Patent Publication Number: US-11650006-B2

Title: Systems and methods for remotely monitoring the cryogenic processing of samples

Description:
CROSS REFERENCES TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 16/463,705 filed on May 23, 2019, which claims the priority benefit of PCT/GB2017/053532 filed on Nov. 24, 2017 which claims priority benefit of Great Britain Application No. 1620017.2 filed Nov. 25, 2016. The entire contents of which are hereby incorporated by reference herein. 
    
    
     BACKGROUND 
     The present techniques relate to systems and methods for remotely monitoring the cryogenic processing of samples. More particularly, the techniques relate to systems and methods for remotely monitoring the cryogenic freezing, the cryogenic storing, the cryogenic transportation and the cryogenic thawing of samples. 
     Cryogenic processing of a sample involves temperatures below −90° C. (−130° F.). The cryogenic freezing of a sample involves reducing the temperature of the sample to, or below,
         90° C. The cryogenic thawing of a sample involves increasing the temperature of the sample from −90° C. or below. The cryogenic storing and the cryogenic transportation of a sample involves maintaining the temperature of the sample at, or below, −90° C. In most instances the cryogenic storing and the cryogenic transportation of a sample involves maintaining the temperature of the sample at the temperature at which it was cryogenically frozen.       

     Cryogenic processing can be utilised in many different fields, such as regenerative medicine, biobanks, atmospheric microphysics, conservation, assisted reproduction, transgenics, food processing, freeze drying. Cryogenic processing can be used for a variety of products, these include cells and tissues for clinical application for example in the fields of regenerative medicine, transplantation, transfusion and vaccination, where the requirement is to maintain cell viability and function on thawing, or tissue integrity and functionality. Cryogenic processing can be used can also be used with non cellular materials, for example with traditional vaccines and for acellular samples for biobanking. 
     SUMMARY OF THE INVENTION 
     The cryogenic processing described herein may be used for the transport of samples such as T cells and haematopoietic cells from patients to centres which manufacture immunotherapies or gene therapies, or biopsies from the operating theatre to biobanks for long term storage. The cryogenic processing described herein may also be used to transport manufactured cell products such as immunotherapies or gene therapies from the site of manufacturing to the patient. 
     In order to maintain, and confirm, the integrity of a sample at every point throughout its processing, from freezing to storage to transporting and to thawing, close monitoring of the sample is required. 
     According to a first aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to a second aspect of the present techniques, there is provided a method for remotely monitoring cryogenic processing of a sample. 
     According to a third aspect of the present techniques, there is provided a cryogenic freezer for freezing a sample in accordance with a sample freezing profile. 
     According to a fourth aspect of the present techniques, there is provided a cryogenic thawing machine for thawing a sample in accordance with a sample thawing profile. 
     According to a fifth aspect of the present techniques, there is provided a cryogenic transportation device for transporting a cryogenically frozen sample in accordance with a sample transportation profile. 
     According to a sixth aspect of the present techniques, there is provided a remote server for remotely monitoring cryogenic processing of a sample. 
     According to a seventh aspect of the present techniques, there is provided a computer program product comprising computer code for performing any of the methods described herein. 
     According to an eighth aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to a ninth aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to a tenth aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to an eleventh aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to a twelfth aspect of the present techniques, there is provided a system for remotely monitoring cryogenic processing of a sample. 
     According to a thirteenth aspect of the present techniques, there is provided a method for remotely monitoring cryogenic processing of a sample. 
     According to a fourteenth aspect of the present techniques, there is provided a method for remotely monitoring cryogenic processing of a sample. 
     Preferred features are set out in the appended dependent claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Embodiments will now be described with reference to the accompanying Figures of which: 
         FIG.  1    schematically illustrates a cryogenic freezer; 
         FIG.  2    illustrates a predetermined freezing profile; 
         FIG.  3    illustrates a detected plate temperature during a freezing cycle; 
         FIG.  4    illustrates a detected sample temperature during a freezing cycle; 
         FIG.  5    illustrates the predetermined freezing profile of  FIG.  2   , the detected plate temperature of  FIG.  3    and the detected sample temperature of  FIG.  4   ; 
         FIG.  6    schematically illustrates a remote server; 
         FIG.  7    schematically illustrates a system for monitoring one or more cryogenic freezers; 
         FIG.  8    illustrates a graph of the detected plate temperature of  FIG.  3    and the detected sample temperature of  FIG.  4    and annotated with “observations”; 
         FIG.  9    schematically illustrates an overview of the processing of a biological sample; 
         FIG.  10    schematically illustrates a thawing machine; 
         FIG.  11    illustrates a thawing profile; 
         FIG.  12    illustrates a detected sample temperature during a thawing cycle; 
         FIG.  13    schematically illustrates a system for monitoring one or more thawing machines; 
         FIG.  14    illustrates the detected sample temperature of  FIG.  12    as transferred to the server of  FIG.  6    and annotated with “observations”; 
         FIG.  15    schematically illustrates a storage device; 
         FIG.  16    schematically illustrates schematically a remote system for monitoring one or more devices for use in the cryogenic processing of a sample; 
         FIG.  17    illustrates a graph of two different sets of detected thawing temperatures; and 
         FIG.  18    illustrates a graph of the power required to cool a biological sample through the ice formation region. 
     
    
    
