In . J. Mol. Sci. 2009, 10, 656-673; doi:10.3390/ijms10020656
In e na ional Jou nal o
Molecula Sciences
ISSN 1422-0067
www.mdpi.com/jou nal/ijms
Re iew
Quan um Do s — Cha ac e iza ion, P epa a ion and Usage in
Biological Sys ems
Jana D bohla o a 1,*, Voj ech Adam 2, Rene Kizek 2 and Ja omi Hubalek 1
1 Depa men o Mic oelec onics, Facul y o Elec ical Enginee ing and Communica ion, B no
Uni e si y o Technology / Údolní 53, 602 00 B no, Czech Republic;
E-Mail: [email p o ec ed] (J.H.)
2 Depa men o Chemis y and Biochemis y, Facul y o Ag onomy, Mendel Uni e si y o
Ag icul u e and Fo es y / Zemědělská 1, 613 00 B no, Czech Republic;
E-Mails: [email p o ec ed] (V.A.); [email p o ec ed]uni.cz (R.K.)
* Au ho o whom co espondence should be add essed; E-Mail: [email p o ec ed];
Tel. +420-541-146-163; Fax: +420-541-146-298
Recei ed: 8 Janua y 2009; in e ised o m: 13 Feb ua y 2009 / Accep ed: 18 Feb ua y 2009 /
Published: 20 Feb ua y 2009
Abs ac : The use o luo escen nanopa icles as p obes o bioanaly ical applica ions is
a highly p omising echnique because luo escence-based echniques a e e y sensi i e.
Quan um do s (QDs) seem o show he g ea es p omise as labels o agging and imaging
in biological sys ems owing o hei imp essi e pho os abili y, which allow long- e m
obse a ions o biomolecules. The usage o QDs in p ac ical applica ions has s a ed only
ecen ly, he e o e, he esea ch on QDs is ex emely impo an in o de o p o ide sa e
and e ec i e biosensing ma e ials o medicine. This e iew epo s on he ecen
me hods o he p epa a ion o quan um do s, hei physical and chemical p ope ies,
su ace modi ica ion as well as on some in e es ing examples o hei expe imen al use.
Keywo ds: Quan um do s; biosensing; biolabeling; empla e me hods; TiO2.
1. In oduc ion
In ew pas yea s, esea che s in Chemis y and Physics ha e ocused a g ea pa o hei in e es in
ab ica ion o nanopa icles such as nanowi es, quan um do s, nano ods, nano ubes o nano ilms [1].
OPEN ACCESS
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The easons o his a e he possible applica ions o nanopa icles in se e al ex emely impo an
ields, e.g. in ca alysis, coa ings, ex iles, da a s o age, bio echnology, heal h ca e, biomedical and
pha maceu ical indus ies. Conce ning he medical applica ions, sphe ical nanopa icles a e he mos
widely de eloped and u ilized [2]. Nanopa icles can be p epa ed using me allic, me al oxide–ce amic,
polyme , ca bon, co e-shell, alloy, composi e, and biological componen s.
Nanome e -sized c ys als, o en e e ed o as quan um do s (QDs), ha e been also in ensi ely
in es iga ed. Typical QD sizes ange be ween 2–20 nm [3], bu acco ding o some li e a u e hei
diame e should be s ic ly below 10 nm [4,5]. Howe e , he dimensions o QDs depend mainly on he
ma e ial used o p epa e hem. Gene ally we call a sys em a QD when he quan um con inemen e ec
occu s, i. e. when he nanopa icle adius a is lowe han one o his magni udes: ae, ah and aexc (Boh
adius o elec on, hole and exci on, espec i ely). I is known he Boh adius depends on he ma e ial
(e.g. 36 nm o InAs, 0.7 nm o CuCl, e c.) and he e o e he e is no a clea line o say ha a
nanopa icle is a QD o no , i one only conside s i s size. QDs can be based on me allic (e.g. Ni, Co,
P , Au) [6] o (mos ly) on semiconduc o ma e ials. Mo eo e , some esea ch in o me alloid QDs such
as silicon has been done [7]. Because o hei educed size, QDs beha e di e en ly om bulk solids
due o he quan um-con inemen e ec s ha a e esponsible o hei ema kably a ac i e p ope ies.
