Biobank

With the rapid advances in biomedical and genetic technologies, collections of biological materials have attracted increasing attention from the research community since they represent a fundamental resource for a deeper understanding of different pathologies, and the study of possible therapeutic applications. Such collections, named biobanks, are commonly divided into tissue and genetic biobanks according to the types of biological materials they store. The BioBanking Management Module addresses both issues.

The scope of this module spans a wide range of activities, including management of biological samples and associated pathological information, as well as support to a number of laboratory-related procedures. In particular, the module can currently handle the following activities and the corresponding data.

Collection (fresh tissues)

The collection of new samples coming from a surgical intervention is the primary source of the biobank. To enable the employment of barcode readers and thus streamline data entry procedures, most pieces of experimental equipment (i.e., clinical folders, plates, tubes) are bar-coded by the institution prior to their use. Sample collection consists of two phases. In the first phase, the researcher inputs preliminary information about the collection event and selects one or more sample types. For instance, it is possible to insert an identifier for the patient. Besides the “Add clinical parameters” functionality allows the management of several kinds of clinical data, categorized according to an internal ontology. Some of these parameters depends on the selected “Tumor type”. For example, “Histological classification” in the “Pathological features” menu is a drop-down list whose values are shown according to the selected “Tumor type”.

In the next phase, the researcher can add one or more samples for each of the sample types chosen. Figure 1 depicts the interface for the collection of biological samples, which is designed to closely match the physical working environment of the researcher. The collection plates are organized on screen into different tabs, so that types of aliquots that are usually collected together appear in the same tab. For instance, Figure 1 reports the panel containing the containers for viable, ffpe, RNA later, and snap-frozen aliquots that are usually collected for in-vivo and in-vitro experiments.

The rectangular boxes represent the physical working plates in which sample aliquots are stored. First user sets the selector “Tube/Plate” and then he can insert the corresponding container barcode. Plates have to be already present in the system, so they have to be inserted in LAS through the special interface of the Repository module. Whereas tubes could not be present and if so, they were created at the same time of the creation of the aliquot stored in it. For more information about containers, please refer to the description of the repository module.

Inserting an aliquot in a given plate position is done by simply clicking on the corresponding cell, which can be comfortably achieved on a touch-screen device without resorting to a mouse. This results in a reduced number of lean interactions with the system, allowing the researcher to focus on the experimental task at hand, rather than on data entry operations.

Figure 1- Collection interface

Collection (archive samples)

This procedure manages the collection of samples already archived from other researchers, maybe in other hospital. In this case sample to archive do not come directly from a surgical intervention, they are not fresh, but they are already archived in some container. Maybe as a result of a collaboration between research center, an operator has to insert in the storage some external samples. This can be done through these interfaces. User has to select if creating a new collection or joining these new samples to an existing one. The first option is useful if new samples come from a new patient whose aliquots were never collected, or if the user wants to independently process these new samples. The second allows to add new samples to the aliquots already collected for a patient.

Collection (batch)

This procedure manages the collection of samples like the previous two, but the difference is that in this one the input data are sent to the system through a file. In the interface there is an example to explain how this file has to be formatted.

Collection (cell lines)

The LAS allows the collection of new cell lines. User has to insert tumor type and cell line name and optionally he can insert a datasheet file and an invoice file. In the next interface he has to define other parameters and the position in the storage in which he is going to archive the line.

Add clinical parameters

The system allows to insert new clinical parameters for an existing collection. Collections can be searched according to patient information, informed consent, protocol, barcode or Geneaolgy ID. When clicking on a collection, a new window will appear, where you can insert the new parameters.

Aliquot planning

Most of the procedures (derivation, split, experiments, revaluation, transfer, slides preparation) described below has a planning phase in which user selects the aliquots involved and an operator to whom assign the work. To identify the aliquots it is possible to use their genealogy ID or the barcode of any container (e.g., plate, rack, freezer), thus scheduling all the aliquots stored in it.

Aliquot validation

For certain procedures a validation phase is required. This comes before the execution phase and is useful to inform the system about what tube has been taken from the storage. Since every tube has a unique barcode, inserting this code permits to avoid tube confusion.

During this validation, in addition to the single tube barcode, it is possible to insert the barcode of the father container to validate all the aliquots stored in it at once. To take advantage of this feature, it is necessary that all the aliquots stored in the validated container have been planned for the current procedure. For instance, if a plate contains 30 samples, but only 25 of them have been planned for derivation, the plate barcode may not be used as a shortcut to validate the aliquots.

Derivation

Through this procedure, user can derive new biological materials (e.g., DNA, cDNA) from samples stored in the biobank. In particular it is possible to extract DNA, RNA and proteins from tissue samples or obtain complementary DNA (cDNA) or RNA (cRNA) from RNA samples. Procedure has a planning phase followed by an execution one divided into four steps. In the first step user selects the samples to work with and validate them inserting their tube barcode. Then he chooses the derivation protocol to follow. The order in which aliquots are presented in steps 2, 3 and 4 depends on the order in which they were validated here. In the second part we have kit selection (for more information, please refer to the next section). If user is extracting proteins, insertion of a derivation kit is not required. Thus, at the end of step 1 the system will skip to step 3.In the third part user has to insert the values of the measures he made for the samples involved. According to the measurement protocol chosen, he will insert certain measures and he can also insert some measures not expected by the protocol.

