WO2013171483A1 - Vessel of thermally conductive plastic for freeze - drying - Google Patents
Vessel of thermally conductive plastic for freeze - drying Download PDFInfo
- Publication number
- WO2013171483A1 WO2013171483A1 PCT/GB2013/051247 GB2013051247W WO2013171483A1 WO 2013171483 A1 WO2013171483 A1 WO 2013171483A1 GB 2013051247 W GB2013051247 W GB 2013051247W WO 2013171483 A1 WO2013171483 A1 WO 2013171483A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vessel
- freeze
- stopper
- vessel according
- drying
- Prior art date
Links
- 238000004108 freeze drying Methods 0.000 title claims abstract description 49
- 239000004033 plastic Substances 0.000 title claims abstract description 29
- 229920003023 plastic Polymers 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 41
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 239000000463 material Substances 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- 229920000642 polymer Polymers 0.000 claims description 13
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 150000007523 nucleic acids Chemical class 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- 230000003321 amplification Effects 0.000 claims description 10
- 238000005842 biochemical reaction Methods 0.000 claims description 10
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 238000003752 polymerase chain reaction Methods 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 5
- 230000008014 freezing Effects 0.000 claims description 5
- 239000002322 conducting polymer Substances 0.000 claims description 4
- 229920001940 conductive polymer Polymers 0.000 claims description 4
- 229910052582 BN Inorganic materials 0.000 claims description 3
- PZNSFCLAULLKQX-UHFFFAOYSA-N Boron nitride Chemical compound N#B PZNSFCLAULLKQX-UHFFFAOYSA-N 0.000 claims description 3
- 238000010240 RT-PCR analysis Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002923 metal particle Substances 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims 1
- 238000009472 formulation Methods 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 11
- 239000011521 glass Substances 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- -1 polypropylene Polymers 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000004020 conductor Substances 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000001746 injection moulding Methods 0.000 description 3
- 239000004417 polycarbonate Substances 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229920001169 thermoplastic Polymers 0.000 description 2
- 239000004416 thermosoftening plastic Substances 0.000 description 2
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical class [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 2
- FRWYFWZENXDZMU-UHFFFAOYSA-N 2-iodoquinoline Chemical compound C1=CC=CC2=NC(I)=CC=C21 FRWYFWZENXDZMU-UHFFFAOYSA-N 0.000 description 1
- 229910017083 AlN Inorganic materials 0.000 description 1
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 description 1
- 229910052580 B4C Inorganic materials 0.000 description 1
- 229910001369 Brass Inorganic materials 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004734 Polyphenylene sulfide Substances 0.000 description 1
- 239000004954 Polyphthalamide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000006230 acetylene black Substances 0.000 description 1
- XECAHXYUAAWDEL-UHFFFAOYSA-N acrylonitrile butadiene styrene Chemical compound C=CC=C.C=CC#N.C=CC1=CC=CC=C1 XECAHXYUAAWDEL-UHFFFAOYSA-N 0.000 description 1
- 239000004676 acrylonitrile butadiene styrene Substances 0.000 description 1
- 229920000122 acrylonitrile butadiene styrene Polymers 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- LTPBRCUWZOMYOC-UHFFFAOYSA-N beryllium oxide Inorganic materials O=[Be] LTPBRCUWZOMYOC-UHFFFAOYSA-N 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- INAHAJYZKVIDIZ-UHFFFAOYSA-N boron carbide Chemical compound B12B3B4C32B41 INAHAJYZKVIDIZ-UHFFFAOYSA-N 0.000 description 1
- 239000010951 brass Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000006229 carbon black Substances 0.000 description 1
- 239000003575 carbonaceous material Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 238000007496 glass forming Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000052 poly(p-xylylene) Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000069 polyphenylene sulfide Polymers 0.000 description 1
- 229920006375 polyphtalamide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 1
- 229910001887 tin oxide Inorganic materials 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
- B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0278—Physical preservation processes
- A01N1/0289—Pressure processes, i.e. using a designated change in pressure over time
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F26—DRYING
- F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
- F26B5/00—Drying solid materials or objects by processes not involving the application of heat
- F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
- F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
Definitions
- the present invention relates to containers for use in chemical and biochemical reactions and procedures, in particular freeze-drying or lyophilisation procedures, as well as methods for preparing these containers and their use.
