Development
HEnRY is released under the MIT licence [15]. The client is under development since 2014 using C# [16] with Windows Presentation Foundation (WPF) [17] and the. NET 4.5 [18,19,20] framework by an agile structured team. An installer package for Windows platforms (Windows 7 up to Windows 10), as well as the source code are available upon request. The manual and short instructions for the program are available on the website www.tp-hiv.de. A first production version was made available for participants of the TP-HIV on the February 15th, 2017.
All data is stored in a Microsoft SQL (MSSQL) database on a MSSQL Server 2012 or greater [21]. It is recommended to install the server and the databases in a protected network suitable for highly detailed and potentially stigmatizing patient data with considerable potential for misuse. For additional information, see Supplementary material 1, Supplementary material 2 and Supplementary material 3.
During the developmental process of HEnRY, a close collaboration with the laboratory staff, which represents the primary target group of the tool, and study coordinators was established. Both user groups gave continuous feedback to developed and requested new features, which were tailored to their needs.
User feedback in the form of meetings and questionnaires was obtained at regular intervals. Requests and bugs were fixed in the context of monthly updates. Additionally, the lead developer accompanied the lab employees in their daily work routine with HEnRY to streamline the program to the actual workflow in the lab.
The HEnRY LIMS software is in use at the University of Cologne since 2016, with currently seven active working groups.
Workflow
HEnRY specializes in the documentation of the storage and processing of blood samples and aliquots in analytically working laboratories. It simplifies and accelerates laboratory work, increases the quality of documentation and minimizes potential sources of errors. Information about studies, patients, samples, aliquots and processing steps is stored in a structured manner (see Fig. 1). This information can be exchanged via pseudonym export and import functions, which improves cooperation between different participants of the studies. Additional information can be found in Supplementary material 4, Supplementary material 5 and Supplementary material 6.
Figure 2 shows a diagram of the workflow for multicenter studies and the use of HEnRY. An unlimited amount of users per study site is supported. Online access is available using the sites own Citrix access [22]. A study supervisor or study coordinator can develop the study properties, drawing schemes and processing steps and send the study design as an XML file to other participating centers.
In a setting of limited resources, HEnRY can be used as a standalone LIMS on one computer with e.g. SQL Server Express editions for structured documentation of biomaterial and self-adhesive label creation. Via the transfer of XML files, data for biomaterial can be shared with other laboratories, clinics or project partners.
Study management
HEnRY offers the opportunity to manage any number of studies and respective workflows to support practical work in the laboratory. The name of the study, start and end date, contact persons, and whole laboratory books, down to descriptions of the chemicals to use, can be added to a study (see Fig. 3). More importantly, a scheme for blood draws, samples, and aliquots can be created for each study visit, allowing rapid processing of incoming samples. Information about the storage location can also be stored in the study scheme (see Fig. 4). A study scheme contains all information for samples after processing. E.g., if after processing 50 aliquots are derived from one sample, all information about creation date, aliquot type, amount, volume, container, study and location are the same for the 50 aliquots. By applying a study scheme, 50 aliquots with all properties are created in one click. Aliquots created via a study scheme are directly linked to the selected study. Different processing steps, including the used chemicals, are stored with the sample, if the processing has previously been assigned to the study (see Fig. 4).
Multicentre studies
Study schemes with all the practical information (visits with respective sampling procedures, processing steps, chemicals to use, addresses, contact persons, and more) can be exported to XML files [23]. A study coordinator can centrally design a study in HEnRY and distribute the XML file to all participating centers. For imported studies, all study specific fields are read-only and cannot be changed by the participating center. These fields are predefined by the protocol of the study (e.g. way of shipment for aliquots, addresses of participating centers, processing steps, and visit plans with respective sampling schemes). Only information specific to the local center, e.g. storage location, can be added to the imported drawing scheme.
This procedure was initially developed for the TopHIV study, which is centrally coordinated from working groups in Cologne and Hannover. The XML files for the study are available for download on the website of the TP-HIV [24].
Backend
HEnRY offers the opportunity to work with different databases. The user chooses the database to work with when starting the program. Samples processed for different working groups or studies can be stored in separate databases to expedite analysis and restrict accessibility of the data.
Storage management and documentation
Patient records can be created directly in HEnRY or linked to another clinical database. One such interface is available for the HIV Observation Software (HIObS) of the German Robert Koch-Institute, Berlin [25]. For data security reasons, HEnRY allows only pseudonymous patient records. Any number of IDs used in different studies can be stored as aliases for one patient record.