     DETAILED DESCRIPTION 
     A remote system for monitoring and controlling one or more devices for use in the cryogenic processing (e.g. freezing, cooling and/or thawing) of a sample is provided. The remote system may use freezing profile data and/or thawing profile data for the cryogenic processing. A remote server is capable of transmitting freezing profile data to one or more freezers, transmitting storage profile data to one or more storage devices and/or transportation devices, and transmitting thawing profile data to one or more thawing devices. The remote server is also capable of receiving detected data from the one or more freezers relating to the freezing of a sample in accordance with the freezing profile data, receiving detected data from the one or more storage devices and/or transportation devices relating to the storage and/or transportation of a sample in accordance with the storage profile data, and receiving detected data from the one or more thawing machines relating to the thawing of a sample in accordance with the thawing profile data. The detected freezing data and/or the detected thawing data may be recorded/stored, and may be provided to a user/third party. 
     In order to cryogenically freeze a sample, a cryogenic freezer, such as a freezer in the VIA FREEZE range by ASYMPTOTE can be used.  FIG.  1    schematically illustrates a cryogenic freezer  1 . As can be seen from  FIG.  1   , a cryogenic freezer  1  comprises a freezer compartment  28 , within which a sample  30  to be frozen may be provided, coupled to a heat removal unit  32 . The freezer  10  also comprises a control module  10  comprising at least one processor  12  coupled to at least one memory  18 , at least one user interface  14 , at least one communications interface  26 , at least one data store  16 , and at least one sensor  20 ,  22 ,  24  . . . n. The freezer  10  may also comprise other elements which are not illustrated. 
     The memory  18  may comprise program memory for storing computer program code to control the heat removal unit  32  in order to freeze a sample  30  as described herein, and working memory for storing data, programs, or instructions received or processed by the processor  12 . The memory  18  and/or the data store  16  may comprise a volatile memory such as random access memory (RAM), for use as a temporary memory. Additionally or alternatively, the memory  18  and data store  16  may comprise non-volatile memory such as Flash, read only memory (ROM) or electrically erasable programmable ROM (EEPROM). 
     The processor  12  may comprise processing logic to process data (for example, data received from the sensors  20 ,  22 ,  24 , . . . n, programs, instructions received from a user via the user interface  14  etc.) and generate output signals in response to the processing. The control module  10  may comprise any suitable circuitry or logic, and may, for example, comprise any one or more of the following: a field programmable gate array (FPGA), system on chip device, microprocessor device, microcontroller, and one or more integrated circuits. The control module  10  is coupled to the heat removal unit  32  in order to control the temperature in the freezer compartment  28 . 
     The user interfaces  14  may be one or more of a computer screen, a touch screen, a keyboard, a mouse, speakers, a bar code scanner, a fingerprint scanner etc. 
     The communication module  26  may be conFigured to receive data or data signals from one or more external devices (such as a remote server as described herein). The communication module  26  may be a communication interface or unit. The communication module may be conFigured to receive data via a wired or wireless network, such as the internet. The communication module may also be conFigured to transmit data or data signals to one or more external devices (such as a remote server) via a wired or wireless network, such as the internet. 
     The data store  16  may be conFigured to store data from the sensors  20 ,  22 ,  24 , . . . n. The data store  16  may be coupled to the at least one communication module  26  and the at least one processor  12 . 
     The components of the control module  10  may be a combination of hardware and software components, all software components, or all hardware components. 
     Cryogenic freezers, such as illustrated in  FIG.  1   , cryogenically freeze a sample in accordance with a freezing profile. It is known that each sample variation requires its own freezing profile to be predetermined by a skilled scientist. A freezing profile is determined by a skilled scientist based on numerous factors such as the composition of the sample, the cell type or types used, the size (weight) of the sample, the nucleation temperature, the amount of cryoprotectant used, the container within which the sample is provided etc. Compounds with a protective impact during cryopreservation are referred to as cryoprotectants. In some embodiments, the cryoprotectant may be selected from dimethyl sulfoxide (DMSO), glycerol, glucose, propylene glycol, polyethylene glycol, sugars, alcohols, sugar alcohols, apoptosis inhibitors, ficoll, polyvinylpyrollidine, or a combination of two or more of these cryoprotectants, at concentrations ranging from 0 to 100%. 
     A freezing profile is specific to the factors upon which it is determined. For example, a freezing profile which is determined for 2 ml of sample A may be different from a freezing profile determined for 250 ml of sample A, or a freezing profile which is determined for 200 ml of sample A with 10% DMSO may be different from a freezing profile determined for 200 ml of sample A with 12% DMSO. 
       FIG.  2    schematically illustrates an exemplary predetermined freezing profile for a sample (illustrated using a graph of temperature v&#39;s time). A freezing profile comprises a set of instructions, regardless of format, which are input into a freezer, and which define the rate of cooling of the sample during a freezing cycle. A freezing cycle begins at time t=0 minutes, when a sample is placed in a freezer. In most instances, a sample will be between room temperature and the sample&#39;s freezing point at the beginning of the freezing cycle. A freezing cycle ends when the sample has reached the desired temperature, which is defined in the freezing profile. For example, according to  FIG.  2   , the freezing cycle ends at time t=180 minutes. 
     A freezing profile may comprise different linear cooling rates (ramps), as well as constant-temperature holding times (dwells) etc. and may include linear and non-linear cooling protocols. As stated above, a freezing profile is predetermined for each sample variety. Whenever a sample is to be frozen, which has the same sample composition, sample size, amount of cryoprotectant, and container etc. as defined in a predetermined freezing profile, then that predetermined freezing profile is required to be programmed into the freezer. According to known systems, each predetermined freezing profile is provided to a human operator in paper form, normally as part of an instruction manual, and the human operator is required to enter the predetermined freezing profile via the user interface  14  at the freezer. 
     However, since the predetermined freezing profile is entered manually by a user, errors may occur, for example, typographical errors may be entered by the user of the system when copying the predetermined freezing profile from the paper version. 
     As stated above, the freezer  10  comprises at least one sensor  20 ,  22 ,  24  . . . n. One, or more, of the sensors  20 ,  22 ,  24  . . . n comprises a temperature sensor provided to monitor the temperature within the freezer compartment  28  during a freezing cycle. The temperature sensors detect the temperature at one or more different locations within the freezer compartment  28 , such as at the plate within the freezer compartment  28 . The temperature is detected during the freezing of a sample, in accordance with a predetermined freezing profile, and the data store  16  stores the detected temperatures together with the location of the sensors and/or a sensor ID and the time at which the temperature was sensed. 
       FIG.  3    schematically illustrates a detected plate temperature v&#39;s time during the freezing of a sample in accordance with the predetermined freezing profile of  FIG.  2   . 
     In addition to detecting the temperature at different locations within the freezer compartment  28 , one or more sensors  20 ,  22 ,  24  . . . n, can also be provided to detect the actual temperature of the sample during the freezing cycle. The sensors  20 ,  22 ,  24  . . . n, detect the actual temperature during the freezing of a sample, in accordance with a predetermined freezing profile, and the data store  16  stores the detected temperatures together with the location of the sensor and/or a sensor ID and the time at which the temperature was sensed. 
       FIG.  4    schematically illustrates a detected sample temperature v&#39;s time during the freezing of the sample in accordance with the predetermined freezing profile of  FIG.  2   . 
       FIG.  5    schematically illustrates the predetermined freezing profile of  FIG.  2   , the detected plate temperature of  FIG.  3    and the detected sample temperature of  FIG.  4   . As is understood in the art, and as illustrated in  FIG.  5   , the actual detected freezing of a sample achieved by each freezer may vary from the predetermined freezing profile. Variations can occur as a result of numerous factors, such as the accuracy of the preparation of the sample. For example, a particular predetermined freezing profile may require 200 ml of sample A, mixed with 10% DMSO. However, one user  120 ,  121 ,  122 , . . . ,  12   n  may inadvertently add 195 ml of sample A mixed with 10.5% DMSO, or 202 ml of sample A mixed with 11% DMSO etc. Variations may also occur as a result of variations at the freezer, for example a freezers heat removal unit  32  may not be functioning as efficiently as possible. 
