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Breakthrough Directions of Scientific Research at MEPhI
MEPhI’s Section of the Scientific Session on
“Breakthrough directions of scientific research at MEPhI:
Development prospects within the Strategic Academic Units”
Volume 2018
Conference Paper
Highly Stable, Water-Soluble
CdSe/ZnS/CdS/ZnS Quantum Dots with
Additional SiOshell
D.O. Volodin1, S.V. Bozrova1, D.S. Dovzhenko1, M.A. Zvaigzne1, P.A. Linkov1,
G.O. Nifontova1, I.O. Petrova1, A.V. Sukhanova1,2, P.S. Samokhvalov1, and
I.R. Nabiev1,2
1Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow
Engineering Physics Institute), 115409 Moscow, Russian Federation
2Laboratoire de Recherche en Nanosciences, LRN-EA4682, Universite� de Reims Champagne-
Ardenne, 51100 Reims, France
Abstract
Quantum dots (QDs) are fluorescent nanocrystals extensively used today in research
and applications. They attract much interest due to the high photostability and
fluorescence quantum yields close to 100%. The best QDs are made by synthesis in
organic media, and they have to be transferred into aqueous solutions if biomedical
applications are concerned. An advanced method for rendering QDs water-soluble
is to coat them with hydrophilic SiO-layer. However, growing a silica shell with
a predetermined thickness is a problem, because uncertain values of the molar
extinction coefficients (ε) of core/shell QDs made it impossible to calculate precise
yields of the chemical reactions involved. Here we suggest an approach to solving this
problem by constructing the structural models of per se and silica-coated QDs followed
by measuring ε in a course of the QD synthesis, thus carrying out precise quantitative
reactions. Proceeding in such a way, we prepared the CdSe/ZnS/CdS/ZnS QDs with
the structure predicted by the model and coated by silica shell. Prepared QDs are
characterized by a narrow size distribution and the same fluorescence parameters as
the original QDs in the organic medium. Developed approach permitted efficient QDs
water-solubilisation and preparation of stable nanoparticles for plethora of biomedical
applications.
Keywords: Quantum dots, QD, silica shell, core-shell.
1. Introduction
The semiconductor nanocrystals called quantum dots (QDs) are used as fluorescent
labels in a growing number of practical biomedical applications and research. This
is related to their unique properties that give them advantages over organic dyes
How to cite this article:D.O. Volodin, S.V. Bozrova, D.S. Dovzhenko, M.A. Zvaigzne, P.A. Linkov, G.O. Nifontova, I.O. Petrova, A.V. Sukhanova, P.S.
Samokhvalov, and I.R. Nabiev, (2018), “Highly Stable, Water-Soluble CdSe/ZnS/CdS/ZnS Quantum Dots with Additional SiOshell” in MEPhI’s Section
of the Scientific Session on “Breakthrough directions of scientific research at MEPhI: Development prospects within the Strategic Academic Units”, KnE
Engineering, pages 449–456. DOI 10.18502/keg.v3i6.3026
Page 449
Corresponding Author:
I.R. Nabiev
igor.nabiev@univ-reims.fr
Received: 22 July 2018
Accepted: 9 September 2018
Published: 8 October 2018
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Breakthrough Directions of
Scientific Research at MEPhI
Conference Committee.
Breakthrough Directions of Scientific Research at MEPhI
traditionally used for this purpose. First, QDs are more photostable than organic flu-
orophores [1], which provides a more precise detection of a weak fluorescent signal
under the conditions of a long exposure or multiple accumulation. In addition, the use
of QDs widens the possible range of simultaneous detection of several biomarkers,
because QDs has narrow photoluminescence (PL) peaks with a half-width-at-half-
maximum of 20–35 nm. Furthermore, unlike organic dyes, QDs with different PL bands
can be excited with a single source in the blue spectral region. Finally, the PL quantum
yields of some QDs are almost as high as 100% [2].
The main obstacle for wider use of QDs in biomedical practice is that the best QDs, in
terms of their morphology and PL characteristics, are obtained by synthesis in organic
media, yielding nanocrystals with a hydrophobic surface. Since most biomedical appli-
cations deal with aqueous media, QDs used there should be made water-soluble by
means of special procedures, which often entail the side effects of decreased PL quan-
tum yield and/or nanoparticles colloidal stability.
Two methods of QD hydrophilization are commonly used. The first one deals with a
ligand exchange on the QD-surface thus replacing the original hydrophobic ligands with
their hydrophilic analogues, e.g., thioglycolic acid, dihydrolipoic acid, cysteine, or more
complex substances, bifunctional polyethylene glycol derivatives [3]. The advantage of
this method is that the modification is easy to carry out and control. A major drawback,
however, is that organic ligands are tethered to the QD surface by relatively weak or
labile disulfide (S–S) or ionic Zn-S bonds, which various external factors may break.
