magne ic nanopa icles be o e DFFPBA unc ionaliza ion (easily achie ed by Fe3O4 syn-
hesis in p esence o 1,6-hexanediamine). Fe3O4@NH2 can be di ec ly ea ed wi h DFFPBA
( ea men a oom empe a u e o 24 h) [62] o can be i s silanized wi h TEOS and (3-
Aminop opyl) ie hoxysilane (APTES), leading o (Fe3O4@SiO2@DFFPB) [63]. In addi ion
o DFFPBA, o he bo onic acids such as 4- o mylphenylbo onic acid (FPBA) in combina-
ion wi h sodium cyanobo ohyd ide (NaBH3CN) ha e been ound o be e ec i e o p e-
pa e he su ace o Fe3O4@NH2 [64] o Fe3O4 nanopa icles [65] o syn hesizing MIPs o
p o ein ecogni ion. A simila s a egy has been p oposed using magne i e mic osphe es
coa ed wi h po ous TiO2 ( lowe -like s uc u e Fe3O4@pTiO2 nanopa icles) p epa ed ia
a sol o he mal me hod and u he unc ionalized wi h γ-me cap op opyl ime hox-
ysilane (γ-MPTS) o p omo e he p esence o –SH be o e ancho ing he bo onic acid 4-
inylphenbo onic acid (VPBA) [66]. Mo e binding si es o empla es (ho se adish pe ox-
idase), and hus, highe adso p ion capaci y, we e ound when using Fe3O4@pTiO2 as a
magne i e
(Fe
3
O
4
)
polye hylene glycol
(PEG)
ul asounds
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
O
OH
H
n
ul asounds
DVB/ AIBN
MIP
N
O
O
O
O
N
O
O
O
O
cocaine
EDMA
(a)
(b)
Figu e 2.
Schema ic ep esen a ion o binding mechanism be ween magne i e nanopa icles and polye hylene glycol (PEG)
(a) and MMIP p epa a ion (b), Adap ed wi h pe mission om Re . [55]. Copy igh 2016 Else ie .
The main ad an age o using hese eagen s o magne i e su ace modi ica ion is he
simplici y o he p ocedu e and he mode a e ope a ing condi ions ( oom empe a u e o
ice-ba h). In addi ion, su ace unc ionaliza ion wi h hese eagen s a oids he elec os a ic
agglome a ion o magne i e, which ensu es he uni o mi y o magne ic nanopa icles in
he p e-polyme iza ion solu ion and a u he MIP homogeneous embedding. Howe e ,
d as ic condi ions, such as ex eme pHs, when emo ing he empla e a e MMIP syn hesis
can damage he link be ween he nanopa icle and he unc ionaliza ion laye , which leads
o a sepa a ion o he MIP laye (shell) om he magne i e nanopa icles (co e).
Simila ly, he p esence o hyd oxyl g oups on he nanopa icle su ace can also be
achie ed by using bo onic acids ha bind cis-diol-con aining compounds and esul as ade-
qua e o imp in ing la ge biomolecules, such as p o eins, and achie ing o ien ed su ace
imp in ing, depending on he a ini y be ween he empla e molecule and he bo ona e
esidues [
62
–
67
] (Table 1). The bo onic acid 2,4-di luo o-3- o myl-phenylbo onic acid
(DFFPBA) has been p oposed o p epa ing MMIPs, which equi es amino- unc ionalized
magne ic nanopa icles be o e DFFPBA unc ionaliza ion (easily achie ed by Fe
3
O
4
syn-
hesis in p esence o 1,6-hexanediamine). Fe
3
O
4
@NH
2
can be di ec ly ea ed wi h DFF-
PBA ( ea men a oom empe a u e o 24 h) [
62
] o can be i s silanized wi h TEOS
Sepa a ions 2021,8, 99 7 o 32
and (3-Aminop opyl) ie hoxysilane (APTES), leading o (Fe
3
O
4
@SiO
2
@DFFPB) [
63
]. In
addi ion o DFFPBA, o he bo onic acids such as 4- o mylphenylbo onic acid (FPBA)
in combina ion wi h sodium cyanobo ohyd ide (NaBH
3
CN) ha e been ound o be e -
ec i e o p epa e he su ace o Fe
3
O
4
@NH
2
[
64
] o Fe
3
O
4
nanopa icles [
65
] o syn-
hesizing MIPs o p o ein ecogni ion. A simila s a egy has been p oposed using
magne i e mic osphe es coa ed wi h po ous TiO
2
( lowe -like s uc u e Fe
3
O
4
@pTiO
2
nanopa icles) p epa ed ia a sol o he mal me hod and u he unc ionalized wi h
γ
-
me cap op opyl ime hoxysilane (
γ
-MPTS) o p omo e he p esence o –SH be o e ancho -
ing he bo onic acid 4- inylphenbo onic acid (VPBA) [
66
]. Mo e binding si es o empla es
(ho se adish pe oxidase), and hus, highe adso p ion capaci y, we e ound when using
Fe
3
O
4
@pTiO
2
as a suppo ing ma e ial han when using Fe
3
O
4
@SiO
2
co es [
65
,
66
]. In addi-
ion, he s ong elec on-wi hd awing e ec s o Ti(IV) endow he bo onic acid wi h lowe ed
pK
a
alue ha makes he Fe
3
O
4
@pTiO
2
@MIPs cap u e glycop o eins unde mode a e
acidic condi ions [66].
Finally, bo ona e-a ini y magne ic hollow molecula ly imp in ed polyme so ben s
o sialic acid (a compound exhibi ing a cis-diol s uc u e) ha e been also p epa ed by
using mesopo ous silica sphe es (MCM-48) as a sac i icial suppo , glycidyl me hac yla e
(GMA) as a co-monome o chemiso b Fe
3
O
4
nanopa icles, and 3-aminophenylbo onic
acid (APBA) as bo onic acid [
67
]. A e MCM-48@APBA p epa a ion, he empla e, he
c oss-linke , and he ini ia o a e added o pe o ming MIP syn hesis, ollowed by MCM-
48 dissolu ion in a hyd o luo ic/e hanol mix u e (B-hMIP composi e). Fe
3
O
4
nanopa icles
a e hen syn hesized (co-p ecipi a ion) in he p esence o he p epa ed composi e (B-hMIPs),
leading o he magne ic hollow adso ben [67].
Su ace Func ionaliza ion wi h Silica-Based Reagen s
Silica-based eagen s (Table 1) a e an al e na i e o inyled and diol-based compounds
in magne i e su ace unc ionaliza ion p ocedu es o o e coming p oblems de i ed om
co e–shell b eakdown as consequence o ex eme pH and empe a u e ope a ing condi ions,
since he esul ing composi es exhibi g ea s abili y [
52
]. TEOS is a ypical silica-based
compound used o Fe
3
O
4
modi ica ion a mode a e ope a ing condi ions, esul ing in
Fe
3
O
4
@SiO
2
composi es. The TEOS laye o e he magne i e nanopa icles is a sou ce o
hyd oxyl g oups o u he in e ac ions wi h he p e-polyme iza ion eagen s [
68
–
89
]. A
ypical diag am o a magne ic silica-based composi e is illus a ed in Figu e 3.
An imp o ed deg ee o unc ionaliza ion can be achie ed by using silica-based
eagen s con aining o he unc ional g oups such as inyl, amino, and halide g oups
(Table 1). This is he case o eagen s such as 3-( ime hoxysilyl)p opyl me hac y-
la e (TMSMA) [
103
], 3-me hac yloxyp opyl ime hoxysilane (MPS, also known as
KH-570) [
71
,
72
,
75
–
77
,
80
–
82
,
84
,
104
–
114
], inyl ime hoxy silane (VTMOS) [
72
], and
inyl ie hoxy silane (VTEO o VTES) [
115
–
118
], which p omo e he p esence o inyl
g oups on he Fe
3
O
4
su ace o on he Fe
3
O
4
@SiO
2
su ace when Fe
3
O
4
nanopa icles
a e p e iously unc ionalized wi h TEOS (ex a unc ional g oups on he Fe
3
O
4
@SiO
2
su ace allowing i s in e ac ion wi h inyled silica eagen s). Func ionaliza ion wi h
inyl-based silica eagen s can also be pe o med a e a p e ious oleic acid unc ional-
iza ion (Fe
3
O
4
@oleic acid ia a co-p ecipi a ion echnique) ollowed by modi ying he
su ace o he nanopa icles wi h a silica laye (TEOS) and double bonds in oduc ion
on o he Fe3O4@SiO2wi h KH-570 [90].