     In addition to detecting the actual temperatures during a freezing cycle, one or more sensors  20 ,  22 ,  24  . . . n may be provided to detect the external temperature at the freezer during a freezing cycle. In addition, one or more sensors may be provided to detect when the door of the freezer is opened, when the door of the freezer is closed, the time and date at which the door is opened/closed, and/or the duration of time the door was open. 
     According to one embodiment, the sensors  20 ,  22 ,  24  . . . n detect continuously during a freezing cycle. According to another embodiment, the sensors  20 ,  22 ,  24  . . . n detect periodically during a freezing cycle. 
     The sensor data detected by the sensors  20 ,  22 ,  24  . . . n relates to the freezing of a sample in accordance with a freezing profile. The sensor data detected by the sensors  20 ,  22 ,  24  . . . n may comprise one or more of: the temperature at one or more different locations within the freezer compartment  28  during a freezing cycle; the temperature of the sample during a freezing cycle; the external temperature at the freezer during a freezing cycle; freezer door data, such as when the door of the freezer is opened and/or closed during a freezing cycle and the duration of time the door was open for. For each detection, the time and date of the detection is also recorded together with an indication of the detecting sensor. 
     In addition to the sensor data detected by the sensors  20 ,  22 ,  24  . . . n, the control module  10  is also capable of detecting and storing other data which relates to the freezing of the sample in accordance with the freezing profile. The other data may comprise freezer data and/or sample data and/or user data etc. The control module  10  may store freezer data such as: a freezer identifier; freezer energy consumption (the energy consumed by the freezer during the freezing cycle and/or the energy consumed by different components of the freezer during the freezing cycle); freezer location (the actual location of the freezer and/or the freezers IP address); freezer alarm data (such as whether an alarm was activated at the freezer, for example, a door open alarm, and/or whether any action was taken in response to the alarm, for example, the door was closed). The control module  10  may store sample data such as: a sample identifier; sample composition data (such as information regarding the composition of the sample); sample size/weight data (such as information regarding the size/weight of the sample); sample container data (such as information regarding the sample container); the predetermined freezing profile; sample freeze date (such as the date the sample was frozen in accordance with the freezing profile); sample freeze time (such as the start time of the freezing cycle, the end time the freezing cycle, and/or the duration of the freezing cycle). The control module  10  may store user data such as: a user identifier; user observations, discussed in further detail below. 
     The sensor data detected by the sensors  20 ,  22 ,  24  . . . n, as well as the freezer data and/or sample data and/or user data, all of which relates to the freezing of a sample in accordance with a freezing profile, is of interest to a user. However, the user may not be at the location of the freezer, for example, because the user requires data from multiple freezers, or because the user is performing a clinical trial which requires data from multiple locations. Therefore, the communication module  26  may be used to transfer the data to a remote server. 
       FIG.  6    illustrates schematically a remote server  50 . The remote server  50  comprises at least one processor  52 , at least one working memory  54 , at least one stored program memory  58 , at least one data store  56  and at least one communication module  60 . The remote server  50  may also comprise other components which are not illustrated. The components of the remote server  50  may be a combination of hardware components and software components, may be all software components, or may be all hardware components, 
     The remote server is communicatively coupled to at least one freezer. According to one embodiment, the communication module  60  is used to connect the remote server  50  to at least one cryogenic freezer over a network, such as the Internet. The connection may be wired or wireless. The at least one cryogenic freezer is then able to exchange data with the remote server  50 . For example, the at least one cryogenic freezer is capable of transmitting data to the remote server  50 , and the remote server  50  is capable of receiving the transmitted data from the at least one cryogenic freezer. In addition, the remote server  50  is capable of transmitting data to the at least one cryogenic freezer, and the at least one cryogenic freezer is capable of receiving the transmitted data from the remote server  50 . 
     According to one embodiment, the data which is transferred between the freezer and the server is encrypted. For example, using a private/public key pair etc. 
     A user can access the remote server  50  from any computing device (such as a laptop computer, a tablet, a smart phone, a personal computer etc.) via a web browser. According to one embodiment, the user may be required to log into and have an account at the remote server. Following connection to the remote server  50 , the user is able to access the data from the freezers. According to one embodiment, a data mining process may be applied to the data gathered at the remote server, in order to extract information and/or patterns from the data which would not have been possible without collating of the data. 
       FIG.  7    illustrates schematically a system for monitoring one or more cryogenic freezers. A plurality of cryogenic freezers  100 ,  101 ,  102 , . . . ,  10   n  are illustrated in  FIG.  7   . For the avoidance of doubt, a plurality may be any number, including one. Each of the plurality of freezers  100 ,  101 ,  102 , . . . ,  10   n  may be provided at the same, or at different locations from the other freezers. Each freezer  100 ,  101 ,  102 , . . . ,  10   n  may be operated by a human operator (users  120 ,  121 ,  122 , . . . ,  12   n ). In addition, each freezer  100 ,  101 ,  102 , . . . ,  10   n  is communicatively coupled to a remote server  130 . The remote server  130  is capable of receiving data from the freezers in order to monitor the freezers as well as transmitting data to the freezers. 
     As stated above, freezing profiles are predetermined by skilled scientists. The predetermined freezing profiles are then provided together with their associated criteria, such as the composition of the sample, the size of the sample, the amount and composition of cryoprotectant to be added to the sample, the type of container in which the sample is to be provided etc., to the remote server  130 . According to one embodiment, the remote server  130  transmits the predetermined freezing profiles to the plurality of freezers  100 ,  101 ,  102 , . . . ,  10   n . According to one embodiment, the predetermined freezing profiles may be transmitted to the plurality of freezers at substantially the same time. By transmitting the predetermined freezing profiles to the plurality of freezers, consistency can be increased, since the instances of human error when inputting the predetermined freezing profiles is reduced. 
     When a sample is required to be frozen at one of the plurality of freezers, the user  120 ,  121 ,  122 , . . . ,  12   n  at the freezer is only required to select the appropriate predetermined freezing profile, from a plurality of predetermined freezing profiles, via the user interface  14 , such as a touch screen, at the freezer. The user  120 ,  121 ,  122 , . . . ,  12   n  at the freezer is not required to manually enter the predetermined freezing profile into the freezer. The user at the freezer may also be required to enter their user ID, via the user interface  14 , before using the freezer. The user at the freezer may also be required to enter the sample ID, via the user interface  14 , such as by using a touch screen, a bar code scanner when the sample ID is stored as a bar code, an imaging device when the sample ID is stored as a QR code etc. 
     Transmitting the predetermined freezing profiles to the plurality of freezers is also advantageous in that the user  140  at the remote server  130 , can then guarantee that each freezer is using the same predetermined freezing profiles, when freezing the same sample. This is useful when identifying anomalies in data gathered from a plurality of freezer all running the same predetermined freezing profiles. Furthermore, when a predetermined freezing profile is updated by the skilled scientist, for example as a result of new data becoming available, an updated version of the predetermined freezing profile can be distributed to the plurality of freezers from the remote server, enhancing consistency across the network of freezers. According to one embodiment, the updated predetermined freezing profiles may be transmitted to the plurality of freezers at substantially the same time. 
     The predetermined freezing profiles may be provided to the plurality of freezers as a graph, such as illustrated in  FIG.  2   , or as a set of instructions. An exemplary set of instructions for the graph illustrated in  FIG.  2    could be represented as: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 STEP 
                 TIME (minutes) 
                 TYPE 
                 TEMPERATURE (° C.) 
               
