EP2084475A2

EP2084475A2 - Method and system for checking a cryopreservation installation

Info

Publication number: EP2084475A2
Application number: EP07858584A
Authority: EP
Inventors: Christiano Guglielmetti; Matteo Polese
Original assignee: Air Liquide Sante International SA; Air Liquide Sanita Service SpA
Current assignee: Air Liquide Sante International SA; Air Liquide Sanita Service SpA
Priority date: 2006-10-25
Filing date: 2007-10-15
Publication date: 2009-08-05
Also published as: CA2662957C; WO2008050035A3; CA2662957A1; EP1916492A1; US20080104976A1; WO2008050035A2

Abstract

The invention relates to a method of checking and controlling a cryopreservation installation comprising at least one container or at least one refrigerator (3, 4) in which specimens to be preserved are placed, in a refrigerated atmosphere, said at least one container or refrigerator (3, 4) being placed in at least one room (A). According to this method, a check is made, preferably remotely, upon receiving one or more items of data coming from or representative of at least one container and/or refrigerator (3, 4) containing the specimens, so as to verify the state of the cryogenic fluid that is present therein or the state of the electrical supply for said container and/or refrigerator (3, 4), the state of the means for opening/closing said container and/or refrigerator (3, 4), or of the temperature within said container and/or refrigerator (3, 4), of a cryogenic fluid feed line (2) connecting at least one storage tank (1) to at least one container and/or refrigerator (3, 4), of at least one valve placed on said feed line (2) or of said storage tank (118) containing the cryogenic fluid, of at least one ambient condition prevailing in the room (A) or of the specimens preserved. At least some of the data collected is associated with the specimens and stored so as to be associated with the specimens. Associated system.

Description

Method and control system of a cryopreservation facility

The subject of the present invention relates to a method and a system for controlling and managing, in particular at a distance, a plant for cryopreservation of samples or biological or similar materials.

A cryopreservation plant is an installation typically having one or more holding vessels or tanks, and / or one or more mechanical refrigerators, in which one or more are stored in a cooling atmosphere obtained with a cryogenic fluid, such as liquid nitrogen or similar, or by means of a mechanical system, for example by means of mechanical freezers or refrigerators with compressors or other technology, samples or biological products, such as cells, plasma, tissues, organs or other biological, chemical or biochemical and the like. The vessel or vessel is supplied with cryogenic fluid from, via a suitable line or supply line, a reservoir containing a cryogenic fluid, for example liquid nitrogen. Usually, one or a plurality of containers is, moreover, disposed in a closed room, in which only the personnel and / or authorized operators have access, including personnel with a key or an electronic access card. (badge) that allows them to enter this room.

In addition, in the cryopreservation room, sensors or sensors of ambient conditions, such as temperature, humidity, etc., are often present, able to determine whether the conditions prevailing in the room correspond to parameters prefixed so as to have an operating mode. equipment and to ensure the safety of operators and samples or biological products.

In such an installation are, moreover, usually present alarm instruments, such as flashers, audible alarms or the like, which are activated or which are activated automatically when a danger situation is detected, for example linked to a malfunction or a malfunction of a container, or the detection of incorrect or non-compliant ambient parameters. This is especially described in WO-A-93/03891.

However, monitoring the ambient conditions or the accesses to the room is clearly insufficient to be able to guarantee an optimal conservation of the preserved samples. There is therefore a real need to be able not only to monitor the cryopreservation facilities but also and above all to be able to act immediately in response to the detection of a non-compliant data or parameter so as to allow optimum conservation of the samples. Document CA-A-2419647 teaches, meanwhile, a product storage cold room equipped with various detectors for monitoring different parameters and to trigger an alarm, if necessary.

However, the current systems do not make it possible to know the complete history of a given sample, that is to say to have a maximum of information relating to the life of this sample, thus to ensure an effective traceability of each sample.

The object of the present invention is therefore to provide an improved method and control system of a cryopreservation plant samples or other similar biological products to ensure effective traceability of the samples that are stored there. In particular, an object of the invention is to provide such a control system that takes into account the different organs or control devices cryogenic conservation facilities, currently independent of each other.

Another aim is to propose a method and a control system of the aforementioned type which allow a collection and storage of a plurality of data from the various organs or controlled elements of the installation, and a management of these data in automatic mode. to generate an alarm adapted to the gravity of the situation and possibly corrective measures in the installation, when these data do not correspond to prefixed parameters.

Another aim is to carry out the control and management of the installation with a high level of security, from the point of view of the communication of the data recorded during the control, the resistance of said control devices to internal malfunctions and the resistance of said control devices of preservation facilities to aggressive agents, such as dust, gas or moisture.

Another purpose is to provide a high security of data storage, including in case of widespread damage of the installation.

Another aim is to propose a method and a control system of the aforementioned type that allows remote control and / or local control of the cryopreservation installation via several communication systems, such as personal computer PC, cell phones, palm devices or the like. Another aim is to propose a method that crosses all the data relating to the cryopreservation facility to check the quality of the conservation of samples or biological products.

Another aim is to propose a control system of the type raised which can be extended to all the apparatus and premises inherent to the cryopreservation installation.

