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      Zirconia microbead-assisted ball milling
and BASD are now mainly used for the
formation of single-digit dentonated nanodiamonds
for research, in particular, for adsorption and delivery of insoluble
anti-cancer therapeutics. Both techniques needs the use of ?30 ?m
ZrO2 microbeads. In BASD, for example, the dense ZrO2
microbeads, propelled by the energy of cavitation, collide and crush nanodiamonds
 aggregates trapped in-between (figure
5). BASD yields the stable single-digit ND   col-loids 
upto 10 wt% concentration with up to 80% yield relative to the initial
ND mass. However, BASD, as well as ZrO2 microbead-assisted ball
milling have some disadvantages, such as
a high cost (ZrO2 microbeads are
expensive, special mills have to be designed for the process, separation of
microbeads from NDs is also costly) and difficult
to remove ZrO2 debris (harsh acid or base treatment is
required to dissolve ZrO2, which have negatively impacts on production safety and contributes to the cost
of the purified ND). On the other hand, if ZrO2 is not removed completely, then the presence of this
contaminant in uncontrolled quantities may negatively effect the prospects of
clinical approval for ND enabled theranostic platforms73. Thus, ZrO2 and similar ceramic contaminants may pose
a serious obstacle on the way to low-cost and safe ND therapeutics. On
the contrary, water-soluble dry media-assisted attritor milling and SAUD
utilize inexpensive, non-toxic, and non-contaminating crystalline milling media
such as sodium chloride or sucrose. Upon completion of the deg-gregation
process, the milling media can be easily washed out with water, providing a
remarkable advantage over a process containing insoluble ceramic beads.
However, during the dry media-assisted attritor milling, parts of the mill
contaminate nanodiamonds with Fe, Ni, and other components of steel, so it
required an extra purification step. Moreover, significantly
reducing the aggregate size from micrometer
scale down to 50–30 nm, dry media-assisted attritor
milling does not yield truly single-digit nanodiamonds unless the dispersion pH
is adjusted to ?11
upon completion of milling83,84. SAUD
uses ultrasonic power transport by a standard lab horn sonicator into suspensions
of different water-soluble crystalline media (e.g.,
sodium chloride, potassium chloride, sodium acetate, etc)
to yield single-digit nanodiamonds colloids without any pH adjustments (figure
5).

      Since no ZrO2 is used, SAUD
completely eliminates zirconia or any other difficult-to-remove
impurities in nanodiamonds85. The
mechanical action of salt crystals in SAUD is combined with formation of a corresponding salt of Na+,
K+, etc with COO? groups of nanodiamonds, thus
improving the stability of single-digit nanodiamonds colloid. In another
approach, hydrogen annealing of nanodiamonds at 800 °C–850
°C gives rise to deaggregated
hydrogen and –OH-terminated
nanodiamonds. These hydrogenated nanodiamonds show high colloidal stability in
water due to their high positive zetapotential86,87.

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