The p esence o amino (
−
NH
2
) g oups is gua an eed by using APTES (Table 1),
and MIP syn hesis can be pe o med di ec ly by mixing he unc ionalized nanopa icles
wi h he polyme iza ion eagen s [
78
,
119
]. On o he occasions, he monome , such as
me hac yloyl chlo ide, can be ixed o he unc ionalized silica laye a e eac ion wi h
he immobilized amino g oups [
125
]. In addi ion, p e iously modi ied Fe
3
O
4
wi h TEOS
(Fe
3
O
4
@SiO
2
) can be hen co e ed wi h APTES o p omo ing he p esence o
−
NH
2
g oups [105,120–123].
Sepa a ions 2021,8, 99 8 o 32
Sepa a ions 2021, 8, x FOR PEER REVIEW 8 o 36
Sepa a ions 2021, 8, x. h ps://doi.o g/10.3390/xxxxx www.mdpi.com/jou nal/sepa a ions
suppo ing ma e ial han when using Fe
3
O
4
@SiO
2
co es [65,66]. In addi ion, he s ong
elec on-wi hd awing e ec s o Ti(IV) endow he bo onic acid wi h lowe ed pK
a
alue
ha makes he Fe
3
O
4
@pTiO
2
@MIPs cap u e glycop o eins unde mode a e acidic condi-
ions [66].
Finally, bo ona e-a ini y magne ic hollow molecula ly imp in ed polyme so ben s
o sialic acid (a compound exhibi ing a cis-diol s uc u e) ha e been also p epa ed by
using mesopo ous silica sphe es (MCM-48) as a sac i icial suppo , glycidyl me hac yla e
(GMA) as a co-monome o chemiso b Fe
3
O
4
nanopa icles, and 3-aminophenylbo onic
acid (APBA) as bo onic acid [67]. A e MCM-48@APBA p epa a ion, he empla e, he
c oss-linke , and he ini ia o a e added o pe o ming MIP syn hesis, ollowed by MCM-
48 dissolu ion in a hyd o luo ic/e hanol mix u e (B-hMIP composi e). Fe
3
O
4
nanopa icles
a e hen syn hesized (co-p ecipi a ion) in he p esence o he p epa ed composi e (B-
hMIPs), leading o he magne ic hollow adso ben [67].
Su ace Func ionaliza ion wi h Silica-Based Reagen s
Silica-based eagen s (Table 1) a e an al e na i e o inyled and diol-based com-
pounds in magne i e su ace unc ionaliza ion p ocedu es o o e coming p oblems de-
i ed om co e–shell b eakdown as consequence o ex eme pH and empe a u e ope a -
ing condi ions, since he esul ing composi es exhibi g ea s abili y [52]. TEOS is a ypical
silica-based compound used o Fe
3
O
4
modi ica ion a mode a e ope a ing condi ions, e-
sul ing in Fe
3
O
4
@SiO
2
composi es. The TEOS laye o e he magne i e nanopa icles is a
sou ce o hyd oxyl g oups o u he in e ac ions wi h he p e-polyme iza ion eagen s
[68–89]. A ypical diag am o a magne ic silica-based composi e is illus a ed in Figu e 3.
Figu e 3.
Schema ic o he ixa ion o he e e sible addi ion
−
agmen a ion chain- ans e (RAFT)
agen on o silica nanopa icles and he g ow h o he MIP shell om silica nanopa icles ia su -
ace RAFT polyme iza ion, Adap ed wi h pe mission om Re . [
79
]. Copy igh 2016 Ame ican
Chemical Socie y.
In oduc ion o ca boxyl g oups on o he Fe
3
O
4
@SiO
2
su ace is pe o med by ea -
ing unc ionalized Fe
3
O
4
@-SiO
2
–NH
2
nanopa icles (TEOS and APTES co e ing) wi h
poly(e hylene glycol)bis(ca boxyme hyl) e he be o e MIP syn hesis [
123
]. Compa ison be-
ween Fe
3
O
4
@SiO
2
–COOH@MIP and Fe
3
O
4
@-SiO
2
–NH
2
@MIP showed ha he la e had
high speci ic su ace a ea and as mass ans e a e owa d he a ge (aminopy alid) [
123
].
Simila ly, KH-570 (p esence o inyl g oups) and APTES (p esence o amino g oups)
ha e been also used o modi ying Fe
3
O
4
@SiO
2
su aces o u he MIP polyme iza ion
by RAFT mechanisms [
27
,
58
,
124
] (Table 1). Howe e , magne i e unc ionaliza ion wi h
–Cl g oups is commonly p e e ed o RAFT syn hesis, and silica-based eagen s such
as 4-chlo ome hyl phenyl ichlo osilane (4-CPS) ha e been widely used o eac ing
wi h Fe
3
O
4
@SiO
2
(magne i e unc ionalized wi h TEOS) and p omo ing –Cl be o e MIP
syn hesis by RAFT polyme iza ion [
74
,
77
,
126
–
131
]. O he eagen s, such as 3-b omop opyl
ime hoxy silane (BPTS), ha e been also used when pe o ming MIP syn hesis by RAFT,
al hough hey a e used di ec ly on Fe3O4 o p omo e –B g oups [132] (Table 1).
These silaniza ion p ocedu es a e ime-consuming p ocesses since hey equi e a p e i-
ous silaniza ion s age (Fe
3
O
4
@SiO
2
) ollowed by a ea men o inco po a ing he desi ed
unc ional g oups. In addi ion, he desc ibed p ocedu es a e epo ed o equi e eac ion
empe a u es achie ed by e luxing sys ems. The e o e, he e ha e been desc ibed se e al
one-s ep Fe
3
O
4
syn hesis (sol o he mal me hod) and su ace unc ionaliza ion p ocedu es
by inco po a ing in o he eac ion medium diol-based eagen s such as PEG and e hylene
Sepa a ions 2021,8, 99 9 o 32
glycol (EG) [
133
–
140
], and inyled eagen s (oleic acid [
141
] and hexanediamine [
140
]).
Since he sol o he mal me hod is equi ed o Fe
3
O
4
nanopa icle syn hesis, special lab-
o a o y de ices such as Te lon-lined s ainless s eel eac o s a e needed. In addi ion, he
syn hesis/ unc ionaliza ion is pe o med a high empe a u e (200
◦
C) and o long imes
(up o 24 h).
One-s ep p ocedu es o Fe
3
O
4
silaniza ion (Fe
3
O
4
@SiO
2
) and modi ica ion wi h unc-
ional g oups such as
−
NH
2
ha e been also desc ibed o speeding-up he unc ionaliza ion
s ep. The use o APTES as a silica-based eagen (silaniza ion) p omo es he simul aneous
unc ionaliza ion wi h amino unc ional g oups. In addi ion, i he modi ica ion is pe -
o med using APTES and mono ac ylic acid a once, he esul ing co e ing will also be ich
in inyl g oups [
142
]. On o he occasions, a e Fe
3
O
4
unc ionaliza ion wi h oleic acid, a
u he eac ion wi h KH-570 ensu es s abili y (silica co e ing) and abundan inyl g oups
o u he MIP syn hesis [90].
