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Controlled Growth of Monodisperse Silica Spheres

in the Micron Size Range 1
Department of Radiation Biology and Biophysics, Medical School, University of Rochester,
New York 14620


Max-Planck-Institut fi~r experimentelle Medizin, GOttingen, Germany
Received August 3, 1967

A system of chemical reactions has been developed which permits the controlled
growth of spherical silica particles of uniform size by means of hydrolysis of alkyl
silicates and subsequent condensation of silicie acid in alcoholic solutions. Ammonia
is used as a morphological catalyst. Particle sizes obtained in suspension range from
less than 0.05 t, to 2 ~ in diameter.

In many experimental studies which in- and have been described in the literature
volve the use of colloidal suspensions of (2). However, no successful attempt has
matter in form of hydrosols and aerosols, it been made to generate monodisperse suspen-
would be desirable to have the suspended sions of silica particles. A commercial form
phase consisting of homogeneous particles of of highly disperse silica produced by com-
uniform shape and size. Such monodisperse bustion of silicon tetraehloride in a hydrogen
particulate suspensions offer many experi- torch (3) consists of primary silica spheres of
mental and theoretical advantages. They sizes below 0.1 u, but they are aggregated to
not only facilitate easy calibration proce- coarse and irregular clusters which cause a
dures for analytical equipment, but also very poorly defined state of suspension.
simplify data reduction, evaluation and in- The following investigation was made to
terpretation of experiments designed to elu- explore the possibilities of producing mono-
cidate physicoehemieal properties or physi- disperse suspensions of silica spheres in the
opathological effects of colloids and aerosols. colloidal size range. Such material can be
The results would no longer be biased by used in both hydrosol and aerosol studies.
parameters of size and shape distributions. It will be of particular interest to investi-
Some monodisperse suspensions of parti- gators in the medical field because of its
cles in the colloidal size range are available known eytotoxicity and inhalation hazard.
in form of spheres of organic high polymers The experiments were based on the fact
(1). In the aerosol field, they are primarily that silica particles can be produced by
used as model substances and for calibration chemical reaction of tetraesters of silicie
purposes. Generators producing monodis- acid (tetraalkyl silicates) with certain solu-
perse particle clouds from soluble or volatile tions. In 1956, Kolbe (4) described the
materials are used in various aerosol studies formation of silica particles by reacting
tetraethyl silicate in alcoholic solution with
I This paper is based in part on work performed water in the presence of certain bases. With
under contract with the U.S. Atomic Energy
Commission at the University of Rochester
very pure reactants he observed in several
Atomic Energy Project and has been assigned eases a slowly proceeding reaction leading
Publication No. UR-49-815. to the formation of uniform spherical silica

particles. In an attempt to duplicate these At the beginning of each series of tests,

