WO2005093641A1

WO2005093641A1 - Biological samples localisation, identification and tracking, system and method using electronic tag

Info

Publication number: WO2005093641A1
Application number: PCT/BE2005/000040
Authority: WO
Inventors: Michel Milinkovitch; Cedric Szpirer; Philippe Gabant; David Vecchia Dalla; Pascal Dal Farra; Daniel Penninck
Original assignee: Universite Libre De Bruxelles
Priority date: 2004-03-26
Filing date: 2005-03-25
Publication date: 2005-10-06

Abstract

The present invention is related to a detection system adapted for a localisation, an identification and/or a tracking of a biological sample included in or present on a solid support, said detection system comprising an electronic tag localised in or on the support so as to obtain a labelled support, said labelled support comprising information data relative to localisation, identity and/or biological and/or physical state of the biological sample and reading apparatus able to read and record these information(s) data (cfr claim 1).

Description

BIOLOGICAL SAMPLES LOCALISATION, IDENTIFICATION AND TRACKZNG, SYSTEM AND METHOD USING ELECTRONIC TAG

Field of the invention [0001] The present invention is related to a tracJcing and detection system and method adapted for the localisation, identification and/or tracking of one or more biological sample (s) included in/or present in different supports by using electronic tag with or without integrated sensors.

Background of the invention

[0002] Biological laboratories (especially in the fields of genetic engineering, proteomic, ...) require the manipulation of a large ^"number of different biological samples and media for the culture of said samples which are often submitted to various temperatures comprising between the extreme of about - 178° C and about + 120 ° C. [0003] In particular, the temperature of 120° C or more is used for obtaining a sterilization of various supports for said biological samples; while the biological samples can be maintained at different temperatures for different purposes (room temperature, 4°C, - 16°C - 178 °C for conservation of the biological samples, etc.) [0004] Various solid supports such as cylindrical laboratory tubes (of a few centimetres of diameter) , mic-rro- tubes (well-plates) or microarrays conserved in specific packaging or boxer (made of expanded polystyrene or ottier polymeric materials) are usually disposed in specific compartments of a freezer. Therefore, a freezer could contain up to several thousand different biological samples. [0005] The physical stress cycle on the samples (as a temperature cycle for example) can have an important impact on the quality of the reagent/biological sample itself. In the extreme case, bad cycles can cause the complete deterioration of the content.

[0006] Some samples have an expiration date associated. This expiration date can be associated to a specific time (absolute time) or to a specific manipulation (relative time) (example: this sample must be used in the minutes following defrost) . [0007] The history process of a sample, corresponding to the manipulation cycle, (preferably under an established protocol) this sample in a laboratory, is a succession of physical stress cycles (temperature, humidity, centrifugation,...) , add of new reagent (s) or biological component (s) , and interaction with different kind of apparatus (centrifuge, magnetic stirrer, pipette,...). [0008] Until now, said biological samples were identified by a bar code or by a manual registration (ink) printed on the support. However, said identification system is not adequate for obtaining a precise and efficient localization, identification and tracking of different biological samples present in a laboratory unit. [0009] A bar code or a manual registration system used in an identification of various biological samples required that each support was extracted from the freezer and manipulated at room temperature. Said manipulation generates solid condensation phenomena (inverse sublimisation) upon the label. Therefore, the support of the biological sample is covered with ice which renders the identification of the biological sample complex or even renders impossible the reading of the bar code .