- diagnostic tests have been carried out in laboratory environment, there is an increasing trend towards "point-of-need" diagnostic tests that can provide rapid results, whilst the patient waits, for example in the clinic.
- These methods currently utilise dedicated integrated instruments which are specifically designed for the purpose, including conducting reactions such as nucleic acid amplifications like the polymerase chain reaction (PC ).
- PC polymerase chain reaction
- the vials have convex or flat bases that are not ideal for the removal of solutions formed by dissolution of the contents using conventional aspiration methods such as pipettes or syringes that are commonly employed in particular in the sort of automation used in life science methods.
- glass is generally not biocompatible with enzymes and nucleic acids that are the subject of biochemical analysis. It is therefore necessary to use blocking or other reagents to address biocompatibility issues, leading to further complication of the formulation and possible regulatory issues.
- a stopper is inserted into the vial post-drying using a descending shelf provided in the freeze-dryer.
- This stopper provides a means to seal the vial under vacuum to provide a good shelf life for the contents.
- the stopper then acts as a septum, and must be pierced by the clinician using a needle in order to access the contents. This may not be acceptable within some molecular laboratories as the use of needles presents a 'sharps' hazard.
- the volume of the vials conventionally used in these processes is in the ml range for example from 3 to 10 ml.
- freeze-dried formulations of reagents are commercially available, including for example the so-called 'PC -ready' beads. However, these have handling issues of their own since they are small and light and so may be lost or misplaced as they are being be moved into the vessel in which the analysis is to be conducted.
- the applicants have developed a vessel in which reagents can be freeze-dried and which may be suitable for use directly in subsequent standard laboratory procedures including those using automation, and possibly even PCR.
- a vessel comprising a thermally conducting plastic in a freeze drying procedure.
- the vessels used suitably comprise a thermally conducting plastic in at least a region thereof, said region being arranged to contact contents placed in the vessel.
- thermally conducting plastic means that a good thermal union can be achieved between the contents of the vessel and the means used to carry out freeze-drying or lyophilisation, which will generally be a freeze-drying shelf of a freeze dryer.
- the vessels can be used to produce uniform cakes of freeze-dried material.
- a plastics vessel may be economical to produce. It is also safe and easy to handle, as well as being of low density and therefore lighter to transport. In addition, it has a lower thermal mass to freeze compare to a corresponding glass vessel.
- Suitable thermally conducting plastics include polymeric materials that contain particles of thermally conducting materials distributed throughout a polymer matrix. In a particular embodiment, the particles are homogenously distributed throughout the polymer matrix.
- the polymer matrix may comprise a wide range of polymeric materials including include polypropylene, polyethylene (including high and low-density polyethylene as well as derivatives such as polyethylene terephthalate and polytetrafluoroethylene) polyester, polyacrylate, polystyrene, polyamide, polycarbonate, polyphthalamide, polyphenylene sulfide and polyvinyl polymers such as polyvinylchloride and nylon, as well as co-polymers containing these such as acrylonitrile-butadiene-styrene.
- polypropylene polyethylene (including high and low-density polyethylene as well as derivatives such as polyethylene terephthalate and polytetrafluoroethylene) polyester, polyacrylate, polystyrene, polyamide, polycarbonate, polyphthalamide, polyphenylene sulfide and polyvinyl polymers such as polyvinylchloride and nylon, as well as co-polymers containing these such as acrylonitrile-
- the particles of thermally conducting material that may be present within the polymeric matrix may be selected from a wide range of materials including metals such as aluminium, nickel, gold or silver or alloys containing these or other alloys such as brass or stainless steel, metal or metalloid salts such as boron nitride, boron carbide, alumina, aluminium nitride, aluminum oxide, magnesium oxide, titanium oxide, iron oxide, tin oxide, beryllium oxide, zinc oxide, and calcium carbonate, carbon based materials such as graphite, carbon in the form or carbon fibre, powder or flake, acetylene black or carbon black, as well as other materials such as glass or ceramics or mixtures or combinations of these.
