Thawing device for thawing frozen biological material

Abstract

The present invention provides a thawing device 1 for thawing frozen biological material concurrently in a multiplicity of vials 10. The thawing device 1 comprises a heating assembly 300 for heating the biological material in the multiplicity of vials 10, the heating assembly 300 including a multiplicity of receptacles 330, each receptacle 330 being configured to receive one vial 10 and being formed by at least a first heating block 334 and a second heating block 332, the first heating block 334 being movable relative to the second heating block 332 from an open position in which a vial 10 is insertable into the receptacle 330 to a heating position in which the biological material is heated in the vial 10. The thawing device 1 further comprises an agitation assembly 400 for agitating the biological material in the multiplicity of vials 10 during heating, wherein all first heating blocks 334 of all receptacles 330 are collectively movable from the open position to the heating position. The present invention also provides the use of the previous thawing device for thawing frozen biological material and a method for thawing frozen biological material concurrently in a multiplicity of vials 10 using the previous thawing device.

Description

DescriptionTitle of Invention : THAWING DEVICE FOR THAWING FROZEN BIOLOGICAL MATERIALTechnical Field

[0001] The present invention relates to a thawing device for thawing frozen biological material concurrently in a multiplicity of vials, a method for thawing frozen biological material and the use of a thawing device for thawing frozen biological material.Background Art

[0002] Biological material refers to any substance that is present or produced in a living organism.. It can be classified into two categories: natural materials and human-made materials. Natural materials include organic matter, biogenic substances, biotic materials, biomass, body fluids, cellular components, tissues, and viable materials. Human-made materials, on the other hand, include biobased materials, biocomposites, and biomaterials. Biomaterials are substances that have been engineered to interact with biological systems for medical purposes, e.g. cells derived from the human body, engineered cells for cell therapy, viruses, and viral vectors.

[0003] Biological materials are often stored at cryogenic temperatures to preserve their stability and function. However, in order to use these biological materials for further analysis, they must first be thawed. For example, blood samples are thawed before further testing can be carried out, cells are thawed prior to culturing or experiments, and tissue is thawed before histological examination can be conducted.

[0004] The purpose of a biological material thawer is to thaw biological material evenly and under controlled conditions to prevent damage. If the biological material is thawed too quickly, it can denature, which may compromise its quality or even render it unusable. A biological material thawer ensures that the biological material thaws slowly and evenly to prevent this.

[0005] There are different types of biological material thawers, each with its own mode of operation and performance characteristics. Some biological materialthawers use water to thaw the biological material, while others use air, ultrasound waves, magnetic fields, infrared, laser or microwave radiation all resulting in different thawing patterns of the biological material, that is thawing the biological material from the inside outwards, or from the outside inwards or more or less evenly.

[0006] Some biological material thawers are designed for use in laboratories, while others are suitable for use in doctor's offices or other medical facilities.

[0007] The choice of the right biological material thawer depends on a number of factors, such as the type and volume of the biological material to be thawed, the desired thawing rate, and the budget.

[0008] Biological material thawers are an essential tool for working with biological samples. They allow scientists and medical professionals to thaw biological material safely and efficiently so that they can be used for further analysis.

[0009] JP 6035178 B2 and EP 2 914 104 B1 describe different thawing devices used to thaw cryo-preserved (frozen) biological materials.

[0010] Typically, the biological material is received and stored in a vial. A vial is a small container, typically made of glass (for example, type I borosilicate glass) or plastic. Vials are commonly used in the pharmaceutical industry to store and transport vaccines, drugs, and other medical products.. But they can also be used in scientific research to store and transport samples. Vials are usually sealed with a rubber stopper or a plastic cap to prevent contamination. The volume of a vial can vary depending on its size and shape. For example, a typical vial used for vaccines may have a volume of 5 ml.

[0011] Prominent vials are the so-called “Coming® Cryogenic Vials”. These are round-bottomed and self-standing vials that are designed to withstand temperatures as low as -196°C and have an internal thread. Another example are Brooks® Azenta vials.Summary of InventionTechnical Problem

[0012] There may therefore be a need for providing an improved biological material thawer that mitigates the drawbacks of conventional biological material thawers.Specifically, the present invention aims to provide a thawing device for frozen biological material which shortens the thawing time, yet improves the quality of the thawed biological material.Solution to Problem

[0013] This and possibly other objects of the present invention are solved by the subject matter of the independent claims. Optional or preferred features of the present invention are indicated in the dependent claims.

[0014] According to a first aspect, there is provided a thawing device for thawing frozen biological material concurrently in a multiplicity of vials, comprising a heating assembly for heating the biological material in the multiplicity of vials, the heating assembly including a multiplicity of receptacles, each receptacle being configured to receive one vial and being formed by at least a first heating block and a second heating block, the first heating block being movable relative to the second heating block from an open position in which a vial is insertable into the receptacle to a heating position in which the biological material is heated in the vial, and an agitation assembly for agitating the biological material in the multiplicity of vials during heating, wherein all first heating blocks of all receptacles are collectively movable from the open position to the heating position.