[0010] Furthermore, said direct manipulation of the solid support is dangerous due to the temperature of the solid support, while the size of said solid support does not always allow the use of protective gloves. [0011] Furthermore, a direct contact with the solid support could lead to the destruction of the bar code or the manual registration printed upon the solid support and (due to the modification of temperature) it could affect the characteristics of the biological sample (rapid heating at room temperature of the biological sample which could lead to a partial or a complete destruction of the biological sample) . [0012] Furthermore, as a fridge may contain up to several thousand different biological samples, it is not obvious for the operator to identify directly the correct biological sample, in the correct box of a correct compartment . [0013] Furthermore, if different persons in the same laboratory should share a single fridge, it is not possible to maintain for long time a clear classification of the different biological samples in a single fridge. [0014] Furthermore, it is difficult to trace (tracking) which actions different persons have conducted on these samples . [0015] Finally, some biological samples should be maintained at very low temperatures in liquid nitrogen. [0016] Therefore, a direct manipulation of the biological samples in liquid nitrogen can be extremely dangerous (use of low temperatures, intoxication by nitrogen, etc) . [0017] Furthermore, samples are displaced form one room to another or from one analysis unit to another (potentially in another building or another research center) again this increase the importance of an efficient labelling/tagging and again underline the importance of samples location during analysis.

[0018] Another drawback of the standard label (ink, or bare code) is that these technologies are sensitive to solvent (Alcohol, phenol,...) used in laboratories and used during the analysis processes and used to sterilised the external of some containers when entering and/or coming out controlled area (GMP production, cell culture, SFP animal house, contained pathogen production rooms,...) . [0019] Furthermore, at the present time it does not exist an automatic tracking system and method for biological samples (which allows to obtain complete history process and logistic of the submitted biological sample) during a lifecycle in the laboratory or during usual manipulation protocol .

Aims of the invention [0020] The present invention aims to provide a new tracking and detection system and method, as well as any devices (apparatus, freezers, reading apparatus, computer,...) comprising it adapted for the localization, the identification and/or the tracking of a biological sample included in or present in a support which does not present drawbacks of the state of the art and which is simple, efficient and not expensive.

Summary of the invention [0021] The present invention is related to a detection system and method adapted for the localization, the identification and/or tracking of a biological sample or chemical reagents that can react with a biological sample included in or present in a solid support. Said system comprising: a software designed for tracking information related to a life cycle of a biological sample and related to this biological sample (including specific data, like taxonomic identity of the sample, taxonomic sequences of nucleic acids, vector information (such as restriction map of viruses, plasmids, etc) , protocol to use, added biological component (s) or reagent (s) to the initial sample, temperature and other physical stress (osmotic pressure, pH, modification, ...) submitted to the sample, apparatus (pipette, vortex, centrifuge) , sequencer, cycler, ...) used during the sample lifecycle and configuration parameters (t°, time, number of cycles ...) of these apparatus, sample expiration date, stock location reference, etc; all these information (s) can be associated to a specific time or to a period of time (example 10° form a date until another date dd/mm/yy hh/ss) , and, an electronic tag, preferably localized in/or on a solid support so as to obtain a labelled support, said labelled support comprising information data relative to the localization, the identity and the biological and/or physical state or life cycle of the biological sample; [0022] In the system according to the invention, the electronic tag can integrate different type of sensors, such as temperature sensors, moisture sensors, pH sensors, pressure sensors used to obtain a measurement or a monitoring of a physical stress during the sample life cycle. [0023] The information contained in the sample is of the same type as the information in the software database. [0024] The system according to the invention could also comprise mobile or fixed reading apparatus with reading means that are able to read (and record) information contained in the tag and possibly in the associated sensors, and possibly transfer (by wireless mode) these information (s) to a database. [0025] The reading apparatus could also be used to write information (s) in order to include additional information (s) into the tag and possibly in the associated sensors. Such apparatus could be any apparatus which allows a treatment of the biological sample during its life cycle. Example of these apparatus are centrifuges, magnetic stirrer, pipettes, ... involved in the treatment of the biological sample or allowing addition of reagents to the biological sample.