All or part of these goals are achieved by means of a method of controlling and managing a cryopreservation facility comprising at least one container or at least one refrigerator, in which refrigerated samples are placed in a refrigerated atmosphere. , said at least one container or refrigerator being disposed in at least one room, wherein: a) a check is made, preferably remotely, with collection of one or more data derived or representative:

at least one container and / or refrigerator containing the samples so as to check the state of the cryogenic fluid which is present therein or of the electrical supply of said container and / or refrigerator, of the state of the opening means closing said container and / or refrigerator, or the temperature in said container and / or refrigerator,

a cryogenic fluid supply line connecting at least one tank to at least one container and / or refrigerator, at least one valve arranged on said supply line, or said tank containing the cryogenic fluid,

at least one ambient condition prevailing in the room, or

conserved samples, characterized in that at least a portion of the data collected in step a) are associated with the samples and stored in a manner associated with the samples so as to know the history of each sample considered and to be able to ensure effective traceability.

Depending on the case, the method according to the invention may comprise one or more of the following characteristics:

- The collected data is sent to an organ of the management facility to determine the operating status of the installation and intervene remotely in case of malfunction. the data collected in step a) are stored and stored in a database in which the samples are identified, listed and classified, thereby creating a direct virtual link with the samples.

- It is carried out a survey, preferably continuously, the open or closed state of at least one valve, in particular a solenoid valve, or a means of opening / closing the container and / or the refrigerator , in particular the lid or the door of each container or refrigerator.

the ambient conditions prevailing in the room which are controlled in step a) are chosen from the percentage of oxygen in the room air, the temperature in the room, the pressure in the room and / or the humidity of the room; local, preferably said control is operated so as to detect a leakage of cryogenic fluid from one of the containers.

the activation of an alarm is provided when at least one of the controlled data comes out of an interval of prefixed values, preferably said alarm is activated remotely by the remote management member of the installation. . The alarm can be an audible and / or visual alert, or it can be an alert sent to the operator of the installation by an appropriate means of communication, in particular a message sent on his mobile phone, for example of the SMS type. (Short Message Service), an electronic message, for example of the email type sent to a computer or a telephone, or a conventional telephone call. - It also operates a control of the access of the room where the container is arranged by means of an access indicator present in said room or in its vicinity, and / or a control of access to the samples.

each sample or biological product is associated in the cryopreservation phase with a code or a marking able to allow its traceability, in particular in case of displacement of said sample.

the data exchanges and / or the communication between the measurement sensor (s) and the remote management unit of the installation are carried out by means of an internet, Ethernet or intranet network.

the data relating to said checks are stored by the management body so as to allow, for each sample, a reminder of the history of the biological material conserved and / or the conditions of its conservation.

the remote management unit is able to intervene autonomously on the installation in order to modify at least one of said controlled parameters or data. when a discrepancy or difference is detected between the data recorded from said parameter and those prefixed.

it comprises the additional step of generating an alarm or incident anomaly information when at least one of the controls of step a) determines an anomaly or a difference with respect to a prefixed state.

in step a), a control is carried out with collection of one or more data from or representative of the temperature in said container or refrigerator and preserved samples.

in step a), a control is carried out with the collection of a plurality of data derived from or representative of the stored samples, the data being chosen from: a description of the sample, a code or identification marking of the sample, the identity of any person handling the sample, the date on which each sample handling procedure took place, a history of each operation or manipulation performed on the sample, a list of the product (s) used to treat the sample sample, the place of storage of the sample, a history of the temperature monitoring of the sample with indication of any alarm, a history of the temperature drops of the refrigerators / freezers where the sample has been stored, and the sample shipping temperature measured at the time of sample delivery. The invention also relates to a control system of a cryopreservation installation comprising at least one container and / or at least one refrigerator in which, in a refrigerated atmosphere, samples are stored, said at least one container and / or refrigerator being disposed in at least one room with limited and controlled access, comprising: means for controlling each container and / or refrigerator containing said samples in order to check the state of the cryogenic fluid, the temperature in said container and / or refrigerator, from the supply line of said cryogenic fluid connecting a cryogenic fluid reservoir to said container and / or refrigerator, and said cryogenic fluid reservoir, means for controlling at least one ambient condition prevailing in the room,

and / or means of control of the preserved samples, and

- a remote management body, and data transmission means able to send the data relating to said checks to the remote management unit, characterized in that the system further comprises means associating the data recorded with each sample and means storing the data. taken together with the samples.

Depending on the case, the system of the invention may include one or more of the following features:

the control means of each container comprise level sensors able to raise the level of cryogenic fluid in the container, temperature sensors capable of raising its temperature, and opening / closing sensors able to determine the opening of the container; a container.

- Each container is associated with an identification and control device connected to at least one of said sensors and at least one control unit remotely connected to the remote management body of the installation. two redundant control units are provided, connected to a data transfer line to which is further connected the identification and control device.

- Means for measuring the ambient conditions, in particular ambient air, are provided in the room. Preferably, ventilating means of said local are activated according to the raising of such conditions.

the measuring means are chosen from an air pressure sensor, a temperature and / or humidity sensor, and an oxygen content sensor in the air of the room where the cryopreservation containers are placed.

- The measuring means are connected to the remote management member of the installation.

- The remote management body of the installation is connected to at least one server capable of collecting the data found in the containers and / or in the room where they are arranged.

the remote management unit is connected to the server by means of a network connection, in particular Ethernet type.

the remote management unit may be a computer equipped with an internet browser. the data transmission means are designed and able to send the data relating to said checks to the remote management member so as to determine the operating state of the cryopreservation installation and to intervene in the event of a malfunction or when the data recorded is different from the corresponding data prefixed

it furthermore comprises alarm means designed for and capable of triggering an alarm or delivering incident fault information when at least one of the controls operated by the remote management unit determines an anomaly or a difference from a prefixed state. The present invention will now be better understood, thanks to the following description, given by way of illustration but not limitation, and with reference to the appended figures, among which:

- Figure 1 generally shows an installation in which is used a system and a control method according to the invention; FIG. 2 is a general view of the system used in the installation of FIG. 1;

- Figure 3 shows schematically, from the logical / functional point of view, the control system according to the invention; and

FIG. 4 represents a detailed block diagram of part of the system of FIG. 3.