[0015] The provision of a multiplicity of receptacles, each of which is configured to receive one vial with frozen biological material therein, allows a whole batch of vials to be thawed at the same time. And by collectively moving the first heating blocks towards the second heating blocks of all receptacles, the thawing process of the frozen biological material in the multiplicity of vials starts and ends at the same time, which yields comparable and possibly equal thawing results. The agitation assembly helps to thaw each biological material more uniformly and evenly as it keeps the biological material in each vial in motion during the thawing process.

[0016] In an embodiment, for each receptacle, the first heating block is linearly movable relative to the second heating block. The linear movement of the first heating block may preferably be carried out by using a linear rail assembly along which movement of the first heating block can precisely be controlled.

[0017] In an embodiment, the thawing device further comprises a proximity sensor which is configured to detect movement of the first heating blocks beyond a predetermined distance. When a vial is to be inserted into a receptacle of the thawing device, the movable first heating block needs to be moved away from the stationary second heating block. However, the movement of the first heating block needs to be controlled such that it is not moved too far away from the second heating block. For that purpose, a proximity sensor detects when the opening movement of the first heating block reaches a predetermined length of travel, and so any further movement of the first heating block beyond that predetermined distance can reliably be stopped.

[0018] In an embodiment, for each receptacle, the second heating block is stationary. This facilitates the mechanical structure of the heating assembly because only one of the heating blocks needs to be moved.

[0019] In an embodiment, for each receptacle, the first heating block is spring-biased towards the heating position. To move the first heating block to the heating position, no motorized movement is needed. The first heating block is moved towards the heating position only due to the force of a spring. The spring constant of the spring is selected such that the risk of damaging to the vial is minimized when the first heating block reaches the heating position in which the heating block touches the vial. The spring constant may also be chosen depending on the type, size and material of the vial.

[0020] In an embodiment, for each receptacle, the first heating block and the second heating block are spaced apart from one another in the heating position. Because the first heating block is spring-biased towards the second heating block, and the fact that there is a spacing between them in the heating position, the first and second heating blocks cannot interfere with each other as a result of which the first and second heating blocks would touch each other instead of touching the vial. In addition, no heat transfer from one heating block to the other heating block can occur if there is a spacing between them in the heating position.

[0021] In an embodiment, for each receptacle, the first heating block is movable from the heating position to the open position using a linear motor drive. A linear motor drive ensures uniform movement of each first heating block from the heatingposition to the open position. The linear motor drive also allows precise control of that movement.

[0022] In an embodiment, all first heating blocks of all receptacles are mechanically couplable to a movable plate, and all second heating blocks of all receptacles are mechanically coupled to a stationary base plate. The provision of a movable plate and a base plate greatly facilitates the overall construction of the heating assembly of the thawing device of the present invention. Any drive, for example the aforementioned linear motor drive, for moving the first heating blocks, needs only be operatively connected to or engaged with the movable plate, instead to or with all first heating blocks individually. This ensures uniform movement of the first heating blocks. And the base plate, on which all second heating blocks are fixedly mounted, can be used to attach the aforementioned linear motor drive.

[0023] In an embodiment, for each receptacle, the first heating block is engageable with and disengageable from the movable plate using the linear motor drive. As mentioned before, movement of the first heating block away from the second heating block is effected by preferably the linear motor drive, whereas movement of the first heating block in the opposite direction, that means towards the second heating block, is not a motorized motion, but instead is effected by the action of a spring. Therefore, the linear motor drive needs to be engaged with the movable plate only when a vial is to be inserted into or taken out from a receptacle, but may be disengaged from the movable plate when each receptacle is to be closed.

[0024] In an embodiment, for each receptacle, each of the first and second heating blocks includes a cavity in which a heating element is positioned. By positioning a heating element into a cavity in each of the first and second heating blocks, the heating blocks can be quickly heated to a predetermined temperature as all heat generated by the heating element is used to heat the first and second heating blocks. Thus, heating efficiency is enhanced. Between the heating element and the heating blocks, means for optimizing the heat transfer may preferably be provided, such as a thermally conductive material that is placed between the heating element and the heating blocks.

[0025] In an embodiment, the heating element is an electric cartridge heater. The ability of a cartridge heater to transfer heat without almost any heat loss is ofgreat advantage. As a consequence of this, the amount of energy required to thaw frozen biological material in a whole batch of vials is reduced which renders the thawing device of the present invention very economical. In addition, in case of failure of a cartridge heater, it can easily be replaced by another cartridge heater.

[0026] In an embodiment, for each receptacle, each of the first and second heating blocks includes a temperature sensor for measuring the temperature of the respective heating block. Providing a temperature sensor for each heating block, one can accurately monitor the temperature of each heating block during the thawing process, and issue an alert signal in case of failure of the heating element or even overheating of a heating block. This may be important in case of replacement of the heating element by another heating element not having identical heating characteristics for some inexplicable reasons.

[0027] In an embodiment, for each receptacle, the shape of the first and second heating blocks is semi-cylindrical. As vials are usually tubular, the heat transfer between semi-cylindrical heating blocks and a tubular vial is optimized due to the contact area between each heating block and the vial being enlarged compared to other geometrical shapes of heating blocks.

