RESULTS AND DISCUSSION
Creating and uniformly distributing cryogenic ice fog
A key challenge for the commercial implementation of the ice-fog technique has been the creation of an ice fog that is sufficiently
dense and that can be efficiently distributed to reach all vials in a large-scale lyophilizer. Because of this low density,
not enough fog was available for all vials. Also absent in previous tests was an efficient system to distribute the ice fog
within the freezing chamber and drive it into the vials. The system used in the present study produced a very dense fog and
also distributed the fog throughout the freezing chamber within a short time (i.e., less than a minute). It is also possible,
through this design, to control the density of the ice fog.
Fog creation and distribution were aided by the ejector assembly. The ejector serves two purposes. First, it provides an extremely
efficient means for quickly forming the ice fog. Second, the suitably sized ejector provides enough pumping capacity to circulate
the ice fog throughout the freezing chamber rapidly. It is a significant advantage that the ejector can accomplish both of
these functions without introducing any moving parts or other complicated mechanisms that would be difficult to steam or otherwise
Achieving ice nucleation in all vials at desired temperature
Figures 3 and 4 show the temperature measurements obtained in control and ice fog experiments, respectively, as a function
of time. Ice nucleation was indicated at the point when the temperature of a vial increased sharply. This result is due to
release of the latent heat of fusion of the solution upon freezing.
For the control experiment, the first vial nucleated at a temperature of around –9 °C and the last vial nucleated at around
–18 °C (see Figure 3). About 20 minutes separated these two occurrences, and the remainder of the vials nucleated at various
times inbetween. This variation in ice nucleation time could increase in production-grade environments, where solutions may
be supercooled further due to the absence of any particulates or impurities in the atmosphere.
Based on the data from control experiments, a trigger vial temperature of –6 °C was selected as tg. The choice of this tg was conservative so that all vials were cooled below their freezing point. This choice was to ensure that absence of freezing
was a result of supercooling only, and not because a vial was at a temperature above the freezing point. Sometimes uneven
vial temperatures may occur in laboratory-scale lyophilizers because of nonuniform shelf cooling. In addition, the temperature
probes, except the trigger vial probe, measured the outside vial temperatures which might not reflect the solution temperature
inside the vial at all times. If all vials are cooled below their freezing point, ice fog can be introduced at a much higher
temperature below 0 °C.
Shelves were allowed to cool at a ramp rate of 0.5 °C/min, and the temperature of the trigger vial was constantly monitored.
When trigger vial temperature hit –6 °C, the ice fog was introduced. As seen in Figure 4, all vials nucleated at the same
instant following the introduction of ice fog. Both vial populations, pure water and glycine solution, nucleated at about
the same time on ice-fog introduction, indicating the general applicability of this technique for all supercooled solutions.
Figure 4: Temperature measurements obtained in ice-fog experiments as a function of time.