Abstract:
A method and apparatus for controlling the temperature of a freeze drying chamber shelves and chamber in a refrigeration system having a condenser operatively associated therewith using the circulation of a cryogen through the condenser and of a cryogenically cooled heat transfer fluid through the chamber shelves for controlling the temperature therein, and also where the temperature of the cryogenically cooled heat transfer fluid having been regulated by an exchange of heat with the cryogen.

Description:
FIELD OF THE INVENTION 
     This invention relates to freeze drying, and more particularly, to a method and apparatus for improving the precision and efficiency of freeze drying using a reduced amount of cryogen consumption. 
     BACKGROUND OF THE INVENTION 
     Cryogenic heat exchanger are attractive design alternatives from the standpoint that they do not use environmentally damaging refrigerants, but instead use a cryogenic heat transfer fluid such as a liquefied atmospheric gas. 
     Previous work in this area does not address the issue of making efficient use of cryogens. In many cases, the temperature and energy requirements of the cryogen and/or other coolant fluids, heat exchanging apparatuses and heat storage apparatuses do not match, thus causing inefficiencies in the freeze drying method and apparatus. 
     There has been an attempt to ensure the equal heat distribution in the water-ice condenser which leads to the freeze drying chamber. In U.S. Pat. No. 5,456,084 to Ron Lee, an attempt is provided for a cryogenic heat exchange system in which water-ice build-up on a condenser heat exchanger surface employed in the cryogenic heat exchanger system is more uniform as compared to that of the then prior art heat exchangers which utilize a cryogenic heat exchange fluid. In that sense, attempts were made to provide better control over the temperature in which the heat transfer using the cryogenic heat exchanger system takes place. 
     In U.S. application Ser. No. 08/709,027 filed Sep. 6, 1996 entitled “Method and Apparatus for Controlling Freeze Drying Process”, which is incorporated herein by reference, there is provided a method and process which utilizes a single heat exchanger, cooled by a cryogenic refrigerant, to deliver cold heat transfer fluid directly to a condenser and, independently, to a freeze dryer or other refrigeration system, either directly or through a heater circuit, for cooling or heating the freeze dryer. 
     Notwithstanding the above, there is a need in the art for a method and apparatus to refrigerate the chamber shelves and water condenser of a freeze drying chamber utilizing a dispensable cryogen (primarily liquid nitrogen) and to allow the exhaust/waste gas from the cryogen supply to exit from the system at the warmest temperature possible, while at the same time, accomplishing with minimal pumping energy thereby for completing each freeze drying cycle with minimal refrigeration cost. 
     OBJECTS OF THE INVENTION 
     It is therefore an object of the invention to provide a method for improving the matching of the condenser cooling demands with the low demands of the cryogenically cooled heat transfer fluid in the art. 
     Another object of this invention is to provide a method and apparatus to store excess refrigeration with the heat transfer fluid. 
     Yet another object of this invention is to provide a method and apparatus for supplying cryogen directly to vacuum condensers to achieve lower temperatures. 
     Another object of this invention is to provide a method and apparatus for recycling cold gas from the condensers for increased operating efficiency. 
     Another object of this invention is to provide a method and apparatus for condensing a refrigerant that does not require the mechanical compression and expansion. 
     SUMMARY OF THE INVENTION 
     As will be discussed hereinafter, the present invention provides a method and apparatus for improving the match of the condenser cooling demands with the varying demands of the cryogenically cooled heat transfer fluid to that which have been found in the art. This matching of cooling demands during a programmed freeze dry recipe provides a more efficient utilization of the cryogen. The freeze dry cycle process typically includes 1) temperature ramp-down; 2) temperature soak; 3) vacuum induction; and 4) temperature ramp-up. This process will contain heat loads that vary by factors of at least 2:1, and can most economically be handled by choosing the pump and heat exchanger combination that will best fit the heat load. The freeze chamber and shelves must operate at a warmer temperature than the condenser. Therefore, a heater is usually used even during the cool down cycle to form a second heat transfer fluid recirculating loop. Such a process produces a high energy waste. This invention avoids the use of a heater during the cool down cycle, thus improving the efficiency. This selection method prevents the physically larger equipment from operating when not needed, thereby preventing large static and dynamic heat leaks, and allowing the smaller pumps/heat exchangers to handle the smaller heat loads more precisely and efficiently. 
