Apparatus for maintaining a controlled environment

Patent metadata

Field	Value
Publication number	US-11035613-B2
Application number	US-201916560476-A
Country	US
Kind code	B2
Filing date	Sep 4, 2019
Priority date	Aug 3, 2015
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

A lyophilization nest and method of using the same is described herein. In various embodiments, the lyophilization nest is configured to support one or more receptacles each supporting one or more substances within an interior space of the lyophilization nest. The interior space may be in fluid communication with the exterior of the lyophilization nest through one or more vent holes extending through a surface of the lyophilization nest. Each of the one or more vent holes have a corresponding sealing element configured to selectively form an air-tight seal within the vent holes, such that a controlled environment may be maintained within the interior space when the ambient conditions surrounding the lyophilization nest are not lyophilization conditions. The one or more sealing elements may be operable while the lyophilization nest is positioned within a sealed lyophilizer by depressing the sealing elements into corresponding vent holes to form the air-tight seal.

First claim

I claim:

1. A receptacle for receiving one or more substances to be lyophilized, the receptacle comprising:
one or more wells, each well configured to hold a substance to be lyophilized and comprising an at least substantially hemispherical shaped bottom interior surface; and
a sealable upper surface configured such that a seal may be applied thereto and sealed such that each of the one or more wells is individually sealed and isolated from an uncontrolled external environment,
wherein an exterior shape of at least a bottom portion of the receptacle is configured to conform and engage with one or more receptacle receiving portions of a lyophilization nest, so as to maximize a surface contact area between the receptacle and the one or more receptacle receiving portions, and
wherein the receptacle comprises a low vapor transmission rate material configured to impede migration of water vapor through the material.

2. The receptacle of claim 1 , wherein the receptacle is a single-well receptacle comprising one well, or a multi-well receptacle comprising multiple wells.

3. The receptacle of claim 1 , wherein the low vapor transmission rate material comprises a cyclic olefin copolymer or polypropylene.

4. The receptacle of claim 1 , further comprising a seal attached to the sealable upper surface, wherein the seal comprises an adhesive low moisture vapor transmission material that secures to the sealable upper surface of the receptacle.

5. The receptacle of claim 4 , wherein the adhesive low moisture vapor transmission material is a film, and wherein the film is a laminate structure comprising a layer of aluminum foil.

6. The receptacle of claim 1 , wherein each of the one or more wells has an associated sealing cap configured to be secured within the well to provide an air-tight seal around the perimeter of the well.

7. The receptacle of claim 1 , wherein each of the one or more wells comprises a flat bottom exterior surface, a V-shaped bottom exterior surface, or an at least substantially hemispherical shaped bottom exterior surface corresponding to the at least substantially hemispherical shaped bottom interior surface.

8. The receptacle of claim 1 , further comprising one or more substances to be lyophilized wherein the one or more substances to be lyophilized comprises at least one of a pure chemical; a chemical mixture; a biologic sample; a biological agent; a label; and a reaction mixture.

9. The receptacle of claim 2 , comprising a multi-cell receptacle of 6, 12, 24, 96, 384, or 1536 wells.

10. The receptacle of claim 1 , wherein each of the one or more wells has a volume in a range of about 300-400 μL.

11. The receptacle of claim 1 , wherein each of the one or more wells has a volume in a range of about 1 nL-10 mL.

12. A lyophilization nest for preparing lyophilized substances, the nest comprising:
a base comprising a bottom plate having a base edge extending upwardly from a perimeter thereof, the bottom plate having a top surface adapted to support at least one receptacle of claim 1 ;
a cover comprising a top plate having a cover edge extending downwardly from a perimeter thereof, the top plate having one or more vent holes extending therethrough;
an interior space defined by the base and the cover when the base and the cover are in a closed relationship, the interior space being sized to accommodate the at least one receptacle; and
one or more sealing elements, each of the sealing elements being in closeable engagement with a corresponding one of the vent holes, such that the sealing elements and the corresponding vent holes are operable between:
an open configuration in which positions of the sealing elements relative to the corresponding vent holes permit fluid communication between the interior space and air external to the nest when the base and the cover are in the closed relationship; and
a closed configuration in which positions of the sealing elements relative to the corresponding vent holes do not permit fluid communication between the interior space and air external to the nest when the base and the cover are in the closed relationship, such that the interior space is sealed off to air external to the nest when the base and the cover are in the closed relationship.

13. The lyophilization nest of claim 12 , further comprising one or more receptacle frames situated on a top surface of the bottom plate, each of the receptacle frames being configured to support the at least one receptacle, wherein each of the receptacle frames comprises aluminum.

14. A method for sealing a lyophilized substance in a receptacle, the method comprising:
preparing a lyophilized substance in a receptacle, the receptacle comprising one or more wells, wherein preparing a lyophilized substance in a receptacle comprises:
placing a substance to be lyophilized in the one or more wells of the receptacle;
positioning the receptacle within a lyophilization nest, the lyophilization nest comprising an interior space that is in fluid communication with air external to the nest through one or more vent holes extending through a top plate of a cover of the lyophilization nest, and wherein each of the vent holes has a sealing element in closeable engagement therewith; and
placing the lyophilization nest within a chamber of a lyophilizer and creating lyophilization conditions within the chamber for a period of time sufficient for the substance contained in receptacle to be lyophilized;

removing the lyophilization nest from the chamber of the lyophilizer;
accessing and removing the receptacle from the lyophilization nest; and
securing a low moisture vapor transmission film to a top surface of the receptacle, such that each of the one or more wells are individually sealed and isolated from an uncontrolled external environment,
wherein the low moisture vapor transmission film is a laminate comprising a layer of aluminum foil.

15. The method of claim 14 , wherein securing a low moisture vapor transmission film to a top surface of the receptacle is performed in a space that is not controlled for humidity.

16. The method of claim 14 , comprising placing about 75-200 μL of the substance to be lyophilized in the one or more wells of the receptacle.

17. The method of claim 14 , wherein the low moisture vapor transmission film further comprises an adhesive; or wherein the low moisture vapor transmission film further comprises a plastic liner for affixing the film to the top surface of the receptacle.

18. A system for maximizing heat transfer within a lyophilization nest, the system comprising:
a lyophilization nest, the nest comprising:
a cover comprising a top plate having a cover edge extending downwardly from a perimeter thereof, the top plate having one or more vent holes extending therethrough; and
a base comprising a bottom plate having a base edge extending upwardly from a perimeter thereof and defining a base interior, the base interior comprising one or more receptacle receiving portions configured to support one or more receptacles therein,
wherein each receptacle comprises:
one or more wells, each well configured to hold a substance to be lyophilized and comprising an at least substantially hemispherical shaped bottom interior surface; and
a sealable upper surface configured such that a seal may be applied thereto and sealed such that each of the one or more wells are individually sealed and isolated from an uncontrolled external environment, and

wherein an exterior shape of at least a bottom portion of each receptacle is configured to conform and engage with

Assignees

• Gen Probe Inc

Inventors

• Knight Byron J

Classifications

• F26B5/06 Primary

  the process involving freezing · CPC title

• A01N1/165 Primary

  Pressure processes, e.g. following predefined pressure changes over time · CPC title

• A01N1/144

  for temperature control, e.g. refrigerators or freeze-drying apparatus · CPC title

• A01N1/162

  Temperature processes, e.g. following predefined temperature changes over time · CPC title

• B01L1/02

  Air-pressure chambers; Air-locks therefor · CPC title