Biomedical Engineering Reference
In-Depth Information
NP and molecules
10 nm GNP
Liquid bilayer
Albumin protein
DNA
Tissue
Cell
1 mm
10 µm
100 nm GNP
100 nm GNP
10 nm
100 nm
FIGURE 18.4 Relative dimensions of interacting components, including tissue, cell, NP, and molecules. The size of NPs are comparable with
some macromolecules (lipid bilayer, albumin protein, DNA) but are much smaller than the cell and tissue.
(FDTD) (Myroshnychenko 2008, Schatz 2007) can be used to
estimate GNP optical properties. Experimental measurement of
NP-system optical properties rely on UV-vis-IR spectrophotom-
etry for optical extinction of ensemble NPs and electron micros-
copy (EM) for the geometry of single NPs. Combining theoretical
and experimental characterization methods, the absorption and
scattering properties are then obtained (Ungureanu 2010). While
one can use the traditional combinatorial approach, new devel-
opments using dark field scattering and photothermal imaging
to probe both the scattering and absorption directly at the single
NP level have been recently published (Tcherniak 2010).
For more detailed discussion of GNP optical properties, read-
ers are directed to the classic topic by Bohren and Hufman
(Bohren 1983) and several more recent reviews (Link 2000,
Myroshnychenko 2008). The chemistry and synthesis of GNP is
also discussed elsewhere and will not be discussed further here
(Burda 2005, Daniel 2004, Huang 2009, Yu 1997, Sau 2004). As
reviewed previously, the absorption cross section is a represen-
tative property that characterizes the light-to-heat conversion
within a GNP. The ensuing thermal response of NP-laden sys-
tems will be discussed next.
is important to have a sense of the length scales for detailed heat
transfer analysis. An NP is typically 10 to 100 nm in diameter.
When compared with typical biological systems as shown in Figure
18.4, NP size is comparable to macromolecules, such as proteins
and DNA, enabling a number of interesting nano-bio interfacing
applications (Nel 2009). On the other hand, an NP is more than 100
times smaller than a human cell (~10 μm), and over five orders of
magnitude smaller than a tumor (cm). Because of the large differ-
ences in length scales, the thermal responses are quite different in
terms of magnitude and time scale.
To illustrate the importance of scaling, we analyze the tem-
perature response of three biologically relevant situations, also
shown in Figure 18.4: (1) the heating of a single NP and its imme-
diate surrounding; (2) the heating of a single cell loaded with
GNPs; and (3) the heating of a tumor loaded with GNPs. The
question of how a single NP heats and affects its immediate sur-
rounding is the most fundamental question, with impact in all
three situations. In addition, single NP heating has some inter-
esting and unique applications in its own right, such as nano-
or molecular surgery (Csaki 2007) and photothermal imaging
of single GNPs beyond the diffraction limit (Boyer 2002). The
heating of a single cell loaded with GNPs is important for selec-
tive cell ablation, for example, detecting and treating circulating
tumor cells (Galanzha 2009). Finally, the heating of the entire
tumor loaded with GNPs (i.e., GNP photothermal surgery) leads
to thermal injury and subsequent tumor necrosis and regres-
sion, a topic of increasing clinical interest.
18.5 Laser GNp Effects I thermal
response at Multiple Scales
Having characterized the optical properties and laser fluence
along with the number of GNPs present, one can estimate the
SAR and temperature change by using the tools discussed ear-
lier. Alternatively, the temperature change can be measured
directly to estimate SAR. In either case the temperature rise in
the system is the desired effect. In this section, scaling of tem-
perature rise during GNP photothermal therapy at the single
NP, single cell, and tissue level are presented and discussed. The
concept of thermal confinement, , important in SAR estimation
and treatment planning, is then introduced.
18.5.2 thermal response of GNp Heating
18.5.2.1 Nanoscale Heating (t nano )
The heating of a single GNP and the interaction with its
immediate surroundings can be treated as the heat dissipa-
tion from a sphere to its surroundings medium (i.e., water in a
biological environment as shown in Figure 18.5a) (Goldenberg
1952). To justify the use of continuum theory for the analy-
sis, the mean free path for gold and water and the Knudsen
numbers for different length scales are listed in Tables 18.3
and 18.4 along with other thermal properties. The mean free
path of water is about 0.2 nm, which is two orders of magni-
tude smaller than the NP size (10~100 nm), so it can be safely
18.5.1 Heat Generation and Scaling
The light to heat conversion in a NP-impregnated system and
the resulting bulk temperature increase determines the outcome
of photothermal therapy. To analyze this process thermally, it
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