[0028] In an embodiment, the agitation assembly is configured to effect collective orbital motion of the multiplicity of vials. In principle, different types of motion effected by the agitation assembly are conceivable. However, a continuous orbital motion with no abrupt stops, starts and changes in direction which would otherwise possibly cause damage to the biological material is thought to be advantageous.

[0029] In an embodiment, the agitation assembly includes a rotatable plate which is configured to be driven by an off-axis drive shaft. By using only one off-axis drive shaft, an eccentric orbital motion can be generated. In addition, the mechanical construction of the agitation assembly is facilitated.

[0030] In an embodiment, the drive shaft is coupled to a stepper motor. Stepper motors are relatively low-cost motorized drives, and their availability is fairly large. They can be installed by plug and play, and they are easy to configure and fairly easy to use. In addition, stepper motors offer excellent speed control as well asprecise positioning and repeatability of movement. Hence, they are of great benefit for driving the agitation assembly.

[0031] In an embodiment, a radiation thermometer is attached to the rotatable plate such that at least a bottom of one vial is in the field of view of the radiation thermometer. The radiation thermometer offers a contactless, non-destructive measurement of the surface temperature of the vial. By measuring the surface temperature of the vial and correlating the vial’s surface temperature to the temperature of the biological material inside the vial, for example by using a lookup table, the temperature of the biological material can be closely monitored during the thawing process. As for the radiation thermometer, an infrared sensor with a measuring range from -30°C to +150°C may preferably be used.

[0032] In an embodiment, the thawing device of the present invention further comprises a tray assembly having a multiplicity of apertures, wherein each aperture is configured to receive one vial, and wherein a spring clip in the proximity of each aperture is configured to frictionally engage the vial, and wherein the tray assembly includes at least one guide pin which is insertable into a respective hole in the heating assembly. The tray assembly of this embodiment of the invention is able to receive a multiplicity of vials in each of the apertures provided in the tray assembly. The spring clip ensures that the vials cannot move within each aperture. The spring clip further has the advantage that different types and sizes of vials may be accommodated in each aperture, and so one and the same tray assembly may be used for different types of vials. The guide pin allows for an accurate positioning of the vials in the receptacles of the heating assembly in a consistent and invariable manner.

[0033] In an embodiment, the thawing device of the present invention further comprises a housing assembly having a movable lid assembly to open and close the housing assembly, wherein the heating assembly and the agitation assembly are positioned within the housing assembly. The housing assembly provides a dust-proof enclosure for the internal components of the thawing device, such as the heating assembly and the agitation assembly. Yet, the lid assembly allows easy access to the inside of the housing assembly. And because the lid assembly can be closed, the vials are protected during the thawing process. Also, when the thawing device is not in use, it can easily be stored away by closing the lidassembly, thus protecting the internal components of the thawing device from environmental impact, such as dust or other type of contamination, humidity, etc.

[0034] In an embodiment, the thawing device of the present invention further comprises an identification unit, wherein the identification unit is configured to at least identify a batch ID containing characteristics of the biological material in the multiplicity of vials, and a recipe ID containing characteristics of the thawing process to be used to thaw the frozen biological material in the multiplicity of vials. An operator ID which may be implemented softwarewise in the graphical user interface of the thawing device unambiguously identifies an operator handling the thawing device. It also prevents unauthorized use of the thawing device by an operator who is not qualified or otherwise permitted to use the thawing device. The batch ID unambiguously identifies the biological material to be thawed. For example, the type and the volume of the biological material to be thawed may be characterized by the batch ID. The batch ID may also indicate the origin of the biological material and the type of vial used for thawing the biological material. The recipe ID includes details of the thawing process, such as thawing duration, thawing temperature, thawing rate, type of movement of the agitation assembly, etc. The recipe ID may also include information about to what degree the biological material is to be thawed. For example, there may be biological material that needs to be thawed until the entire biological material is liquid, or there may be biological material that needs to be thawed only partially. The batch ID and the recipe ID can be identified by the identification unit which is provided preferably on the outside of the housing of the thawing device.

[0035] In an embodiment, the thawing device of the present invention further comprises a memory configured to store an operator ID, the batch ID and the recipe ID. By storing an operator ID, the batch ID and the recipe ID, the entire thawing process from the very beginning to the very end can be rendered transparent and allows even many years later an identification of the operator, the batch of biological material and certain details of the thawing process, for example, to fulfill possibly existing documentation requirements.

[0036] In an embodiment, the identification unit is fixedly mounted to an exterior surface of the housing. As a result, the identification unit is easily accessible by the operator.

[0037] According to a second aspect, there is provided the use of the thawing device according to the first aspect for thawing frozen biological material

[0038] According to a third aspect, there is a provided a method for thawing frozen biological material, wherein the method uses the thawing device according to the first aspect.

[0039] It is noted that the above embodiments (features) may be freely combined with each other irrespective of their order and the aspect they relate to.