               
                   
               
             
            
               
                 1 
                 t = 0 
                 — 
                 22° C. 
               
               
                 2 
                 t = 0 to t = 20 
                 Ramp 
                 from 22° C. to 4° C. 
               
               
                 3 
                 t = 20 to t = 58 
                 Dwell 
                 at 4° C. 
               
               
                 4 
                 t = 58 to t = 154 
                 Ramp 
                 from 4° C. to −92° C. 
               
               
                 5 
                 t = 154 to t = 165 
                 Ramp 
                 from −92° C. to −100° C. 
               
               
                 6 
                 t = 165 to t = 180 
                 Dwell 
                 at −100° C. 
               
               
                   
               
            
           
         
       
     
     When a predetermined freezing profile is selected at one of the plurality of freezers, the detected sensor data, freezer data, sample data and/or user data which relates to the freezing of a sample in accordance with the freezing profile is transmitted from the freezer to the remote server  130 . The data may be transferred from the freezer to the remote server continuously, periodically or at the end of the freezing cycle, as required. Accordingly, the remote server may receive the data in near-real time. The remote server  130  stores the received data in the data store  56 . 
     The detected freezing data, which relates to the freezing of a sample in accordance with a predetermined freezing profile, may be transferred from the freezer to the remote server  130  as a graph, such as illustrated in  FIG.  4   . Alternatively, the detected freezing data, which relates to the freezing of a sample in accordance with a predetermined freezing profile, may be transferred from the freezer to the remote server  130  as a plurality of data logs. In another alternative, the detected freezing data, which relates to the freezing of a sample in accordance with a predetermined freezing profile, may be transferred from the freezer to the remote server  130  as a combination of graph(s) and/or a plurality of data logs. 
     When the remote server  130  receives a plurality of detected data logs, the remote server may generate an actual freezing graph from the plurality of data logs representing the freezing of the sample, such as the graph illustrated in  FIG.  4   . 
     A user  140  can access the received freezing data, which relates to the freezing of a sample in accordance with a predetermined freezing profile, at the remote server  130 . The server  130  can provide the user with the data from one or more freezers and/or one or more freezes. For example, a clinical trial may involve the freezing of a plurality of samples (of the same type) at a plurality of different freezers, all the freezers using the same freezing profile. The received data, regarding the plurality of freezes at a plurality of different freezers can then be presented to the user  140  in a user-friendly format. For example, the remote server  130  may generate a “freezing consistency report” from the received data. A “freezing consistency report” may provide the received freezing data, received from the plurality of freezers, on one graph, such that it easy for a user to look across a range of different freezers and/or freezes and to compare, for example, minimum, maximum and average freeze times. In addition, a tight grouping may indicate very consistent performance, whereas a wide spread may suggest something was not being well controlled. Furthermore, any anomalies in the received freezing data can be easily identified by a user. The “freezing consistency report” may also provide drop down filters so the user  140  can further tighten the analysis e.g. to a single freezer, a single user, a single freezing profile etc. The ability to store the data received from a plurality of different freezers regarding a plurality of different freezes is advantageous as anomalies can be identified quickly by a remote user. This is particularly beneficial for a user running a clinical trial, where previously a remote user would not have received the data, for maybe weeks after the freeze, and/or would not have received the same quantity or quality of data, since previously only the sensor freezing data would have been provided. 
     According to one embodiment, the remote server  130  may annotate the received freezing data with “observations”.  FIG.  8    illustrates an actual freezing graph which the remote sever has generated from the received data logs, and annotated with observations. The observations are generated by the remote server based on the data received from the freezer. For example, with reference to  FIG.  8   , the observation is “lid closed”. The observation “lid closed” is determined from the received sensor data, for example, the door sensor data indicates that the door sensor detected that the lid was closed, at time 01:43. Therefore, the remote server adds an observation “lid closed” at time 01:43 to the received freezing data. 
     In addition, the operator of the freezer, user  120 ,  121 ,  122 , . . . ,  12   n , may create user observations and add notes, which are transferred from the freezer to the remote server  130 . For example, when a biological sample is being frozen as part of a clinical trial, the user  120 ,  121 ,  122 , . . . ,  12   n  may add an observation, such as the time that the sample was obtained from the patient, prior to the sample being frozen. These user observations are added at the freezer via the user interface  14  and transferred to the remote server  130  as user data together with the other data which relates to the freezing of a sample in accordance with a predetermined freezing profile. 
     The received sensor data, freezer data, sample data and/or user data, which relates to the freezing of the sample in accordance with the freezing profile, received at the remote server  130  can also be analysed in order to perform checks on the freezing process. For example, a predetermined freezing profile may require approximately 500 joules of energy to complete the freeze. When five of the freezers transfer data indicating that they completed the freezing cycle in accordance with the predetermined freezing profile using approximately 500 joules of energy, but one of the freezers transfers data indicating that it completed the freezing cycle in accordance with the predetermined freezing profile using 800 joules of energy, then it is possible to determine that an unknown event has occurred at that freezer, and further investigation is required. Previously it would not have been possible to compare such data and therefore, it would not have been possible to identify that an unknown event has occurred at the freezer which required further investigation. 
     According to one embodiment, the remote server may provide a suggestion as to what the event might be. For example, if additional power was required to freeze the sample, then the server may suggest that the sample was of a size greater than that indicated for the selected predetermined freezing profile. According to one embodiment, the server may provide alerts to a user. For example, most freezers comprise an alarm to indicate to a user in the proximity of the freezer when a door has been left open. However, the remote server may also provide alerts direct to a user, such as to a user&#39;s mobile device, when an event has occurred at the freezer. The alerts may be visual and/or audible alerts. 
     The cryogenic freezing of a sample is normally only one stage in the processing of a biological sample.  FIG.  9    illustrates schematically a simple overview of the processing of a biological sample. As illustrated in  FIG.  9   , the sample is obtained at step S 200 . The sample is then frozen at a controlled-rate, in accordance with a predetermined freezing profile, at step S 210 , such as described above. Following freezing, the sample may be required to be stored and/or transported to another location at step S 220  prior to controlled thawing at step S 230 , and utilisation at step S 240 . In between freezing and thawing, the sample is required to be cryogenically stored whilst being transported, if required to another location. It is important to the integrity of the sample that the sample be kept in predetermined conditions at all of these stages. 
     Data recorded at each of these stages may be transferred to the remote server  130 , either continuously, periodically or at the end of each stage in the process, as required. 
     A thawing machine, for example, a VIA THAW machine by ASYMPTOTE may be used to provide controlled thawing of a sample.  FIG.  10    schematically illustrates a thawing machine  350 . As can be seen from  FIG.  10   , a thawing machine  350  comprises a thawing compartment  370 , for example, a water bath, within which a sample  30  to be thawed may be provided, coupled to a heating unit  380 . The thawing machine  350  also comprises a control module  360  comprising at least one processor  361  coupled to at least one memory  363 , at least one user interface  363 , at least one communications interface  365 , at least one data store  364 , and at least one sensor  366 ,  367 ,  368 , . . .  36   n . The thawing machine  350  may also comprises other elements which are not illustrated. 
     The memory  363  may comprise program memory for storing computer program code to control the heating unit  380  in order to thaw a sample  30  provided in the thawing compartment  370 , as described herein, and working memory for storing data, programs, or instructions received or processed by the processor  361 . The memory  363  and/or the data store  364  may comprise a volatile memory such as random access memory (RAM), for use as temporary memory. Additionally or alternatively, the memory  363  and data store  364  may comprise non-volatile memory such as Flash, read only memory (ROM) or electrically erasable programmable ROM (EEPROM). 
     The processor  361  may comprise processing logic to process data (for example, data received from the sensors  366 ,  367 ,  368 , . . .  36   n , programs, instructions received from a user via the user interface  363  etc.) and generate output signals in response to the processing. The control module  360  may comprise any suitable circuitry or logic, and may, for example, comprise any one or more of the following: a field programmable gate array (FPGA), system on chip device, microprocessor device, microcontroller, and one or more integrated circuits. The control module  360  is coupled to the heating unit  380  in order to control the temperature in the thawing compartment  370 . 
     The user interfaces  363  may be one or more of a computer screen, a touch screen, a keyboard, a mouse, speakers, a bar code scanner, a fingerprint scanner etc. 
     The communication module  365  may be conFigured to receive data or data signals from one or more external devices (such as a remote server as described herein). The communication module  365  may be a communication interface or unit. The communication module  365  may be conFigured to receive data via a wired or wireless network, such as the internet. The communication module  365  may also be conFigured to transmit data or data signals to one or more external devices (such as a remote server) via a wired or wireless network, such as the internet. 
     The data store  364  may be conFigured to store data from the sensors  366 ,  367 ,  368 , . . .  36   n . The data store  364  may be coupled to the at least one communication module  365  and the at least one processor  361 . 
     The components of the control module  360  may be a combination of hardware and software components, all software components, or all hardware components. 
     Cryogenic thawing machines, such as illustrated in  FIG.  10   , thaw a sample in accordance with a thawing profile. Each sample requires its own thawing profile to be determined by a skilled scientist. As with the freezing profile, each thawing profile is determined based on numerous factors such as the composition of the sample, the size (weight) of the sample, the amount of cryoprotectant added to the sample prior to freezing, the container within which the sample is provided etc. 