In gene al, quan iza ion e ec s in semiconduc o s uc u es can be di ided in o h ee g oups,
depending on whe he he cha ge ca ie s a e con ined in one, wo o h ee dimensions [8].
Con inemen in one di ec ion c ea es wo-dimensional (2D) s uc u es ha ha e been e med quan um
wells o quan um ilms. Ca ie con inemen in wo di ec ions p oduces one-dimensional (1D)
quan um wi es and con inemen in h ee dimensions p oduces al eady men ioned quan um do s o
quan um boxes, whe e he elec ons a e mos ly localized; hese s uc u es a e ze o-dimensional (0D).
Typically, QDs a e ep esen ed by a omic clus e s o nanoc ys alli es. QDs usually consis o ew
hund eds o a ew millions o a oms, bu only a small numbe o elec ons (≤100) a e ee [9]. In
addi ion, depending on elec on con inemen , i is possible o dis inguish be ween plana , e ical and
sel -assembled QDs, whe eas he e y i s expe imen s we e made wi h he plana s uc u es. In
plana and e ical QDs, elec os a ic con inemen leads ypically o dimensions a ound 100 nm and
s uc u al con inemen is o he o de o 10 nm, while in sel -assembled QDs he s uc u es a e a he
py amidal o lens-shaped wi h sizes o app oxima ely 10 nm. These py amidal QDs a e e y p omising
o lase applica ions [10,11].
2. Quan um do s usage
2.1. The main c i e ia o using QDs in Medicine
Un o una ely, mos QDs a e oxic, which implies a po en ial dange , especially o u u e medical
applica ions. The mos widely used and s udied QDs consis o a co e o cadmium selenide o ellu ide,
because hei quan um con inemen egion spans he en i e op ical spec um [12]. Walling and
colleagues epo ed in hei e iew on in i o QDs applica ion ha cadmium ions we e de e mined as
he p ima y cause o cy o oxici y, because hey a e able o bind o hiol g oups on c i ical molecules in
he mi ochond ia and cause enough s ess and damage o cause signi ican cell dea h [13]. Howe e he
elease o Cd2+ could be educed o elimina ed by adding addi ional su ace coa ings. Scien is s in
I eland ha e been using gela in du ing he p oduc ion o CdTe QDs, he eby educing he oxici y o
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he pa icles [14]. In o he case, Qian e al. used as s abilize he ipep ide glu a hione, which exis s in
mos o ganisms and hus can be applied o de oxi y Cd2+ ions in Medicine due o i s chela ing
capabili y [15]. Iye e al. epo ed ha pep ides could be used as an excellen ligand o coa ing he
su ace o QDs o se e al easons: 1) pep ides mimic he biological en i onmen and a e s able a
physiological pH; 2) eac i e g oups (amines, ca boxyl, hiol, and pep ide ags) can be dialed in o he
hyd ophilic domain o he pep ide sequence and enable enzyma ic o s anda d conjuga ion chemis y
o ob ain biomolecules o in e es ; 3) molecula e olu ion s a egies o andomize pep ides can be
adap ed o selec high-a ini y binde s o he QD su ace; and 4) he e is he possibili y o c ea ing
mul i unc ional QDs by mixing pep ide sequences in ce ain mola a ios in a single s ep o in i o
and in i o s udies (e.g., a QD wi h bio in and PEG, conjuga ing ecep o ligand and PEG, e c.) [16].
In o he wo ds, su ace unc ionaliza ion plays he key ole in nanopa icle oxici y. I was ound he
imp o ed biocompa ibili y ha ce ain su ace coa ings p o ide could a ise om dec eased cellula
up ake o hese nanopa icles o cellula deg ada ion [17]. Acco ding a e iew o Ha dman, QD
abso p ion, dis ibu ion, me abolism, exc e ion and oxici y depend on mul iple ac o s de i ed om
bo h inhe en physico-chemical p ope ies and en i onmen al condi ions; QD size, cha ge,
concen a ion, ou e coa ing bioac i i y (capping ma e ial and unc ional g oups), and oxida i e,
pho oly ic, and mechanical s abili y ha e each been implica ed as de e mining ac o s in QD oxici y
[18]. I his oxici y p oblem could be add essed, QDs migh one day be sa ely used as luo escen
p obes o biological imaging, o moni o a ge ed d ug deli e y and o con olled modi ica ion o
s uc u al and unc ional p ope ies o in acellula componen s. An in e es ing s udy in his ield was
pe o med by Choi and colleagues, who examined he epigenomic and geno oxic esponse o cadmium
ellu ide QDs in human b eas ca cinoma cells [19]. They sugges h ee le els o nanopa icle-induced
cellula changes: non-genomic, genomic and epigene ic. Epigene ic changes may ha e long- e m
e ec s on gene exp ession p og amming long a e he ini ial signal has been emo ed, and i hese
changes emain unde ec ed, i could lead o long- e m un owa d e ec s in biological sys ems.