     This invention is directed to a method for controlling the temperature of freeze drying chamber shelves and chamber in a refrigeration system having a condenser operatively associated therewith. This is done by circulating a cryogen through the condenser and circulating a cryogenically cooled heat transfer fluid through the chamber shelves for controlling the temperature therein. The temperature of the cryogenically cooled heat transfer fluid is regulated by an exchange of heat with the cryogen. The temperature of the cryogenically cooled heat transfer fluid is regulated by the exchange of heat with the cryogen through a plurality of heat exchangers, and further by a heating unit. Circulation of the cryogenically cooled heat transfer fluid is accomplished by using a plurality of pumps and valves. At the beginning of a temperature ramp down cycle, the temperature of the heat transfer fluid is first regulated by passing the heat transfer fluid through a precooling medium. At the middle of the ramp down cycle, the temperature is then regulated by passing the cooled heat transfer fluid through a second heat exchanger cooled with a cryogen. A refrigeration recovery unit may be used to maintain the temperature and to recycle the cryogenically cooled heat transfer fluid. A liquid refrigerant may also pass through the condenser. 
     This invention is also directed to a method for freeze drying by providing a freeze drying chamber having a condenser operatively associated therewith, circulating a cryogen through the condenser, and circulating a cryogenically cooled heat transfer fluid through the chamber shelves for controlling the temperature therein. The temperature of the cryogenically cooled heat transfer fluid is regulated by an exchange of heat with the cryogen. 
     This invention is also directed to a freeze drying apparatus comprising a freeze drying chamber for subjecting substances to a freeze drying process in which moisture or solvent contained within the substances is frozen and sublimed into a vapor, a series of shelves within the chamber, a condenser operatively associated with the freezing chamber for freezing the vapor and for accumulating the vapor in solid form. The condenser has at least one pass for receiving a cryogen for freezing the vapor. A plurality of heat exchangers is used to exchange heat between the cryogen and a cryogenically cooled heat transfer fluid. A cryogenically cooled heat transfer fluid circuit in which the temperature of the cryogenically cooled heat transfer fluid is regulated by the plurality of heat exchangers, and in which the cryogenically cooled heat transfer fluid passes through the freeze drying chamber to freeze a substance by separating at least a portion of liquid therefrom. The cryogen circuit in which the cold of the cryogen is transferred to the cryogenically cooled heat transfer fluid through the heat exchangers and the cryogen is passed through the condenser. A plurality of valve means regulates the flow of the cryogen, and at least one circulation means for circulating the cryogenically cooled heat transfer fluid through the cryogen circuit. During the initial part of the temperature ramp down cycle, the temperature of the heat transfer fluid is regulated by transferring cold to the heat transfer fluid by a precooling medium. During the temperature ramp up cycle, the temperature of the heat transfer fluid is regulated by passing the heat transfer fluid through a heating unit. A waste refrigeration recovery unit may be used to maintain the temperature and to recycle the cryogenically cooled heat transfer fluid. A liquid refrigerant circuit for feeding the condenser may be used. 
     For purposes of this invention, the term cryogen as used herein and in the claim means a substance existing as a liquid or solid at temperatures below those normally found in ambient, atmospheric conditions. Examples of cryogens are liquefied atmospheric gases, for instance, nitrogen, oxygen, argon, helium, carbon dioxide, etc. 
     The term low boiling point (LBP) refrigerant means a substance existing as a gas or vapor with boiling point below those normally found in ambient, atmospheric conditions. However, the LBP refrigerant can be readily condensed into a liquid upon heat exchange with a cryogen. For the purpose of this invention, the LBP refrigerant is selected so that the boiling point is the same as the operating temperature of the condenser. Examples of LBP refrigerants used in this invention include chloroform (b.p. −63.5° C.), ethane (b.p. −88.6° C.), dichlorofluoride (b.p. −78.4° C.), monochlorotrifluromethane (b.p. −114.6° C.) and other fluids that condense readily by heat exchange with a cryogen without compression but boils off into a gas or vapor when losing their refrigeration values. An example of the liquid refrigerant used in this invention is monochlorotrifluromethane. 