     A thawing profile is normally simpler than a freezing profile and specifies, for example: a heating unit temperature; container type; container size (ml); what temperature will trigger a “too warm” alert when a sample is loaded into the thawing machine for thawing; what time will trigger a “too long” alert when a sample has taken too long to thaw. According to one embodiment, a thawing profile is defined as a list of instructions.  FIG.  11    illustrates an exemplary thawing profile. 
       FIG.  12    illustrates an exemplary detected thawing sample temperature (continuous line) together with the heater temperature (dotted line). 
     A thawing profile comprises a set of instructions, regardless of format, which are input into a thawing machine, and which defines the rate at which a sample heats up during a thawing cycle. A thawing cycle begins at time t=0 minutes, when a sample is placed in a thawing machine. A thawing cycle ends when the sample has reached the desired temperature, which in most instances is just above the sample&#39;s melting point. 
     As stated above, the thawing machine  350  comprises at least one sensor  366 ,  367 ,  368 , . . .  36   n . One, or more, of the sensors  366 ,  367 ,  368 , . . .  36   n  comprises a temperature sensor provided to monitor the temperature within the thawing compartment  370  during a thawing cycle. The temperature sensors also detect the temperature at the heating unit  380  during a thawing cycle. The detected temperatures are stored in the data store  364  together with the location of the sensor and/or a sensor ID and the time at which the temperature was sensed. 
     In addition to detecting the temperatures within the thawing machine during a thawing cycle, one or more sensors  366 ,  367 ,  368 , . . .  36   n  may be provided to detect the external temperature at the thawing machine during a thawing cycle. In addition, one or more sensors may be provided to detect when the door of the thawing machine is opened, when the door of the thawing machine is closed, the time and date at which the door is opened/closed, and/or the duration of time the door was open. 
     According to one embodiment, the sensors  366 ,  367 ,  368 , . . .  36   n  detect continuously during a thawing cycle. According to another embodiment, the sensors  366 ,  367 ,  368 , . . .  36   n  detect periodically during a thawing cycle. 
     The sensor data detected by the sensors  366 ,  367 ,  368 , . . .  36   n  relates to the thawing of a sample in accordance with a thawing profile. The sensor data detected by the sensors  366 ,  367 ,  368 , . . .  36   n  may comprise one or more of: the temperature, at one or more locations within the thawing compartment during a thawing cycle; the temperature at the heating unit during a thawing cycle; the external temperature at the thawing machine during a thawing cycle; thawing machine door data, such as when the door of the thawing machine is opened and/or closed during a thawing cycle. For each detection, the time and date of the detection is also recorded together with an indication of the detecting sensor. 
     In addition to the sensor data detected by the sensors  366 ,  367 ,  368 , . . .  36   n , the control module  360  is also capable of detecting and storing other data which relates to the thawing of the sample in accordance with the thawing profile. The other data may comprise thawing machine data and/or sample data and/or user data etc. The control module  360  may store thawing machine data such as: a thawing machine identifier; thawing machine energy consumption (for example, the energy consumed by the thawing machine during a thawing cycle and/or the energy consumed by different components of the thawing machine during a thawing cycle); thawing machine location (for example, the actual location of the thawing machine and/or the thawing machines IP address); thawing machine alarm data, such as whether an alarm was activated at the thawing machine (for example, a sample too warm alarm) and/or whether any action was taken in response to the alarm. The control module  360  may store sample data such as: a sample identifier; sample composition data (such as information regarding the composition of the sample); sample size/weight data (such as information regarding the size/weight of the sample); sample container data (such as information regarding the sample container; the predetermined thawing profile; sample thaw date (such as the date the sample was thawed in accordance with the thawing profile); sample thaw time (such as the start time of the thawing cycle, the end time the thawing cycle and/or the duration of the thawing cycle). The control module  10  may store user data such as: a user identifier; user observations, discussed in further detail below. 
     The sensor data detected by the sensors  366 ,  367 ,  368 , . . .  36   n , as well as the thawing machine data and/or sample data and/or user data, all of which relates to the thawing of a sample in accordance with a thawing profile, is of interest to a user. However, the user may not be at the location of the thawing machine, for example, because the user requires data from multiple thawing machines, or because the user is performing a clinical trial which requires data from multiple locations. Therefore, the communication module  365  may be used to transfer the detected data from the thawing machine to a remote server  50 , such as described above and illustrated in  FIG.  6   . 
       FIG.  13    illustrates schematically a system for monitoring one or more thawing machines. A plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  are illustrated in  FIG.  13   . Each of the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  may be provided at the same, or at different locations from the other thawing machines. In addition, each of the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  may be provided at the same location as a freezer, or at different location from a freezer. Each thawing machine  300 ,  301 ,  302 , . . . ,  30   n  may be operated by a human operator (users  320 ,  321 ,  322 , . . . ,  32   n ). In addition, each thawing machine  300 ,  301 ,  302 , . . . ,  30   n  is communicatively coupled to a remote server  130 . 
     The remote server  130  is communicatively coupled to at least one thawing machine. According to one embodiment, the communication module  60  is used to connect the remote server to at least one thawing machine over a network, such as the Internet. The connection may be wired or wireless. The plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  are able to exchange data with the remote server  130 . For example, the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  are capable of transmitting data to the remote server  130 , and the remote server  130  is capable of receiving the transmitted data from the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n . In addition, the remote server  130  is capable of transmitting data to the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n , and the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  are capable of receiving the transmitted data from the remote server  130 . 
     According to one embodiment, the data which is transferred between the thawing machine and the server is encrypted, for example, using a private/public key pair etc. 
     As stated above, the thawing profiles are predetermined by skilled scientists. The predetermined thawing profiles are provided together with their associated criteria, such as the composition of the sample, the size of the sample, the amount of cryoprotectant to be added to the sample, the type of container in which the sample is to be provided etc. to the remote server  130 . According to one embodiment, the remote server  130  transmits the predetermined thawing profiles to the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n . The predetermined thawing profiles may be transmitted to the plurality of thawing machines  300 ,  301 ,  302 , . . . ,  30   n  at substantially the same time. When a predetermined thawing profile is updated by a skilled scientist, an updated version of the predetermined thawing profile may be distributed to the plurality of thawing machines from the remote server. The updated predetermined thawing profiles may be transmitted to the plurality of thawing machines at substantially the same time. 
     When a sample is required to be thawed at one of the plurality of thawing machines, the user  320 ,  321 ,  322 , . . . ,  32   n  at the thawing machine is only required to select the appropriate predetermined thawing profile, from a plurality of predetermined thawing profiles, via the user interface  363 , such as a touch screen, at the thawing machine. The user  320 ,  321 ,  322 , . . . ,  32   n  at the thawing machine is not required to manually enter the predetermined thawing profile into the thawing machine. The user  320 ,  321 ,  322 , . . . ,  32   n  at the thawing machine may also be required to enter their user ID, via the user interface  363 , before using the thawing machine. The user at the thawing machine may also be required to enter the sample ID, via the user interface  363 , such as by using a touch screen, a bar code scanner when the sample ID is stored as a bar code, an imaging device when the sample ID is stored as a QR code etc., before using the thawing machine. 
     As is understood in the art, an actual thawing temperature achieved by each thawing machine may vary from the predetermined thawing profile. Variations can occur as a result of numerous factors, such as the accuracy of the preparation of the sample. For example, a predetermined thawing profile may specify that thawing begins at the temperature at which the sample is frozen and/or stored (as appropriate). However, the actual sample will start thawing the moment it is removed from its storage unit, therefore, the actual temperature of the sample when it enters the thawing machine may be different from that defined in the thawing profile. This is particularly evident when the transfer of the sample from the storage device to the thawing machine is not instantaneous. For example, when a sample is being kept at −196° C., it will start thawing very quickly when removed from its storage environment to room temperature prior to been provided in the thawing machine. Such variations from the specified criteria of the predetermined thawing profile may result in detected thawing data, such as the sample temperature, which is different from the predetermined thawing profile. 
     When a predetermined thawing profile is selected at one of the plurality of thawing machines, and a sample is thawed in accordance with the selected predetermined thawing profile, the detected sensor data, thawing machine data, sample data and/or user data, which relates to the thawing of the sample in accordance with the predetermined thawing profile, is transmitted from the thawing machine to the remote server  130 . The data may be transferred from the thawing machine to the remote server continuously, periodically or at the end of the thawing cycle, as required. Accordingly, the remote server may receive the data in near-real time. The remote server  130  stores the received data in the data store  56 . 
     The detected thawing data, which relates to the thawing of a sample in accordance with the predetermined thawing profile, may be transferred from the thawing machine to the remote server  130  as a graph, such as illustrated in  FIG.  12   . Alternatively, the detected thawing data, which relates to the thawing of a sample in accordance with the predetermined thawing profile, may be transferred from the thawing machine to the remote server  130  as a plurality of data logs of what actually happened whilst the sample was being thawed. In another alternative, the detected thawing data, which relates to the thawing of a sample in accordance with the predetermined thawing profile, may be transferred from the thawing machine to the remote server  130  as a combination of graph(s) and/or a plurality of data logs. 
     When the remote server  130  receives a plurality of data logs, the remote server may generate an actual thawing graph from the plurality of data logs, representing the thawing of the sample, such as the graph illustrated in  FIG.  12   . 