[0040] These and other aspects of the present invention will become apparent from and elucidated with reference to the embodiments described hereinafter.Brief Description of Drawings

[0041] Exemplary embodiments of the invention will now be described in the following with reference to the drawings.Fig.1

[0042] [Fig.1 ] shows an exploded view of the main components of the thawing device according to a preferred embodiment of the invention;Fig.2

[0043] [Fig.2] is a perspective illustration of the heating assembly according to a preferred embodiment of the invention;Fig.3

[0044] [Fig.3] is an exploded view of the heating assembly shown in Fig. 2;Fig.4a

[0045] [Fig.4a] shows an upper perspective view of a receptacle;Fig.4b

[0046] [Fig.4b] shows a lower perspective view of the receptacle of Fig. 4a;Fig.5

[0047] [Fig.5] shows a cross-sectional view of the receptacle of Fig. 4a;Fig.6a

[0048] [Fig.6a] is a cross-sectional view of the heating assembly shown in Fig. 2;Fig.6b

[0049] [Fig.6b] is an enlarged view of a nose portion of the receptacle of Fig. 4a;Fig.7

[0050] [Fig.7] is an exploded view of the agitation assembly according to a preferred embodiment of the invention;Fig.8a

[0051] [Fig.8a] shows a cross-sectional view of the agitation assembly of Fig. 7;Fig.8b

[0052] [Fig.8b] is a top view of the agitation assembly of Fig. 7;Fig.9a

[0053] [Fig.9a] is a perspective view of the agitation assembly of Fig. 7;Fig.9b

[0054] [Fig.9b] shows a radiation thermometer positioned below a vial;Fig.10a

[0055] [Fig.10a] is a perspective view of the tray assembly according to a preferred embodiment of the invention;Fig.10b

[0056] [Fig.10b] is a side view of the tray assembly of Fig. 10a;Fig.10c

[0057] [Fig.10c] is a bottom view of a modified tray assembly according to another preferred embodiment of the invention;Fig.11

[0058] [Fig.11 ] is a perspective view of the thawing device with the tray assembly being taken out from the housing;Fig.12

[0059] [Fig.12] is a flow diagram of a preferred mode of operation of the thawing device.Description of Embodiments

[0060] In principle, the thawing device of the present invention can be used to thaw any type of biological material received in any known type of vial. The biological material considered in the context of the present invention may be a natural material, such as organic matter, biogenic substances, biotic materials, biomass, body fluids, cellular components, tissues and viable materials, or human-made materials, such as bio-based materials, biocomposites and biomaterials. Biomaterials are substances that have been engineered to interact with biological systems for medical purposes, e.g. cells derived from the human body, e.g. stem cells, engineered human cells for cell therapy, viruses, and viral vectors.

[0061] The biological material is conventionally stored in vials at cryogenic temperatures, and so the frozen biological material must first be thawed before they can undergo further analysis. The vials considered in the context of the present invention may be made from glass, such as type I borosilicate glass, or plastic. These vials may be sealed with a rubber stopper or a plastic cap to prevent contamination. The volume of the vials typically ranges from 1 - 50 ml. Typical vials used in the context of the thawing device of the present invention may have a volume of 1 ml or may have a volume of 5 ml. Examples of such vials are the so-called “Coming® cryogenic vials”, Brooks® Azenta vials and Aseptic Technologies AT-Closed Vials®.

[0062] It is noted that some aspects of the thawing device of the present invention are described with reference to constructional features, whereas other aspects of the thawing device of the present invention are described with reference to its use. A person skilled in the art, however, will gather from the above and the following description that these constructional features may well be combined with any use features, for example by “means plus function” features, unless otherwise notified. Such combinations are therefore considered to be disclosed in this application.

[0063] Fig. 1 shows a simplified, exploded view of the main components of the thawing device 1 according to a preferred embodiment of the invention. These main components include a lid assembly 100, a tray assembly 200, a heating assembly 300, an agitation assembly 400 and a housing assembly 500. These main components are described in more detail with reference to Figs. 2 to 11 below.

[0064] The heating assembly 300 is shown in a perspective view in Fig. 2. The heating assembly includes a multiplicity of receptacles 330 which are circularly arranged in the heating assembly 300. Each receptacle 330 defines a cavity 331 which is configured to receive one vial in which the biological material to be thawed is contained. Each receptacle 330 is formed or comprises a movable first heating block 334 and a stationary second heating block 332. Movement of the first heating block 334 is caused by a drive 340, preferably a motorized drive. The heating assembly 300 further includes a base plate 320 and a movable plate 310. Each first heating block 334 is mechanically couplable or mechanically engageable with the movable plate 310, whereas the second heating blocks 332 are fixedly mounted on the base plate 320.

[0065] The heating blocks 334, 332 are preferably made from aluminium due to its superior thermal conductivity and low weight.

[0066] Fig. 3 is an exploded view of the heating assembly 300 of Fig. 2. From top to bottom, Fig. 3 shows the movable plate 310, the drive 340, the multiplicity of receptacles 330 and the base plate 320 which are described in more detail below.