[0026] Furthermore, the tag of the system could be also used for obtaining an identification of the person which has performed one or more steps of an established laboratory protocol to be applied upon the biological sample. The added reagents are also identified with an electronic tag integrated into the recipient of these reagents. Furthermore, the operator working with the sample are also identified by various means, such as a card embedded with an electronic tag, present on the clothes of the operator. [0027] When an operator enters into a laboratory, the fridge can identify him or her and records which sample has been removed or added. The information can be recorded either on the memory of the tag associated to the sample or by a separated data base or both. The reagents and samples are identified. Consequently, the operator can automatically record which reagent has been or should be (according to a specific laboratory protocol) added to a specific sample, either with a desktop or a mobile application. The operator can input the quantity of reagents used. With integrated reader, writer ... the apparatus can combine its own data (parameters, calibration, ...) and communicate them to a database and/or to the manipulated samples. [0028] Advantageously, the detection system of the invention comprises an anti-collision mode so that a specific information may be read or written thereon and therein, even when trie labelled support is present among other labelled supports (different supports present in the same box or in the same compartment of a fridge) .

[0029] The biological sample, or its reagents, is any biological sample which could be used in a laboratory for specific biological experiments (laboratory protocol) or is part of a collection of micro-organisms. [0030] The said biological sample and reagents comprise but are not limited to cells (eukaryote cells or prokaryote cells, such as animal (including human) cells, plant cells, yeast cells, bacteria cells, micoplasms, viruses, peptides and proteins, amino-acids, nucleotides and nucleotide sequences, vectors, saccharides, antibiotics, lipids and lipid vesicles, vitamins, physiological media (such as buffers) , comprising each of said elements and a mixture thereof . [0031] In the detection system according to the invention, the solid support could be also further labelled by means of another detection system such as a bar code. The solid support used in the detection system according to the invention could be a laboratory tube, a micro-tube, a test- tube, flasks, pipettes, infusion bottles (baxters) , microarirays (biochips) , plates, multi well-plates, etc.

[0032] The tag system according to the invention could be an active or a passive system associated physically, directly or indirectly to the support comprising the biological sample or reagents or a container comprising multiple supports for said biological sample. [0033] Preferably, the electronic tag is used for three different purposes, it contains an electronic identification card which can be read without contact, it comprises a system for the localization of the biological samples or its solid support and it comprises a "stress" registration system of the biological and/or physico-chemical modifications of the biological sample based on sensors that can be integrated to the tag. [0034] Preferably, a tag can comprise specific sensors with temperature pressure and movement measurements that can record relevant physical information (s) directly in own memory. Such temperature sensor allows the monitoring of storage and manipulation temperature. These temperature measurements could be made at regular intervals or at programmed time. One or several movement sensors which allow the measurements of the chock received by the sample, for example a sample with a screwing top, the sensor could record when the samples have been obtained or closed. [0035] Furthermore, a pressure sensor could detect when a sample has been autoclaved. [0036] The electronic tag can comprise additional data related to the characteristic of the sample and reagents or the protocol submitted by the sample or to be applied to the sample . [0037] Furthermore, the operator can be identified by another electronic tag enabling the system (reading apparatus) to automatically trace which operator has performed a given step of a treatment protocol to be applied to the said sample.

[0O38] The detection system of the invention may also comprise a controller (in the reading apparatus) allowing a specific identification of which solid support has to be used in a specific laboratory protocol (manipulation process of the biological sample) and possibly an alarm device for the operator manipulating the apparatus with an unidentified solid support or with a solid support that should not be used in this specific laboratory protocol.

[0039] This electronic tag could be directly linked to the biological sample in the form of a sterilised and watertight capsule or physically associated with the container (system introduced into the top of the container, system glued to the container, etc.)

[0040] Furthermore, the electronic tag according to the present invention was tested and presents unexpectedly a higher resistance (resistance to high temperature (up to 120°C or higher) , resistance to high pressure (up to 1 bar, above atmospheric pressure, or higher) , resistance to low temperature (up to -80°C or lower) for long period (several months) , to high stress induced by centrifuge, magnetic stirrer, ...) compared to a bar code and therefore can be present in the packaging of the support and does not require a visibility to obtain the information reading (advantageously, the box, the fridge or the solid support should not be present in an open position and several electronic tag can be identified and differentiated among other electronic tag present in the same fridge at the same time) .