- the particles may take the form of fibres, flakes, powders, whiskers or microspheres.
- the thermally conducting plastic has thermoplastic or elastomeric properties that allow it to be shaped using a conventional technique such as injection molding.
- the plastic may be electrically conducting or electrically insulating.
- the plastic is electrically conducting.
- the vessel may be utilized in reaction which requires the application of heat, either as a thermostat (as described for example in WO99061578) or a means for thermally cycling the contents of the vessel (as described for example in WO98024548).
- the plastic is electrically insulating.
- thermally conducting plastics are available from Cool Polymers Inc.
- Such polymers which are electrically conducting include those sold under the trade names CoolPoly ® E8103, CoolPoly ® E2, CoolPoly ® E3607, CoolPoly ® E4501, CoolPoly ® E4505, CoolPoly ® E4507, CoolPoly ® E1201, CoolPoly ® E3603, CoolPoly ® E3606, CoolPoly ® E5101, Cool Poly ® E5107, CoolPoly ® E8103 and CoolPoly ® E5109.
- polymers which are electrically non-conducting include those sold under the trade names CoolPoly ® D8104, CoolPoly ® D8102, CoolPoly ® D4301, CoolPoly ® D5108,
- the thermally conducting plastic is a Coolpoly ® polymer.
- the thermally conducting plastic is a polymer containing boron nitride or metal particles as described above.
- the thermally conducting plastic has a high level of biocompatibility so that it may be used to contain a chemical or biochemical reaction that utilises enzymes and/or nucleic acids such as a nucleic acid amplification reaction without the need for the use of protective measures such as the use of blocking agents and the like.
- the thermally conducting material may also be made inert or biocompatible through the use of a coating such as thin walled over moulded sheath, or a deposited polymer coating such as a parylene coating.
- Novel vessels described herein form a further aspect of the invention. These include vessels that are electrically insulating.
- the thermally conducting plastic is formed into a vessel that is suitable for use a freeze- dryer.
- the vessel may be in the form of a composite with other materials such as other non- thermally conducting polymers, provided the thermally conducting polymer is provided in the region of the vessel that will be in contact with materials placed in the vessel. It will generally therefore also be in contact with the freeze drying shelf in a freeze dryer.
- the vessel is constructed entirely of thermally conducting polymer.
- the vessel is suitably shaped so that it is compatible with chemical or biochemical reactions that are conventionally carried out in the automated devices used in the life science industry. This means that the contents may be used directly in such a reaction.
- reagents useful in a chemical or biochemical reaction may be freeze-dried in a vessel which is then used directly in a subsequent analysis.
- reagents necessary for carrying out a reaction or analysis of a sample may be freeze-dried in the vessel, and then later rehydrated with a sample that is required to be tested using that reaction.
- the use of a single vessel for both operations will minimise contamination risks and avoid problems associated with the handling and potential loss of freeze-dried reagents.
- the vessel may comprise a generally cylindrical section which is open at a first end and closed by means of a base at the other end.
- the internal surface of the base is generally conical so that contents gather in the lower apex, allowing efficient removal of solutions, even of low volumes, using conventional aspiration means such as pipettes and syringes, in particular during automated processes.
- the concentration of the contents of the vessel within the small volume apex of the cone may assist with vapour release during the sublimation part of the freeze drying process by having the highest proportion (by mass) near the surface of the sample to be dried.