FIG. 1 schematically shows a cryopreservation installation according to the invention which comprises a restricted access room A in which cryogenic containers 3 and mechanical freezers 4 are placed in which samples and / or chemical and biochemical products are housed. or biological to keep. For the sake of simplification, in the context of the present invention, the generic term "samples" will be used to designate the different biological, biochemical, chemical or other materials to be preserved which are stored in the tanks 3 or refrigerators 4. The samples after a timely treatment, are kept in the (or) container or tank 3 or freezer 4 until their removal, which can occur after a long period, for example after months or years.

In each cryogenic container 3 is present a cryogenic fluid, which is usually nitrogen at cryogenic temperature used to maintain in the container itself an appropriate temperature (for example <-150 ° C) to the conservation some samples. The cryogenic fluid is stored in at least one tank 1 and is conveyed to the containers 3 via a supply line 2 in cryogenic fluid.

In the room A, there are also one or more mechanical freezers 4 or refrigerators which allow the storage and freezing of the samples according to another preservation technique usually used in a cryopreservation plant. These freezers 4 can also use cryogenic fluid in case of malfunction of their refrigeration system and, for this reason, they are also connected to the line 2 to be supplied with liquid nitrogen from the tank 1.

The cryogenic fluid supply of the two types of devices 3, 4 is carried out through the control of a main valve 8 located on the line 2 and an exhaust valve 9 and supply valves 23 located on the lines connection 24 connected, on the one hand, to each container 3 or mechanical freezer 4 and, secondly, to the line 2 of nitrogen supply.

To guarantee the safety of personnel who have access to room A, in particular in order to limit the risks of anoxia related to the presence of liquid gas, and to maintain adequate ambient parameters for the handling of samples and the operation of the equipment present in the room. this atmosphere is preferably provided with room sensors 6, connected to sound and light alarm devices 5, which are internal and external to room 7, and to a ventilation system of room 7.

In such an installation, it is absolutely essential to maintain inside each container 3 or freezer 4, the desired prefixed cryopreservation temperature.

In addition, regarding the cryogenic receptacles 3, it must always be possible to control the correct level of liquid nitrogen present therein. This control must be operated in continuous mode and, preferably, without the dedicated personnel entering each room A where the containers 3 and / or the freezers 4 are located, and limiting the opening of the containers to a minimum. 3, in order to avoid the degradation of the biological material therein, to avoid possible contamination of the room A while reducing the management costs of the installation 1 and to prevent access to the room by persons not allowed.

In addition, it is important to detect and quickly resolve any anomalies in the nitrogen supply and operation of the containers 3 or freezers 4 and maintain a history of all the parameters, in particular the ambient parameters, coming from the devices and the sensors 6, which contribute to a good preservation of the samples.

For this purpose, using the system according to the invention, it is possible to collect the data of each container 3 and freezer 4 and of each sensor 6 present in the room A, and then intervene to avoid endangering the biological material of the samples.

For this, we implement, as shown schematically in Figure 2:

a plurality of sensors 6 and couplers 1 13, present in the installation, which are devices which translate the signal of the sensors 6 into a network protocol (blocks 13 and 15);

access control devices, such as a card reader 10, code or a biometric recognition device, and actions performed in the room (block 14);

a control center 1 1, connected thereto via a network 16 of data, such as an Ethernet network, where the data recorded are collected and processed, and in which interventions are automatically activated to solve any problems that may arise; occur during the cryopreservation of equipment;

one or more main servers 12 (if necessary) can be connected to the control center 11 via a data network 17, in which the collected data are stored and which manages the interface with the user. In particular, the control center 1 1, connected to each main server 12, performs the following functions:

. collect and store data from field devices, ie sensors and other devices mentioned above;

. perform actions on the field devices on behalf of an operator or automatically in response to exceeding a threshold value of a parameter controlled by said devices;

. generate critical alarms to the staff or the operator via GSM (SMS), E-mail, WEB, and voice;

. provide a supervisory interface based on network technologies (Web) that can be used both over the Internet and on an intranet.

In addition, in order to guarantee continuity of service, the supervision system meets the following needs: Upgrading: it is possible to add servers in operating equilibrium to make the response time of the control center 11 almost constant in the face of an increase in operation;

- Reliability, availability: the operability of the system is a guarantee even in case of damage of one of its components through the use of the following technologies:

° Redundancy support for servers and application services;

° Redundancy in network connectivity (network plugs, switches, signal converters, access points for wireless connection);

° Load balancing that allows the redirection of requests from the different organs or sensors connected to an available server in case of degradation of one of the servers;

° Interactivity with already existing equipment of the installation and with other equipment that may be added to it, which are based on current or future standards. The data network 16 is based on Ethernet technology. This allows an optimal connection between the various points of the installation and the control center 11 and allows, among other things, a quick connection and activation of the various members of the system according to the invention with said center 11, a significant simplification remote technical intervention on the various system components, a high flexibility of the installation insofar as new devices (sensors and devices) can be connected quickly to the system without any negative effect on the operation of the system and bodies present beforehand. This network topology also allows a fast connection to an existing intranet network, for example a hospital.