[0067] The movable plate 310 exhibits a planar circular shape. It includes a multiplicity of openings 312, 314. A central opening 314 is for the accommodation of the drive 340 which projects vertically therethrough (see Fig. 2 and Fig. 6). The multiplicity of openings 312 are circularly arranged in the movable plate 310. The size and shape of the openings 312 varies. The purpose, however, of each opening 312 is essentially the same. These openings 312 serve the purpose to accommodate therein the receptacles 330. A mount 316 is fixedly mounted to the upper surface of the movable plate 310, the purpose of which will be explained below.

[0068] The drive 340 is preferably a motorized drive, more preferably a linear motor drive. Two linear guide rails 342a, 342b are provided to guide movement of the movable plate 310 along a linear path along the guide rails 342a, 342b. Fig. 3 shows a motorized drive 340 which includes a drive shaft 348 and a drive nut 344.

[0069] As explained above, each receptacle 330 includes a movable first heating block 334 and a stationary second heating block 332. The number of receptacles 330 is preferably 10, but may well be in a range from 2 to 30. In principle, thenumber of receptacles 330 may depend on the size of the thawing device 1 and the size of the vials used in the context of the thawing device 1.

[0070] The base plate 320 also has a planar circular shape. It includes a multiplicity of openings 322 the number of which corresponds to the number of receptacles 330. It also includes a central opening 321 into which a portion of the motorized drive 340 projects. The base plate 320 includes a vertically extending abutment 327 with which the motorized drive 340 is connected. A guide 328 with a through- hole is arranged at a predetermined distance from the abutment 327. In the assembled state, the free end of the drive shaft 348 extends into the through-hole of the guide 328. Two recesses 325, 326 are positioned on opposite sides of the central opening 321 and the abutment 327, and serve the purpose to receive therein the guide rails 342a, 342b of the motorized drive 340. The guide rails 342a, 342b are preferably fixed in the recesses 325, 326 using screws. The base plate 320 further includes several fixations 324 for fixedly mounting the second heating blocks 332 to the base plate 320, and two vertically extending tubular posts 329 the purpose of which will be explained further below.

[0071] Fig. 4a shows a perspective top view of one receptacle 330. As mentioned above, each receptacle 330 includes a movable first heating block 334 and a stationary second heating block 332. Both heating blocks 332, 334 have a cross- sectional shape of a semi-circle and define a cavity 331 into which a vial can be inserted. The first heating block 334 is spring-biased towards the second heating block 332. Preferably, two springs 335a, 335b are positioned on opposite sides of the tubular cavity 331 . The spring constant of the two springs 335a, 335b is selected such that when the first heating block 334 can freely move, it smoothly touches the outer surface of the vial without the risk of damaging the vial.

[0072] The first heating block 334 includes a nose portion 334a with a vertically extending through-hole into which a post 318 (shown in Fig. 6b) engageable or engaged with the movable plate 310 can project. A pin 333 extends along a horizontal through-hole, and it is the pin 333 which engages the post 318 (Fig. 6b) of the movable plate 310 during movement of the first heating block 334. The stationary second heating block 332 includes two shoulder portions 332a, 332b by means of which the second heating block 332 can fixedly be connected with the base plate 320 by means well known to the skilled person.

[0073] Fig. 4b shows a perspective bottom view of the receptacle 330 of Fig. 4a. To avoid undue repetitions, only those aspects of the receptacle 330 will be described now, which cannot clearly be seen from the perspective top view of Fig. 4a.

[0074] Each heating block 332, 334 includes a cavity into which a portion of a heating element assembly 336, 338 can be inserted. Each heating element assembly 336, 338 includes a heating element 336b, 338b, which is preferably a cartridge heater. These heating elements 336b, 338b are received in the cavities of the heating blocks 332, 334 and are wired, using electrical leads 336a, 338a, to the main PCB (printed circuit board) control 430 (Fig. 7) of the thawing device 1 of the present invention. Each heating block 332, 334 also includes a temperature sensor assembly 337, 339 to measure the temperature of each heating block 332, 334 during the thawing process. Each temperature sensor 337a, 339a, which is preferably a thermocouple, is also wired, using an electrical lead 337a, 339a, to the main PCB control 430 of the thawing device 1 of the present invention.

[0075] Fig. 5 shows a cross-sectional view of the receptacle 330 into which a vial 10 has been inserted. As can clearly be seen in Fig. 5, a heating element 336b, 338b extends vertically through each heating block 332, 334 approximately from the bottom of the inserted vial 10 almost up to the upper end of each heating block 332, 334. In addition, a temperature sensor 337b, 339b is received within each heating block 332, 334. The location of the temperature sensor 337b, 339b is such that it measures the body or core temperature of each heating block 332, 334. For this reason, the temperature sensors 337b, 339b should not be positioned too close to the heating elements 336b, 338b.

[0076] Fig. 6 shows a cross-sectional view of the assembled heating assembly 300. A number of vials 10 are received by the heating assembly 300. Specifically, one vial 10 is received in the cavity 331 of each receptacle 330 which is defined by the first heating block 334 and the second heating block 332. The movable plate 310 is located above the base plate 320.