Acco ding o many s udies, sho - e m (acu e) and long- e m oxici y o QDs is an impo an issue
o QD applica ions in bio sys ems; no only a he cellula le el, bu also in animal models [20-22].
Cell dea h caused by cadmium ion elease is no he only ype o oxici y exhibi ed by nanopa icles.
Quan um do s can also damage DNA and dis up no mal cell ac i i y caused by ac o s such as he
su ace coa ings hemsel es [13]. Geys e al. de e mined he acu e in i o oxici y o QDs wi h
ca boxyl and amine su ace coa ings du ing in es iga ion o he in lamma o y p ope ies, issue
dis ibu ion, and p o h ombo ic e ec s a e in a enous injec ion in o mice [23]. Yong demons a ed
ha doping o QDs by manganese and hei subsequen su ace unc ionaliza ion wi h lysine makes
hem s ably dispe se in aqueous media and mo eo e hese QDs, emi ing in he nea -in a ed (NIR),
e eals no long- e m oxic e ec s when injec ed o mice body [24]. The e o e he supposed hese
mul imodal Mn-doped QDs ha e po en ial as p obes o ea ly panc ea ic cance imaging and de ec ion.
Chen and colleagues obse ed he iabili y, li espan, beha io and heal h o he mice a e in a enous
injec ion o hiol-capped CdHgTe QDs o h ee mon hs [25]. They ound ha injec ion o 2 μg/g
CdTeHg QDs did no exhibi signi ican oxici y, and no abno mal beha io o he mice was obse ed
in any o he in i o imaging expe imen s. Ne e heless, a key ques ion is s ill open: whe he QDs can
be used di ec ly in clinical phase s udies? Consequen ly in eg a ed cellula oxici y s udies and he
comple e in i o oxicology o QDs s ill need o be e alua ed be o e hei use in human applica ions.
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The o he impo an c i e ia o QDs using in medicine a e p e en ion o nanopa icle agg ega ion
in a biological en i onmen and e ec i e supp ession o non-speci ic adso p ion o biomolecules a he
nanopa icle su ace. The insu icien colloidal s abili y can be imp o ed by unc ionaliza ion o QDs
su ace wi h hyd ophilic polyme s such as PEG [26] o wi h adso bed pep ides [27]. Con enien ly, he
long- e m s abili y o QDs can be imp o ed by s o ing hem in lyophilized composi ion, in he absence
o ligh and a educed empe a u e (e.g. a 4 °C) [28].
In con as o o ganic luo opho es, QDs ha e some unique pho ophysical p ope ies. They ha e
a con inuous abso p ion spec um o wa eleng hs sho e han he wa eleng h o luo escence
emission. QDs can be syn hesized o be e ec i ely monodispe sed which is a cause ha hei emission
spec a a e qui e na ow and symme ic, and do no show any ed- ail. In his way many di e en
colo s can be exci ed wi h jus one wa eleng h o exci a ion and can be spec ally well esol ed [29].
Fo example, Liu and colleagues employed adi ionally used luo escence esonance ene gy ans e
echnique (FRET) o s udy he molecula in e ac ion be ween an an ibody and immunoglobulin G
(IgG) on li e cell memb anes using QDs o wo di e en colo s, g een and ed, which we e used as
FRET dono s and accep o s, espec i ely, a he same ime wi hou o ganic dyes being in ol ed [30].
The do s a e claimed o be 20 imes as b igh and 100 imes as s able agains pho obleaching, when
compa ed o con en ional luo opho es [31].