The system according to the invention is logically subdivided into four logical areas, shown in FIG. 3. The sub-division made is purely logical / functional and does not necessarily reflect the hardware actually used, which will be detailed hereinafter. According to this sub-division, said system comprises the following areas:

FIELD / FIELD DEVICES: the area 31 is composed of all the devices that make up the instrumentation of the cryopreservation installation 1 and their possible communication interfaces.

- FIELD AUTOMATION: Area 32 consists of one or more field supervisors in redundant configuration, and is used for device automation and data collection. - MAIN DATABASE: the area 33 is composed of one or more servers 12 provided with a database or main database and adequate multichannel communication systems, for the historical consolidation of data and the management of the services of the interface user U. - USER INTERFACE: area 34 is composed of computers or portable devices that allow the user to operate U on the cryopreservation facility 1.

These four levels communicate with each other through three communication systems schematized in Figure 3. - AUTOMATION CONTROLS 35: They are used to collect and send data and signals through devices and interfaces, data for the management of automation of the installation and for the collection of data.

- DATA COLLECTION 36: it is used to manage the data communication of the field supervisors and the configuration of the installation. - INTERFACE SERVICES 37: they are used to manage the multichannel interface of the main database with the user U.

The level relative to the field automation 32 and the level relative to the main database 33 represent the logic control center 11 of the entire system according to the invention. Each level is characterized by a plurality of process algorithms

(software) of different types, which will be detailed below.

Level n. 1: FIELD DEVICE

This logic area takes care of collecting the physical signals coming from the field or from the different sensors (13-15) and control devices 11, and transforming them by means of appropriate couplers of low logic level into data intelligible to the higher logical levels and, vice versa, to transform the actions controlled by the higher levels into intelligible signals by the devices and the field actuators. Special low level couplers are used to manage these automation features which concern the safety of the operators in the installation or which are considered critical according to the proposed objectives of the installation.

These are programmed through PLC logic (Logic Controller programmable) to guarantee their operation also in case of serious malfunction of higher level logic.

There is normally at least one coupler programmed so that, implanted on the field device for the control of the ambient parameters (ambient sensor 6), it follows the following sequences:

- constantly check that the supervision system is active: monitoring function;

- check that the oxygen level does not fall below two critical thresholds, for example 19% and 17%; and - generating an audible alarm by means of a sound frequency modulation of a sound generator (off, 1 Hz, 2 Hz, continuous sound) - of each alarm device 5 - when the supervision system remains inactive and the level of oxygen in the room A, controlled by the sensor 6, is below the critical thresholds.

There are also at this level field devices that have an advanced communication protocol and are able to communicate with the higher level directly or through a protocol coupler. Such devices may be, for example, cryogenic tank supervision electronics or refrigerators 4, but also centrifuges or laboratory incubators.

Level N. 2: AUTOMATION OF FIELD

This logic area 32 contains all the informative automation processes of the field devices. In particular, such components are shown diagrammatically in FIGS. 3 and 4, and comprising:

the CrioFieldManager 47 having the following functions: either perform the pooling of the field devices to remove the data based on the configuration read by the main database 40 (area 33 described below) or postpone the monitoring contactor of a device 37 able to perform the ambient control to allow the device to generate independent alarms (via a corresponding warning device) which may concern the safety of the users in the installation (eg under-oxygenation) or which are considered critical according to the objectives prefixed with the installation, in case of malfunction of the supervision system; . or postpone / monitor a shared monitoring timer with the CrioFieldManager 47 in active / passive mode to manage the redundancy of the service;

° Store field data in a field database 49 field devices; ° Perform actions on field devices, imposed by the operator or automatically, and generate alarms.

- CrioLocalExchanger 48 with the following functions: o replicate the data on the field devices and the alarms, incorporated in the database 49 of the CrioFieldManager 47 service, in the main database 40; transfer from the main database 40 to the database 49, the actions on the field devices imposed by the operator; o Restart the CrioFieldManager 47 service when changing the configuration or field settings. The database 49 is the support database connected to this logical area 33. It contains the data read by the CrioFieldManager 47 service by the field devices and the current field configuration.

The communication via a logical area CrioDBInterface 41 of the supervisor 100 is a service via internet or network (web service) used by the service CrioFieldManager 47 and CrioLocalExchanger 48 to access the main database 40.

All the components that make up this area are always redundant: it is therefore always at least two processes of this type for each installation and as many databases 49, among which at least one is active; the other, passive, continuously check the functionality of the active process (s), ready to activate in the event of system failure, while at the same time triggering a malfunction alarm.

Level n. 3: MAIN DATA DATABASE

This logical area 33 collects all the data recorded by the databases 49 and consolidates them in the main database 40 permanently; and vice versa, as mentioned above, restores the usual configuration and the actions commanded by the operator on the database database (s) 49. In addition, it manages the services (interface services) that allow the interface with the user. This database also contains all the commands and actions entered by the user.

The communication system via areas 32 and 33 ("Data Collection" 36 in Figure 3) is based on an evolved and asynchronous protocol, ie which guarantees the integrity of data and which also works in case of discontinuity communication via levels 32 and 33.