findings, many of our experiments resulted pure alcohol or alcohol mixtures, saturated
in gel formation and only in a few cases did alcoholic ammonia solution, ammonium
the electron mierographs show particles of hydroxide, and water were mixed in Erlen-
ellipsoidal shape and a size range near meyer flasks with ground stoppers or in
0.08 t~. Then, a systematic study of the rubber sealed injection bottles in the de-
reaction parameters was made and after sired concentrations of ammonia and water.
some drastic changes of the experimental Actual ammonia contents were measured
conditions, quasi-monodisperse suspensions by withdrawing small samples and titrating
of silica spheres of sizes up to 2 ~ were with 1 N hydrochloric acid. Total water
finally obtained within less than an hour contents were computed by adding up the
and the reaction no longer required ex- fractional amounts introduced by the com-
tremely pure reactants. ponents. Subsequently the alkyl silicate was
added and the flasks were mounted either
EXPERIMENTAL on a shaker or in a water bath under ultra-
Reagents sonic vibration. Some tests were made
while the solution was agitated by a mag-
Methanol, ethanol, n-propanol and n-
netic stirrer. Either way of agitation was
butanol used as solvents were of analytic
effective and kept the particles in suspen-
reagent quality.
sion after they had formed.
Tetraesters of silieic acid (tetraalkyl
The total amount of solution in each test
silicates) were either supplied in technical
varied between 50 and 110 ml. One large
grade (methyl, ethyl) or prepared by react-
scale experiment with 2 liters of solution
ing silicon tetrachloride and alcohol (n-
gave the same result as a test with 80 ml of
propyl, n-butyl, wpentyl). All esters were
a solution containing the same concentra-
redistilled before used in the experiments.
tions of solutes.
Ammonia (anhydrous, 99.99%) from a
Except for the initial exploratory tests at
tank was passed through a drying column
low concentrations, the condensation reac-
filled with sodium hydroxide pellets and
tion generally started within 10 min. This
bubbled through the alcohol at OC. Con-
could easily be observed, because, after an
eentrations obtained were about 8 M in
invisible hydrolytic reaction forming silieie
methanol, 5 M in ethanol, 3 M in n-pro-
acid, the condensation of the supersaturated
panol, n-butanol and n-pentanol.
silieie acid was indicated by an increasing
Ammonium hydroxide, 26P~., U.S.P.,
opalescence of the mixture starting 1-5
was used as supplied. Titrations indicated
rain after adding the tetraalkyl silicate.
an ammonia concentration of 14.2 M.
After this initial phase, the transition to a
Instruments turbid white suspension occurred regularly
within a few more minutes.
Electron microscopes Zeiss E M 9 and As a standard procedure, samples for
Philips E M 100 B and partiee size analyzer electron microscopic investigation were
Zeiss TGZ 3 were used. taken after 120 min, although a series of
Procedures samples taken at different times from the
same test solution indicated that particles
Throughout the investigation, ammonia sometimes reach their final size after about
was used as the catalyst causing the forma- 15 min. All sampling for size determination
tion of spherical particles. In many cases, it was done by dipping electron microscopic
was applied by adding saturated alcoholic carrier grids covered with Formvar films
solutions of ammonia to the reaction vessel. into the suspension, subsequently putting
In other cases, particularly when high them on filter paper to remove excessive
ammonia concentrations were desired, satu- solution from the grid, and taking electron
rated ammonium hydroxide solution was mierographs of the particles retained on the
used and the water content was taken into fihn.
account. Random mierographs of the samples tom-

prising between 100 and 1000 particles were in logarithmic size increments and plotted
evaluated by means of a semiautomatic on log-probability paper. The median pro-
particle size analyzer. The cumulative dis- jected diameter and, in some cases, the
tribution curve of the particles was recorded approximate logarithmic standard deviation
were taken from the graph.
_~- .... _-~-~-~-~-~'-~'- ...... _ .... --i 1.0

For the different alcoholic solvents, reac-

-0.5 tion rates were fastest with methanol,
10 slowest with n-butanol. Likewise, final par-
titles sizes obtained under comparable con-
ditions were smallest in methanol and
~, o.s +% biggest in n-butanol. However, there was a
tendency toward wide size distributions
with the higher alcohols. Methanol-butanol
0~ ~0~1 mixtures in a ratio of 1:1 provided more
0 5 10 15 uniform big particles.
MOL/LITER H20 A similar relationship with regard to
FIG. 1. Final particle sizes as obtained by reaction rates and particle sizes was found
reacting 0.28 mole/liter of tetraethyl silicate with when comparing results with different
various concentrations of water and ammonia in alkyl silicates. Fastest reactions (less than
ethanol. 1 rain) and smallest sizes (less than 0.2 t~)

FIG. 2. Electron micrograph of a sample of silica spheres obtained in the ethanol-ethyl ester system.