Howe e he e a e wo disad an ages in compa ison o classic luo escen dyes. The i s nega i e
poin o QDs is he lack o s ong pola iza ion o he emi ed pho ons, mainly in he case o elonga ed
QDs, also called nano ods [32]. The second sho coming is hei insolubili y in wa e . This insolubili y
is gene ally caused by he use o o ganic sol en s (e.g. ioc ylphosphine oxide, TOPO) o hei
p epa a ion and hence by he p esence o hyd ophobic molecules. This p oblem can be sol ed by
embedding o QDs in o a shell (e.g. silica) o s able su ac an laye .
As i is known, he pho oac i a ion o he semiconduc o nanopa icles is highly a ec ed by se e al
pa ame e s. Dembski and colleagues ha e sys ema ically in es iga ed he ole o hose pa ame e s on
he pho on-induced pho oluminescence enhancemen o CdSe/ZnS QDs embedded in silica colloids
(mul ico e pa icles) and polyme -s abilized CdSe/ZnS QDs in a ious en i onmen s [33]. The s udied
pa ame e s included he local en i onmen o he QDs (polyme shell o silica ma ix), he hickness o
he ou e silica shell o he mul ico e pa icles, he dispe sion medium, as well as he wa eleng h and
in ensi y o he inciden adia ion. Zhang e al. also ound he pho oluminescence li e ime o
in acellula hiol-capped CdTe QDs a ied g ea ly depending on he in acellula en i onmen : in he
acidic lysosomes (wi h a pH o a ound 4.5–5.0) was ema kably sho e han hose in o he pa s o he
cell [34]. On he o he hand, he pho oluminescence li e imes o QDs in li ing cells we e gene ally
sho e han hose in aqueous solu ions wi h simila pH. The e o e he acidic en i onmen and he
in e ac ions o QDs wi h biomolecules a e wo o he possible easons o he sho ening o
pho oluminescence li e imes o in acellula QDs. I is also known ha he II-IV semiconduc o QDs
pho oluminescence depends on empe a u e: as he empe a u e inc eases, he pho oluminescence peak
o QDs edshi s. Despi e his ac , Zheng´s g oup obse ed ha in he empe a u e ange o 120–
300 K, he pho oluminescence peak o CdSe QDs ini ially blue-shi s and hen ed-shi s wi h
inc easing empe a u e a ising om he he mally ac i a ed de apping o ca ie s [35].
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2.2. Some impo an applica ions o QDs
Conce ning he biological applica ions o QDs, wo main g oups may be ci ed: biosenso s and labels
in biological imaging. A ew examples o each g oup can be seen on he schema below (Figu e 1).
Figu e 1. Examples o QDs’ bioanaly ical and biomedical applica ions.
QDs a e excellen candida es o biosensing owing o hei unique physical and op ical p ope ies
and possibili y o a aching a ious biomolecules o hei su ace [36]. Some new assays o QDs’
usage, which can imp o e he cu en me hods o DNA and p o ein de ec ion, we e pe o med [37, 38].
Fo example, a de ec ion me hod o adenosine- iphospha e (ATP) using a QD agged ap ame (nucleic
acids ha bind o ce ain molecula a ge s such as h ombin, adenosine, o cocaine) has been
desc ibed [39].
Mos biomolecules ha e been linked o wa e -soluble QDs and i was ound he binding has no
e ec ei he on he QDs’ op ical signa u e o on he unc ionali y o he biomolecules. Biomolecules
can be bound o he su ace o QDs ei he di ec ly (co alen ly o non-co alen ly) o a ached ia
a s abilizing laye which ac as a c osslinke be ween he ligand and eac i e su ace o he
nanopa icle. Non-co alen di ec binding can be achie ed by applying o elec os a ic-based coupling
s a egy. Compa ed o he con en ional co alen echniques, he elec os a ic non-co alen sel -
assembly app oach is simple , mo e ep oducible, and mo e easily achie ed [40]. This app oach has
been used o example o bind cys eamine-s abilized CdTe QDs wi h single s anded DNA h ough
elec os a ic a ac ion be ween posi i e amino unc ion g oups on he su ace o CdTe quan um do s
and nega i ely cha ged DNA [41].