The interface of the last step is reported in Figure 2. In the top side of the interface, information related to the derivation protocol and the output is visualized. In block B, the details for each derivative are reported to guide the user through the preparation of the aliquots. Some parameters (e.g., volume and concentration) can be changed at will by the user for each aliquot, and clicking on “Recalculate values”, the system will automatically update the values of the others to match the protocol rules. Once the technician has prepared the aliquots, he should position them in one or more containers (block C). First he sets the selector “Tube/Plate” and then he can insert the corresponding container barcode. Plates have to be already present in the system, so they have to be inserted in LAS through the special interface of the repository module. Whereas tubes could not be present and if so, they were created at the same time of the creation of the aliquot stored in it. For more information about containers, please refer to the description of the repository module. Newly generated aliquots are then placed in the available positions using drag and drop. When all aliquots have been processed, a final report is shown.

Kits

Related to derivation process before explained, we have kit management. For example during the extraction of DNA, it needs a series of reagents and chemical compounds that form the so called derivation kit. Kits are grouped in categories called kit type and a type is joined to a derivation protocol. For instance to extract RNA we can have three different protocols and every protocol has its kit type. The LAS has an interface to insert kit type and one to insert a single kit. A kit has to be present in the system before it can be used during step 2 of derivation process.

Figure 2- Derivation interface

Split

It is used to create one or more samples starting from an aliquot. It can be done only on derived (liquid) one. First user chooses the aliquots that will be divided into parts, then in the execution phase he sets the number of samples he wants to create and, for everyone, digits the volume and concentration value. The last part is the positioning in a container: first user sets the selector “Tube/Plate” and then he can insert the corresponding container barcode. Plates have to be already present in the system, so they have to be inserted in LAS through the interface of the repository module. Whereas tubes could not be present and if so, they were created at the same time of the creation of the aliquot stored in it. For more information about containers, please refer to the description of the repository module. Then user can choose to proceed with the splitting of next aliquot planned or to finish the procedure and, if so, a final report is shown.

Slides

The LAS allows the management and tracking of slides (menu item “Slides preparation”, under menu category “Aliquots”). Similar to the other procedures, the main steps are planning and execution. In the first step (i.e., planning) the user selects the aliquots to be used and the user who will carry out the procedure. The aliquots can be “Formalin Fixed” or “OCTFrozen”. The execution step initially requires the choice of a protocol. Two protocols are currently available: “Microtome” and “Cryostat”. The user should then validate the samples and finally create and place the slices on slides. In the latter step, three fields are automatically filled out, based on the selected protocol, but can be modified at will by the user if required. These parameters are: (i) the thickness of the slices, (ii) the number of slices for each slide and (iii) the number of slices obtained from the original aliquot. Positioning is performed automatically: once the code of a slide has been read, several slices are placed in the first free places according to the settings specified by the user. Additional slices can be placed by clicking on the empty positions of a slide. The user can always cancel each operation by means of the summary table at the bottom of the page.

QC / QA

This procedure permits the insertion of aliquot physical characteristics, such as volume, concentration, purity and quality and can be done only on derived (liquid) samples. It is used to revalue an aliquot already present in the system and to save who, when and what parameter was measured. After a planning and a validation phase, user inserts the measures according to a protocol and he can set the volume used for the revaluation procedure. Optionally it can be set an “Exhausted” flag on one or more aliquots.

Transfer

This procedure permits to share some aliquots between LAS users, so there is a sender (user currently logged in that plans the procedure) and a receiving. The latter can be a member belonging to other WGs than the sender one. In this way, the aliquots will be automatically shared with the selected WG.

In the planning part, sender has to select the operator who will carry out the procedure, the addressee and the aliquots involved. Then the in charge operator executes the shipment, validating the samples and selecting the courier. Once the addressee received the aliquots can acknowledge it validating the samples received and so terminating the transfer procedure.

Experiments

The LAS allows the execution of some molecular experiments in which there is a planning phase and an execution one. In the biobank there is the planning part for all of them, but the execution only for some. For the others the execution is managed by the related module. For more information, please refer to the section 7 “Molecular Experiments”.

In the planning part user selects the experiment type, the operator who will carry out the procedure and the aliquots involved. During the execution phase the in charge operator validates the planned aliquots, so confirming that the experiment has been executed. Optionally it can be set an “Exhausted” flag on one or more aliquots.

Patients

A collection is related to surgical intervention performed on a patient. However, the same patient may be subject to several surgical interventions that will produce independent collections. In some experimental procedures, it is very important to identify the aliquots coming from the same patient to compare possible mutations over time. To retrieve the target aliquots, researchers and technicians may choose one of two alternatives: (i) use the Query Module to build a query that retrieves the aliquots of interest, and (ii) use the patient interface in the BioBank. The first scenario is mainly targeted at more experienced users, who know the relationships among biological entities and which entities contain the information relevant for search. To enhance the flexibility and the usability of the system, we introduced an ad-hoc interface in the BioBank module to identify aliquots related to the same patient. In this interface, reported in Figure 3, the user can set filtering parameters for the collections, and define security settings. According to the latter, the information in blocks B and C can be displayed in an anonymized form. Block B shows the list of patients satisfying the filtering criteria, while block C shows the aliquots related to the selected patient, along with their characteristics. At this point, the user can select one or more aliquots which are moved to the list in block D. When the selection of target aliquots is complete, different actions can be performed (e.g., derivation, molecular experiment). The system will automatically check if the aliquot types are consistent with the target action.

Figure 3- Patient-based filter interface

Admin

Through this procedure it is possible to add some elements to certain predefined lists used by the system in some interfaces. For instance it can be added a tumor type or a tissue type to the list that is shown in the collection interface. Or it is possible to insert a courier to the list that is shown during transfer procedure.