2.1.3. Magne i e Su ace Func ionaliza ion o Magne ic Nano ube-Suppo ed and
Magne ic Nanoshee -Suppo ed MIPs
As summa ized in Table 2, su ace unc ionaliza ion o mixed magne ic compos-
i es in ol ing he p esence o CNTs [
31
] and MWCNTs [
143
–
145
] has been e icien ly
achie ed by using diol-based eagen s such as EG and PEG [
31
,
143
,
146
,
147
], al hough
some au ho s ha e desc ibed he con enience o a p e ious MWCNT@Fe
3
O
4
com-
posi e oxida ion [
144
], educ ion [
145
], o ca boxyla ion [
32
,
148
] s age be o e unc-
ionaliza ion/MIP syn hesis. The ac i a ed su ace o CNTs/MWCNTs imp o es he
nanopa icles dispe sion and he in e ac ion o monome s wi h he CNTs/MWCNTs.
Howe e , some o hese p ocedu es equi e high empe a u es and long imes a e also
needed o comple e he eac ions [
31
,
32
,
143
,
148
]. A e MWCNT@Fe
3
O
4
composi e
syn hesis, silaniza ion p ocedu es ha e also been epo ed by using KH-570 unde
mode a e eac ion condi ions (s i ing/sonica ion, N
2
a mosphe e, 70
◦
C, 10 min),
which leads o a s able magne ic composi e and also inc eases he eac i e ac i i y as a
consequence o he ancho ed inyl g oups [
149
]. Func ionaliza ion wi h KH-570 can
be also pe o med a e a p e ious silaniza ion o he p epa ed MCNTs wi h TEOS
(MCNTs@SiO
2
) [
150
]. Me hac yloxyp opyl ime hoxysilane (MAPTMS) has been also
p oposed as a silanizing agen and as a inyled monome o u he IIP syn hesis
(Pb (II) ions as empla e and di hizone as a ligand) [148].
Rega ding magne ic nanoshee -suppo ed MIPs (Table 2), he GO@Fe
3
O
4
su ace is
usually unc ionalized by g a ing wi h ac ylic acid as shown in Figu e 4[
33
,
151
], which
ensu e he p esence o inyl g oups o u he polyme iza ion. Ac ylic acid was also used
o su ace modi ica ion o chi osan based GO@Fe
3
O
4
composi es [
152
]. Silaniza ion wi h
TEOS o p epa e MGO@mSiO
2
(mesopo ous silica) has been also epo ed o di ec MIP
syn hesis [
153
] and o a u he unc ionaliza ion wi h inyl ime hoxysilane (VTTS) [
34
]
and APTES [
154
] in o de o acili a e he subsequen polyme iza ion ia inyl o amino
g oups, espec i ely. Howe e , p epa ed GO@Fe
3
O
4
nanopa icles [
155
,
156
], as well as
3D magne ic GO-CNT composi es [
35
], we e also di ec ly used o MIP syn hesis wi hou
unc ionaliza ion.
Sepa a ions 2021,8, 99 16 o 32
Table 3. Con .
Sample Ta ge Composi e Reagen s/Monome De ec ion
Technique Sample P e-T ea men : Pe o mance: LOD and
Analy ical Reco e y Re .
Wa e , ice,
ege ables As Fe3O4@OA-IIP 2-ABT/4-VP HG-AAS
So ben : Fe3O4@OA-IIP (88.18 mg)
Sample olume: 4.0 mL se um, 20 mL u ine (wa e and
acid diges s adjus ed a pH 7.25)
Rebinding media: Wa e
Ex ac ion ime: 47.63 min, 30 ◦C (ul asound
dispe sion)
Deso p ion sol en : 0.75 M ni ic acid (0.50 mL)
LOD: 0.003 µg L−1
Reco e y: 88.2–101.2% [164]
2-ABT, 2-ace yl benzo u an hiosemica bazone; 4-VP, 4- inylpy idine; ACN, ace oni ile; APBA, 3-amino phenylbo onic acid; APTES, (3-aminop opyl) ie hoxysilane; APTMS, 3-aminop opyl ime hoxysilane;
CD, cyclodex in; Chm, chi osan; CTAB, ce yl ime hylammonium b omide; CS, magne ic chi osan; DAD, diode a ay de ec o ; DCC, N, N-dicyclohexylca bodiimide; DCMA, 2-(dodecyl hioca bono hioyl hio)-
2-me hylp opionic acid; DES-1, deep eu ec ic sol en 1; GC, gas ch oma og aphy; GMA, glycidilme hac yla e; HG-AAS, hyd ide gene a ion—a omic abso p ion spec ome y; HPLC. High pe o mance
liquid ch oma og aphy; LOD, limi o de ec ion; MAA, me hac ylic acid; MHPMIP, magne ic hollow po ous molecula ly imp in ed polyme ; MMC@MIP, magne ic mesopo ous ca bon-molecula ly imp in ed
polyme ; MMIR, hyd ophilic magne ic molecula imp in ed esin; MNPC, magne ic nanopo ous ca bon; MOF, me al-o ganic amewo k; MPS, 3-me hac yloxyp opyl ime hoxysilane; MS, mass spec ome y;
MS/MS, andem mass spec ome y; NPs, nanopa icles; OA, oleic acid; PAEs, ph hala es es e s; PDA, pho odiode a ay de ec o ; SMIBP, supe pa amagne ic molecula ly imp in ed biopolyme ; SPE, solid
phase ex ac ion; SPME, solid phase mic oex ac ion; TEOS, e ae hyl o hosilica e; TEPA, e ae hylenepen amine; UHPLC, ul a-high pe o mance liquid ch oma og aphy; UV, ul a iole ; ZIF-8, zeoli e
imidazola e amewo k-8 coa ed magne ic i on oxide. (*) monome was no used.
Sepa a ions 2021,8, 99 17 o 32
2.1.5. O he Mixed Composi es o MMIPs
Va ious ypes o magne ic composi es (Table 3) ha e been used as magne ic co es o
MMIPs such as me al-o ganic amewo ks (MOFs) and zeoli e imidazola e amewo ks
(ZIFs). In some cases, he syn hesis o Fe
3
O
4
nanopa icles ollowing he hyd o he mal
p ocess is pe o med in he p esence o he amewo k (HKUST-1, a Cu-based po ous MOF)
and EG (diol g oups), which also ac as capping agen s o a oiding agg ega ion [
157
].
Su ace unc ionaliza ion is u he pe o med wi h VTMOS [
157
]. The p ocedu e is ime-
consuming, and a Te lon-lined s ainless s eel au ocla e (syn hesis a 200
◦
C) is equi ed.
On o he occasions, he p e iously syn hesized magne i e nanopa icles a e allowed o
eac wi h he amewo k a mode a e empe a u es and sho imes. This is he case o
Fe
3
O
4
@ZIF-8 composi es, in which poly (s y enesul ona e sodium sal ) is added o he
eac ion medium o allow he ZIF-8 shell g ow h (wi h he p esence o 2-me hylimidazola e
as a p ecu so ), and o which a u he su ace unc ionaliza ion is no equi ed [
158
].
Mo eo e , ZIF-L-based Co-based magne ic nanopo ous ca bon (Co-MNPC) is also di ec ly
mixed in he polyme iza ion medium o p epa ing a magne ic selec i e Co-MNPC@MIP
so ben o a la oxins [159].
Ni@MIL-100(Fe) MOF has also been used as a suppo o MIP syn hesis [
160
]. In
his case he amewo k exhibi s magne ic p ope ies, and a e mixing wi h he empla e
(hyd oxychlo oquine) and wi h he unc ional monome (APTES) and he c oss-linke
(TEOS), MIP syn hesis can be di ec ly ca ied ou .