     A user  140  can then access the received data, which relates to the thawing of a sample in accordance with the predetermined thawing profile, at the remote server  130 . The server  130  can provide the user with the data from one or more thawing machines and/or one or more thaws. For example, a clinical trial may involve the thawing of a plurality of samples (of the same type) at a plurality of different thawing machines, all of the thawing machines using the same predetermined thawing profile. The data regarding the plurality of thaws at the plurality of different thawing machines can then be presented to the user  140  in a user-friendly format. For example, the remote server  130  may generate a “thawing consistency report” from the received data. A “thawing consistency report” may provide the received thawing data, received from the plurality of thawing machines, on one graph, such that it easy for a user to look across a range of different thawing machines and/or thaws and to compare, for example, minimum, maximum and average thaw times. In addition, a tight grouping may indicate very consistent performance, whereas a wide spread may suggest something was not being well controlled. Furthermore, any anomalies in the received thawing data may be easily identified by a user. The “thawing consistency report” may also provide drop down filters so the user can further tighten the analysis e.g. to a single thawing machine, a single user, a single thawing profile etc. The ability to store the data received from a plurality of different thawing machines regarding a plurality of different thaws is advantageous as anomalies can be identified quickly by a remote user. This is particularly beneficial for a user running a clinical trial, where previously a remote user would not have received the data, for maybe weeks after the thaw, and/or would not have received the same quantity of data, since previously only the detected temperature data may be provided. 
     According to one embodiment, the remote server  130  may annotate the received thawing data with “observations”.  FIG.  14    illustrates a detected thawing sample temperature annotated with observations. The observations are generated based on the data received from the thawing machine. For example, with reference to  FIG.  14   , the observation is “User loaded the vial”. The observation “User loaded the vial” is determined from the received sensor data, for example, the time at which the thawing machine sensed that a vial had been added. 
     In addition, the operator of the thawing machine, user  320 ,  321 ,  322 , . . . ,  32   n , may also create user observations and add notes, which are also transferred from the thawing machine to the remote server  130 , as user data. For example, when a biological sample is being thawed as part of a clinical trial, the user  320 ,  321 ,  322 , . . . ,  32   n  may add observations, such as the time that the sample was administered to the patient, following thawing of the sample. These user observations are added at the thawing machine via the user interface and transferred to the remote server  130 . According to another embodiment, user observations may be added via an application, to the remote server  130 . 
     The received sensor data, thawing machine data, sample data and/or user data, which relates to the thawing of the sample in accordance with the predetermined thawing profile received at the remote server  130  can be analysed in order to perform checks on the thawing process. For example, a predetermined thawing profile may require approximately 500 joules of energy to complete the thaw. When five of the thawing machines transfer data indicating that they completed the predetermined thawing profile using approximately 500 joules of energy, but one of the thawing machines transfers data indicating that it completed the predetermined thawing profile using 800 joules of energy, then it is possible to determine that an unknown event has occurred at that thawing machine, and further investigation is required. Previously it would not have been possible to compare such data and therefore, it would not have been possible to identify that an unknown event has occurred at the thawing machine which required further investigation. 
       FIG.  17    illustrates a graph of two different sets of detected thawing temperatures, both of which relate to the thawing of a sample in accordance with the same predetermined thawing profile. The two different sets of thawing temperatures were recorded by temperature sensors at a thawing machine and were received at the remote server  130 . The solid line indicates the temperatures detected whilst thawing a sample having a 10% aqueous DMSO solution, and the dashed line indicates the temperatures detected whilst thawing a sample having an ‘incorrectly’ formulated solution, where the DMSO was not added. It would be apparent to any skilled person in the field when viewing the graph of  FIG.  17   , that due to the different warming rates—as well as the much higher temperature plateau which is indicative of the melting point of a solution—that the ‘incorrectly’ formulated solution deviated from a correct formulation. The ability to compare data from a plurality of different thawing machines and/or a plurality of different thaws is advantageous since incorrect thaws can be identified quickly, which can act as a quality control of the solutions. In addition, the data received at the server  130  can be referred to immediately after a thaw, and may also be referred back to at a later time, since the data is saved at the server. 
     According to one embodiment, the remote server may provide a suggestion as to what the cause of a deviation from a predetermined thawing profile and/or a deviation between data detected using the same predetermined thawing profile might be. For example, when the thawing temperature plateaus are different, then the remote server may indicate that the freezing solution has been incorrectly formulated. 
     According to one embodiment, the remote server may also be able to provide alerts to a user. For example, the thawing machine may comprise an alarm to indicate to a user in the proximity of the thawing machine that the added vial is too hot. However, the remote server may also be able to provide alerts direct to a user, such as to users mobile device, when an event has occurred at a thawing machine. The alerts may be visual and/or audible alerts. 
     Further quality control information and other information can be determined through differential thermal analysis (DTA) on the detected data which is transmitted to the remote server. DTA can be performed on the data received from freezers, thawing machines and transportation devices (described below). The following example refers to data received from a freezer. As described above, a freezer transmits detected sensors data (such as the detected temperature of the sample plate during the freezing cycle), and/or freezer data (such as the voltage supplied to the freezer during the freezing cycle) and/or sample data (such as the selected predetermined freezing profile) and/or user data etc. By, for example, integrating the detected power curves shown in  FIG.  18   , it is possible to calculate the energy required for the freezing cycle. 
     From the measured power-time curve for the sample freezing example illustrated in  FIG.  18   , it is possible to relate the measured power consumed during the freezing cycle (the solid line) to the expected power removed from the sample during the freezing cycle (the dashed line). After nucleation and during the bulk of the phase change there is a large increase in power required to maintain the linear rate of temperature reduction (power is illustrated with a solid line in  FIG.  18   ) which may be recorded and transmitted to the remote server. Before nucleation and also after the bulk of the freezing,  FIG.  18    shows that the measured power is increasing approximately linearly with time—this is how the dashed expected power line is derived. However, it is known that before nucleation the rate of heat removal from a sample (with constant mass and specific heat capacity) must be constant when the temperature is being reduced linearly. This means that the approximately linear power, prior to nucleation must represent a constant “baseline” rate of heat removal from the sample (dashed line  FIG.  18   ), together with an additional linearly increasing power requirement of the freezer to supply the plate itself and any losses in the system. This recorded power data profile before and after bulk ice formation (dashed line in  FIG.  18   ) can readily be subtracted from the measured power being removed from the sample (solid line in  FIG.  18   ), and obtain direct estimates of the changes in heat release during freezing. 
     To do this for this, for example, the regions between the curves in  FIG.  18    can be integrated, using Simpson&#39;s rule or any other appropriate method clear to a skilled person, between nucleation, where the lines diverge, and the point where the lines re-join. 
     This data can be used to determine the total amount of ice formed, and if different from a predicted or separate control sample would indicate to the skilled person that for example, either volume or composition of the freeing sample was incorrect. In addition, the large increase in power which is recorded at the freezer and transmitted to the remote server indicates when ice nucleated during the freezing cycle and at what temperature. 
     Additionally, according to another example, the power recorded at a thawing machine and transmitted to the remote server during a thawing cycle may be used to determine the heat capacity of the solution, which can be compared with known values for quality control. 
     Returning to  FIG.  9   , following freezing, a sample may be required to be stored and/or transported to another location prior to thawing. To simplify tracking of each sample, each sample may be provided with a unique identifier (sample ID), such as a bar code, a QR code or an identification code, which may be any combination of numbers and/or letters. When a sample is frozen, it&#39;s sample ID may be input by a user  120 ,  121 ,  122 , . . . ,  12   n  at the freezer  100 ,  101 ,  102 , . . . ,  10   n . For example, when the sample ID is a bar code, then the user may scan the bar code prior to freezing the sample using a bar code scanner. The sample ID is then associated with the predetermined freezing profile which is selected by the user  120 ,  121 ,  122 , . . . ,  12   n , the detected sensor data, the freezer data, the sample data and/or the user data, which relates to the freezing of a sample in accordance with the predetermined freezing profile, as discussed above. 
     In addition, when a sample is to be thawed, it&#39;s sample ID may be input by a user  320 ,  321 ,  322 , . . . ,  32   n  at the thawing machine  300 ,  301 ,  302 , . . . ,  30   n . For example, when the sample ID is a bar code, then the user may scan the bar code prior to thawing the sample using a bar code scanner. The sample ID is then associated with the predetermined thawing profile which is selected by the user  320 ,  321 ,  322 , . . . ,  32   n , the detected sensor data, the thawing machine data, the sample data and/or the user data, which relates to the thawing of a sample in accordance with the predetermined thawing profile, as discussed above. 
     It is possible for a user  140  of the remote server to search for all entries associated with a specific sample ID. The user  140  is then able to track the sample, from freezing to thawing. 
     The remote server is capable of transmitting a predetermined transportation profile to a transportation device which transports (and stores) a sample following cryogenic freezing to a different location. As with a thawing profile, a transportation profile is normally simpler than a freezing profile and specifies, for example: a temperature at which the sample is to be stored; container type; container size (ml); a minimum and maximum humidity for the sample; a minimum and maximum g force for the sample; what temperature will trigger a “too warm” alert; what temperature will trigger a “too cold” alert; what time will trigger a “too long” alert when a sample has been stored for too long etc. According to one embodiment, a transportation profile is defined as a list of instructions. 
     A user at a transportation device is only required to select the appropriate predetermined transportation profile, from a plurality of predetermined transportation profiles, via the user interface  14 , such as a touch screen, at the transportation device. The user at the transportation device may also be required to enter their user ID, via the user interface  14 , before using the transportation device. The user at the transportation device may also be required to enter the sample ID, via the user interface  14 , such as by using a bar code scanner etc., before using the transportation device. 
     The remote server is also capable of receiving data from a transportation device which stores and transports a sample following cryogenic freezing.  FIG.  15    schematically illustrates a cryogenic transportation device  500 . A cryogenic transportation device  500  comprises a portable power supply  550 , such as a battery, and/or may also be connected to a power supply provided in a transportation vehicle. 