More particularly, the area 100 of FIG. 4 comprises the following components: CrioDBInterfae 41 is an internet or network service (web service) used by the CrioFieldManager 47 and CrioLocalExchanger 48 services to access the main database 40;

- CrioSMTPGateway 45 is an algorithm that extracts from the main database 40, the alarms to be sent via e-mail and sends them to an SMTP server; CrioPhoneCell 46 is an algorithm that extracts from the main database, the alarms to be sent via SMS or voice and sends them to the SMS sending system or voicemail system;

Level n. 4: USER INTERFACE This logical area 34 summarizes all the communication strategies with the user. The main interface with the user is web-based and can work through any computer or PC with a standard internet browser. The user interface access policy is based on user profiles: a user authenticates only once and only accesses the features for which they are authorized. The level of authorization may be related to the type of samples retained.

Each action, activation or modification performed by the user is plotted in the system. The functionalities of the main interface are explained to the user through three application areas of the supervisor 100:

- Control Panel 42: An Internet or Intranet-enabled network application that allows operators to monitor the status of field devices, perform actions, and view active alarms. - Sample Management 43: Network application accessible via Internet or Intranet that allows operators to view the archiving and movement of cryocon serve samples.

- Administration 44: application of network accessible by Internet or Intranet which allows the administrators to visualize the monitored devices, their typology, the parameters ...

Also included in this area 34 are the interfaces predisposed for portable devices (PDAs or the like) for inputting and viewing the user data of the wireless channels.

LOGICAL ARCHITECTURE OF THE INSTALLATION

The logical architecture of the invention described above can be broken down, in various ways, in the devices installed in the cryopreservation plant.

The physical configuration of the installation is determined in fact not only by the devices present in the installation but also by the requirements of redundancy and level of service required for the objectives prefixed in the installation itself.

Concerning level 31, it is normally implemented through the following devices:

- A / D (analog / digital) signal acquisition and control stations: based on PLC couplers, allow acquisition and control of A / D field signals. These can also include acoustic and light signals, and implement standalone features;

- Serial / Ethernet coupling stations: based on low level protocol linkages, allows the translation of serial network-based protocols over the Ethernet network.

- Reader of electronic cards or proximity badges, to allow the access to the room to the authorized ones only. To enhance security at the entrance, it is possible to require the user to dial a code and / or perform a biometric recognition of his thumb. - Telecamera, with revealing presence, who realize the acquisition of the images of each action operated on the devices present in the room. The operating logic of these two devices is managed by the central supervisor, connected to them by Ethernet network. In the typical configuration of a cryopreservation plant, whose main components have been described above, level 1 is structured as follows:

for each branch or connection line 24 of the nitrogen supply line 2 are provided two control stations and A / D signals for managing the cooling of the connection line 24, and two Ethernet serial coupling stations; for the translation of signals;

- For each room A is provided at least one control station A / D signals for controlling the atmosphere of the room, at least one badge reader 10 and at least one Webcam 1 14 connected to the network 16;

- For each nitrogen tank 3 is provided a control station A / D signals to determine the level and pressure of the tank itself;

the levels or areas 32, 33, 34 may be implemented on one or more physical devices provided they have the functionality of a computer (PC). The typical configuration is illustrated in Figure 3:

- level 32 is preferably installed on two or more industrial PCs, designed to resist dust and water, arranged in the vicinity of the installation;

the level 33 is preferably installed on two or more servers, provided with at least doublings in power supply and mass storage devices. It can also be arranged in a site remote from the installation 1, connected to the system via any type of Internet network infrastructure;

- The level 34 is obtained at the cross of fixed PCs or laptops arranged at the entrance of the cryopreservation facility;

- The data network 16 connecting the different devices is of the Ethernet type or leading to Ethernet via suitable couplers 1 13;

the network interconnections are structured in such a way that each device can be connected through at least two distinct and independent network paths (see Ethernet 1 and 2 in Figure 2);

- in general, the configuration can be fully doubled / redundant, in whole or in part, according to the customer's requirements to ensure the availability of the application in accordance with the objectives of the cryopreservation facility.

The operation of the system according to the invention will now be described in the context of a typical cryopreservation installation, schematized in FIGS. and 2 to explain how logical and physical interfaces can be implemented.

In Figures 1 and 2, we see a part of an installation comprising in particular, the containers or tanks 3 and the mechanical freezers 4 in which are disposed the biological materials to be preserved. As mentioned above, the containers receive liquid nitrogen from a tank 1 through a feed line 2. Each of said containers 3, tank 1 and line 2 is controlled by the control center 11 so as to maintain, for all the biological material, optimal conditions for its conservation over time (even prolonged). More particularly, each container or tank 3 is provided with dedicated sensors

(Not shown) able to raise the level of nitrogen inside, the temperature, the state of the lid and the solenoid valve supplying the container.

Each container 3, in addition, is provided with a control device which is connected to said sensors which collects data from said container and makes them available on a network interface which is typically, but not necessarily, asynchronous serial, which may be connected in cascade to several containers, thus forming a chain. At the end of this chain are connected two couplers, the first being the main unit which, while the second (backup) intervenes in the event of damage to the main unit, guarantees the continuity of acquisition of the data that comes from devices.

In order to allow the filling of the container with nitrogen in the liquid phase, the main coupler also manages the cooling of the nitrogen line 2, being connected to a solenoid valve 23 and to a temperature sensor (not shown) arranged on said line. When a container 3 needs a filling of cryogenic fluid, the solenoid valve 23, arranged at the end of the supply line, opens allowing gas-phase fluid to escape to the outside atmosphere. When the temperature detected by the sensor falls below a value compatible with the presence of cryogenic fluid in the liquid phase, the solenoid valve 23 is closed. In order to optimize the cryogenic fluid consumption, the system controls the filling of all the devices (3-4) present on the line 2.