[0041] In addition, the reading and/or writing step could be advant geously performed simultaneously. [0042] Furthermore, the information capacity of this system is more important than the one of a bar code system and this reading and writing system allows the possible reuse of the electronic tag upon another support for the identification, localization and/or tracking of other biological samples .

[0043] According to the type of support or localisation of the biological sample, different radio- frequencies labelling of different frequencies could be used.

[0044] This system will also allow a rapid detection of samples and reagents to be used in a test and also integrated these data in a LIMS system (Laboratory Integrated

Management system) that will re-order reagents (information to providers) and/or inform on the status of the sample

(information to customers) , the information being sent via any electronic support .

[0045] The present invention is also related to any device (apparatus, fridge, box, automate performing purification sequencing, amplification, identification or quantification steps upon biological sample ...) , operator² clothes or plant (rooms of production, of sample collection, etc.) comprising chemical or biological samples and said system and the software able to conduct said identification, localisation and tracking of biological samples with the system of the invention, possibly combined with one or more database (s), comprising collected information (s) and protocols to be used.

[0046] Furthermore, the complete system composed of the software, the tags on the different component (s) and apparatus allow tracking all the processes on the sample during his lifecycle in an automatic way.

Example 1. Electronic identification card by lecture without contact [0047] An electronic tag (chip) contained into a capsule comprises an unique numeric alpha code which identify a sample or its container and could also be used to comprise (totally or partially) the genetic or proteic sequence of the samples or any other information (by using a genetic code - ACGT letter for DNA sequences and letters or triplets for amino acids sequences) . [0048] Therefore, the operator could directly identify correctly the sample by a direct lecture of the sequence or through a coupling of the system to a database. Other information regarding the characteristics of the biological sample could be also incorporated upon the chips. [0049] Advantageously, a lecture of the information without any direct contact with the biological sample or its support will avoid all the above-mentioned drawbacks of the state of the art, especially drawbacks which may affect the quality of information reading or induce a possible deterioration of the identification system. [0050] The electric tag used in the present invention, hereafter also called "radio frequency label" comprises chips which contain all the required information (unique alphanumeric code and possibly a memory unit which may comprise additional information which are specific of the biological samples of interest) and a reading encoder connected to an antenna. This system can be active or passive (which means that it can comprise its own battery for having autonomy of several months up to several years) . [0051] The electronic tag according to the invention allows the following functions: reading (the electronic tag comprises only an unique code integrated during the production of the chips) ; reading and writing system (the electronic tagging comprises in addition to its unique code, one or more memory units which allows the reading and the writing of additional data) ; an anti-collision mode (this function present in the electronic tag allows that a specific information may be read or written thereon and therein, even when the labelled support is present among other labelled supports) ; - EAS system (this function allows the detection of the presence of different electronic tags in the field of a single antenna) .

Example 2. a complete tracking solution integrating sample- apparatus - operator [0052] The biological samples and reagents used in a process are identified with an electronic tag that could integrate different kind of physical stress sensors (temperature sensor, pH sensor, moisture sensor,...) . [0053] Electronic tag or reader/writer can be associated with specific apparatus (centrifuge, magnetic stirrer, pipette,...). With integrated reader/writer, the apparatus can combine its own data (parameters, calibration...) and communicate them to the central system and/or to the manipulated sample. [0054] A apparatus used for taking small volumes (< 1 μl up to 5 ml) comprises a RFID reader/writer system that identifies correctly the laboratory tube comprising a specific tag and that records volume taken. This information can be written on the specific sample or it can be communicated to a data base of the system. [0055] The complete system allows the tracking of all the information. This communication is between 1 [sample, reagent, apparatus (centrifuge, magnetic stirrer, pipette,...), operator] and 2 [reader, integrated reader (in apparatus, in specific sample, in specific reagent,...)] That way, it is possible to track all the information corresponding to a process [origin of the sample, quantity used, physical stress constraints (temperature,...), apparatus process/ parameters/ calibration, person doing a specific manipulation, ...] for each sample. [0056] This information is managed by a software and its corresponding database that allows to see how a specific sample is managed and to dynamically link all the information between all the different interactions corresponding to the steps leading to the final result. [0057] In case of compliance of the experience, the system can generate the corresponding manipulation protocol (based on one or several experiences) . [0058] The system can also be used to insure that a specific manipulation has been realized in accordance with a specific protocol . The pipette containing the reader/writer system is able to control if all the steps of a protocol are realized sequentially or in parallel by identification of the tubes (containing each a RFID tag) . The pipette is also able, with or without communication with another device (computer, alarm device) , to warn the operator or to stop or to modify the protocol when a specific step is forgotten or cancelled.

