Historical Perspective on Nanoparticles in Imaging from 1895 to 2000 - Nanotechnology for Biomedical Imaging and Diagnostics - page 14

TOP-Se
TOPO-Cd

Shell growth
T = 220°C

Growth
T = 290°C

Nucleation
T = 320°C

figure 1.10 High-temperature synthesis of colloidal cdSe quantum dots. a cd precursor
is dissolved in the tri-n-octylphosphine oxide (TOPO)-coordinating solvent. Under continuous
stirring at high temperature (∼320°c), a Se precursor dissolved in tri-n-octylphosphine (TOP)
is injected into the flask, initiating nucleation of cdSe nanoparticles. The growth phase occurs
at lower temperature (to ∼ 290°c). When the desired size has been obtained, the solution is
cooled (∼220°c) to prevent further particle growth. a passivating layer of ZnS is deposited by
injection of zinc and sulfur precursors dissolved in TOP. Upon cooling to room temperature,
these core-shell QDs are isolated via precipitation. (Based on ref. [57].)

bioimaging applications have been made in following years. The first step was to
increase the brightness and stability of QDs with a protective layer. The synthesis
of such protected cdSe/ZnS QTs with tunable emission was developed by the
M. Bawendi group [57] and is shown in figure 1.10. The produced QDs were highly
fluorescent but only soluble in organic solvents such as toluene. Hence, another criti-
cal step toward biomedical applications was making the QDs hydrophilic. In 1998,
two groups led by P. alivisatos at Uc, Berkeley, and S. Nie at Indiana University,
Bloomington, independently demonstrated that QDs could be made water soluble and
could be conjugated with biological molecules [58, 59]. The final step toward in vivo
imaging was the development of QDs emitting above 700 nm. This step was intro-
duced only in 2004 in a joint publication from Bawendi and frangioni [60] and is part
of the new history of imaging nanoparticles.

1.6.3 nanoparticles as Photoacoustics contrast agents

One of the promising applications of optical nanoparticles is their utility as contrast
agents in photoacoustics. although the effect of photoacoustics or (optoacoustics) has
been demonstrated long time ago in 1880 with the pioneering work of alexander graham
Bell, photoacoustics became an imaging modality only recently. The early works by
Oraevsky et al . [61] and Kruger et al . [62] demonstrated the value of photoacoustic signal
in imaging of deep tissue in the early 1990s. Several years later, prolated metal nanoparti-
cles absorbing at 1064 nm were suggested as contrast agents by Oraevsky's group [63, 64].

1.7 ultrasound microbubble contrast agents (1970s-2000)

Technically, microbubbles are vehicles that exceed the size of nanoparticles with a
diameter in the 1-10 µm range. However, the recent trend of minimizing their size to
nanosized scales prompts us to cover microbubbles in this chapter.