     The term cryogenically cooled heat transfer fluid is a material that is capable of transferring heat to and/or from another source of differing temperature. This fluid may be commercially available under the name of D&#39;Limonene (available from Florida Chemical Co.), Lexsol (available from Santa Barbara Chemical Co.), or as silicone oil, a derivative of any of the above mentioned fluid, or other equally suitable fluid known to those skilled in the art. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Other objects, features and advantages will occur to those skilled in the art from the following description of preferred embodiments and the accompanying drawings, in which: 
     FIG. 1 is a schematic flow diagram illustrating the method and apparatus embodying the features of this invention; and 
     FIG. 2 is a schematic flow diagram illustrating the method and apparatus of FIG. 1 with the alternative embodiment of an additional refrigeration unit and the optional inclusion of a stream wherein a liquid refrigerant is passed through the condenser. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     This invention may be accomplished by a method and apparatus as described by the figures. 
     A unique feature in this invention is the use of multiple heat exchangers to handle the heating and cooling cycle requirements typical of the freeze dryer. The heat transfer fluid passes through multiple heat exchangers to achieve the most efficient use of the energy in controlling the temperature of the freeze drying shelves and chamber. 
     Another aspect of the invention as shown in the figures is the unique use of the cryogen. In one sense, the cryogen is used as directly in the condenser (cold trap). In another sense, the cryogen is used as a primary coolant in the heat exchangers for regulating the temperature of the heat transfer fluid. 
     Yet another aspect is the improved efficiency through the sequential operation of various components of this invention. The novel use of the heat exchangers as shown by the possibility for passing a variety of coolant through the heat exchangers as well as the novel nature of the cryogen flow paths provide efficient use of resources. 
     As provided in FIG. 2 below, it is shown that a storage for heat transfer fluid (a refrigeration recovery unit) may be used to recover waste refrigeration and store excess refrigerant to meet cyclic refrigeration/heating demands. 
     Also shown in FIG. 2 is the use of an alternate LBP refrigerant, such that the condensation and evaporation of the LBP refrigerant (subjected to heat exchange with the cryogen) alleviates the need for mechanical compression and expansion. 
     With reference to the flow diagram of FIG. 1, refrigeration system  10  is provided. Precooling liquid  20  is passed through the inlet of heat exchanger  52  to emerge from its outlet as warmer precooling liquid  22 . The precooling liquid may typically range from about 15° C. to about −40° C. Examples of precooling liquid may be a water cooler (in the temperature range of from about 15 20   C. to about 2° C.) and glycol chiller (in the temperature range of from about 2° C. to about −40° C.). 
     Cryogen  30  is initially split into streams  32  and  42 . Cryogen stream  42  passes through the inlet of heat exchanger  54  and emerges from its outlet as cryogen stream  44 . Cryogen stream  32  is split into cryogen streams  34  and  36 . 
     Cryogen stream  36  passes directly into the inlet of condenser (cold trap)  18  for cooling materials in the vapor phase to solid phase coming from the freezing chamber shelves  97  inside freezing chamber  16 . Emerging from the outlet of condenser  18  is cryogen stream  38 , which splits into cryogen streams  39  and  46 . Cryogen stream  46  may combine with cryogen stream  34  to form combined cryogen stream  48 , which is passed into the inlet of heat exchanger  56 . Cryogen stream  50  emerges from the outlet of heat exchanger  56  and combines with cryogen stream  44  forming combined cryogen stream  52 . Thereafter, cryogen streams  52  and  39  are combined to form combined cryogen stream  40 , which passed as gaseous cryogen stream  40 . 