- the volume of the vessel will suitably be similar to that required for use in chemical and biochemical reactions carried out in the life sciences field, and in particular will be in the range of from 100 to 2000 ⁇ . Examples of such vessels are illustrated in Figure 3 hereinafter.
- the vessel may resemble in form the well-known "Eppendorf" tubes that are in widespread use in the life sciences arena. Such tubes can be produced in a standard size and would be readily located for use or storage in the racks and storage products already in use in the automated apparatus and equipment in use life sciences industry.
- the external surface of the base of the vessel may also be conical. However, this may mean that it is difficult to position on a freeze-drying shelf of a freeze-dryer whilst ensuring maximum thermal contact between the vessel and the shelf, because the contact area may be confined to the apex of the conical section. It may be provided with a "skirt" region that extends around the conical portion of the vessel and provides an essentially cylindrical profile along the entire length of the vessel.
- the vessel may be self supporting and so may be easily positioned in a variety of devices including standing directly on the drying shelf of a freeze dryer.
- the presence of an air-gap provided within a conventional 'skirted' tube may reduce the efficiency of the thermal contact.
- the thermally conducting plastic extends outwards of the internal conical surface of the base to form a flat external surface.
- the thermal contact of the vessel and its contents with the drying shelf is maximised.
- vessels comprising thermally conducting plastic may be in the form of a vessel having multiple containers, which are suitably arranged in an array.
- a particular example of such a vessel are multi-well plates such as microtitre plates that conventionally contain 96 individual wells.
- the drying process is not limited as much by a large volume with a high aspect ratio (tube with higher surface to area ratio). This is because the thermal control from the shelf will be efficiently conducted to the sample through the walls of the vessel. This will assist with controlling the sample temperature in larger volumes. It may also decrease the hold times with a freeze drying cycle required to freeze or thaw, or heat a sample.
- the thermal conductivity of the wall provides a convenient way to maintain a frozen sample within a high aspect tube, since when the tube is placed on a cold surface, the high thermal conductivity of the polymer would transmit this throughout the sample. This makes it easier to freeze reagents prior to freeze drying.
- reagents may be frozen in layers that would otherwise become homogenous if they were be maintained in a frozen state. This is useful for example, if there are two freeze drying formulations that are incompatible. For example, some fluorescent dyes that may be required to be used for example in formulations required to be used in a reaction may have different pH requirements for longevity to the remainder of the components of the formulation. Similarly, formulations may be required to contain both enzymes and enzyme substrates for use in a subsequent reaction. However, there is benefit here in keeping the enzyme separate from a substrate in the dried formulation.
- the cake structure may be formed from two or more layers of different reagent formulations.
- the purpose of this may be to enhance either the resulting cake stability and/or the performance of the final reaction upon dissolution.
- the active formulation of many reactions may compromise the optimum stability of one or more specific components.
- One or more of these components may be included in a separate reagent layer.
- fluorophores have a greater stability at particular pH's.
- Fluorescein derivatives prefer basic environments, whereas, cyanine derivatives prefer neutral pH's which are not consistent with the final amplification optimum range described above.
- Standard cakes prepared at pH 8-9 would compromise the stability of cyanine fluorophores. However, they may be combined with a suitable glass-forming agent and any stabilisers or other excipients required in the freeze-drying process at their optimum pH and frozen in an individual 'layer' within a structure formed with other components that may be similarly frozen. If this frozen layered structure is then freeze-dried, the final cake will also be similarly layered.
- polymerases may be delineated into their own layer such that they are not available to interact with specific reaction components such as primers or probes. This would provide a pseudo hotstart during the lyophilisation process, the resulting reaction only becoming active after dissolution of both layers.
- Each layer may contain one or more of the reagents from the final amplification formulation.
- the layers would be formed by freezing each layer individually, one on top of the other, prior to freeze drying.
- the formulations of each layer would be formulated as to provide the optimal final composition upon co-dissolution, whilst drying to form a single cake structure
- Vessels of the invention may be used in processes in which such reagents are frozen individually in layers prior to freeze drying. Such a process is novel and forms a further aspect of the invention.