Fas p ocedu es o syn hesizing magne ic composi es ha e been also desc ibed o
hiola ed
β
-cyclodex in assembled o gold nanopa icles (
β
-CD/Au), whose p esence du -
ing he Fe
3
O
4
syn hesis (co-p ecipi a ion me hod) leads o a
β
-CD/Au/Fe
3
O
4
composi e
unc ionalized o u he MIP syn hesis [
161
]. O he p oposals sugges ed he p e ious syn-
hesis o Fe
3
O
4
@mSiO
2
unc ionalized wi h APTES (p esence o
−
NH
2
g oups) magne ic
co e be o e su ace g a ing o
β
-CD and MIP syn hesis (ph halic acid es e as a empla e)
o p epa ing magne ic plas icize MIPs [
162
]. In addi ion o he high selec i i y inhe en
o he MIP laye , he p epa ed composi e ma e ial was ound o show la ge adso p ion
capaci y and as kine ic equilib ium.
The aminopolysaccha ide na u e o he biopolyme chi osan (CS) has also aken ad-
an age o modi ying magne i e o achie ing a su ace ich in unc ional g oups o u he
polyme iza ion. P epa a ion o Fe
3
O
4
@CS nanopa icles is easily pe o med ollowing
he hyd o he mal syn hesis o Fe
3
O
4
in he p esence o CS [
163
]. Finally, one-s ep co-
p ecipi a ion unde alkaline condi ions (Fe
3
O
4
syn hesis) in he p esence o he diazonium
sal BF
4
(
+
N
2
–C
6
H
4
–CH
2
–DEDTC) also gene a es a magne ic co e ha o e s adequa e
unc ional g oups o mixing wi h he p e-polyme iza ion mix u e and s a ing he MIP
syn hesis [
165
]. On o he occasions, su ace-modi ied Fe
3
O
4
wi h oleic acid was allowed
o polyme ize wi h a senic (III)- 2-ace yl benzo u an hiosemica bazone complex as em-
pla e, and me hac ylic acid as a monome (ionic imp in ed polyme o As(III)) be o e a
Picke ing emulsion in he p esence o nanopa icles o chi osan [
164
]. Ex ac ion o As(III)
om acid diges s om ice and ege able was achie ed a e pH adjus men , assis ing he
loading/elu ion p ocess by ul asounds [164].
2.2. Dispe si e Solid Phase Ex ac ion and Mic osolid Phase Ex ac ion wi h Non-Magne ic MIPs
As p e ious commen ed, dSPE/D-
µ
-SPE [
9
–
11
] can be pe o med by dispe sing MMIP
nanopa icles, and also non-magne ic MIP beads, by o ex and ul asound s i ing [
10
].
Table 4summa izes he main ea u es ega ding dSPE/D-
µ
-SPE wi h non-magne ic MIPs.
The adso ben s can be ob ained by p ecipi a ion [
166
–
174
], and bulk [
175
–
177
] polyme iza-
ion has been used o dSPE/D-
µ
-SPE by shaking he sample/ex ac -MIP bead mix u es
o imes a ying om 5.0 min [
166
] o 3.0 h [
169
]. Abso p ion imes can be educed o
1 min when assis ing he p ocedu e by ul asounds, enough ime o isola ing phenolic
compounds in aqueous samples using 10 mg o MIP [
170
]. Howe e , sonica ion imes
o 3.0 h ha e been p oposed o luo oquinolone p e-concen a ions om wa e s using a
dual- empla e MIP (d -MIP) o no loxacin and en o loxacin as empla es [
172
]. Au ho s,
Sepa a ions 2021,8, 99 18 o 32
howe e , did no epo insigh s ega ding low adso p ion a e o eaching he equilib ium
be ween he a ge s and he d -MIPs. The p ocedu es we e ound o be e ec i e and selec-
i e o isola ing ungicides om cucumbe [
168
], sul onamides om milk [
166
], bioac i e
compounds (polyda in) om a ’s plasma and u ine [
169
], p oges e one ho mones om
plasma, u ine and wa e s [
175
], and also o pu i ying ex ac s (p e-concen a ing a -
ge s) such as polyda in om Chinese medical medicines [
169
], an ibio ics om po k [
167
],
a la oxins om cul u ed ish [
171
], py aclos obin om ginseng [
174
], olic acid om
oods u [176], and he bicides om shell ish [177].
Sepa a ions 2021,8, 99 19 o 32
Table 4. Dispe si e solid phase ex ac ion and mic osolid phase ex ac ion wi h non-magne ic MIPs.
Sample Ta ge Composi e Reagen s/Monome De ec ion
Technique Sample P e-T ea men : Pe o mance: LOD and
Analy ical Reco e y Re .
U ine Glibenclamide HPMIP
TEOS, CTAB/MAA
HPLC-UV
So ben : MHPMIP pa icles (30 mg)
Sample olume: 10 mL (pH adjus ed a 4.0)
Rebinding media: Wa e
Ex ac ion ime: 15 min (ul asound dispe sion)
Deso p ion sol en : 5:5:1 DMSO/e hanol/ace ic acid
(3.0 mL), esuspension
LOD: 3.5 µg L−1
Reco e y: 87.7–104.3% [38]
Wa e Bisphenol A HM-DMIP TEOS/ICPTES HPLC-UV
So ben : HM-DMIP pa icles (30 mg)
Sample olume: 10 mL
Rebinding media: Wa e
Ex ac ion ime: 30 min (s a ic abso p ion condi ions)
Deso p ion sol en : 90:10 me hanol/ace ic
acid (3.0 mL), s a ic abso p ion condi ions
LOQ: 0.2 mg L−1
Reco e y: 98.7–101.7% [39]
Milk Sul ame hazine MIP –*/MAA CE-UV
So ben : MIP pa icles (10 mg)
Sample olume: 10 mL (pH adjus ed wi h 20 mM
phospha e bu e )
Rebinding media: Wa e
Ex ac ion ime: 5.0 min (mechanical shaking)
Deso p ion sol en : 9:1 me hanol/ace ic acid (0.30 mL),
10 min (mechanical shaking)
LOD: 1.1 µg L−1
Reco e y: 89–110% [166]
Po k mea MALs MIP –*/MAA HPLC-MS/MS
So ben : MIP pa icles (20 mg)
Sample olume: 5.0 mL (1% ( / ) ace ic acid in ACN
ex ac om 1.0 g o sample)
Rebinding media: ACN
Ex ac ion ime: 30 min (mechanical shaking)
Deso p ion sol en : 10% ( / ) ace ic acid in me hanol
(5.0 mL), 10 min (ul asound dispe sion)
LOD: 0.2–0.5 µg kg−1
Reco e y: 68.6–95.5% [167]
Cucumbe Azoxys obin HMIM –*/HPMA HPLC-UV
So ben : HMIM pa icles (100 mg)
Sample olume: 5.0 mL (me hanol ex ac om 25 g o
sample)
Rebinding media: Me hanol
Ex ac ion ime: 30 min (wa e -ba h oscilla ion plus 30
min wi hou oscilla ion)
Deso p ion sol en : 9:1 me hanol/ace ic acid (8.0 mL),
wa e -ba h oscilla ion
LOD: 0.324 µg kg−1
Reco e y: 85.9–88.9% [168]
Sepa a ions 2021,8, 99 20 o 32
Table 4. Con .
Sample Ta ge Composi e Reagen s/Monome De ec ion
Technique Sample P e-T ea men : Pe o mance: LOD and
Analy ical Reco e y Re .