     Cryogenically cooled heat transfer fluid stream  60  (the “cryogenically cooled heat transfer fluid” is hereinafter designated as “transfer fluid stream”) is passed through the inlet of three-way electrically operated modulating control valve  64  by the activation of fluid pump  12 . Transfer fluid streams  61  and  64  emerges from the outlets of three-way valve  63 . During the start of the temperature ramp down cycle, stream  60  can be as hot as 80° C. (due to steam sterilization procedure). The three-way valve will activate and allow transfer fluid stream  61  to pass through heat exchanger  52  to emerge the outlet therefrom as cooler transfer fluid stream  62 . When the temperature of the stream  60  reaches the range of 0° C. to −30° C., the three-way valve will activated again to allow only the other transfer fluid stream  64  to pass through the inlet of heat exchanger  54  emerging from the outlet as further cooled transfer fluid stream  65 . It is contemplated that heat exchanger  52  provides the means for cooling the transfer fluid stream in a temperature range of from about 60° C. to about −30° C., and heat exchanger  54  provides the means for cooling the transfer fluid stream in a temperature range of from about 0° C. to about −90° C. In practice, the choice of operating either or both heat exchanger depends on the temperature of the transfer fluid  60  and the temperature cycle of the freeze drying process. The three-way control valve  63  can switch the flow from stream  60  to stream  61  or alternatively from stream  60  to stream  64 . Cooled transfer fluid streams  62  and  64  are regulated alternatively to form fluid stream  66 . 
     Transfer fluid stream  70 , which had been partially recycled from freeze drying shelves  97  and chamber  16 , passes through the inlet of heat exchanger  56  by the activation means of pump  14 , to emerge through the outlet of heat exchanger  56  as transfer fluid stream  74 , which in turn passes through the inlet of heating unit  58  to emerge the outlet therefrom as transfer fluid stream  76 . The flow of heat transfer fluid streams  72 ,  74  and  76  is controlled primarily by the activation means of pump  14 . Heat is supplied to heating unit  58  only during the temperature ramp-up cycle. During this cycle, heating unit  58  and pump  14  completely regulate the temperature by which the heat transfer fluid passes through the freeze drying shelves  97  and chamber  16 . At this cycle, pump  12  will stop circulating the heat transfer fluid to the heat exchangers. During cool down cycle, heat transfer fluid streams  66  and  76  may combined to form heat transfer fluid stream  78  to direct to the inlet of the freeze drying shelves  97  and chamber  16  assembly. In practice, heat transfer fluid stream  78  passes through each of the freeze drying shelves  97  and chamber  16  to effectuate freeze drying of materials within freeze drying shelves  97  and chamber  16 . 
     Emerging from the outlet of freeze drying shelves  97  and chamber  17  is exhausted transfer fluid stream  80 , which in turn is separated into heat transfer fluid streams  70  and  82  for recycling. During the cool down and soak cycles, one of the transfer fluid stream  70  passes through the inlet of pump  14  to emerge through the outlet therefrom as transfer fluid stream  72  if pump  14  is activated. The other transfer fluid stream  82  passes through the inlet of pump  12  emerging from its outlet as transfer fluid stream  60 . 
     Any frozen volatile substance will be vaporized through sublimation under high vacuum and is passed out of the freeze drying chamber  16  as stream  90 . Emerging from the outlet of condenser  18  is the remaining waste stream  94  as it is drawn from vacuum pump  95 . Waste stream  96  that emerges from the outlet of vacuum pump  95  is removed. 
     In general, the operation of the refrigeration system involves the use of a cryogen stream which passes directly to a condenser. Heat transfer fluid is cooled in sequence with a pre-cooled media and than cryogenically by the cryogen through a plurality of heat exchanger means, passed into the freeze drying shelves and chamber, and is recycled. The system provides for a particularly effective use of the cryogen for cooling the temperature of the heat transfer fluid, thus requiring the minimal amount of cryogen necessary to cool the heat transfer fluid and freeze dry the substances in the freeze drying shelves and chamber. 
     Since the freeze chamber  16  and shelves  97  must operate at a warmer temperature than the condenser  18 , using the cryogen in the condenser  18  eliminate the need to turn on the heater  58  during the cooling cycle and to generate a separate heat transfer reciruclating loop. Therefore, the process is more efficient and less capital intensive. 
