Biomedical Engineering Reference
In-Depth Information
infrared absorption angiography of a monkey's brain vasculature [45]. following
intra-arterial Icg injection, the brain was illuminated by a flash from a bright
lamp, and images were recorded on a Kodak ektachrome film with sensitivity
up to 900 nm. However, the method did not work with intravenous injections. In
the early 1970s, r. flower and B. Hochheimer at Johns Hopkins discovered the
NIr fluorescence of Icg that was especially strong in blood samples and that could
be visualized with night vision scopes or sensitive NIr films. In 1972, the first intra-
venously injected Icg fluorescence angiograms were produced. The early history
of these events and their following development are described in references
43 and 46.
following its success in ophthalmology, Icg was exploited in cancer diagnostics
in 1994 to delineate tumor margins [50]. To overcome the disadvantage of fast
clearance (half-life is 3.4 min in humans) and for better confinement in blood vessels,
Devoisselle with colleagues prepared Icg incorporated in liposomes [51]. expectedly,
a substantially longer residence time (>60 min) was achieved when administered to
rodents compared to the free dye.
The use of Icg was restricted to mostly simple formulations or direct injections of the
dye. lack of active functionalities precluded the use of Icg for labeling. a. Waggoner
from carnegie Mellon University addressed this problem by developing a set of cyanine
dyes including NIr dye cy7 with reactive functionalities such as NHS esters and isothio-
cyanate [47, 48]. cy7 commercialized by amersham (now ge Healthcare) became one
of the most utilized NIr dyes in the 1990s. In parallel, S. achilefu (then at Mallinckrodt,
Inc.) developed cypate, an activatable analog of Icg, with almost identical optical prop-
erties to Icg (molar absorptivity, quantum yield) [49]. Other reactive NIr dyes followed
[52], and the imaging using the dyes of conjugated to antibodies and small peptides has
been demonstrated
in vivo
in mouse models [53]. These functionalizable NIr dyes have
later become the dyes of choice for labeling many types of nanoparticles.
1.6.2
qds
The term “quantum dots” was coined by Mark reed (then at Texas Instruments) in
his paper published in 1988 [54]. The introduction of QDs started with the realization
that the optical properties of semiconductor particles were strongly dependent on
particle size due to the quantum confinement of the charge carriers in small spaces.
Thus, at a certain small size, the semiconductors could turn into bright emitters. a
theoretical framework for these size-dependent properties was first described by
brothers alexander and aleksei efros from Ioffe Institute in the USSr in 1982 [55].
Shortly after their publication, publications describing synthesis of QDs emerged
from several researchers. among them, l. Brus (from Bell labs) was awarded with
the first Kavli Prize in Nanoscience in 2008 for his pioneering efforts in this field
[56]. (The prize was actually shared with Sumio Iijima, of Meijo University in Japan,
for his discovery of carbon nanotubes—another prominent imaging agent—of which
its potential in imaging became recognized in the 2000s.)
for almost a decade, QDs with their low quantum yield and instability remained a
subject of interest chiefly among physicists and material scientists. Three steps toward
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