PCRR, and plasma
and u ine om a Polyda in MIP –*/4-VP HPLC-UV
So ben : MIP pa icles (10 mg o PCRR, 5.0 mg o
plasma and u ine)
Sample olume: 1.5 mL (ex ac s om PCRR), 0.20 mL
(plasma), 0.050 mL (u ine)
Rebinding media: 8:2 wa e /me hanol (ex ac s om
PCRR), wa e (plasma and u ine)
Ex ac ion ime: 3.0 h, mechanical shaking
Deso p ion sol en : 1.5 mL o 8:2 wa e /me hanol and
3.0 h (mechanical shaking)
LOD: 0.125 mg L−1
Reco e y: 89.2–91.6% [169]
Wa e Phenolic
compounds MIP –*/MAA CE-DAD
So ben : MIP pa icles (10 mg)
Sample olume: 10 mL
Rebinding media: Wa e
Ex ac ion ime: 1.0 min (ul asound dispe sion)
Deso p ion sol en : 9:1 ACN/ace ic acid (30 µL), 4.0
min (ul asound dispe sion)
LOD: 0.18–0.44 µg L−1
Reco e y: 70.7–106.7% [170]
Fish A la oxins MIP –*/MAA HPLC-MS/MS
So ben : MIP pa icles (40 mg)
Sample olume: 1.5 mL (60:40 ACN/phospha e bu e
ex ac om 1.g o sample)
Rebinding media: 60:40 ACN/phospha e bu e , pH 6.0
Ex ac ion ime: 3.0 min (mechanical shaking)
Deso p ion sol en : 97.5:2.5 ACN/ o mic acid (0.50
mL), 4.0 min (mechanical shaking)
LOD: 0.29–0.61 µg kg−1
Reco e y: 83–98% [171]
Wa e FQs d -MIP –*/MAA HPLC-DAD
So ben : d -MIP pa icles (10 mg)
Sample olume: 10 mL
Rebinding media: Wa e
Ex ac ion ime: 3.0 h (mechanical shaking)
Deso p ion sol en : 90:10 me hanol/ace ic acid (0.15
mL), 5.0 min (ul asound dispe sion)
LOD: 0.2 (NOR) and 0.67
(ENR) µg L−1
Reco e y: 80.9–101.0%
[172]
Rice Ino ganic As IIP 1- inylimidazole-
/MAA HPLC-ICP-MS
So ben : IIP pa icles (50 mg)
Sample olume: 1.5 mL (1:1 me hanol/wa e ex ac
om 1.g o sample)
Rebinding media: 1:1 me hanol/wa e (pH 8.0)
Ex ac ion ime: 1.0 min (mechanical shaking)
Deso p ion sol en : wa e (0.15 mL), 1.0 min
(mechanical shaking)
LOD: 0.20 (As(III)) and
0.41 (As(V)) µg kg−1
Reco e y: 95–103%
[173]
Ginseng Py aclos obin MIP –*/MAA HPLC-UV
So ben : MIP pa icles (100 mg)
Sample olume: 2.0 mL (ACN ex ac om 25 g o
sample)
Rebinding media: ACN
Ex ac ion ime: 50 min (mechanical shaking)
Deso p ion sol en : 9:1 me hanol/ace ic acid (8.0 mL),
50 min (mechanical shaking)
LOD: 0.01 mg kg−1
Reco e y: 95–103% [174]
Sepa a ions 2021,8, 99 21 o 32
Table 4. Con .
Sample Ta ge Composi e Reagen s/Monome De ec ion
Technique Sample P e-T ea men : Pe o mance: LOD and
Analy ical Reco e y Re .
Wa e , u ine, se um P oges e one MIP –*/py ole GC-FID
So ben : MIP pa icles (100 mg)
Sample olume: 20 mL (pH adjus ed a 6.5)
Rebinding media: Wa e
Ex ac ion ime: 35 min (ul asound dispe sion)
Deso p ion sol en : me hanol (0.5 mL), 40 min
(ul asound dispe sion)
LOD: 0.625 µg L−1
Reco e y: 88–101% [175]
Food Folic acid MIP –*/VBTMAC HPLC-MS
So ben : MIP pa icles (50 mg)
Sample olume: 10 mL (aqueous ex ac )
Rebinding media: Wa e
Ex ac ion ime: 20 min (mechanical shaking)
Deso p ion sol en : 1:1 me hanol/hyd ochlo ic acid
(10 mL), 30 min (mechanical shaking)
LOD: 0.003 mg L−1
Reco e y: 79–83% [176]
Sea ood He bicides MIP –*/MAA GC-MS/MS
So ben : MIP pa icles (50 mg)
Sample olume: 10 mL (ACN/ace ic acid aqueous
ex ac om 2.0g o sample)
Rebinding media: ACN/wa e
Ex ac ion ime: 15 min (mechanical shaking)
DSPE o clean-up
LOQ: 0.03–8.88 µg kg−1
Reco e y: 81–109% [177]
Chicken mea TCs MIP-MOF
UiO-66 MOF/MAA
HPLC-UV
So ben : MIP-MOF pa icles (5 mg)
Sample olume: 10 mL (aqueous ex ac , pH adjus ed
a 4.0, om 1.0 g o sample)
Rebinding media: Wa e
Ex ac ion ime: 15 min (mechanical shaking)
Deso p ion sol en : me hanol (1.0 mL), 5.0 min
(mechanical shaking)
LOD: 0.2–5.0 µg L−1
Reco e y: 69.6–94.7% [178]
U ine, milk Nico inamide MIP-MOF HKUST-1
MOF/MAA
UV-Vis
spec opho ome y
So ben : MIP-MOF pa icles (2 mg)
Sample olume: 10 mL (pH adjus ed a 5.0)
Rebinding media: Wa e
Ex ac ion ime: 5.0 min (ul asound dispe sion)
Deso p ion sol en : ACN (0.20 mL)
LOD: 1.96 µg L−1
Reco e y: 95.8–101.3% [179]
Wa e Es ogens MIHS Colloidal silica,
KH570/MAA HPLC-UV
So ben : MIHS pa icles (10 mg)
Sample olume: 1.0 mL
Rebinding media: Wa e
Ex ac ion ime: 15 min (dispe sion)
Deso p ion sol en : 8:2 me hanol/ace ic acid (1.0 mL)
LOD: 0.1–0.26 µM L−1
Reco e y: 69.6–94.7% [180]
U ine Valsa an and
losa an HP-MIN CNPs/TEOS HPLC-UV
So ben : HP-MIN pa icles (40 mg)
Sample olume: 15 mL (pH adjus ed a 6.0)
Rebinding media: Wa e
Ex ac ion ime: 27 min (ul asound dispe sion)
Deso p ion sol en : 90:10 me hanol/ace ic acid
(2.0 mL), ul asound dispe sion
LOD: 1.5 (VAL) and 1.4
(LOS) µg L−1
Reco e y: 93–99%
[181]
Sepa a ions 2021,8, 99 22 o 32
Table 4. Con .
Sample Ta ge Composi e Reagen s/Monome De ec ion
Technique Sample P e-T ea men : Pe o mance: LOD and
Analy ical Reco e y Re .