     Turning now to FIG. 2, there is shown an embodiment of system  210  wherein refrigeration recovery unit  245  is used to maintain the temperature and to recycle the heat transfer fluid. Also, a separate liquid LBP refrigerant system  298  provides a LBP refrigerant to pass through condenser  218 . 
     Precooling liquid  220  is passed through the inlet of heat exchanger  252  to emerge as warmer precooling liquid  222 . As discussed previously, precooling liquid  220  may be cooling water, glycol chiller or other similar liquid coolant for operation at a temperature of from about −40° C. 
     Cryogen  230  is initially split into streams  232  and  242 . Cryogen stream  242  passes through the inlet of heat exchanger  254  and emerges the outlet therefrom as cryogen stream  244 . Further, cryogen stream  232  is split into cryogen streams  234  and  236 . 
     Cryogen stream  236  passes directly into a LBP refrigerant condenser  213 . Emerging from the outlet of LBP refrigerant condenser  213  is cryogen stream  238 , which splits into cryogen streams  239  and  246 . During the cool down and soak cycles, cryogen stream  246  may combine with cryogen stream  234  to form combined cryogen stream  248 , which is passed into the inlet of heat exchanger  256 . Warmer cryogen stream  250  emerges from the outlet of heat exchanger  256  and combines with cryogen stream  244  forming combined cryogen stream  252 . Cryogen streams  252  and  239  are combined to form combined cryogen stream  240 , which in turn splits into cryogen streams  241  and  243 . One of the cryogen stream  243  passes into the inlet of refrigeration recovery unit  245  and emerges as warmer cryogen stream  247 . Therefore, waste refrigeration from stream  243  is recovered and stored. If the stream is warmer than the refrigeration recovery unit  245 , e.g., during initial cool down or the heat transfer fluid becomes excessively cold (approaching its freezing point), the other cryogen stream  241  will bypasses refrigeration recovery unit  245  and may combine with cryogen stream  247  forming cryogen stream  249  for passing as wasted or gas storage. 
     Heat transfer fluid stream  260  passes into the inlet of three-way electrically operated modulating control valve  263  by the use of fluid pump  212 . During the initial cool down and soak cycle, the three-way control valve will allow only transfer fluid streams  261  to emerge from the outlets of valve  263 . Transfer fluid stream  261  passes through the inlet of heat exchanger  252  to emerge as cooler transfer fluid stream  262 . When the temperature approaches the range of 0° C. to −30° C., the three-way control valve will then allow only the transfer fluid stream  264  to pass through the inlet of heat exchanger  254  emerging from the outlet thereof as further cooled transfer fluid stream  265 . It is contemplated that heat exchanger  252  provides the means for cooling the transfer fluid stream in a temperature range of from about −5° C. to about 50° C., and that heat exchanger  254  provides the means for cooling the transfer fluid stream in a temperature range of from about 0° C. to about −80° C. In practice, the choice of operating either heat exchangers largely depends on the temperature cooling cycle of the freeze dryer, the temperature of the transfer stream  260 , the type of cryogens and transfer fluid used in the system, and the flow of the transfer fluid streams through control valve  263 . Cooled transfer fluid streams  262  and  264  may be combined to form fluid stream  266 . 
     Transfer fluid stream  272 , which is split from transfer fluid stream  280  emerging from the outlet of freeze drying shelves  297  and chamber  216 , passes through the inlet of heat exchanger  256  using the activation means of pump  214 , and emerges through the outlet of heat exchanger  256  as transfer fluid stream  274 , which in turn passes through heating unit  258  to emerge from the outlet therefrom as transfer fluid stream  276 . The flow of heat transfer fluid streams  272 ,  274  and  276  is controlled primarily by the activation of pump  214 . Heat is supplied to the heating unit  258  only during the warm up or temperature ramp-up cycle of the freeze drying process. Heating unit  258  and pump  214  partially regulate the temperature by which the heat transfer fluid passes through the freeze drying shelves  297  and chamber  216 . 