.,' 17
! 999

moles/liter, while different ester concentra-
tions between 0.02 and 0.50 mole/liter had
no significant influence on the particle size.
The three-coordinate graph in Fig. 1 repre-
MQ - 950 sents the general correlation between par-
~ D
900 title size, water, and ammonia concentra-
800 tion obtained with an ester concentration of
7oo 0.28 mole/liter. The actual particle sizes
- 500 observed varied between 0.05 and 0.90
and were uniform in each test. Figure 2
3o.o i shows an electron mierograph of a sample
- 20.0
from this series, and Fig. 3 indicates the
100 cumulative size distribution curve of the
5.0 same sample as plotted on log-probability
20 paper. The geometric standard deviation
05 derived from the graph is 1.04. This value
0 023 025 027 was quite typical for most of these tests. It
0.22 0.24 0.26 0.28 indicates that only 5% of the particles
differ from the median size by more than
Fro. 3. L o g - p r o b a b i l i W p l o t of the c u m u l a t i v e The generation of particles larger than 1
size distribution curve of the sample shown ]n could not be effeeted with the ethanol-ethyl
Fig. 2. ester system but required the use of esters
of higher alcohols. Various tests with these
esters indicated that, under comparable
were observed with tetramethyl ester, while conditions, the condensation reaction slowed
tetrapentyl ester reacted slowly (up to 24 down with increasing molecular weight of
hours for quantitative condensation) and the ester, while, at the same time, particles
produced big particles which, in n-propanol of larger size with a fair degree of uniformity
and n-butanol, reached sizes somewhat were produced. The reaction could be
scattered around 2 ~. More uniform par- further slowed down by using higher alco-
ticles were obtained in 1:3 mixtures of hols as solvents. In these cases, however,
methanol-n-propanol. the median particle size and the spread of
A systematic investigation of the influence the size distribution increased simultane-
of different concentrations of water, am- ously. Sometimes the samples also con-
monia and ester was made with the ethanol- tained two distinctly different particle sizes.
ethyl ester system. The condensation rate Thus, special precautions had to be taken
depends strongly upon the water content of to reduce these adverse effects. To achieve
the system. In the absence of ammonia, the this, isothermal conditions (22C) and
silica flocculated in irregularly shaped par- homogeneous particle suspension maintained
titles and no spheres could be observed during the reaction by gentle agitation
under the electron microscope. Thus, am- proved effective.
monia apparently influenced the morphol- An extensive investigation was made with
ogy, and created spherical particles when- tetrapentyl ester. Particles were grown
ever it was present during the reaction. An under various conditions by using different
increase in ammonia concentration (up to 8 component concentrations and several al-
moles/liter) under otherwise constant ex-
cohols or alcohol mixtures as solvents.
perimental conditions caused larger par-
ticle sizes. Accordingly, the largest spheres In the simple ethanol-pentyl ester system,
were obtained when the reaction mixture at ester concentrations sufficiently low
was saturated with ammonia. When the (< 0.2 mole/liter) to provide miscibility
water concentration under these conditions over the considered range of water concen-
was varied, maximum particle size was trations (< 10 moles/liter), the results
obtained at water concentrations around 6 resembled the pattern given in Fig. 1.

Within this range, the ester concentrations more prominent one is close to a log-normal
( > 0:03 mole/liter) again had little influ- distribution having a geometric standard
ence on the final size of the particles, but deviation of 1.08 and covering the upper
the particles obtained in these tests were size range. I t comprises about 93% of the
definitely bigger than those grown under particles. This result is quite typical for
comparable conditions from ethyl ester. most of the size distributions obtained in
The maximum values obtained for fairly tests designed to produce particles of sizes
uniform batches of particles were about bigger than 1 a.
1.5 ~ in diameter. The sample shown in Fig. At high pentyl ester concentrations, the
4 was grown from 0.2 mole/liter of pentyl ester formed a separate phase at the bottom
ester in a solvent saturated with ammonia of the reaction vessel, thus providing a
and containing 5 moles/liter of water. The substrate reservoir for the hydrolysis pro-
median particle size is 1.38 u as derived from ceeding in the upper phase. In this way,
the cumulative size distribution curve shown continued particle growth up to sizes 3 u in
as a log-probability graph in Fig. 5. This diameter was effected, but apparently, the
graph indicates that the sample consists of reservoir was also continuously supplying
two superimposed size distributions; the new condensation nuclei so that the particle

FIG. 4. Electron micrograph of a sample of silica spheres obtained in the ethanol-pentyl ester system.

999 sizes in the final dense suspension were no

longer a p p r o x i m a t e l y u n i f o r m . I n s t e a d , the
99o sizes were scattered in high c o u n t frequen-
%0 cies b e t w e e n values of 0.5 a n d 3 u. E m u l s i -
fying the ester d u r i n g the reaction b y vio-
s00 lent a g i t a t i o n did n o t significantly i m p r o v e
these results. Tests with higher alcohols or
5O0 their m i x t u r e s w i t h m e t h a n o l proved to be
t,.t more effective. While b u t a n o l gave particle
200 p o p u l a t i o n s of poor u n i f o r m i t y , the tests
with p r o p a n o l were satisfactory. M a x i m u m
.50 particle sizes were o b t a i n e d a t an o p t i m u m
w a t e r c o n t e n t of 5 m o l e s / l i t e r a n d at high
!2 c o n c e n t r a t i o n s of a m m o n i a a n d ester.
U n d e r these conditions, m e d i a n d i a m e t e r s
05 07 09 ]2 ]6 20 were observed b e t w e e n 1.5 a n d 2 ~. T h e
PARTICLESIZE IN y best growth of fairly u n i f o r m particles of 2
FIG. 5. Log-probability plot of the cumulative t* d i a m e t e r was facilitated b y using mix-
size distribution curve of the sample shown in tures of m e t h a n o l with b u t a n o I (1:1) a n d
Fig. 4. p r o p a n o l (1:3) as solvents. Yigure 6 shows

