224 EARL W. FLOSDORF 



uct at temperatures below —30°, permitting the tissue to warm very 

 slowly from the freezing temperature to the dehydration temperature. 

 Paraffin was not used for embedding in microchemical studies. The 

 lower temperature by-passed the greatest objection to the technique 

 thus far for cytological studies by making the size of the ice crystals 

 smaller with rapid freezing so as to reduce the artifacts to below the 

 resolving power of the microscope. Thus we see that the entire trend 

 is one of lower and lower temperature for the product. 



In Scott's opinion (47) a dehydrating temperature of —20° does 

 not give particularly good results when one is interested in the elec- 

 trolytes found in tissues. The reason is, of course, that the eutectic 

 point of many of the salts normally found in tissue is considerably 

 lower than — 20°C. Consequently, it is impossible to keep them in a 

 salt-ice equilibrium at —20°. 



The theoretical temperatures of dehydration run as low as —54.9°. 

 Even lower temperatures would not be out of place. But for prac- 

 tical reasons it is very difficult to dehydrate tissues in these extremely 

 low temperature ranges. The vapor pressure of ice becomes very 

 low and an adequate pressure differential is difficult to obtain. The 

 dehydration is consequently slowed down tremendously. It would 

 take about six weeks or so to dehydrate 20 g. of ordinary tissue at 



— 65°C. Consequently, Scott (47) set a drying temperature of 



— 32.5° and states that this is not theoretically correct but that it is 

 practical and feasible. In general, Scott found that it gave excellent 

 results. 



3. Production Scale Processing 



Because of the larger quantities that must be handled on a produc- 

 tion scale basis, and in order to carry out freeze-drying at a commer- 

 cially economical cost, the equipment often is considerably complex. 

 Mechanical refrigeration for production of low temperatures is em- 

 ployed. The services of skilled mechanics as well as production 

 laboratory personnel are required. Many of the products are for 

 parenteral use and asepsis must be maintained, so that m^uch atten- 

 tion must be given to the handling of such products in a sterile 

 fashion. It is not always possible to carry on manipulations in a 

 closed system, therefore the workers must use surgical technique 

 with face masks and the other usual precautions. Filtered, dehumidi- 

 fied air should be circulated and sterile lamps widely distributed 

 around the working areas. 