The co alen bioconjuga ion app oach is based on he eplacemen o hiol acids p esen on he
QDs’ su ace wi h hiola ed biomolecules. This ype o binding was chosen, o example, o co alen ly
link s ep a idin maleimide [42] o o conjuga ed ans e in and mouse an i-human CD71 monoclonal
an ibody o CdSe/ZnS QDs [43]. Use o wa e -soluble 1-e hyl-3(3-dime hylaminop opyl) ca bodi-
imide hyd ochlo ide (EDC) and N-hyd oxysul osuccinimide (NHS) o o m he QD-p o ein co alen
conjuga es is one o he mos equen coupling me hods. The esea ch g oup o Wang de e mined ha
3-me cap op opyl acid-s abilized wa e -soluble CdTe nanopa icles syn hesized in aqueous solu ion
we e able o conjuga e wi h pep ides o p o eins media ed by NHS [44]. These s able QDs
pep ides/p o ein conjuga es can p o ide g ea po en ial powe in cell labeling applica ion.

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In hese applica ions, co e-shell s uc u ed QDs a e mo e a o able, whe e CdSe is e e ed o a
co e and ZnS o a shell [45-47]. The dimension o he co e de e mines he bandgap and hence he colo
o emission. I is known, ha an inc ease in pa icle sizes p oduces a edshi in he emission spec um
[48]. In p inciple, he emission o QDs can be coa se- uned by he choice o he ma e ial and la e ine-
uned by playing wi h he size o he co e (see Figu e 2). The emission colo can be also uned om
he UV/blue spec al egion (ZnSe) o he isible one (CdSe) by changing he composi ion, ha is, he
Cd:Zn a io, wi hou changing he nanoc ys al size [49]. Many co e-shell QDs ha e been p epa ed by
capping an emissi e semiconduc o co e (CdSe, CdTe, e c.) wi h a hin shell o a highe band gap
ma e ial (ZnS, CdS, ZnSe, e c.) [50-52]. Fo example, he co e-shell CdSe/ZnS a e abou 20–50×
b igh e han CdSe co es and hei quan um yield can each 30–50%.
Figu e 2. An example o QDs so ed by size emi ing ligh o di e en colo s exci ed
simul aneously by a single exci a ion wa eleng h.
The e a e se e al possibili ies o using QDs in biolabeling and cellula imaging bo h in i o and in
i o. Scien is s ha e de eloped hyb id unc ionalized QDs-liposome nanopa icles and ound hey
we e e icien ly up aken by li ing cells in he absence o cell dea h and can he e o e be used as
luo escen p obes o ex i o cell-labeling s udies wi h mos ypes o wa e -soluble QD wi hou
u he modi ica ions [53]. Mo eo e , hese QDs exhibi ed enhanced pene a ion and e en ion in o he
umo in e s i ium bo h in i o ( umo sphe oids) and in i o (subcu aneous solid umo s). Pan and
colleagues e alua ed in i o QDs loaded in poly(lac ide)- i amin E TPGS (d-α- ocophe yl
polye hylene glycol 1000 succina e) nanopa icles o cellula and molecula imaging [54]. Ke man e
al. s udied an applica ion o QD-labeled biomolecules in a sandwich- ype immunoassay o de ec ion
o o al p os a e-speci ic an igen (TPSA), which is an impo an cance ma ke , on a sc een-p in ed
ca bon subs a e in connec ion wi h luo escence imaging [55]. Simila QD-label-based
elec ochemical immunoassay s udy o PSA was pe o med by Wang and colleagues [56].
QDs can be applied in molecule acking in immunochemis y, whe e hey eplace he luo escen
beads used o he s udy o he dynamics o neu o ansmi e ecep o s. Due o hei much smalle size
(abou 10–20 nm) compa ed o la ex beads (app ox. 500 nm), he la e al mo emen o indi idual
ecep o can be s udied in g ea de ail [57]. Ano he example o an applica ion o QDs is in gene ic
disease sc eening and diagnos ics, whe e in combina ion wi h s age-scanning con ocal mic oscopy
p o ide he imaging o QDs ee o ch oma ic abe a ions and wi h esolu ion be e han 10 nm [58,
59]. In a ed QDs we e also ound o be use ul p obes o non-in asi e de ec ion in i o, mainly inside
small animals, whe e hey can subs i u e con en ional o ganic luo opho es emi ing in he IR, which
su e om poo s abili y and quan um yield [25, 60, 61]. Lin e al. e alua ed in i o mul iplex
imaging o mouse emb yonic s em (ES) cells labeled wi h pep ide-based Q acke deli e ed QDs [62]
(see Figu e 3.). They show ha labeling mouse ES cells wi h QDs does no ad e sely a ec ES cell
iabili y, p oli e a ion, and di e en ia ion.