- the invention further provides a process for preparing a freeze dried composition comprising multiple components, said method comprising (i) freezing a solution of a first component to form a first frozen layer, (ii) adding a second solution of a second component and freezing the second solution into a distinct layer, (iii) optionally repeating step (ii) until all components of the composition are present in a frozen layers, and (v) freeze-drying the resultant structure.
- the vessel is provided with a stopper which can close the open first end in a manner which will allow freeze-drying to take place within the vessel.
- Suitable stoppers are similar to those conventionally used in the freeze-drying vessels.
- These are provided with a vent means arranged to allow gas exchange when said stopper is partially inserted into the said first end. This provides for efficient sublimation during the drying process.
- the vents are generally provided in the side walls and may comprise one or more indentations or openings in the side walls. Various designs of such stoppers or "bungs" are illustrated in Figure 2.
- each of the wells is provided with a stopper.
- the stoppers for each container or well will be connected together so that a stopper may be fitted into each container within a particular array.
- the stoppers are pushed further into the vessel using for example a descending shelf in the freeze dryer, whereupon the upper region of the stopper provides a complete closure of the vessel within the inert atmosphere (e.g. of nitrogen) or vacuum that is present in the freeze-dryer or lyophilisation chamber.
- the inert atmosphere e.g. of nitrogen
- vacuum that is present in the freeze-dryer or lyophilisation chamber.
- the bottom of the stopper is arranged to meet the surface of the freeze dried reagents after drying and closure of the stopper by the freeze dryer descending shelf. This then holds the freeze dried "cake” in place and mechanically stops the cake from moving or dislodging during transport. The presence of the stopper further ensures that the cake is in place for dissolution during the resuspension by an automated pipette.
- an upper surface of the stopper is provided with a pierceable seal, such as a pierceable foil seal.
- a pierceable seal such as a pierceable foil seal.
- the vessel is provided with a secondary closure member that fits over the stopper, providing a secondary closure and a reseal option.
- This secondary closure member may take the form of a screw threaded cap, where the outer surface of the vessel is provided with a screw thread arranged to engage with that of the cap, or a snap-fit cap.
- thermoly conducting plastic is a thermoplastic that is capable of injection moulding and so vessels as described above can be prepared using this technique.
- They are suitably disposable or consumable and so may be for a "single-use" apparatus.
- the invention provides a process for freeze drying a material, said method comprising placing material to be freeze dried in a vessel as described above and thereafter subjecting said vessel to a lyophilisation procedure.
- the lyophilisation procedure is suitably carried out by placing the vessel on the drying shelf of a freeze-dryer or lyophilisation chamber.
- a stopper is partially inserted into the open end of the vessel in particular by lowering a shelf within the freeze-dryer or lyophilisation chamber so as to apply a limited amount of pressure to the stopper, ensuring that the stopper is partially inserted but that vents in the stopper remain open allowing gas exchange between the vessel and the atmosphere in the chamber. Lyophilisation conditions are then induced within the chamber so that liquid within the contents of the vessel sublimates off.
- the stopper may be fully inserted into the vessel by further lowering the shelf, thus sealing the vessel.
- the chamber is evacuated or may be back filled with and inert atmosphere such as nitrogen prior to stoppering.
- the chamber may then be brought to atmospheric pressure and the contents removed.
- any secondary closure member such as a screw cap can be positioned on the vessel.
- each vessel will comprise a mixture of components that are required for carrying out a chemical or biochemical reaction.
- nucleic acid amplification reactions such as a polymerase chain reaction, or reverse-transcriptase polymerase chain reaction.
- the vessels may be used directly in subsequent analytical processes, for example in automated analysis apparatus. Any secondary closure member may be removed at the point of use, the vessel loaded into a suitable holder or rack which is then inserted into the apparatus.
- Such apparatus will generally include means to pierce the seal within the stopper and insert for instance, a rehydration liquid and/or a sample.