Be e ages DOP MWCNT-MIP MWCNTs/MAA GC-MS
So ben : MWCNT-MIP pa icles (60 mg)
Sample olume: 20 mL (ACN ex ac )
Rebinding media: ACN
Ex ac ion ime: 30 min (oscilla ion)
Deso p ion sol en : 9:1 me hanol/ace ic acid
LOD: 2.3 ng L−1
Reco e y: 88.6–93.0% [182]
Wa e DEHP GO-MIP GO/MAA HPLC-UV
So ben : GO-MIP pa icles (20 mg)
Sample olume: 600 mL
Rebinding media: Wa e
Ex ac ion ime: 30 min (mechanical shaking)
Deso p ion sol en : ace one (6.0 mL), 5.0 min
(ul asound dispe sion)
LOD: 0.92 µg L−1
Reco e y: 82–92% [183]
AAm, ac ylamide; 4-VP, 4- inylpy idine; ACN, ace oni ile; CE, capilla y elec opho esis; CNPs, ca bon nanopa icles; CTAB, ce yl ime hylammonium b omide; DAD, diode a ay de ec o ; DEHP,
bis(2-e hylhexyl) ph hala e; DOP, dioc yl ph hala e; DSPE, dispe si e solid phase ex ac ion; d -MIP, dual- empla e molecula ly imp in ed polyme ; ENR, en o loxacin; FID, lame ioniza ion de ec o ; FQs,
luo oquinolones; GO, g aphene oxide; HM-DMIP, hollow mesopo ous silica su ace dummy molecula ly imp in ed polyme ; HMIM, hyd ophilic molecula ly imp in ed mic osphe e; HPLC, high pe o mance
liquid ch oma og aphy; HPMA, hyd oxyp opyl me hac yla e; HPMIP, hollow po ous molecula ly imp in ed polyme ; HP-MIN, hollow po ous molecula ly imp in ed nanosphe e; ICP, induc i ely coupled
plasma; ICPTES, (3-isocyana op opyl) ie hoxysilane; IIP, ionic imp in ed polyme ; KH570,
γ
-me hac yloxyp opyl ime hoxysilane; LOD, limi o de ec ion; LOQ, limi o quan i ica ion; LOS, losa an; MAA,
me hac ylic acid; MALs, mac olide an ibio ics; MIH, molecula ly imp in ed hollow sphe e; MIP, molecula ly imp in ed polyme ; MOF, me al-o ganic amewo ks; MS, mass spec ome y; MS/MS, andem mass
spec ome y; MWCNTs, mul iwalled ca bon nano ubes; NOR, no loxacin; PCRR, Polygoni Cuspida i Rhizoma e Radix; SiO
2
@MPS, me hac yloxyp opyl modi ied silica nanopa icle; TCs, e acyclines; TEOS,
e ae hyl o hosilica e; UHPLC, ul a-high pe o mance liquid ch oma og aphy; UV, ul a iole ; VAL, alsa an; VBTMAC, inylbenzyl ime hylammonium chlo ide; VTTS, inyl ime hoxysilance. (*) no
eagen was used.
Sepa a ions 2021,8, 99 23 o 32
Ionic molecula ly imp in ed polyme s (IIPs) ha e also been p oposed o dSPE [
173
].
The bi unc ional monome 1- inylimidazole was used o eac ing wi h he empla e
((me a)a seni e, As(III)) and p o iding inyl g oups o polyme iza ion [
173
]. The dSPE
implied po ions o 50 mg o IIP and o exing a 1000 pm o 1 min allowed he selec i e
p e-concen a ion o ino ganic a senic species (As (III) plus As(V)) om ice ex ac s [
173
].
MIP syn hesis a ound non-magne ic nanopa icles, such as silica nanopa icles, has
been also pe o med o ob ain s able adso ben s. The e o e, silica nanopa icles unc ional-
ized wi h KH-570 (SiO
2
@KH-570) by a base-ca alyzed eac ion o TEOS and KH-570 ha e
been used as a co e o p epa ing a selec i e MIP composi e o he enan iosepa a ion
o acemic yp ophan (L- yp ophan ecogni ion) in aqueous solu ions [
184
]. Expe i-
men s we e pe o med by oscilla ing he MIP-aqueous sample mix u es o 32 h a oom
empe a u e and using only 2 mg o adso ben [184].
In addi ion, he excellen p ope ies o MOFs ha e led o p epa a ion o MOF-MIP com-
posi es based on UiO-66 MOF [
178
] and HKUST-1 MOF [
180
] by di ec MIP polyme iza ion
on he MOF’s su ace. The dSPE was pe o med wi h 5 mg o UiO-66-MIP and shaking o
15 min o eco e e acyclines om chicken ex ac s [
178
]; whe eas 2 mg o HKUST-1-MIP
( o exing o 2 min) p o ed adequa e o nico inamide p e-concen a ion [179].
Hollow non-magne ic composi es based on silica [
180
] and ca bon [
181
] ha e been
also p epa ed o dSPE/D-
µ
-SPE. In bo h cases, a e MIP syn hesis o e he nanopa -
icle, he suppo ing ma e ial was emo ed (hyd o luo ic acid o silica [
180
], and calci-
na ion a 500
◦
C o ca bon [
181
]) leading o a po ous ma e ial wi h high su ace a ea.
Syn hesis o hollow silica-based MIP composi es equi ed unc ionaliza ion wi h KH-
570 (sou ce o inyl g oups) o an e ec i e MIP syn hesis and ancho age (es ogen
ecogni ion/p e-concen a ion om wa e [
180
]). Howe e , TEOS and aluminum chlo ide
we e used o MIP syn hesis ( alsa an as a empla e) when p epa ing he hollow ca bon-
based aluminum-doped silica composi e, p omo ing hyd olysis o gene a e silanol g oups
(Si
−
OH) ollowed by condensa ion o he silanols o ob ain a polysiloxane (O
−
Si
−
O) [
181
].
Es ogen p e-concen a ion was designed by using 10 mg o he composi e and shaking
o 1.0 h [
180
]; whe eas, alsa an and losa an isola ion equi ed 40 mg o adso ben and
sonica ion o 27 min [181].
O he composi es such as MWCNT-MIPs ha e also been demons a ed o be e ec i e
adso ben s o dSPE o dioc yl ph hala e in be e age samples [
182
]. Vinyl g oups we e
inco po a ed on MWCNTs by eac ion wi h sodium e hoxyla e be o e MWCNT oxida ion
(p esence o ca boxyl g oups), and MIP (dioc yl ph hala e as a empla e) was u he
syn hesized. The dSPE p ocedu e was pe o med by mixing 60 mg o MWCNTs-MIPs
wi h ea ed be e age samples (juice, dai y d inks, and ca bona ed d inks) and incuba ing
a oom empe a u e o 30 min on an oscilla o [
182
]. Finally, g aphene oxide-based
MIPs (GO-MIPs) ha e also been used o dSPE when p e-concen a ing bis(2-e hylhexyl)
ph hala e om wa e s by shaking 20 mg o adso ben wi h he sample (wa e ) a 600 pm
o 30 min [183].
3. D awbacks and Fu u e P ospec s
MIMSPE p ocedu es ha e been e ealed as excellen app oaches o minia u iza-
ion o SPE-based echniques in analy ical chemis y, o e ing selec i e ex ac ion/p e-
concen a ion when analyzing complex samples. Dispe si e SPE/
µ
-SPE p ocedu es based
on MIPs (mainly MMIPs) ha e shown high po en ial o minia u iza ion, which implies he
use o low amoun s o adso ben s as well as low olumes o o ganic sol en s o pe o ming
he elu ion s age.
Howe e , MIPs and MMIPs ace a numbe o challenges du ing he p epa a ion
(syn hesis) s age and also du ing he applica ion. MMIPs a e syn hesized in nonpola
sol en s o a oid he dis up ion o he hyd ogen bonding be ween monome and empla es.
The gene a ed hyd ophobic su aces lead o adso p ion o in e e ences such as p o eins.
RAFT polyme iza ion is a good al e na i e o o e come his p oblem since i allows he
p epa a ion o highly hyd ophilic MIPs (o MIP ex e nal laye s o e nanopa icles), which
Sepa a ions 2021,8, 99 24 o 32
can lead o e icien adso ben s o samples o a wide pola i y ange. Imp o emen s ha e
also been add essed o au oma e he echniques (simila o on-column/ca idges SPE)
since ba ch MIMSPE p ocedu es equi e se e al s eps (condi ioning, loading, washing,
elu ion) and he p ocedu es a e no appealing p ocesses when coping wi h hund eds o
samples. In addi ion, he coupling (and also au oma ion) o he MIMSPE de ices di ec ly
wi h analy ical ins umen s has no been explo ed ye .
In any case, MIMSPE p ocedu es open a ascina ing window o analyzing compounds
om complex ma ices, and con inuous e o s in his esea ch a ea should open mo e and
mo e no el applica ions.
Au ho Con ibu ions:
G.D.T.M.J.: Fo mal analysis, In es iga ion, Valida ion, Visualiza ion, W i ing—
O iginal d a p epa a ion; A.M.-P.: Resou ces, P ojec adminis a ion, Funding acquisi ion, Supe i-
sion, Da a cu a ion, So wa e, Valida ion, W i ing—Re iewing and Edi ing. All au ho s ha e ead
and ag eed o he published e sion o he manusc ip .