     As can be seen from  FIG.  15   , a transportation device  500  comprises a storage compartment  570 , within which a sample  30  is provided, coupled to a heating unit  580  and a heat removal unit  590 . The storage device is required to keep the sample at a constant temperature. The transportation device  500  also comprises a control module  560  comprising at least one processor  561  coupled to at least one memory  563 , at least one user interface  563 , at least one communications interface  565 , at least one data store  564 , at least one sensor  566 ,  567 ,  568 , . . .  56   n , and at least one location detection module  540 . The storage device  500  may also comprises other elements which are not illustrated. 
     The memory  563  may comprise program memory for storing computer program code to control the heating unit  580  and the heat removal unit  590  in order to maintain the sample  30  at a constant temperature in the storage compartment  570 , and working memory for storing data, programs, or instructions received or processed by the processor  561 . The memory  563  and/or the data store  564  may comprise a volatile memory such as random access memory (RAM), for use as temporary memory. Additionally or alternatively, the memory  563  and data store  564  may comprise non-volatile memory such as Flash, read only memory (ROM) or electrically erasable programmable ROM (EEPROM). 
     The processor  561  may comprise processing logic to process data (for example, data received from the sensors  566 ,  567 ,  568 , . . .  56   n , the location detection module  540 , programs, instructions received from a user via the user interface  563  etc.) and generate output signals in response to the processing. The control module  560  may comprise any suitable circuitry or logic, and may, for example, comprise any one or more of the following: a field programmable gate array (FPGA), system on chip device, microprocessor device, microcontroller, and one or more integrated circuits. The control module  560  is coupled to the heating unit  580  and the heat removal unit  590  in order to control the temperature in the storage compartment  570 . 
     The user interfaces  563  may be one or more of a computer screen, a touch screen, a keyboard, a mouse, speakers, a bar code scanner, a fingerprint scanner etc. 
     The communication module  565  may be conFigured to receive data or data signals from one or more external devices (such as a remote server as described herein). The communication module  565  may be a communication interface or unit. The communication module may be conFigured to receive data via a wired or wireless network, such as the internet. The communication module may also be conFigured to transmit data or data signals to one or more external devices (such as a remote server) via a wired or wireless network, such as the internet. 
     The data store  564  may be conFigured to store data from the sensors  566 ,  567 ,  568 , . . .  56   n  and the location detection module  540 . The data store  564  may be coupled to the at least one communication module  565  and the at least one processor  561 . 
     The location detection module  540  may be any device capable of detecting the location of the transportation device  500 , such as a GPS location device. 
     The components of the control module  560  may be a combination of hardware and software components, all software components, or all hardware components. 
     As stated above, the transportation device  500  comprises at least one sensor  566 ,  567 ,  568 , . . .  56   n . One, or more of the sensors  566 ,  567 ,  568 , . . .  56   n  comprise temperature sensors provided to monitor the temperature within the storage compartment  570  during transportation. The detected temperatures are stored in the data store  564  together with a sensor ID and the time at which the temperature was sensed. 
     In addition to detecting the temperatures within the transportation device during storing, one or more sensors  566 ,  567 ,  568 , . . .  56   n  may be provided to detect the external temperature at the transportation device  500 . In addition, one or more sensors may be provided to detect when the door of the transportation device  500  is opened, when the door of the transportation device  500  is closed, the time and date at which the door is opened/closed, and/or the duration of time the door was open. In addition, one, or more of the sensors  566 ,  567 ,  568 , . . .  56   n  may comprise g force sensors provided to detect the g force applied to the transportation device  500  during transportation. In addition, one, or more of the sensors  566 ,  567 ,  568 , . . .  56   n  may comprise humidity sensors provided to detect internal and/or external humidity at the transportation device  500  during transportation. In addition, one or more of the sensors  566 ,  567 ,  568 , . . .  56   n  may detect the orientation of the transportation device  500 . In addition, one, or more of the sensors  566 ,  567 ,  568 , . . .  56   n  may detect the power supply at the transportation device  500 , for example, when the transportation device  500  is connected to a vehicles power supply, when the transportation device  500  requires power form the portable power supply  550 , when the transportation device  500  is running out of power (for example when the portable power supply  550  has only 20% power left etc.). 
     According to one embodiment, the sensors  566 ,  567 ,  568 , . . .  56   n  detect continuously during transportation. According to another embodiment, the sensors  566 ,  567 ,  568 , . . .  56   n  detect periodically during transportation. 
     The sensor data detected by the sensors  566 ,  567 ,  568 , . . .  56   n  relates to the transportation of a sample in accordance with the sample transportation profile data. The transportation sensor data detected by the sensors  566 ,  567 ,  568 , . . .  56   n  may comprise one or more of: the temperature within the storage compartment; the external temperature at the transportation device; transportation device door data, such as when the door of the transportation device is opened and/or closed during storage; g force at the transportation device; orientation of the transportation device; internal and/or external humidity at the transportation device; power connection; battery life. For each detection, the time and date of the detection is also recorded together with an indication of the detecting sensor. 
     In addition to the sensor data detected by the sensors  566 ,  567 ,  568 , . . .  56   n , the control module  560  is also capable of detecting and storing other data which relates to the transportation of the sample. The other data may comprise transportation device data and/or sample data and/or user data etc. The control module  560  may store transportation device data such as: a transportation device identifier; transportation device energy consumption (such as the energy consumed by the transportation device during storage and/or by different components of the transportation device during storage); the location of transportation device (such as the actual location, for example GPS coordinates, of the transportation device); transportation device alarm data, such as whether an alarm was activated at the transportation device (for example, a sample too warm alarm, and whether any action was taken in response to the alarm); the power supply at the transportation device; the amount of power available at the transportation device (for example remaining battery power). The control module  360  may store sample data such as: a sample identifier; information regarding the composition of the sample; information regarding the size/weight of the sample; information regarding the sample container; the predetermined freezing profile; the predetermined transportation profile data; the predetermined thawing profile; the date the sample was frozen. The control module  560  may store user data such as: a user identifier; user observations. 
     The data detected by the sensors  566 ,  567 ,  568 , . . .  56   n , as well as the other data, all of which relates to the transportation of a sample may be transferred to a remote server  50 , such as described above and illustrated in  FIG.  6   , via the communication module  565  at the transportation device. 
       FIG.  16    illustrates schematically a remote system for monitoring one or more devices for use in the cryogenic processing of a sample. As illustrated in  FIG.  16   , the remote server  130  is conFigured to receive data from a freezer  10   n  regarding the freezing of a sample, to receive data from a storage device  420  regarding the storage of the sample, to receive data from a transportation device  440 , when a sample is to be transported to a different location, regarding the storage/transportation of the sample, and to receive data from a thawing machine  30   n  regarding the thawing of a sample. The data recorded at each of these devices may be transferred to the remote server, either continuously, periodically or at the end of each stage in the process as required. Although only one freezer  10   n , storage device  420 , transportation device  440  and thawing machine  30   n  is illustrated in  FIG.  16   , the remote server  130  is capable of communicating with a plurality of freezers  10   n , a plurality of storage devices  420 , a plurality of transportation devices  440  and a plurality of thawing machine  30   n.    
     The remote server  130  is communicatively coupled to at least one transportation device  440 . According to one embodiment, the communication module  60  is used to connect the remote server to at least one transportation device  440  over a network, such as the Internet. The connection may be wired or wireless. The plurality of transportation devices are able to exchange data with the remote server  130 . For example, the plurality of transportation devices are capable of transmitting data to the remote server  130 , and the remote server  130  is capable of receiving the transmitted data from the plurality of transportation devices. In addition, the remote server  130  is capable of transmitting data to the plurality of transportation devices and the plurality of transportation devices are capable of receiving the transmitted data from the remote server  130 . 
     According to one embodiment, the data which is transferred between the transportation device and the server is encrypted, for example, using a private/public key pair etc. 
     The transportation profiles are predetermined by skilled scientists. The predetermined transportation profiles are provided together with their associated criteria, such as the composition of the sample, the size of the sample, the amount of cryoprotectant DMSO to be added to the sample, the type of container in which the sample is to be provided etc. to the remote server  130 . According to one embodiment, the remote server  130  transmits the predetermined transportation profiles to a plurality of transportation devices. The predetermined transportation profiles may be transmitted to the plurality of transportation devices at substantially the same time. When a predetermined transportation profile is updated by a skilled scientist, an updated version of the predetermined transportation profile can may be distributed to the plurality of transportation devices from the remote server. The updated predetermined transportation profiles may be transmitted to the plurality of transportation devices at substantially the same time. 
     When a sample is required to be transported, a user at the transportation device is only required to select the appropriate predetermined transportation profile, from a plurality of predetermined transportation profiles, via the user interface  563 , such as a touch screen, at the transportation device. The user at the transportation device is not required to manually enter the predetermined transportation profile into the transportation device. The user at the transportation device may also be required to enter their user ID, via the user interface  563 , before using the transportation device. The user at the transportation device may also be required to enter the sample ID, via the user interface  563 , such as by using a touch screen, a bar code scanner when the sample ID is stored as a bar code, an imaging device when the sample ID is stored as a QR code etc., before using the transportation device. 
     As is understood in the art, an actual detected transportation data may vary from the predetermined transportation profile. 