- the tube may then be subjected to any other conditions necessary for carrying out the target reaction, such as temperature, or temperature cycling, in the conventional manner.
- Figure 1 shows a range of standard glass vials that are conventionally used for lyophilisation or freeze-drying
- Figure 2 shows a range of stoppers that are used in vessels for freeze-drying and which may be used in the vessels of the present invention
- Figure 3 illustrates the shape of microfuge tubes that are currently available together with an illustration of a rack in which they may be stored;
- Figure 4 is an exploded section of a vessel in accordance with the present invention.
- the vessel (1) illustrated in Figure 4 comprises a cylindrical body section (2) of a thermally conducting plastic as described above.
- the inner surface of the body section (2) is conical in shape in the region of the base (3) meaning that material (4) placed in the vessel becomes concentrated in the small volume found at the apex of the cone.
- the base (3) comprises either a solid mass or skirt of thermally conducting plastic, meaning that there is good thermal union between the material (4) and the surface on which the vessel (1) is placed.
- a stopper (5) is provided which fits into the upper open end of the body section (2).
- the stopper (5) is provided with a vent (6) in a side wall, allowing gas exchange to take place between the inside of the vessel (1) and the surroundings when the stopper (5) is partially inserted as shown in Figure 4.
- the stopper (5) further comprises a flange (7) at the top.
- the flange (7) is arranged to seal the vessel (1) when the stopper (5) is fully inserted into the vessel (1). This will generally be done once a freeze-drying or lyophilisation procedure has been completed.
- a pierceable seal (8) is provided in the upper surface of the stopper (5).
- a secondary closure member in the form of a screw cap (9) is provided, that is able to engage with a screw thread (10) provided on the outer surface of the body section (2) in the region of the open end.
- the vessel (1) may be adapted to contain just sufficient reagents to carry out an individual chemical or biochemical reaction.
- the material placed in the vessel (1) may contain primers, enzymes, salts and optionally probes that are required to carry out a polymerase chain reaction on a particular target nucleic acid. These materials are freeze- dried in the vessel in a conventional manner. However, they can then be rehydrated by introduction of a liquid sample that contains or is suspected of containing the target nucleic acid. This may be done by removing the cap (9) and piercing the seal (8) for example with a pipette containing the liquid sample. The vessel may then be subject to conditions under which the polymerase chain reaction occurs, in particular thermal cycling conditions.
- the resulting reaction may contain multiple reactions that may be dispensed into other vessels after dissolution either prior to, or after the formation of a complete reaction through the addition of other reagents and/or template.
- the procedure can be substantially simplified and the risks of contamination minimised.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Hematology (AREA)
- Dentistry (AREA)
- Mechanical Engineering (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
- Drying Of Solid Materials (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1421188.2A GB2518080A (en) | 2012-05-18 | 2013-05-15 | Vessel of thermally conductive plastic for freeze - drying |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1208808.4A GB201208808D0 (en) | 2012-05-18 | 2012-05-18 | Novel Consumable |
GB1208808.4 | 2012-05-18 | ||
GB1301458.4 | 2013-01-28 | ||
GBGB1301458.4A GB201301458D0 (en) | 2013-01-28 | 2013-01-28 | Novel consumable |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013171483A1 true WO2013171483A1 (en) | 2013-11-21 |
Family
ID=48626463