As a result, ligands may desorb and the colloids aggregate.
The other method is to coat the QDs with an additional hydrophilic shell of silica
(SiO) [4] to attain a more robust passivation of the surface. This approach would
prevent both the diffusion of toxic heavy metals from QD interior to the medium and
the loss of colloidal stability because of ligand desorption. In addition, SiOis low-toxic
and is widely used in medicine [5, 6]. However, obtaining the optimal combination
of the QD PL emission characteristics, colloidal stability, and capacity for penetrating
into cells requires strict control of the synthesized silica shell, which is usually difficult.
The main problem is that the precise amount of the core/shell (e.g., CdSe/ZnS) QDs in
the solution should be known to calculate the reactions, whereas the reference molar
extinction coefficients commonly used for this purpose have been reported only for
the CdSe cores [7, 8]. Application of the same values to CdSe/ZnS QDs leads to large
calculation errors and incorrect thicknesses of the shells grown.
In the present study, we demonstrate the growth of a SiOshell with predetermined
parameters on CdSe/ZnS/CdS/ZnS core/multishell (CdSe/MS) QDs [9]. The accuracy of
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the procedure is ensured by two main factors. First, the molar extinction coefficient of
a given QD sample is precisely measured during the synthesis of the original CdSe/MS
QDs. Second, structural models are constructed for the CdSe/MS QDs themselves and
the silica-coated QDs, which are used for precise calculation of the reactions. Devel-
oped procedure have been used to fabricate CdSe/MS/SiOQDs with an outer silica
shell of 5 nm. The results demonstrate the precision and accuracy of the calculations
and the possibility of obtaining stable, water-soluble QDs with a thin SiOshell.
2. Materials and Methods
2.1. Chemicals
Cadmium oxide (99.5%, powder), 2-ethylhexanoic acid (2-EHA, 99%), 1-octadecene
(ODE, technical grade, 90%), oleylamine (OLA, technical grade, 70%), hexadecylamine
(technical grade, 90%), trioctylamine (TOA, 98%), trioctylphisphine (TOP, technical
grade, 97%), selenium powder (powder, 100 mesh, 99.5%), zinc oxide (puriss, 99–
100%), thiourea (TU, ACS Reagent, 99%), triethylene glycol dimethyl ether (TEGDME,
99%), dioctyl sulfosuccinate sodium salt (AOT, 98%, powder), (3-aminopropyl)-
triethoxysilane (APTES, 98.0%), hexane (99%), sodium hydroxide (98%, pow-
der), tetraethoxysilane (TEOS, 99,0%), and ethanol (99.8%) were purchased from
Sigma-Aldrich. n-Hexadecylphosphonic acid (97%) was from PlasmaChem GmbH.
Methyl acetate (MeOAc, 99%) was from Acros Organics; methanol (99.5%) and
cyclohexane were purchased from the local supplier Ekos-1. All reagents were used
as received without purification. We used Milli-Q deionized water (18.2 MΩ cm) for
preparation of buffer solutions and dissolution of QDs.
2.2. Synthesis of CdSe/MS quantum dots
Synthesis of CdSe/MS “core/multishell” QDs with an emission peak at 610 nm was
performed as reported in Ref. [9]. Briefly, 3.5-nm CdSe cores were synthesized by
the hot injection method using n-hexadecylphosphonic acid as a capping ligand. After
isolation and purification of CdSe nanocrystals from a crude solution, an aliquot con-
taining 100 nmol of the core QDs was transferred into a shell-growth solution, and
alternating ZnS/CdS/ZnS monolayers were deposited using the SILAR technique [10].
After shell deposition was complete, the reaction mixture was cooled down to room
temperature, and an aliquot was taken to measure the molar extinction coefficient
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Breakthrough Directions of Scientific Research at MEPhI
(ε) of the core/multishell QDs. The ε value at the first exciton absorption peak was
calculated as
(1)
where Ais the absorbance at the first exciton absorption peak, Vand Vare the
reaction mixture volumes before and after deposition of the multishell, respectively, lis
the optical path (1 cm), and V and V are the volumes of the solvent used for dilution
of the aliquot and the aliquot itself, respectively. The measurement was performed in
triplicate to minimize the error resulting from the difficulty of taking an exact aliquot
of the viscous reaction solution.