Funding:
This esea ch was unded by Sec e a íaXe al de In es igación e Desen ol emen o—Xun a
de Galicia G upos de Re e encia Compe i i a (p ojec numbe ED431C2018/19), and De elopmen
o a S a egic G ouping in Ma e ials—AEMAT (g an ED431E2018/08).
Con lic s o In e es : The au ho s decla e no con lic o in e es .
Re e ences
1.
Pawliszyn, J. New di ec ions in sample p epa a ion o analysis o o ganic compounds. T ends Anal. Chem.
1995
,14, 113–122.
[C ossRe ]
2.
Tu iel, E.; Ma ín-Es eban, A. Molecula ly imp in ed polyme s-based mic oex ac ion echniques. T ends Anal. Chem.
2019
,118,
574–586. [C ossRe ]
3.
Vasapollo, G.; Sole, R.D.; Me gola, L.; Lazzoi, M.R.; Sca dino, A.; Sco ano, S.; Mele, G. Molecula ly imp in ed polyme s: P esen
and u u e p ospec i e. In . J. Mol. Sci. 2011,12, 5908–5945. [C ossRe ] [PubMed]
4.
Pichon, V.; Delaunay, N.; Combès, A. Sample P epa a ion Using Molecula ly Imp in ed Polyme s. Anal. Chem.
2019
,92, 16–33.
[C ossRe ]
5.
Cap io i, A.L.; Ca alie e, C.; LA Ba be a, G.; Mon one, C.M.; Pio esana, S.; Laganà, A. Recen Applica ions o Magne ic
Solid-phase Ex ac ion o Sample P epa a ion. Ch oma og aphia 2019,82, 1251–1274. [C ossRe ]
6.
Ansa i, S.; Ka imi, M. Recen con igu a ions and p og essi e uses o magne ic molecula ly imp in ed polyme s o d ug analysis.
Talan a 2017,167, 470–485. [C ossRe ]
7.
Spel ini, A.; Scalab ini, A.; Ma aschi, F.; S u ini, M.; P o umo, A. Newes applica ions o molecula ly imp in ed polyme s o
ex ac ion o con aminan s om en i onmen al and ood ma ices: A e iew. Anal. Chim. Ac a 2017,974, 1–26. [C ossRe ]
8.
Azizi, A.; Bo a o, C.S. A c i ical e iew o molecula ly imp in ed polyme s o he analysis o o ganic pollu an s in en i onmen al
wa e samples. J. Ch oma og . A 2020,1614, 460603. [C ossRe ]
9.
Gho bani, M.; Aghamohammadhassan, M.; Chamsaz, M.; Akhlaghi, H.; Ped am ad, T. Dispe si e solid phase mic oex ac ion.
T ends Anal. Chem. 2019,118, 793–809. [C ossRe ]
10.
Gho bani, M.; Aghamohammadhassan, M.; Gho bani, H.; Zabihi, A. T ends in so ben de elopmen o dispe si e mic o-solid
phase ex ac ion. Mic ochem. J. 2020,158, 105250. [C ossRe ]
11.
Ojeda, C.B.; Rojas, F.S. Vo ex-Assis ed Liquid–Liquid Mic oex ac ion (VALLME): The La es Applica ions. Ch oma og aphia
2017
,
81, 89–103. [C ossRe ]
12.
Mo eda-Piñei o, J.; Mo eda-Piñei o, A. Combined assis ed ex ac ion echniques as g een sample p e- ea men s in ood analysis.
T ends Anal. Chem. 2019,118, 1–18. [C ossRe ]
13.
Adewuyi, Y.G. Sonochemis y: En i onmen al Science and Enginee ing Applica ions. Ind. Eng. Chem. Res.
2001
,40, 4681–4715.
[C ossRe ]
14. Galán-Cano, F.; Lucena, R.; Cá denas, S.; Valcá cel, M. Dispe si e mic o-solid phase ex ac ion wi h ionic liquid-modi ied silica
o he de e mina ion o o ganophospha e pes icides in wa e by ul a pe o mance liquid ch oma og aphy. Mic ochem. J.
2013
,
106, 311–317. [C ossRe ]
15.
Cai, Q.; Zhang, L.; Zhao, P.; Lun, X.; Li, W.; Guo, Y.; Hou, X. A join expe imen al-compu a ional in es iga ion: Me al o ganic
amewo k as a o ex assis ed dispe si e mic o-solid-phase ex ac ion so ben coupled wi h UPLC-MS/MS o he simul aneous
de e mina ion o amphenicols and hei me aboli e in aquacul u e wa e . Mic ochem. J. 2017,130, 263–270. [C ossRe ]
16.
Aghaie, A.B.; Hadjmohammadi, M.R. Fe
3
O
4
@p-Naph holbenzein as a no el nano-so ben o highly e ec i e emo al and
eco e y o Be be ine: Response su ace me hodology o op imiza ion o ul asound assis ed dispe si e magne ic solid phase
ex ac ion. Talan a 2016,156, 18–28. [C ossRe ] [PubMed]
Sepa a ions 2021,8, 99 25 o 32
17.
Dil, E.A.; Ghaedi, M.; As a am, A.; Meh abi, F.; Baz a shan, A.A.; Ghaedi, A.M. T ace de e mina ion o sa anin O dye using
ul asound assis ed dispe si e solid-phase mic o ex ac ion: A i icial neu al ne wo k-gene ic algo i hm and esponse su ace
me hodology. Ul ason. Sonochem. 2016,33, 129–140. [C ossRe ] [PubMed]
18.
K awczyk, M.; S anisz, E. Ul asound-assis ed dispe si e mic o solid-phase ex ac ion wi h nano-TiO2 as adso ben o he
de e mina ion o me cu y species. Talan a 2016,161, 384–391. [C ossRe ] [PubMed]
19.
Ansell, R.J.; Mosbach, K. Magne ic molecula ly imp in ed polyme beads o d ug adioligand binding assay. Analys
1998
,123,
1611–1616. [C ossRe ] [PubMed]
20.
Zhang, L.; Li, J.; Zeng, Y. Molecula ly imp in ed magne ic nanopa icles o de e mina ion o he he bicide chlo o olu on by
ga e-con olled elec o-ca aly ic oxida ion o hyd azine. Mic ochim. Ac a 2015,182, 249–255. [C ossRe ]
21.
Ma ín-Es eban, A. Molecula ly-imp in ed polyme s as a e sa ile, highly selec i e ool in sample p epa a ion. T ends Anal. Chem.
2013,45, 169–181. [C ossRe ]
22.
Yang, M.; Zhang, Y.; Lin, S.; Yang, X.; Fan, Z.; Yang, L.; Dong, X. P epa a ion o a bi unc ional py azosul u on-e hyl imp in ed
polyme wi h hyd ophilic ex e nal laye s by e e sible addi ion– agmen a ion chain ans e polyme iza ion and i s applica ion
in he sul onylu ea esidue analysis. Talan a 2013,114, 143–151. [C ossRe ] [PubMed]
23.
Lu, C.-H.; Zhou, W.-H.; Han, B.; Yang, H.-H.; Chen, X.; Wang, X.-R. Su ace-Imp in ed Co e
−
Shell Nanopa icles o So ben
Assays. Anal. Chem. 2007,79, 5457–5461. [C ossRe ]
24.
Chang, L.; Li, Y.; Chu, J.; Qi, J.; Li, X. P epa a ion o co e-shell molecula ly imp in ed polyme ia he combina ion o e e sible
addi ion- agmen a ion chain ans e polyme iza ion and click eac ion. Anal. Chim. Ac a 2010,680, 65–71. [C ossRe ]
25.
Zhang, H. Con olled/“li ing” adical p ecipi a ion polyme iza ion: A e sa ile polyme iza ion echnique o ad anced unc ional
polyme s. Eu . Polym. J. 2013,49, 579–600. [C ossRe ]
26.