     When a predetermined transportation profile is selected at a transportation device, and a sample is transported in accordance with the selected predetermined transportation profile, the detected sensor data, transportation device data, sample data and/or user data, which relates to the transportation of the sample in accordance with the predetermined transportation profile, is transmitted from the transportation device to the remote server  130 . The data may be transferred from the transportation device to the remote server continuously or periodically, as required. Accordingly, the remote server may receive the data in near-real time. The remote server  130  stores the received data in the data store  56 . 
     The detected transportation data, which relates to the transportation of a sample in accordance with the predetermined transportation profile, may be transferred from the transportation device to the remote server  130  as a graph. Alternatively, the detected transportation data, which relates to the transportation of a sample in accordance with the predetermined transportation profile, may be transferred from the transportation device to the remote server  130  as a plurality of data logs of what actually happened whilst the sample was being transportation. In another alternative, the detected transportation data, which relates to the transportation of a sample in accordance with the predetermined transportation profile, may be transferred from the transportation device to the remote server  130  as a combination of graph(s) and/or a plurality of data logs. 
     When the remote server  130  receives a plurality of data logs, the remote server may generate an actual transportation graph from the plurality of data logs, representing the transportation of the sample in the transportation device. 
     A user  140  can then access the received data, which relates to the transportation of a sample in accordance with the predetermined transportation profile, at the remote server  130 . The server  130  can provide the user with the data from one or more transportation devices and/or transportations. The data regarding the plurality of transportations at the plurality of different transportation devices can then be presented to the user  140  in a user-friendly format. 
     The freezer/thawing machine/transportation device transmits the data to the remote server via the internet. According to one embodiment, the freezer/thawing machine/transportation device retains the data in its local data store until receipt of the data by the remote server is confirmed. This ensures that the data is not deleted until it has been safely stored at the remote server, for example in the data store  56 . The freezer/thawing machine/transportation device may then delete the data if required. Whether the freezer/thawing machine/transportation device deletes the transmitted data will depend on the size of the data store provided at the freezer/thawing machine/transportation device. According to one embodiment, the data is stored at the freezer/thawing machine/transportation device for a predetermined period of time, such as one week, one month, one year etc. prior to deletion. 
     A user  140  is then able to review the data received by the remote server  130 . The user  140  is also able to search the data based on criteria, such as the freezer ID, freezing profile, sample ID, thawing machine ID etc. For example, when examining a predetermined freezing profile, it may appear that a better result is achieved by one freezer and/or user; or that one freezer always produces freezing profiles that deviate from the predetermined profile by a greater amount than the other freezers. It is then possible for the user  140  to further investigate that freezer, for example, it may appear that the freezer is not functioning correctly. However, without being able to compare the freezer&#39;s results with other freezers, this malfunction would not be immediately apparent. 
     The ability to compile the data as well as filter and organise the data from a plurality of devices and samples, increases the usability of the data since further analysis can be performed which previously was not possible or not practical. The server can also be used to generate reports and/or graphs as required by the user  140  and discussed above. 
     Since the server  130  is connected to the internet, the user  140  of the server does not need to be at the server  130  in order to access the data. This is particularly useful when clinical trials are being carried out at several different locations. The data regarding each process (i.e. freezing/storing/transporting/thawing etc.) can be transferred in near real time to the user running the trial. 
     An example of a generated report, generated by the remote server, is a report which present the data from multiple freezes (using the same predetermined freezing profile), or multiple thaws (using the same predetermined thawing profile) in such a way as to make an anomaly obvious to the user. According to one embodiment, the data from multiple freezes, or multiple thaws are provided on the same time v&#39;s temperature graph such that an anomaly is clearly visible to the user. 
     The user  140  is able to select the group for which each report is to be generated. For example, the user may select: a plurality of freezer, selected using the freezer ID&#39;s; a plurality of thawing machines, selected using the thawing machine ID&#39;s; a plurality of freezes, selected using the predetermined freezing profile; a user ID&#39;s; a plurality of samples, selected using the sample ID&#39;s etc. It is also possible for the user  340  to select a group for which each report is to be generated based on the country in which the machines are based, selected using the location ID; or all the devices owned by a particular company, selected using the device ID (freezer ID, thawing machine ID, transportation device ID etc.); or all the devices taking part in a particular trial, selected using the device ID (freezer ID, thawing machine ID, transportation device ID etc.). 
     Furthermore, since the remote server provides the predetermined freezing profile, thawing profile and/or transportation profile to the freezers, thawing machines and/or transportation devices, it is possible to select a group of devices to receive each specific profile, and different devices may receive different profiles/version of profiles based on a user selected criteria. For example, all devices belonging to the same company may receive a first predetermined profile, whereas all devices belonging to a different company may receive a different predetermined profile. 
     It is further possible for a user to create rules which are then applied to an individual device, all the devices, or a subset of the devices as required by the user. An example, of such as rule predefined at the remote server, may be the thawing machine determines that the sample is too warm when it was loaded, from the temperature data, and the thawing machine generates a warning locally at the thawing machine, the rule might be that the remote server also generates a task for a user to review this log because it has an associated warning. Other examples of rules are: if a freeze or thaw log is missing information like details of the sample being processed, the remote server generates a task for a user to add this information; a summary of the previous week&#39;s equipment logs is emailed to a specified user weekly at a set time; if any thaws are aborted or fail at thawing machines A, B or C, email User Y immediately to warn them etc. 
     According to another embodiment, the remote server is also capable of transmitting instructions to the freezer/thawing machine/transportation device as required. For example, the remote server may send instructions to a freezer to begin cooling down in the early hours of the morning in order to prepare for use when an operator gets into work. 
     According to another embodiment, the remote server is also capable of generating and transmitting alerts, such as door open, temperature too hot/too cold etc. There may be an alarm which is active at the device. However, the server may also generate and transmit alerts to a user, for example via a user&#39;s mobile device. The user&#39;s response to the alert may also be recorded, such as user cancelled action, user over rid the alarm etc. 
     According to another embodiment, the remote server may also be used to prompt a user at the freezer/thawing machine to perform a task—for example, once a sample has defrosted, a user may be prompted by the remote server to remove the sample from the thawing machine. This may be in addition to alerts set at the freezer/thawing machine. 
     According to another embodiment, a user at the remote server may also interact with the remote server, for example, via a web page in order to add observations and/or annotate observations regarding the received thawing, freezing or transport data logs. For example, the user may add an observation to explain an anomaly once it has been investigated. 
     According to another embodiment, the remote server may generate invoices. For example, once a sample has been thawed for use, the remote server generates an invoice from the manufacture of the sample to the user of the sample. 
     As will be appreciated by one skilled in the art, the present techniques may be embodied as a system, method or computer program product. Accordingly, the present techniques may take the form of an entirely hardware embodiment, an entirely software embodiment, or an embodiment combining software and hardware. 
     Furthermore, the present techniques may take the form of a computer program product embodied in a computer readable medium having computer readable program code embodied thereon. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable medium may be, for example, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. 
     Computer program code for carrying out operations of the present techniques may be written in any combination of one or more programming languages, including object oriented programming languages and conventional procedural programming languages. 
     For example, program code for carrying out operations of the present techniques may comprise source, object or executable code in a conventional programming language (interpreted or compiled) such as C, or assembly code, code for setting up or controlling an ASIC (Application Specific Integrated Circuit) or FPGA (Field Programmable Gate Array), or code for a hardware description language such as Verilog™ or VHDL (Very high speed integrated circuit Hardware Description Language). 
     Code components may be embodied as procedures, methods or the like, and may comprise sub-components which may take the form of instructions or sequences of instructions at any of the levels of abstraction, from the direct machine instructions of a native instruction set to high-level compiled or interpreted language constructs. 
     It will also be clear to one of skill in the art that all or part of a logical method according to the preferred embodiments of the present techniques may suitably be embodied in a logic apparatus comprising logic elements to perform the steps of the method, and that such logic elements may comprise components such as logic gates in, for example a programmable logic array or application-specific integrated circuit. Such a logic arrangement may further be embodied in enabling elements for temporarily or permanently establishing logic structures in such an array or circuit using, for example, a virtual hardware descriptor language, which may be stored and transmitted using fixed or transmittable carrier media. 
     In one alternative, an embodiment of the present techniques may be realized in the form of a computer implemented method of deploying a service comprising steps of deploying computer program code operable to, when deployed into a computer infrastructure or network and executed thereon, cause said computer system or network to perform all the steps of the method. 
     In a further alternative, the preferred embodiment of the present techniques may be realized in the form of a data carrier having functional data thereon, said functional data comprising functional computer data structures to, when loaded into a computer system or network and operated upon thereby, enable said computer system to perform all the steps of the method. 
     It will be clear to one skilled in the art that many improvements and modifications can be made to the foregoing exemplary embodiments without departing from the scope of the present techniques.