product. To avoid the freezing step and also limit the exposure time
of biologics to these hyper-osmotic environments, an energy deposition drying technology may provide a faster transition through
the moisture regimes where damage accumulates quickly. In this
chapter, we have focused on the potential of two energy disposition
technologies, namely, microwave and laser systems, to enhance the
rate and nature of solution densification for the purpose of anhydrous preservation of biologics.
Currently, there is no standard drying technology for ambient
dehydration processing of biologics. In early research, a range of
nonfreezing moisture removal techniques including air drying [6],
vacuum drying [7], and spray drying [8] have been used to dehydrate drying solutions containing mammalian cells and glassforming solutes such as trehalose. As water is removed from the
sample, the remaining solutes become concentrated, and as long as
the drying solution components do not crystallize, the viscosity
increases with progressive water loss until an amorphous solid is
achieved. Different drying methods produce different drying rates,
leading to dried samples with different end moisture contents and
distributions. Passive droplet drying mechanisms generally do not
yield a spatially uniform distribution of the solid phases. The higher
rates of evaporation on the surface result in extremely steep concentration gradients during passive drying, yielding a glassy skin on
the surface of the droplet. This glassy skin provides mechanical
resistance that indirectly affects evaporation rates by delaying and
sometimes stopping movement of water from the center of droplets. The presence of a wet center and dry peripheral region makes
the determination and predication of local moisture contents from
bulk gravimetric measurements extremely challenging and results
in unstable storage. Furthermore, when drying a droplet of
biological sample, such as a cell suspension, the biological material
can cluster within the central wet region [9]. This complicates
process development that aims to ensure prescribed moisture contents in the region of the biologic.
The challenge of inhomogeneous samples can be circumvented
by using energy deposition technologies like microwave or laser
systems that enhance diffusion and evaporation of water from the
interior of the sample via the delivery and deposition of energy to
yield faster and more predictable drying rates, as well as more
uniform samples, while avoiding thermal injury to the biological
material. The energy deposition enables rapid attainment of the
desired end moisture content of the sample. The end moisture
content drives many of the properties of the glassy state of the
preservation matrix, in particular the glass transition temperature
(T g ). The storage temperature generally needs to be maintained
below T g in order to retain the glassy state of the samples for longterm storage, and thus lower end moisture contents are necessary
for storage at higher temperatures.
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Shangping Wang et al.
of biologics to these hyper-osmotic environments, an energy deposition drying technology may provide a faster transition through
the moisture regimes where damage accumulates quickly. In this
chapter, we have focused on the potential of two energy disposition
technologies, namely, microwave and laser systems, to enhance the
rate and nature of solution densification for the purpose of anhydrous preservation of biologics.
Currently, there is no standard drying technology for ambient
dehydration processing of biologics. In early research, a range of
nonfreezing moisture removal techniques including air drying [6],
vacuum drying [7], and spray drying [8] have been used to dehydrate drying solutions containing mammalian cells and glassforming solutes such as trehalose. As water is removed from the
sample, the remaining solutes become concentrated, and as long as
the drying solution components do not crystallize, the viscosity
increases with progressive water loss until an amorphous solid is
achieved. Different drying methods produce different drying rates,
leading to dried samples with different end moisture contents and
distributions. Passive droplet drying mechanisms generally do not
yield a spatially uniform distribution of the solid phases. The higher
rates of evaporation on the surface result in extremely steep concentration gradients during passive drying, yielding a glassy skin on
the surface of the droplet. This glassy skin provides mechanical
resistance that indirectly affects evaporation rates by delaying and
sometimes stopping movement of water from the center of droplets. The presence of a wet center and dry peripheral region makes
the determination and predication of local moisture contents from
bulk gravimetric measurements extremely challenging and results
in unstable storage. Furthermore, when drying a droplet of
biological sample, such as a cell suspension, the biological material
can cluster within the central wet region [9]. This complicates
process development that aims to ensure prescribed moisture contents in the region of the biologic.
The challenge of inhomogeneous samples can be circumvented
by using energy deposition technologies like microwave or laser
systems that enhance diffusion and evaporation of water from the
interior of the sample via the delivery and deposition of energy to
yield faster and more predictable drying rates, as well as more
uniform samples, while avoiding thermal injury to the biological
material. The energy deposition enables rapid attainment of the
desired end moisture content of the sample. The end moisture
content drives many of the properties of the glassy state of the
preservation matrix, in particular the glass transition temperature
(T g ). The storage temperature generally needs to be maintained
below T g in order to retain the glassy state of the samples for longterm storage, and thus lower end moisture contents are necessary
for storage at higher temperatures.
204
Shangping Wang et al.