Directional freezing

Patent metadata

Field	Value
Publication number	US-10101085-B2
Application number	US-201514605107-A
Country	US
Kind code	B2
Filing date	Jan 26, 2015
Priority date	Jul 26, 2012
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

The invention relates to an apparatus and a method of freezing a liquid substance contained in at least one receptacle, comprising the steps of: providing the liquid substance in at least one receptacle, providing a cooling chamber and a cooling device having a cooling surface; setting the temperature of the cooling surface, starting a freezing procedure by placing the receptacle with the liquid substance therein on the cooling surface to form a seed or initial zone of nucleation; and continuing the freezing procedure to completely freeze the substance.

First claim

The invention claimed is:

1. A freezing apparatus for freezing a liquid substance contained in at least one receptacle, comprising:
a cooling device having a cooling surface adapted to receive thereon in surface contact a plurality of receptacles containing a liquid substance to be frozen, and cooling means adapted to cool the cooling surface to a temperature less than −130° C. in order to cool receptacles placed on the cooling surface and thereby to have a portion of the liquid substance, which is contained in the receptacles in proximity of the cooling surface, form a seed or initial zone of nucleation;
a cooling chamber adapted to receive the receptacles in a cooling region of the cooling chamber and to cool the receptacles received therein to continue freezing of the liquid substances at cooling temperatures in the range between −5° C. and −60° C.; and
a transport means adapted to transfer receptacles from the cooling surface to said cooling region of the cooling chamber before the liquid substance contained in the receptacles has been completely frozen.

2. The freezing apparatus of claim 1 , wherein the cooling surface is arranged outside the cooling chamber and the transport means is adapted to move the receptacle away from the cooling surface into the cooling chamber, or wherein the cooling surface is arranged inside the cooling chamber and the transport means is adapted to move inside the cooling chamber the receptacle away from the cooling surface to said cooling region of the cooling chamber.

3. The freezing apparatus of claim 1 , wherein the cooling surface is horizontally flat and adapted to make a direct surface contact with the receptacle by having the receptacle standing directly on the cooling surface.

4. The freezing apparatus of claim 1 , wherein the cooling surface is the surface of a metal plate or a metal block wherein the metal block comprises a fluid channel for guiding a cooling agent.

5. The freezing apparatus of claim 1 , wherein the transport means comprises a frame, a rack or a grid receiving a plurality of said receptacles, wherein the receptacles are arranged inside the frame or in openings or holes of the grid or rack, and wherein the grid or rack is adapted to suspend the receptacles by holding the receptacles at their upper ends.

6. A freeze dryer for performing the method, comprising the freezing apparatus of claim 1 and further comprising a condensation chamber having a cold condenser and a heater for heating the receptacle containing the substance frozen by the freezing apparatus, so that the frozen substance vaporizes during sublimation, wherein the condenser is adapted to condense said vapor.

7. A method of freezing a liquid substance contained in at least one receptacle comprising the steps of:
providing the liquid substance in at least one receptacle,
providing a cooling chamber and a cooling device having a cooling surface;
setting the temperature of the cooling surface to less than −130° C.;
starting a freezing procedure by placing the receptacle with the liquid substance therein on the cooling surface to make surface contact between the receptacle and the cooling surface to cool the receptacle and thereby to have a portion of the liquid substance, which is contained in the receptacle in proximity of the cooling surface, form a seed or initial zone of nucleation;
continuing the freezing procedure to completely freeze the substance such that, starting from the seed or initial zone of nucleation, directional freezing of the liquid substance with a propagating crystallization front occurs at or near melting point temperature of the substance at the crystallization front;
and transferring the receptacle from the cooling surface to a region of the cooling chamber, with the cooling temperature within said region of the cooling chamber being set to a value in the range between −60° C. and −5° C.,

wherein the step of transferring the receptacle from the cooling surface to the region of the cooling chamber is performed before the liquid substance contained in the receptacle has been completely frozen.

8. The method of claim 7 , wherein containers made of glass are used as receptacles.

9. The method of claim 7 , wherein receptacles with volumetric capacities between 1.0 ml and 100 ml are used.

10. The method of claim 7 , wherein the liquid substance is an aqueous solution of at least one chemical reagent and/or an aqueous solution of biological material.

11. The method of claim 7 , wherein, after having started the freezing procedure, the receptacle is left for a dwell time between 30 s and 20 min on the cooling surface of the cooling device.

12. The method of claim 7 , wherein transferring the receptacle from the cooling surface to said region of the cooling chamber is conducted within a time interval less than 5 min.

13. The method of claim 7 , wherein transferring the receptacle from the cooling surface to said region of the cooling chamber is conducted in a cooled environment having a temperature less than 5° C.

14. The method of claim 7 , wherein a metallic block comprising the cooling surface is provided as a part of the cooling device, said metallic block has an inner hollow space structure through which liquid nitrogen is guided as a coolant.

15. The method of claim 7 , wherein the liquid substance in the receptacle, when placing the receptacle on the cooling surface to start the freezing procedure, has a temperature between 15° C. and 28° C.

16. The method of claim 7 further comprising the step of sublimating ice crystals from the frozen substance by heating the receptacle with the frozen substance therein in a condensation chamber at reduced ambient pressure in said condensation chamber.

Assignees

• Roche Diagnostics Operations Inc
• Roche Diagnostrics Operations Inc

Inventors

• Dittrich Juergen
• Ziegler Guenter

Classifications

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• F25C1/10

  by using rotating or otherwise moving moulds (F25C1/08 takes precedence) · CPC title

• F25C1/16

  by partially evaporating water in a vacuum · CPC title

• F26B5/06 Primary

  the process involving freezing · CPC title