In room A, an A / D signal acquisition and control station

(analog / digital) 13 is connected to sensors 6 oxygen, pressure, temperature and humidity 6. It also allows to control sound and light warning devices 5, to control conventional ventilation devices of local 7 and to control the main solenoid valve 8. In particular, the volume percentage of ambient oxygen must be monitored continuously. The system allows the imposition of two alarm thresholds; typically a non-critical alarm threshold (% <19%) and a critical alarm (% <17%) are imposed.

If the oxygen content reaches the threshold of 19%, the signal acquisition and control station A / D 13 activates the ventilation device 7 to obtain a maximum replacement of air; and a local, bright or / and audible alarm 5 is activated and alerts the staff. The alarm condition disappears when returning the content to a normal level (greater than 19%).

If the oxygen content falls below 17%, the high speed ventilation is confirmed and the main liquid nitrogen feed solenoid valve 8 is closed; and a local, bright and audible alarm 5 is activated to warn the personnel.

The system continuously records all the ambient parameters: each data collected is sent to the control center 11 and then stored in the main database. The couplers are connected to other couplers, via connecting members, and by means of these are connected to a programmable unit for the control of the data of the local A itself connected to the center 11.

The system continuously monitors the pressure and the level of the feed tank 1 by means of readings mounted on the tank. The data is sent to the control center 11 via a series of appropriate couplers. When the level reaches a level of attention, an alarm sounds to inform users of the need for filling. This alarm is normally also sent to a cellular device (not shown) responsible for filling the cryogenic fluid of the supply tank 1.

The system also activates alarms in case of critical level and pressure values, which are indicative of potential malfunction of the cryogenic fluid distribution system. The system allows a continuous control of the nitrogen level and the temperature of the cryogenic containers and at least the temperature of the containers with mechanical technology and the adequate activation of solenoid valves for filling the cryogenic fluid of the tanks. The level of liquid nitrogen is continuously measured by a dedicated capacitive probe in the cryogenic containers 3. It responds in active mode to any filling levels outside critical values, by activating the automatic filling of the container. Each piece of data collected is sent to the control center 11 and then stored by the main database of the server 12. Suitable level alarms are provided and the system malfunctions with organization of critical level thresholds, which will have the filling function for the automatic filling system.

For example, assuming that the start and end levels of loading are 60 and 80%, the established thresholds can be:

- minimum level alarm - non critical:% lower by 5% at the start of loading level; - super minimum level alarm - critical:% lower than 10% at the start of loading level;

- maximum level alarm - critical:% higher by 5% at the end of loading level;

- maximum super level alarm - critical:% higher than 10% at the end of loading level.

When the loading start level is reached (eg 60%), the automatic filling starts with an opening of the filling solenoid valve of the container 23. The solenoid valve remains in the open state until reaching the final loading level (eg 80%), and the solenoid valve closes when it is reached. In the case of mechanical refrigerators 4, the nitrogen supply is optional and used only in case of malfunction of the mechanical cooling system, and arrives via the supply solenoid valve 23. Other cryogenic fluids can also be used for this purpose. end, ie fluids other than liquid nitrogen. The control of the temperature of the nitrogen enables the continuous recording of the temperature values recorded by the probes dedicated to the cryogenic receptacles 3 and the mechanical freezers 4 and the loading of cryogenic fluid in the event of a temperature below the alarm threshold.

Two alarm thresholds are set, for example: non-critical threshold: T> -145 ° C and critical threshold: T> -135 ° C.

Each piece of data collected is sent to the control center 1 1 and then stored in the main database 12. Appropriate alarms of temperature and system malfunction are provided with fixing of the critical thresholds of the system. temperature, which will have the cooling function for the automatic filling system.

In addition, the system plans to monitor and delay the condition of the lid

(opened closed). The data relating to changes in the state of the lid are recorded and stored so as to allow the traceability of the movements of the samples contained therein. The system provides for the activation of an open lid alarm.

Finally, the system makes it possible to directly control the state of the filling solenoid valve of the containers, namely open or closed. In order to conveniently supply liquid nitrogen to the containers 3 and the freezers 4, appropriate control is provided of the main solenoid valve 8 arranged between the tank 1 and the cryopreservation containers. This is normally closed but there is nevertheless a manual bypass that can be used in the event of a voltage drop. There may be more cascading main solenoid valves, depending on the topology of the installation.

The system, via appropriate signal couplers, manages the opening / closing of the solenoid valve of the tank in the following cases:

- closing: the percentage of oxygen raised by any of the measuring devices falls below a prefixed value, for example 17%; - closing: if the super-maximum level alarm level is reached;

- closure: manual intervention in case of loss.

The system reopens the solenoid valve 8 if the aforementioned parameters are returned to normal or in the case of manual intervention.

The system continuously records the state of the main solenoid valve 8. Each collected data is sent to the control center 11 and then stored in the main database 12.

Thanks to the invention, it is possible to supervise an installation of cryopreservation optimally, even remotely, by controlling the parameters specific to each container 3, 4 able to allow such storage, the ambient parameters and also the accesses to each container and at each place where the biological material is conserved. The system is connected to an intranet / internet network and has its own architecture for protecting data access (firewall). It can be accessed using an internet browser.

The system automatically modulates its functionality according to the permissions of the connected user, regardless of the user platform, without requiring the installation of software. It is optionally open to communication with other national and transnational information systems via a dedicated interface.

All features are fully exploitable by each PC networked to the main server 12.