[0077] The motor drive 346 is located in the proximity of the center of the movable plate 310 and the base plate 320. The drive shaft 348 of the motor drive 346extends parallel to the movable plate 310 and the base plate 320. A motor nut 344 is connected to the mount 316 (see also Fig. 3) of the movable plate 310. The motor drive 346 is connected to the abutment 327 of the base plate 320. The drive shaft 346 extends through the abutment 327, the motor nut 344, the mount 316 and the guide 328 of the base plate 320.

[0078] When the motor drive 346 rotates and translates the drive shaft 348 to the left in Fig. 6, that means backwards, the movable plate 310 moves to the left. The posts 318 shown in Fig. 6b which are coupled to the movable plate 310 then engage with the pins 333 (Fig. 4a) and cause movement of the first heating blocks 334 to the left to thus open each receptacle 330 collectively. When the opening position of the first heating block 334 has been reached, a vial 10 can be inserted or taken out from the cavity 331 of each receptacle 330. Once the motor drive 346 is disengaged from the movable plate 310, the springs 335a, 335b cause movement of the movable plate 310 to the right, thereby disengaging the posts (not shown) of the movable plate 310 from the pins 333 and thus closing each receptacle 330 collectively with all other receptacles 330 and bringing the first heating block 334 in direct contact with the vial 10. In the heating position, the first heating block 334 does not contact the second heating block 332.

[0079] A proximity sensor 349a is received in a sensor adaptor 349b and detects movement of the movable plate 310 to the left. The proximity sensor 349a may transmit a signal to the main PCB control 430, when the length of travel of the movable plate 310 exceeds a predetermined threshold value. The main PCB control then sends a signal to the motor drive 346 in order to stop rotation of the drive shaft 348 and to thus stop movement of the movable plate 310 to the left.

[0080] Fig. 7 shows an exploded view of the agitation assembly 400. The agitation assembly 400 predominantly serves the purpose to keep the biological material in motion during the thawing process in order to uniformly, evenly and homogeneously thaw the biological material.

[0081] The agitation assembly 400 includes a rotatable plate 410 which has preferably a circular or ring-shaped base 411 with a vertically extending rim 413 that extends all the way around the base 411 . The base 411 includes a central opening 415 which is preferably also circular, and around which a verticallyextending rim 417 is provided. The rim 417 is discontinuous as it is interrupted by preferably three tubular-shaped apertures 412a, 412b, 414. Another through-hole 416 is provided in the base 411 which serves as a window for a radiation thermometer 450, preferably an infrared sensor, positioned below the through- hole 416.

[0082] One end of a bearing 422a, 422b and 424 is inserted into corresponding aperture 412a, 412b and 414, and the other opposite end of the bearing 422a, 422b and 424 is located within a corresponding aperture 421a, 421 b and 423 provided in a pedestal 420. In an assembled state, the rotatable plate 410 is supported by the pedestal 420, with the bearings 422a, 422b, 424 engaging both the apertures 421a, 421 b, 423 of the pedestal 420 and the apertures 412a, 412b, 414 provided in the rotatable plate 410.

[0083] Below the pedestal 420 is provided the main PCB control 430 that includes all electrical controls (active or passive electrical devices) of the electrical components of the thawing device 1 . A motor 432, preferably a stepper motor, and a main driver 434 are located on top of the PCB board 431 . The drive shaft of the motor 432 extends through the aperture 423, the bearing 424 and the aperture 414. Due to the apertures 414, 423 being off-axis, the motor 432 causes an eccentric orbital motion of the rotatable plate 410. To support and stabilize the eccentric orbital motion of the rotatable plate 410, the rotatable plate 410 is supported by two off-axis and non-concentric bearings 422a, 422b which thus form two off-axis and non-concentric support axes.

[0084] The main PCB control 430 is received within a base 440 of the agitation assembly 400. The base 440 includes a multiplicity of vertically extending mounting brackets 442 arranged on the circumference of a planar plate 441. A barcode reader 443 is fixedly mounted on the top surface of the planar plate 441 of the base 440.

[0085] Fig. 8a shows a cross-section of the assembled agitation assembly 400. The PCB board 431 of the main PCB control 430 is attached to the planar plate 441 of the base 440 using preferably nuts and screws 444. In the assembled state, the PCB board 431 is spaced apart from the plate 441 . The legs of the pedestal 420 rest on the plate 441 . The motor 432 is mounted to the PCB board 431 , and thedrive shaft of the motor 432 extends vertically all the way through the aperture 423, the bearing 424 and the aperture 440. Fig. 8a also shows the off-axis positions of the drive shaft of the motor 432 and the off-axis position of one support axis 422a. In the assembled state, the rotatable plate 410 is positioned above the mounting brackets 442 of the base 440.

[0086] Fig. 8b is a top view of the agitation assembly 400 which clearly shows the non-concentric drive shaft 424 and the non-concentric support axes 422a, 422b. Fig. 8b also indicates the position of the radiation thermometer 450 and shows the barcode reader 443 at a position which is easily accessible by an operator.