Example 3 [0059] A solid support (laboratory tubes) comprising a tag integrated in the solid support material or the top of the laboratory tube or included inside the tube with the biological sample or reagents, has been submitted to various tests summarised in the following table 1. [0060] A pipette used for taking small volumes (< 1 μl up to 5 ml) can comprise a RFID lecture system that identifies correctly the laboratory tube comprising a specific tag and that identifies if the correct volume has been taken. Table 1 Test using RFID tags (glasstag) in a molecular-biology laboratory:

All the tests were conclusive: the tags were readable after (and during) the test .

All the tests were conclusive: the tag's were readable after (and during) the test . NB: 13000 rpm corresponding to 1483 Og

Claims

CLAIMS 1. detection system adapted for a localisation, an identification and/or a tracking of a biological sample included in or present on a solid support, said detection system comprising an electronic tag, localised in or on the support so as to obtain a labelled support, said labelled support comprising information data relative to the localisation, identity and/or biological or physical state of the biological sample able to access or modify these information data and a reading apparatus able to read and record these information data.

2. The detection system according to claim 1, wherein the tag and the apparatus are able to work in a reading mode and in a writing mode.

3. The detection system according to claim 1 or 2, wherein the reading apparatus is coupled to a database.

4. The detection system according to any one of the preceding claims, wherein the electronic tag comprises an anti-collision mode, so that data information may be read or written thereon or therein even when the labelled support is present among other labelled supports.

5. The detection system according to any one of the preceding claims, wherein the biological sample is selected from the group consisting of cells, viruses, peptides, proteins, amino acids, nucleotide sequences, vectors, saccharides, antibiotics, lipids, vitamins, physiological media such as buffers comprising said elements, and a mixture thereof .

6. The system according to any of the preceding claims 1 to 5, wherein the solid support can be further labelled by means of another detection system, such as a bar code.

7. The detection system according to any one of the preceding claims, wherein the solid support is selected from the group consisting of laboratory tubes, micro-tubes, test tubes, flasks, pipettes, infusion bottles (baxters) , microarrays (biochips) , plates or multi well-plates .

8. The detection system according to any of the preceding claims, wherein the reading apparatus is a laboratory apparatus performing manipulation of the biological sample or collecting the biological sample.

9. The detection system according to the claim

8, wherein the laboratory apparatus is selected from the group consisting of pipette, magnetic stirrer, centrifuge, autoclave, sequencer, diagnostic automate, fridge, high through-put screening automate device, or robot producing micro-arrays.

10. The detection system according to any of the preceding claims, wherein the electronic tag can record automatically an electronic identification code of an operator, manipulating the biological sample of the solid support.

11. The detection system according to any of the preceding claims, wherein the electronic tag further comprises a sensor.

12. The detection system according to the claim 11, wherein the sensor is selected from the group consisting of Ph sensors, temperature sensors, moisture sensors and pressure sensors.

13. The detection system according to the claims 8 or 9, wherein the reading and writing apparatus is a pipeting apparatus and wherein the solid support comprising the biological sample is a laboratory tube comprising the electronic tag.

14. The detection system according to any of the claims 1 to 13, wherein the reading and/or writing apparatus comprises a controller that allows an identification of the solid support to be used in a specific laboratory protocol .

15. The detection system according to any of the preceding claims 1 to 14, which further comprises an alarm device for an operator manipulating the apparatus with an unidentified solid support or with a solid support that should not be used in a specific laboratory protocol .