Biomedical Engineering Reference
In-Depth Information
2.2.2 Nanoparticle Agglomerates and Aggregates
Assemblages of nanoparticles are firmly attached at their faces by fusion, sinter-
ing, or growth. They form so-called aggregates that are not readily dispersed. The
specific surface area of an aggregate is smaller than that of the primary particles.
Agglomerates, on the other hand, are formed by particles that are loosely
attached by contact at their corners and edges and exhibit a surface area com-
parable to that of the particles. However, due to the large specific surface of
nanoparticles, even small electrostatic or van der Waals dispersion forces can
result in considerable agglomeration strength. Therefore, also agglomerates and
little interacting but geometrically entangled nanofibers can, in many cases,
not readily be dispersed. As described above, the two terms agglomerates and
aggregates are not synonymous; unfortunately they are not used consistently in
the literature [11].
In many cases, it is necessary to know not only the size of a particle but
also whether a nanoparticle is a primary particle or an agglomerate com-
posed of several primary ones. Agglomerates may, for example, show sig-
nificantly different biological effects because of reduced mobility, delayed
dissolution, and reduced clearance, etc. Since agglomeration generally is
a dynamic phenomenon, the question of nanoparticle agglomeration in
biological media may be a surprisingly complicated one. Agglomeration
forces strongly depend on the composition and properties of the immers-
ing medium. Whether agglomerates are detected in a nanoparticle ensemble
also critically depends on the sample preparation and measuring technique.
Electron microscopic techniques that allow reliable agglomeration analysis
typically require a drying preparation step that may cause agglomeration by
capillary forces during solvent evaporation. Cryogenic preparation for TEM
(Cryo-TEM) analysis, on the other hand, using shock-frozen samples, can give
valuable insights into the dispersion state of nanoparticles [12]. X-ray or light
scattering techniques are important for biological samples since they can be
directly applied to cell culture or biological liquids. In such media, numerous
agents affect the agglomeration or deagglomeration propensity of nanoparticles.
Surface-attaching biomolecules, such as proteins and glycoproteins, can show
surfactant effects that may, dependent on the system, both stabilize dispersions
or induce agglomeration. In any case, biomolecule coating of nanoparticles or
agglomerates can affect cell-membrane interactions. A deagglomeration of
nanoparticle assemblages in biological liquids may also be triggered by pH
change or enzymes. The agglomerate size of the test sample therefore has to be
determined under suspension conditions as similar as possible to the toxicity
testing conditions.
2.2.3 Nanoparticle Suspensions
As introduced, the problem of agglomeration is a fundamental one with
respect to the question of nanoparticle toxicity, as it is directly related to