[0087] With reference to Fig. 9a, which is a perspective view of the assembled agitation assembly 400, the radiation thermometer 450 has a field of view that extends through the aperture 416 (Fig. 7) provided in the base 411 of the rotatable plate 410. The field of view of the radiation thermometer 450, as is shown in Fig. 9b, reaches the bottom of a vial 10. The radiation thermometer 450 can therefore be used to measure the surface temperature of the vial 10. The vial’s surface temperature may be correlated to the core temperature of the biological material contained in the vial 10 using a look-up table. The values of the look-up table may be determined beforehand by a series of experiments carried out under laboratory conditions. The measuring range of the radiation thermometer is preferably from -30°C to +150°C. As is also shown in Fig. 9a, the radiation thermometer 450 is mounted to the rotatable plate 410, and the distance between the radiation thermometer 450 and the vial 10 is selected such that optimized measurement results of the surface temperature of the vial 10 are obtained.

[0088] Fig. 10a shows a perspective view of a tray assembly 200 which includes, in a central portion, preferably two slots 210 sized for the insertion of a hand of an operator manually handling the tray assembly 200. The tray assembly 200 further includes a multiplicity of apertures 202, each of which is configured to receive a vial 10.

[0089] With reference to Fig. 10b, a spring clip 204 is provided in each aperture 202, which frictionally engages a vial 10 (Fig. 10b). The tray assembly 200 further includes at least one, preferably three leveling posts 208 which may be used tolevel the tray assembly 200 over a table. The leveling posts 208 are arranged at positions which enable the tray assembly 200 to rest stably on a flat surface, such as a table. To this end, the leveling posts 208 are preferably equidistantly spaced to one another in proximity of the perimeter of the tray assembly 202. Preferably two positioning pins 206 help to accurately position the tray assembly 200 over the heating assembly 300 by inserting the positioning pins 206 into the tubular posts 329 provided in the base plate 320 of the heating assembly 300.

[0090] Fig. 10c shows a slightly modified tray assembly 202 in order to adapt to another type of vial 10, for example the Brooks® Azenta vial. Again, spring clips 204 are used to fictionally engage each vial 10. The modification here lies in a collar 212 which matingly engages with structure on the cap of the vial 10. This structure on the cap of the vial 10 may preferably be vertically extending ribs arranged around the perimeter of the vial’s cap.

[0091] Fig. 11 shows how the tray assembly 200 is placed inside the housing assembly 500 of the thawing device 1 . The positioning pins 206 are inserted into holes 360. The holes 360 are provided in a circular plate, which is preferably made of aluminum. The circular plate is a part of the heating assembly 300, but is not shown in the exploded view of Fig. 3 and Fig. 1 . The holes 360 align with the tubular posts 329 in the base plate 320. The leveling pin 208 is also inserted through a hole (not shown) of the heating assembly 300. Once the tray assembly 200 is fully inserted and placed inside the housing assembly 500, the lid assembly 100 can be closed. The barcode reader is indicated at reference numeral 443.

[0092] A full batch of vials 10, preferably ten vials, can be loaded into the thawing device 1 using the tray assembly 200. In order to load the batch of vials 10 onto the tray assembly 200, an auxiliary loading plate (not shown) is used which has the same geometrical shape as the tray assembly 200 as well as the same number of apertures at the same location as the apertures 202 of the tray assembly 200. The auxiliary loading plate is manually loaded with the batch of vials 10, and is then placed on top of the tray assembly 200 so that the vials in the auxiliary loading plate align with the apertures 202 of the tray assembly 200. The auxiliary loading plate is then lowered so that the vials are pushed through the apertures 202 and the spring clips 204 in the tray assembly 200. Once a“click” can be heard, the vials have been pushed down far enough into the tray assembly 200. The loading plate can then be lifted upwards as a result of which loading of the tray assembly 200 with the batch of vials 10 is completed.

[0093] The thawing process is now described with reference to Fig. 12. Conventionally, the batch of vials with the frozen biological material therein is conventionally stored in a cryogenic unit, in Fig. 12 named as a cryo-preserve unit, which is usually cooled at -196°C using liquid nitrogen. The batch of vials is first taken out of the cryo-preserve unit and is placed inside a transport cooling chamber by means of which the batch of vials can be transported to the location of the thawing device 1 , for example in a laboratory.

[0094] Before the thawing process can start, the batch ID and the recipe ID are scanned using the barcode reader 443 of the thawing device 1 . Applying the aforementioned loading process of the tray assembly 200, the batch of vials is placed inside the preheated thawing device 1 . The operator then presses the start button, and the recipe ID then governs the entire thawing process, such as “thaw start”, duration, thawing rate and “thaw end”. The duration of the thawing process also depends on the surface temperature of the vial measured by the radiation thermometer 450 at the beginning of the thawing process.