Abdollahi, E.; Abdouss, M.; Salami-Kalajahi, M.; Mohammadi, A. Molecula Recogni ion Abili y o Molecula ly Imp in ed
Polyme Nano- and Mic o-Pa icles by Re e sible Addi ion-F agmen a ion Chain T ans e Polyme iza ion. Polym. Re .
2016
,56,
557–583. [C ossRe ]
27.
Azizi, A.; Shahhoseini, F.; Bo a o, C.S. Magne ic molecula ly imp in ed polyme s p epa ed by e e sible addi ion agmen a ion
chain ans e polyme iza ion o dispe si e solid phase ex ac ion o polycyclic a oma ic hyd oca bons in wa e . J. Ch oma og . A
2020,1610, 460534. [C ossRe ]
28.
Huang, S.; Xu, J.; Zheng, J.; Zhu, F.; Xie, L.; Ouyang, G. Syn hesis and applica ion o magne ic molecula ly imp in ed polyme s in
sample p epa a ion. Anal. Bioanal. Chem. 2018,410, 3991–4014. [C ossRe ] [PubMed]
29.
Aguila -A eaga, K.; Rod iguez, J.; Ba ado, E. Magne ic solids in analy ical chemis y: A e iew. Anal. Chim. Ac a
2010
,674,
157–165. [C ossRe ]
30.
Xie, L.; Jiang, R.; Zhu, F.; Liu, H.; Ouyang, G. Applica ion o unc ionalized magne ic nanopa icles in sample p epa a ion. Anal.
Bioanal. Chem. 2014,406, 377–399. [C ossRe ]
31.
Ma, G.; Chen, L. De elopmen o magne ic molecula ly imp in ed polyme s based on ca bon nano ubes—Applica ion o ace
analysis o py e h oids in ui ma ices. J. Ch oma og . A 2014,1329, 1–9. [C ossRe ]
32.
Ansa i, S.; Masoum, S. A mul i-walled ca bon nano ube-based magne ic molecula ly imp in ed polyme as a highly selec i e
so ben o ul asonic-assis ed dispe si e solid-phase mic oex ac ion o so alol in biological luids. Analys
2018
,143, 2862–2875.
[C ossRe ]
33.
Ning, F.; Qiu, T.; Wang, Q.; Peng, H.; Li, Y.; Wu, X.; Zhang, Z.; Chen, L.; Xiong, H. Dummy-su ace molecula ly imp in ed
polyme s on magne ic g aphene oxide o apid and selec i e quan i ica ion o ac ylamide in hea -p ocessed (including ied)
oods. Food Chem. 2017,221, 1797–1804. [C ossRe ]
34.
Xie, X.; Ma, X.; Guo, L.; Fan, Y.; Zeng, G.; Zhang, M.; Li, J. No el magne ic mul i- empla es molecula ly imp in ed polyme o
selec i e and apid emo al and de ec ion o alkylphenols in wa e . Chem. Eng. J. 2019,357, 56–65. [C ossRe ]
35.
Zhao, X.; Chen, L.; Li, B. Magne ic molecula imp in ing polyme s based on h ee-dimensional (3D) g aphene-ca bon nano ube
hyb id composi es o analysis o melamine in milk powde . Food Chem. 2018,255, 226–234. [C ossRe ] [PubMed]
36.
Zhang, X.-B.; Li, J.; You, B.; Yong, G.-P.; Tong, H.-W.; Liu, S.-M. Hollow po ous molecula ly imp in ed polyme nanosphe e o
as and e icien ecogni ion o bisphenol A. RSC Ad . 2012,2, 9778–9780. [C ossRe ]
37.
Li, H.; Hu, X.; Zhang, Y.; Shi, S.; Jiang, X.; Chen, X. High-capaci y magne ic hollow po ous molecula ly imp in ed polyme s o
speci ic ex ac ion o p o oca echuic acid. J. Ch oma og . A 2015,1404, 21–27. [C ossRe ] [PubMed]
38.
Os o an, A.; Ghaedi, M.; A abi, M.; As a am, A. Hollow po ous molecula ly imp in ed polyme o highly selec i e clean-up
ollowed by in luen ial p e-concen a ion o ul a- ace glibenclamide om bio- luid. J. Ch oma og . A
2017
,1520, 65–74. [C ossRe ]
39.
Li, L.; Yu, K.; Tian, M.; Wang, Y.; Zhang, Z.; Jiang, G.; Li, L. Rapid ex ac ion o ace bisphenol A in eal wa e samples using
hollow mesopo ous silica su ace dummy molecula ly imp in ed polyme s. Anal. Me hods 2018,10, 3926–3932. [C ossRe ]
40.
Hua, S.; Zhao, L.; Cao, L.; Wang, X.; Gao, J.; Xu, C. Fab ica ion and e alua ion o hollow su ace molecula ly imp in ed polyme
o apid and selec i e adso p ion o dibenzo hiophene. Chem. Eng. J. 2018,345, 414–424. [C ossRe ]
41.
Ge, Y.-H.; Shu, H.; Xu, X.-Y.; Guo, P.-Q.; Liu, R.-L.; Luo, Z.-M.; Chang, C.; Fu, Q. Combined magne ic po ous molecula ly
imp in ed polyme s and deep eu ec ic sol en s o e icien and selec i e ex ac ion o a is olochic acid I and II om a u ine.
Ma e . Sci. Eng. C 2019,97, 650–657. [C ossRe ] [PubMed]
Sepa a ions 2021,8, 99 32 o 32
178.
Ma, N.; Feng, C.; Qu, P.; Wang, G.; Liu, J.; Liu, J.X.; Wang, J.P. De e mina ion o Te acyclines in Chicken by Dispe si e Solid Phase
Mic oex ac ion Based on Me al-O ganic F amewo ks/Molecula ly Imp in ed Nano-polyme and Ul a Pe o mance Liquid
Ch oma og aphy. Food Anal. Me hods 2020,13, 1211–1219. [C ossRe ]
179. As a am, A.; Ghaedi, M.; Dash ian, K. Ul asound assis ed combined molecula ly imp in ed polyme o selec i e ex ac ion o
nico inamide in human u ine and milk samples: Spec opho ome ic de e mina ion and op imiza ion s udy. Ul ason. Sonochem.
2017,34, 640–650. [C ossRe ] [PubMed]
180.
Chen, W.; Xue, M.; Xue, F.; Mu, X.; Xu, Z.; Meng, Z.; Zhu, G.; Shea, K.J. Molecula ly imp in ed hollow sphe es o he solid phase
ex ac ion o es ogens. Talan a 2015,140, 68–72. [C ossRe ]
181.
Gholami, H.; Ghaedi, M.; Os o an, A.; A abi, M.; Baghe i, A.R. P epa a ion o hollow po ous molecula ly imp in ed and
aluminum(III) doped silica nanosphe es o ex ac ion o he d ugs alsa an and losa an p io o hei quan i a ion by HPLC.
Mic ochim. Ac a 2019,186, 702. [C ossRe ]
182.
Du, J.; Gao, R.; Mu, H. A No el Molecula ly Imp in ed Polyme Based on Ca bon Nano ubes o Selec i e De e mina ion o
Dioc yl Ph hala e om Be e age Samples Coupled wi h GC/MS. Food Anal. Me hods 2016,9, 2026–2035. [C ossRe ]
183.
Cheng, L.; Pan, S.; Ding, C.; He, J.; Wang, C. Dispe si e solid-phase mic oex ac ion wi h g aphene oxide based molecula ly
imp in ed polyme s o de e mining bis(2-e hylhexyl) ph hala e in en i onmen al wa e . J. Ch oma og . A
2017
,1511, 85–91.
[C ossRe ]
184.
Li, L.; Li, Z.; Jia, L. Molecula ly imp in ed polyme unc ionalized silica nanopa icles o enan iosepa a ion o acemic yp ophan
in aqueous solu ion. Mic ochim. Ac a 2020,187, 1–7. [C ossRe ]