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Figu e 3. Emb yonic s em cells labeled wi h six di e en QDs we e subcu aneously
injec ed on he back o he a hymic nude mice igh a e labeling (image aken wi h
a single exci a ion ligh sou ce igh a e injec ion). Rep in ed wi h pe mission om [62].
Fu he u ili y o QDs ha e been ound in labeling o nucleus in li e cells, howe e his issue has
no been no ully s udied [63]. Fo example, Chen and Ge ion obse ed, ha he i al pep ides called
nuclea localiza ion signals conjuga ed wi h CdSe/ZnS QDs has no oxici y e ec in HeLa cells
ans ec ed wi h he pep ide-coa ed QDs [64].
Lieleg and collegues ha e de eloped a me hod o speci ic labeling o memb ane in eg ins in li ing
os eoblas cells using unc ionalized QDs [65]. They used cyclic A g-Gly-Asp (RGD) ipep ide
sequence and a bio in–s ep a idin linkage o speci ically couple indi idual QDs o in eg ins o li ing
cells. Howe e , hey no iced a d as ic dec ease in he o al numbe o blinking QDs du ing
obse a ion. Fo una ely, acco ding o he simula ions, he blinking p ope ies o QDs do no ha m he
quan i a i e e alua ion o he ob ained in eg in ajec o ies.
I has been p o en ha QDs can se e as luminescen cell ma ke s ha iden i y molecula
s uc u es. Gene ally, e ec i e mul icolo cell labeling using QDs can be achie ed ia ecep o -
media ed up ake o ia nonspeci ic endocy osis which in okes na i e cellula mechanisms o ans e
nanopa icles h ough he cell memb ane. Hence endocy osis is conside ed o be he leas dis up i e
deli e y me hod compa ed o con en ional me hods such as mic ocapilla y injec ion o
elec opo a ion, which a e based on inse ing he nanopa icle ca goes ia mic oscopic mechanical
de ec s in he cell memb ane [66].
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3. Quan um do p epa a ion and cha ac e iza ion
3.1. QD p epa a ion
Two gene al app oaches o he p epa a ion o QDs ha e been epo ed o e he las decade: (1)
o ma ion o nanosized semiconduc o pa icles h ough colloidal chemis y [67,68] and (2) epi axial
g ow h and/o nanoscale pa e ning [69, 70], i.e.. employing li hog aphy-based echnology. The o me
QD syn hesis elies on apid injec ion o semiconduc o p ecu so s in o ho and igo ously s i ed
speci ic o ganic sol en s con aining molecules ha can coo dina e wi h he su ace o he p ecipi a ed
QD pa icles. This syn he ic ou e seems o be acile and can be pe o med in “one-po ” as e e ed in
many pape s [15,71-73]. QDs designed o usage in biological sys ems a e mos ly applied in solu ion
(colloidal o m); ne e heless a demand o QDs deposi ed on a ious solid su aces o biomedical
applica ions was also emphasized in some pape s [69,74]. Fo example, an al e na i e and p omising
s a egy o he use o QDs in bio echnological applica ions is o u ilize bio unc ional ca ie sphe es
ha a e labeled wi h QDs [75].
As men ioned be o e, QDs need o be wa e -soluble. The e o e nume ous e ec i e me hods ha e
been de eloped o c ea ing hyd ophilic QDs, which can be di ided in o wo main ca ego ies [66, 76].