2.3. Precise coating of CdSe/MS quantum dots with a SiOshell
The technique for growing the SiOshell, sketched in Figure 1, is based on the approach
reported in Ref. [4]. A 4.62 10 mol aliquot of the synthesized CdSe/MS QDs was
dissolved in 5 ml of cyclohexane, and 7.5 μl of MPTMS and 1.07 g of AOT preliminarily
dissolved in 12 ml of cyclohexane were added. The mixture was stirred at 1000 rpm
for 45 min. After that, 685 μl of TEOS was introduced dropwise, 230 μl of 0.02 M NaOH
(pH 9–10) was added, and the mixture was left for two days. At the next step, 60 μl of
APTES and 15 μl of 0.02 M NaOH were added, and the mixture was stirred at 930 rpm
for 1 h. Then, cyclohexane was distilled out, 50 ml of methanol and 50 ml of ethanol
were added, and, after stirring at 930 rpm for 10 min, the mixture was centrifuged at
3000 rpm. The pellet was dissolved in 50 ml of methanol, 40 mg of succindialdehyde
was added, and the mixture was stirred for 24 h. After that, it was centrifuged, the
pellet was dissolved in 40 ml of ethanol, the solution was stirred for 10 min and then
centrifuged again. The resultant pellet was dissolved in 25 ml of 0.01 M NaOH.
Figure 1: Schematics of the SiOshell growth.
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3. Results and Discussion
We used CdSe/ZnS/CdS/ZnS core/multishell QDs whose molar extinction coefficient
was measured during their synthesis in an organic medium. This allowed us to precisely
determine the number of QDs in the reaction mixture using the Beer–Lambert–Bouguer
law and, hence, to accurately calculate the silica shell growth reaction using TEOS
as a SiOprecursor. To calculate the necessary amounts of reagents at each step of
the synthesis, we constructed a structural model of a spherical quantum dot 6.5 nm
in diameter with a 5-nm silica shell. The model was used to precisely calculate the
amounts of the reagents (TEOS, MPTMS, APTES, and succinic anhydride) required for
modifying the QD surface. The amount of the TEOS silica precursor for growing a silica
shell of a specified thickness was calculated as
(2)
This equation was derived from the above geometrical considerations. Here, dand d
are the nanoparticle diameters before and after the silica shell growth, respectively;
ρand ρ are the SiOand TEOS densities, respectively; M and M are the
SiOand TEOS molar weights, respectively; and Nis the number of QDs introduced into
the reaction.
Figure 2: Hydrodynamic size distribution of silica-coated QDs.
The fabricated silica-coated QDs were analyzed by the dynamic light scattering
technique. Figure 2 shows the hydrodynamic size distribution of the CdSe/MS/SiO
nanoparticles in an aqueous medium. As seen from these data, we obtained a QD
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sample with a maximum at 18.17 nm and narrow size distribution. This value is well
agreed with the computational model predicting a diameter of 16.5 nm.
Figure 3 shows the absorption and PL spectra of the QDs before and after silica
coating. It is evident from these plots that the additional SiOshell did not substantially
modify the QD optical properties. However, it did cause some decrease in the PL
quantum yield, which was 60% before silica coating and 38.1% after it. In the course
of the shell growth, this change was visually discernible at the very first stage of the
reactions, when the alkaline catalyzer was added after the QD surface was treated
with MPTMS. Afterwards, as the SiOlayer was grown over MPTMS, the QD PL was
gradually restored.
Figure 3: The quantum dots (QDs) optical properties before and after silica coating.
Absorption and photolumineascence spectra of QDs are shown on the panel (a) and
(b), respectively.
We have further studied the morphology of the fabricated CdSe/MS/SiOQDs using
transmission electron microscopy (Figure 4). As seen in the microphotographs, the
particles were spherical, and each QD had a SiOshell, each shell containing only
one QD. It is seen, however, that the nanoparticles aggregated, forming cross-links.
We believe that this was because, first, the microphotographs were made long after
the SiOshell was grown and, second, the sample preparation for microscopy was
accompanied by strong etching of the SiOshell with the alkaline in which the QDs
were dissolved after the silica coating.
4. Conclusion
In this paper, we have demonstrated that a SiOshell of a predetermined thickness can
be grown over CdSe/ZnS/CdS/ZnS core-multishell QDs thus producing a water-soluble
nanoparticle with a known diameter. The synthesized water-soluble nanoparticles
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Figure 4: A transmission electron microscopic image of the silica-coated quantum dots.
have advanced PL properties, which remain basically unchanged after the silica coat-
ing. Suggested approach significantly extends the possible QDs biomedical applications
such as early tumor diagnosis and imaging through the highly sensitive multiplexed
fluorescent detection of cancer biomarkers.
Acknowledgments
This study was supported by the Ministry of Education and Science of the Russian
Federation, grant no. 14.587.21.0039 (ID RFMEFI58717X0039).
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