It is also possible to provide viewing locations in the control rooms with a card reader (badge) to accelerate the authentication operations of the user. For remote locations, authentication is preferably via the user name and a password. The system therefore allows:

- view the parameters relating to the samples themselves, stored in the installation;

- visualize the topographic layout of the room, which summarizes the main parameters measured by the containers, the mechanical freezers or by the ambient survey points and by the ventilation system;

- view the alarms;

- visualize the actions performed on the samples: set up, collected, used, moved; and

- visualize statistics and multidimensional reports. In addition, according to a preferred embodiment, provision is made to associate each retained sample with a unique identification code, for example a bar code or any other marking or identification means capable of allowing identification of the sample. considered, such as a microchip or the like.

Such a code refers for example to the position of the biological material in the room A, in particular a code that takes into account the container, support, level, box, position row / column in the box, visiotube, straw ...

Thanks to such a codification, an operator, after having self-identified via the card or the badge and personal password, can easily receive information on the position and typology of the requested sample (s). During sampling or immersion of the sample, the user will have to co-validate via a code reader the containers as and when the samples taken by receiving a confirmation of the system and visual information on how to proceed. This makes it possible to record any movement of each sample or biological material.

In addition, the system associates with the sample all the data collected in the installation that is related to the sample itself. It is then possible to retrace the complete history of the conservation of the sample.

In other words, thanks to the data collected by the method or system of the invention, it is now possible to monitor the history of each sample by memorizing all the events that have punctuated the life of the sample in question, especially is now possible to know in which tank it has been kept (identification of the tank and its position in the tank, room, hospital ..), how long (date of introduction and / or exit of the tank), under which conditions (temperatures, nitrogen levels, alarms triggered or not, opening of the tank ..), by whom it was handled and when (authorized person with access by badge or the like, ...) ...

All this information from the sample history can be stored on the samples themselves and / or stored in a database in which the different samples are identified, listed, classified etc. in association with all the information concerning their history. Thus, in case of need, all this information can be returned immediately and it is then easy to know all the events of the life of a given sample.

In other words, in this way, an operator selecting a given sample can immediately have important information relating to this sample and the life of this sample, that is to say its history.

Thus, the information or data stored in connection with a given sample are for example:

a description of the sample, that is to say what type or nature of biological product it is, and an identification code or marking, for example a barcode or the like,

- the identity of the persons who manipulated the sample and the date on which each manipulation took place, - the history of each operation or manipulation carried out on the sample, for example support, test, freezing, storage, change of storage position, extraction, delivery ...

- list of all the products used to treat the sample, such as chemical agents, vials ..., for example with their expiry date, the batch number ...

- exact storage location, including country, city, site, laboratory, room, freezer, shelf, box ...

- sample temperature monitoring history with indication of possible alarm triggers (ie excessive temperature),

- history of temperature drops of refrigerators / freezers, including temperature gradients used to freeze the sample, and

- shipping temperature, that is, the temperature measured at the time of sample delivery. Other information can also be stored in a database of the installation without necessarily being connected to a given sample, for example:

- Alarms concerning storage and storage devices, such as containers, refrigerators, etc., including temperature alarms, liquid nitrogen level, open / closed lid, open / closed valve, etc.

- alarms relating to other devices, such as oxygen sensors, liquid nitrogen storage tanks, room access door, webcam, ... including oxygen content (%) or pressure alarms in the room, identification badge by the entry of a person in the room ... In addition, the different alarms can be associated with a ranking of priority so as to define which alarm is the most or the least urgent or critical.

These alarms can also be relayed by sending SMS messages, emails or phone calls to warn people in real time of any malfunction of the installation. Thanks to the present invention, it is now possible to perform a precise and effective monitoring of each preserved sample and easily trace the history of his life in the tank or refrigerator where it was kept. The present invention is particularly useful in the cryopreservation of biological materials of human, animal or plant origin, such as samples of cells, blood, sperm or any other similar biological material.

Claims

1. Method of controlling and managing a cryopreservation plant comprising at least one container or at least one refrigerator (3,4), in which or in which refrigerated samples are arranged, said at least one a container or refrigerator (3,4) being disposed in at least one room

(A), wherein: a) control is carried out, preferably remotely, with collection of one or more data from or representative of: - at least one container and / or refrigerator (3,4) containing the samples in order to check the state of the cryogenic fluid that is present therein or the electrical supply of said container and / or refrigerator (3,4), the state of the opening / closing means of said container and / or refrigerator ( 3,4), or the temperature in said container and / or refrigerator (3,4), of a supply line (2) of cryogenic fluid connecting at least one reservoir

(1) at least one container and / or refrigerator (3,4), at least one valve arranged on said feed line (2), or said reservoir (1 18) containing the cryogenic fluid,

at least one ambient condition prevailing in the room (A), or

conserved samples, characterized in that at least a part of the data collected in step a) are associated with the samples and stored in a manner associated with the samples.

2. Method according to claim 1, characterized in that the collected data or data are sent to a member (1 1) of the management facility for determining the operating state of the installation and intervene, preferably to distance, in case of malfunction.

3. Method according to one of claims 1 or 2, characterized in that the collected data are stored on the samples or stored in a database in which the samples are identified, listed and classified.

4. Method according to one of claims 1 or 3, characterized in that it carries out a survey, preferably continuously, the open or closed state of at least one valve, in particular a solenoid valve, or means for opening / closing the container and / or the refrigerator (3, 4), in particular the lid or the door of each container or refrigerator (3, 4).