The i s ou e is commonly designa ed as “cap exchange”. The hyd ophobic laye o o ganic sol en
can be eplaced wi h bi unc ional molecules con aining a so acidic g oup (usually a hiol, e.g. sodium
hiolycola e) and hyd ophilic g oups ( o example ca boxylic o aminic g oups) which poin ou wa ds
om he QDs su aces owa ds bulk wa e molecules [77-79]. In ac , subs i u ion o mono hiols by
poly hiols o phosphines usually imp o es s abili y. The second ou e is na i e su ace modi ica ion,
o example, adding o a silica shell o he nanopa icles by using a silica p ecu so (usually
alkoxysilanes such as e ae hylo hosilica e, TEOS) du ing he polycondensa ion [80]. Amo phous
silica shells can be u he unc ionalized wi h o he molecules o polyme s. Ano he example can be
in oducing o amphiphilic molecule, such as a phospholipid. This p ocedu e is p e e ed o
comme cially-p oduced biocompa ible QDs. The me hod o QD encapsula ion in o solid lipid
nanopa icles, which a e composed o high biocompa ible lipids o physical and chemical long- e m
s abili y, was also success ully es ed [81]. These lipid nanopa icles a e mo e con enien han small
molecules (e.g. me cap op opionic acid) adi ionally used o QDs su ace modi ica ion, which a e
a he uns able since hey can be easily deg aded by hyd olysis o oxida ion o he capping ligand. To
make wa e -soluble QDs, Zhang e al. employed icopolyme coa ing wi h he oil in a wa e ul asonic
emulsi ica ion me hod, and demons a ed he binding assays based on QD–an ibody bioconjuga es
[82]. Ul asonica ion will accele a e e apo a ion o he o ganic solu ion (in his case dichlo ome hane),
which will sho en he p epa a ion ime.
The la e app oach o QD p epa a ion, li hog aphy based echnology, is widely used o p o ide
QDs p edominan ly by he combina ion o high- esolu ion elec on beam li hog aphy and subsequen
e ching [10,83]. Howe e , i was ound he spa ial esolu ion equi ed o eaching he size egime,
whe e signi ican quan iza ion e ec s can be expec ed ends o be la ge han he desi able le el. In
addi ion, li hog aphic me hods and subsequen p ocessing o en p oduce con amina ion, de ec
o ma ion, size non-uni o mi y, poo in e ace quali y, and e en damage o he bulk o he c ys al i sel
[84]. Finally, i was ound ha adi ional op–down pa e ning me hods like pho oli hog aphy and e-
In . J. Mol. Sci. 2009, 10
664
beam li hog aphy a e ime-consuming and expensi e p ocesses, he e o e he e is a demand o new
mo e sophis ica ed echniques o QDs ab ica ion [85]. One o hese echniques can be an epi axial
g ow h o nanos uc u es, which is gene ally desc ibed by 5 a ious modes. The ab ica ion o
epi axial QDs usually ollows he S anski-K as ano mode o g ow h on we ing laye wi h o ma ion
o cohe en islands (see Figu e 4). He e, no u he e ching p ocess is equi ed.
Figu e 4. Schema o sel -assembled quan um do s g ow h. Rep in ed wi h pe mission
om [86].
Epi axial me hod o QDs p epa a ion is widely used in op oelec onics (lase s, in a ed
pho ode ec o s) and nano echnologies. Howe e , in he nea u u e, i could be e y in e es ing and
p omising o use epi axially g own QDs in in si u biosensing, mainly due o he simplici y o de ec ion,
o example, as a senso a ay o mass sc eening. Thanks o his senso a angemen , whe e each
senso can be c ea ed om QDs emi ing ligh a di e en wa eleng hs, i could be possible o easily
de ec many di e en biomolecules a he same ime. Epi axial me hods can be classi ied acco ding o
phase o igin in o apo phase epi axy (VPE) o liquid phase epi axy (LPE). Al hough LPE is s ill
impo an , his echnique was used mos ly in pas cen u y o p epa e mic ome ic s uc u es. VPE can
be u he ca ego ized acco ding o eac ion ype in o chemical (CVD) o physical apo deposi ion
(PVD). Chemical deposi ion is in e es ing in iew o i s p ice, howe e he mos impo an and mos
widely used echnique in indus y is VPE om me alo ganic medium (MOVPE). Molecula beam
epi axy (MBE) is o he peculia PVD echnique and can be also classi ied in o solid sou ce MBE o
gas sou ce MBE (hyd ide o me alo ganic). Pe haps less well-known app oach o he g ow h o
nanos uc u es using MBE sys em is “d ople epi axy” [87]. He e liquid me al d ople s a e i s o med
as an in e media e g ow h s ep be o e being con e ed in o semiconduc o nanos uc u es.
Conce ning he QDs di ec pa e ning, sel -assembled monolaye s QDs can be coa ed ia
Langmui -Blodge echnique on o hyd ophobic–hyd ophilic pa e n gene a ed wi h employing o
pho oli og aphically p epa ed empla e [69].
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