Components i 2 3

Final pH (~) ~eom 6a) ogeom 0z) Cgeom

10 ml pentyl ester; 10ml ammonium hydrox- 12.7 1.53 1.06 1.35 1.06 1.22 1.10
ide (sat.); 50 ml propanol saturated with
8 ml pentyI ester; 8 ml ammonium hydrox-
ide (sat.)
50 ml propanol-methanol (3:1) saturated 12.7 1.68 1.07 1.26 1.05 1.30 1.50
with NH3
50 ml propanol saturated with NH3 12.6 1.57 1.07 1.21 1.07 1.35 1.45
6 ml pentyl ester
6 ml ammonium hydroxide (sat.); 50 ml 11.8 1.10 1.07 0.42 1.03 0.99 1.09
5 ml ammonium hydroxide (sat.); 50 ml 11.6 0.57 1.06 0.64 1.14 0.42 1.06
4 ml ammonium hydroxide (sat.); 50 ml 11.4 0.60 1.03 0.63 1.08 0.64 1.10
propanol-methanol (3:1)
t ml pentyl ester
4 ml ammonium hydroxide (sat.); 50 ml 11.6 0.29 1.02 0.36 1.05 0.44 1.03
4 ml ammonium hydroxide (sat.); 50 ml 11.5 0.44 1.04 0.66 1.05 0.64 1.06
propanol-methanol (3:1)
3 ml ammonium hydroxide (sat.); 50 nil 11.4 0.25 1.08 0.25 1.06 0.27 1.12
2 ml ammonium hydroxide (sat.); 50 ml 11.3 0.05 1.07 0.08 1.05 0.08 1.05
2 ml ammonium hydroxide (sat.); 50 ml 11.2 0.11 1.06 0.17 1.07 0.20 1.06
propanol-methanol (3:1)

a typical sample as obtained from 0.28 smaller than indicated by a log-normal dis-
mole/liter tetrapentyl ester reacting with tribution relating to the median diameter of
4.5 moles/liter of water and 4.6 moles/liter 1.93 t~ and the geometric standard deviation
of ammonia in a propanol-methanol mixture of 1.07.
(3:1). The log-probability plot in Fig. 7 Finally, a series of experiments was made
shows that about 20 % of the particles are under conditions which may be used for

FIG. 6. Electron micrograph of silica spheres obtained by reacting tetrapentyl silicate with 4.5
moles/liter H20 and 4.6 moles/liter NHa in a 3:1 propanol-methanol mixture.

standard procedures in the production of arrangements and gives the final particle
silica spheres of predetermned size in the sizes obtained under these conditions in a
range of 0.05-2 ~ diameter. Table I lists the number of tests repeated on different days
components for 11 different experimental with different reagents. The results indicate
that the particle sizes are not precisely
99.5~ " 9R9 reproduced and, occasionally, an unusually
- 99.0 high standard deviation of the size distri-
bution is encountered. But, in general, a
~ - 95.0
uniform particle size is predictable from the
k; - 80.0 experimental conditions within a margin of
~} 70.0 about. 30% and the geometric standard
~ - 500 deviation of the size distribution remains
below 1.10.
~ 5.0

20 ~ 10 Phys. 26,864 (1955).

0.5 2. F~:CHS,N. A., ANDSUTLrGIN,A. G., f~ "Aerosol
0.1 Science" C. N. Davies, ed. pp. 1-27. Academic
0.7 09 12 16 20 24
Press, New York (1966).
FIG. 7.~Log-probability plot of the cumulative 72, 744 (1960).
size distributiml curve of the sample shown in 4. KOLBE, G., "Das komplexehemische Verhalten
Fig. 6. der Kiesels~ure," Dissertation, Jena (1956).