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2013/051247 WO2013171483A1 (en) | 2012-05-18 | 2013-05-15 | Vessel of thermally conductive plastic for freeze - drying |
Country Status (2)
Country | Link |
---|---|
GB (1) | GB2518080A (en) |
WO (1) | WO2013171483A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9804644B2 (en) | 2015-01-01 | 2017-10-31 | David Lane Smith | Thermally conductive and vibration damping electronic device enclosure and mounting |
US10638748B2 (en) | 2015-12-22 | 2020-05-05 | Corning Incorporated | Break away/tear away cryopreservation vial and methods for manufacturing and using same |
US11008157B2 (en) | 2013-08-16 | 2021-05-18 | Corning Incorporated | Vessels and methods for cryopreservation |
CN114593563A (en) * | 2022-05-09 | 2022-06-07 | 常州艾立贝医疗科技有限公司 | Freeze-drying instrument for self-packaging loop-mediated amplification reagent tube and packaging method |
US11633736B2 (en) | 2018-03-22 | 2023-04-25 | Talis Biomedical Corporation | Optical reaction well for assay device |
US11649512B2 (en) * | 2013-01-28 | 2023-05-16 | Fluorogenics Ltd. | Freeze-dried composition |
US11684064B2 (en) | 2015-11-16 | 2023-06-27 | Corning Incorporated | Cryogenic vial assemblies |
US11986299B2 (en) | 2019-08-15 | 2024-05-21 | Talis Biomedical Corporation | Diagnostic system |
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US5732837A (en) * | 1994-08-19 | 1998-03-31 | W. L. Gore & Associates, Inc. | Vented vial closure member for freeze-drying which minimizes contamination of freeze-dried products |
EP0949150A2 (en) * | 1998-04-09 | 1999-10-13 | Schott Glas | Container for freeze-drying and storing medical products |
WO2008140524A1 (en) * | 2007-05-14 | 2008-11-20 | Stratagene | Compositions and reaction tubes with improved thermal conductivity |
US20090255938A1 (en) * | 2008-04-15 | 2009-10-15 | Fuja Tannin J | Cryogenic storage container |
-
2013
- 2013-05-15 GB GB1421188.2A patent/GB2518080A/en not_active Withdrawn
- 2013-05-15 WO PCT/GB2013/051247 patent/WO2013171483A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US5732837A (en) * | 1994-08-19 | 1998-03-31 | W. L. Gore & Associates, Inc. | Vented vial closure member for freeze-drying which minimizes contamination of freeze-dried products |
EP0949150A2 (en) * | 1998-04-09 | 1999-10-13 | Schott Glas | Container for freeze-drying and storing medical products |
WO2008140524A1 (en) * | 2007-05-14 | 2008-11-20 | Stratagene | Compositions and reaction tubes with improved thermal conductivity |
US20090255938A1 (en) * | 2008-04-15 | 2009-10-15 | Fuja Tannin J | Cryogenic storage container |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11649512B2 (en) * | 2013-01-28 | 2023-05-16 | Fluorogenics Ltd. | Freeze-dried composition |
US11008157B2 (en) | 2013-08-16 | 2021-05-18 | Corning Incorporated | Vessels and methods for cryopreservation |
US9804644B2 (en) | 2015-01-01 | 2017-10-31 | David Lane Smith | Thermally conductive and vibration damping electronic device enclosure and mounting |
US11684064B2 (en) | 2015-11-16 | 2023-06-27 | Corning Incorporated | Cryogenic vial assemblies |
US10638748B2 (en) | 2015-12-22 | 2020-05-05 | Corning Incorporated | Break away/tear away cryopreservation vial and methods for manufacturing and using same |
US11013230B2 (en) | 2015-12-22 | 2021-05-25 | Corning Incorporated | Break away/tear away cryopreservation vial and methods for manufacturing and using same |
US11633736B2 (en) | 2018-03-22 | 2023-04-25 | Talis Biomedical Corporation | Optical reaction well for assay device |
US11986299B2 (en) | 2019-08-15 | 2024-05-21 | Talis Biomedical Corporation | Diagnostic system |
CN114593563A (en) * | 2022-05-09 | 2022-06-07 | 常州艾立贝医疗科技有限公司 | Freeze-drying instrument for self-packaging loop-mediated amplification reagent tube and packaging method |
Also Published As
Publication number | Publication date |
---|---|
GB2518080A (en) | 2015-03-11 |
GB201421188D0 (en) | 2015-01-14 |
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