     During the cooling and soaking cycles, heat transfer fluid streams  266  and  276  are combined to form heat transfer fluid stream  278 , which is directed to the inlet of the freeze drying shelves  297  and chamber  216  assembly. In practice, heat transfer fluid stream  278  passes through each of the freeze drying shelves  297  and chamber  216  to effectuate the freeze drying of materials within freeze drying shelves  297  and chamber  216 . 
     Emerging from the outlet of freeze drying shelves  297  and assembly  216  is exhausted transfer fluid stream  280 , which in turn is separated into heat transfer fluid streams  281  and  283  by the use of electrically operated modulating three-way control valve  289 . Heat transfer fluid stream  283  splits into  270  and  282 . Transfer fluid stream  270  passes through the inlet of pump  214  to emerge as transfer fluid stream  272  if the activation means of pump  214  is operational. The other transfer fluid stream  282  passes through the inlet of pump  212  emerging from its outlet as transfer fluid stream  260 . During the cooling down and soaking cycles, heat transfer fluid stream  281  passes through the inlet of refrigeration recovery unit  245  and emerges from the outlet therefrom as heat transfer fluid stream  251 . One of the heat transfer fluid streams  251  and  282  are joined to form heat transfer fluid stream  287 . 
     Any frozen volatile substance is vaporized through sublimation and passed out of the freeze drying chamber  216  as stream  290 . Emerging from the outlet of condenser  218  is the remaining waste stream  294  as it is drawn from vacuum pump  295 . Waste stream  296  is removed when it emerges from the outlet of vacuum pump  295 . 
     Additional refrigeration system  298  enables the use of a separate LBP refrigerant to lower the temperature of the condenser. LBP refrigerant  211 , examples of which include those selected from the group consisting of a hydrocarbon and fluorocarbon based gases that can readily be condensed by a cryogen that boils off inside the condenser to provide a fixed cooling temperature. A preferred LBP refrigerant is monochlorotrifluromethane (Freon 13). LBP refrigerant gas  211  passes through the inlet of a LBP refrigerant condenser  213  and emerges through the outlet therefrom as liquefied cold LBP refrigerant  215 , which then passes through pump  217  and exits the outlet of the pump as LBP refrigerant stream  219 . LBP refrigerant stream  219  passes through the inlet of condenser  218  for removal of volatile substances from dry freezing shelves  297  and chamber  216 . LBP refrigerant is boiled off inside condenser  218  to form gas LBP refrigerant  211 . 
     In general, the operation of this second embodiment of the refrigeration system as provided in FIG. 2 involves the use of a refrigeration recovery unit as well as the use of a separate refrigerant for passing into the condenser. The refrigeration recovery unit recovers waste refrigeration from the vaporized cryogen and stores the excess refrigeration from the heat transfer fluid. The separate refrigerant enables the use of a conventional substance which can alleviate the need for certain compression and expanding apparatus and therefore, providing an efficient process. 
     Since the freeze chamber  216  and shelves  297  must operate at a warmer temperature than the condenser  218 , using a LBP refrigerant in the condenser  218  eliminate the need to turn on the heater  258  during the cooling cycle or to generate a separate heat transfer fluid reciruclating loop. Therefore, the process is more efficient and less capital intensive. 
     It will be apparent to those skilled in the art that various changes may be made in the size, shape, type, number and arrangement of parts described hereinbefore. For example, although the freeze dryer system described hereinbefore utilizes the chambers in the hollow shelves as part of the conduit system by which heat transfer fluid is circulated through the system, other refrigeration systems may utilize hollow wall panels, coiled piping, or other forms of chambers in the conduit system for the heat transfer fluid. Various well-known refrigerants and heat transfer fluids may be utilized, as desired. The types of control valves described for use in the conduit system may be replaced by other suitable types. For sake of simplicity, certain check valves, steam valves, flowmeters, pressure transducers and thermocouples are not shown in the figures, but are fully appreciated by those skilled in the art. Accordingly, based on the foregoing, changes can be made without departing from the spirit of this invention and the scope of the appended claims. Alternative embodiments will be recognized by those skilled in the art and are intended to be included within the scope of the claims.