[0095] Once the thawing device 1 indicates “thaw end”, the lid assembly 100 is opened and the batch of vials is taken out using the tray assembly 200. The batch of vials is then transferred into a cooling chamber where the batch of vials remains until further analysis commences. At the end of the thawing process, data recorded by the thawing device 1 during the thawing process are extracted for the sake of proper documentation.Citation List

[0096] Patent Literature

[0097] PTL1 : JP 6035178 B2

[0098] PTL2: EP 2 914 104 B1

Claims

Claims

1. Thawing device (1 ) for thawing frozen biological material concurrently in a multiplicity of vials (10), comprising: a heating assembly (300) for heating the biological material in the multiplicity of vials (10), the heating assembly (300) including a multiplicity of receptacles (330), each receptacle (330) being configured to receive one vial (10) and being formed by at least a first heating block (334) and a second heating block (332), the first heating block (334) being movable relative to the second heating block (332) from an open position in which a vial (10) is insertable into the receptacle (330) to a heating position in which the biological material is heated in the vial (10), and an agitation assembly (400) for agitating the biological material in the multiplicity of vials (10) during heating, wherein all first heating blocks (334) of all receptacles (330) are collectively movable from the open position to the heating position.

2. Thawing device (1 ) of claim 1 , wherein for each receptacle (330), the first heating block (334) is linearly movable relative to the second heating block (332).

3. Thawing device (1 ) of claim 1 or 2, further comprising a proximity sensor (349a) which is configured to detect movement of the first heating blocks (334) beyond a predetermined distance.

4. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), the second heating block (332) is stationary.

5. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), the first heating block (334) is spring-biased towards the heating position.

6. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), the first heating block (334) and the second heating block (332) are spaced apart from one another in the heating position.

7. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), the first heating block (334) is movable from the heating position to the open position using a linear motor drive (346).

8. Thawing device (1 ) of any of the preceding claims, wherein all first heating blocks (334) of all receptacles (330) are mechanically couplable to a movable plate (310), and all second heating blocks (332) of all receptacles (330) are mechanically coupled to a stationary base plate (320).

9. Thawing device (1 ) of claim 8 as far as claim 8 depends on claim 7, wherein for each receptacle (330), the first heating block (334) is engageable with and disengageable from the movable plate (310) using the linear motor drive (346).

10. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), each of the first heating block (334) and the second heating block (332) includes a cavity in which a heating element (336b, 338b) is positioned.

11. Thawing device (1 ) of claim 10, wherein the heating element (336b, 338b) is an electrical cartridge heater.

12. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), each of the first heating block (334) and the second heating block (332) includes a temperature sensor (337b, 339b) for measuring the temperature of the respective heating block (332, 334).

13. Thawing device (1 ) of any of the preceding claims, wherein for each receptacle (330), the shape of the first heating block (334) and the second heating block (332) is semi-cylindrical.

14. Thawing device (1 ) of any of the preceding claims, wherein the agitation assembly (400) is configured to effect collective orbital motion of the multiplicity of vials (10).

15. Thawing device (1 ) of claim 14, wherein the agitation assembly (400) includes a rotatable plate (410) which is configured to be driven by an off- axis drive shaft (432a).

16. Thawing device (1 ) of claim 15, wherein the drive shaft (432a) is coupled to a stepper motor (432).

17. Thawing device (1 ) of claim 15 or 16, wherein a radiation thermometer (450) is attached to the rotatable plate (410) such that at least a bottom of one vial (10) is in the field of view of the radiation thermometer (450).

18. Thawing device (1 ) of any of the preceding claims, further comprising a tray assembly (200) having a multiplicity of apertures (202), wherein each aperture (202) is configured to receive one vial (10), and wherein a spring clip (204) mounted in the proximity of each aperture (202) is configured to frictionally engage the vial (10), and wherein the tray assembly (200) includes at least one guide pin (206) which is insertable into a respective hole (329) in the heating assembly (300).

19. Thawing device (1 ) of any of the preceding claims, further comprising a housing assembly (500) being openable and closable by a lid assembly (100), wherein the heating assembly (300) and the agitation assembly (400) are positioned within the housing assembly (500).

20. Thawing device (1 ) of any of the preceding claims, further comprising an identification unit (443), wherein the identification unit (443) is configured to at least identify a batch ID containing characteristics of the biological material in the multiplicity of vials (10), and a recipe ID containing characteristics of the thawing process used to thaw the frozen biological material in the multiplicity of vials (10).

21. Thawing device (1 ) of claim 20, further comprising a memory configured to store an operator ID, the batch ID and the recipe ID.

22. Thawing device (1 ) of claim 20 or 21 , wherein the identification unit (443) is fixedly mounted on an exterior surface of the housing assembly (500).

23. Use of the thawing device (1 ) of any of the preceding claims for thawing frozen biological material concurrently in a multiplicity of vials (10).

24. Method for thawing frozen biological material concurrently in a multiplicity of vials (10), wherein the method uses the thawing device (1 ) of any one of claims 1 to 22, the method comprising the steps of:loading a multiplicity of vials (10) in a heating assembly (300) of the thawing device (1 ), the heating assembly (300) including a multiplicity of receptacles (330), each receptacle (330) being configured to receive one vial (10) and being formed by at least a first heating block (334) and a second heating block (332); collectively moving all first heating blocks (334) of all receptacles (330) from an open position to a heating position; and starting thawing the frozen biological material concurrently in the multiplicity of vials (10).

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