5. Method according to claim 1, characterized in that the ambient conditions prevailing in the room (A) which are controlled in step a) are chosen from the percentage of oxygen in the air of the room, the temperature in the room. local, the pressure in the room and the humidity of the room (A), preferably said control is operated so as to detect a leakage of cryogenic fluid from one of the containers (3, 4).

6. Method according to one of claims 1 to 5, characterized in that it is expected the activation of an alarm when at least one of the controlled data out of a range of prefixed values, preferably said alarm is activated remotely by the body (1 1) remote management of the installation (1).

7. Method according to claim 1, characterized in that it also operates a control of the access of the room (A) where the container (3, 4) is placed by means of an access indicator ( 60) present in said room (A) or in its vicinity, and / or a control of the access to the samples.

8. Method according to claim 1, characterized in that each sample or biological product in the cryopreservation phase is associated with a code or marking capable of enabling its traceability, particularly in case of displacement of said sample.

9. Method according to claim 2, characterized in that the data exchanges and the communication between one or more measuring sensors and the remote management unit (1 1) of the installation (1) are carried out by means of an internet, Ethernet or intranet network.

10. Method according to one of claims 1 to 9, characterized in that the data relating to said checks are stored by the management member (11) so as to allow, for each sample, a reminder of the history of the material biological preservation and / or conditions of its conservation and / information relating to its handling.

1 1. Method according to claim 1, characterized in that the remote management member (1 1) is able to intervene autonomously on the installation (1) in order to modify at least one of said parameters or data controlled when a discrepancy or difference is detected between the data recorded from said parameter and those prefixed.

12. The method of claim 2, characterized in that it comprises the following additional step: b) generates an alarm or incident anomaly information when at least one of the controls of step a) determines an anomaly or difference from a prefixed state.

13. Method according to claim 1, characterized in that in step a), a check is made with collection of one or more data derived or representative:

the temperature prevailing in said container or refrigerator (3,4) and

- preserved samples.

14. Method according to claim 1, 12 or 13, characterized in that in step a), a control is carried out with collection of several data from or representative of the stored samples, the data being selected from:

- a description of the sample,

a code or identification marking of the sample,

- the identity of any person handling the sample, - the date on which each manipulation of the sample took place,

a history of each operation or manipulation performed on the sample, - a list of the product (s) used to process the sample,

- the place of storage of the sample,

- a history of monitoring the temperatures of the sample with indication of any triggering of the alarm,

- a history of the temperature drops of the refrigerators / freezers where the sample has been stored, and

- the sample shipping temperature measured at the time of sample delivery.

15. Control system of a cryopreservation plant (1) comprising at least one container and / or at least one refrigerator (3, 4) in which, in a refrigerated atmosphere, samples are stored, said at least one container and / or refrigerator (3, 4) being disposed in at least one room (A) with limited and controlled access, comprising: - means of control (20) of each container and / or refrigerator (3, 4) containing said samples in order to verify the state of the cryogenic fluid, the temperature in said container and / or refrigerator (3, 4), of the supply line (2) to said cryogenic fluid connecting a reservoir (1) of cryogenic fluid to said container and / u refrigerator (3, 4), and said reservoir (118) of cryogenic fluid, - means for controlling at least one ambient condition prevailing in the room (A),

and / or means of control of the preserved samples, and

an organ (11) for remote management, and

data transmission means (16) able to send the data relating to said checks to the remote management unit (1 1), characterized in that the system furthermore comprises means associating the data recorded with each sample and means storing the recorded data thus associated with the samples.

16. System according to claim 15, characterized in that the control means of each container (3,4) comprises level sensors able to raise the level of cryogenic fluid in the container, temperature sensors suitable for raise its temperature and open / close sensors able to determine the opening of a container.

17. System according to one of claims 15 or 16, characterized in that each container is associated with an identification and control device (20) connected to at least one of said sensors and at least one connected control unit remotely to the remote management member (11) of the installation (1).

System according to Claim 17, characterized in that two redundant control units are provided which are connected to a data transfer line to which the identification and control device (20) is further connected.

19. System according to claim 15, characterized in that means (6) for measuring the ambient conditions, in particular ambient air, are provided in the room (A). Ventilation means are also preferably provided. (7) of said local activatable depending on the recovery of such conditions.

20. System according to one of claims 15 or 19, characterized in that the measuring means (6) are chosen from an air pressure sensor, a temperature and / or humidity sensor, and a sensor. of oxygen content in the room air

(A) where the cryopreservation containers (3,4) are located.

21. System according to one of claims 18 to 20, characterized in that the measuring means (6) are connected to the member (11) for remote management of the installation.

22. System according to claim 15, characterized in that the device (11) for remote management of the installation is connected to at least one server (12) able to collect the data found in the containers (3, 4). and / or in the room (A) where they are arranged.

23. System according to claim 15, characterized in that the member (11) remote management is connected to the server through a network connection, in particular Ethernet type (16).

24. The system of claim 15, characterized in that the remote management member may be a computer with an internet browser.

25. System according to claim 15, characterized in that the data transmission means (16) are designed and able to send the data relating to said checks to the remote management member (11) so as to determine the operating state of the cryopreservation system and to intervene in case of malfunction or when the data recorded are different from the corresponding data prefixed

26. System according to one of claims 15 or 23, characterized in that it further comprises alarm means designed for and able to trigger an alarm or to issue incident anomaly information when at least one of the checks carried out by the remote management member (11) determines an anomaly or a difference with respect to a prefixed state.