HEnRY offers a large range of properties, which can be documented for each sample or aliquot. Basic data, e.g. type of sample, sampling location, and creation date and time of the aliquot are mandatory. Identification of the person responsible for sample processing is stored with the sample or aliquot record. Container and storage location, including tower and rack (e.g. freezer, nitrogen tank, or breeding bench), are stored (see Fig. 1). For frozen samples, the amount of freezing cycles is notated to further define sample quality.
Samples and aliquots can be created one by one or by using the copy function for existing aliquots. For studies, large amounts of aliquots can be generated by applying study schemes (see above and Fig. 4).
Users can create any amount of storage systems with information on building, floor, room, and type of storage. Virtual boxes can be designed with a name and the box size, in which aliquots are placed. HEnRY will check for each position, if the slot is still free, to avoid doubled placements. A virtual look inside each box is possible (see Fig. 1), such that the user is at any time fully aware of the used space within the box and its content. Mass edit functions for almost all properties of the aliquot are available.
For the unique and secure identification of aliquots and samples, HEnRY provides the opportunity to print own customized labels. Labels can be created with or without QR code. The properties and their order printed on the label are user-customizable with a direct preview in the interface (see Fig. 5). Labels can be stored as templates and are accessible to every user in the database. After printing a label, the printer sign in the bio banking view turns from green to red to avoid double printing of aliquot labels (see Fig. 1).
Shipment module
In the shipment module, aliquots are prepared for the shipment. Users can specify a shipment container and add aliquots for shipment to the box. It is possible to add aliquots to the virtual shipment box via scanning of the QR code or a search function using the patient ID. It is also possible to run full SQL statements from the interface for more complex searches. In cases where the storage box is identical to the shipment box, the whole box and the contained aliquots can be selected, by choosing the box. Reports concerning the content of a package content can be created and printed. The reports available in the shipment module contain a visual layout of the box and a list of aliquots with their properties (in the format. XPS or. CSV). The study supervisor can preselect the properties of the aliquots saved in the .csv file. A customization of the range of properties and their format is possible. In addition, a letter, to address the receiver of the shipment is printable.
Important information such as the reason and way of shipment as well as the delivery address can be given by the study assigned to the aliquots.
User right administration
HEnRY features user management with different levels of access. The study supervisor has the right to manage and add studies within HEnRY. The study supervisor can monitor the completeness and the correctness of information contained in the HEnRY database. This guarantees ongoing and steady control of processing quality. After the end of a study, the study supervisor has the option to anonymize patient data in line with patient privacy rights. Laboratory staff is allowed to edit the sample processing protocol.
If HEnRY is linked to a clinical database, clinical and personal data of patients can be viewed by users with the “physician” right. Otherwise, only pseudonymous data is shown. Users in the “IT” user group can administrate the SQL connection, manage HEnRY users, and adjust printing settings.
Export of aliquot data
Only pseudonymous data can be exchanged. Data of samples and aliquots can be exported into XML files [23], e.g. in order to merge data from one specific center with a central biobank. In our local use-case, merged data is monthly delivered to the LIMS of the DZIF [26].
Queries and reports
HEnRY offers a variety of search functions. Aliquots can be selected by study, visit, storage or site.ne site is available. A graphical user interface offers a virtual view of a selected box, including the amount and placement of aliquots within the box. The monitoring status of all aliquots can be assessed and printed. All lists can be exported as XPS or CSV files.
Data can also be selected via an SQL query interface, and printed as scanable search lists with QR codes for each aliquot. By use of this tool, researchers can perform complex and customized searches covering all data contained in the database.
HEnRY parser
To connect external data sources, a separate module is available for HEnRY, offering extract, transform, and load processes for different source formats (e.g. MDB, CSV, HL7). The parser is not part of the primary program package.
Data protection and security
In view of the increasing requirements towards data protection standards in Europe and especially Germany, data privacy officers and clinical IT departments are sometimes reluctant to allow the use of LIMS tools based on cloud services and web interfaces, especially in the context of potentially stigmatizing diseases such as HIV. HEnRY can run with a locally administrated MSSQL database and offers hierarchical user rights on database and frontend levels. The storage of data, backup plans, and access to the data are fully controlled by the local IT of the hospital. Therefore, this tool can be seamlessly integrated into high security environments.
For large working groups, HEnRY works with a central MSSQL Server [21] and multiple clients. If access from outside the clinical network is necessary, HEnRY can be used via secure remote access solutions and has been successfully integrated into a Citrix Workspace environment [22].