As a result of automation in the pharmaceutical industry, large compound libraries for future analysis and screening for potential drug candidates are routinely created. Alongside an increase in chemical compound samples, the number of biological samples resulting from the expansion of collaborative programs such as cancer screening and the genome project has also escalated and such large numbers of samples put strain on traditional manual methods of sample storage. Manual logging, placement and tracking of large numbers of samples is time-consuming, detracts from the scientist’s research role and is subject to technical error. Faced with these issues, automation of sample storage and retrieval is essential for efficient and fast workflows in laboratories.
Early automated storage systems dedicated to housing large numbers of samples were developed as room-sized stores. Although fully automated, the need to commit and invest in such large storage facilities, before the final library size was known, made it inhibitory for many research establishments.
In early 2000, following discussions with a number of pharmaceutical companies, TTP LabTech provided a solution to this problem with the launch of comPOUND, the world’s first lab-based, transportable and modular compound tube storage system. This low-footprint storage facility permitted the employment of automated sample storage and management in smaller companies within both the life science industry and academia.
During the conceptual development of this system a number of fundamental requirements to ensure ease of management, storage, retrieval and sample integrity were addressed. These requirements appear to be fundamental to the design of other modular storage systems now available such as the A3 SmaRTStore™ (RTS Life Science), the ASM store (Hamilton), the Universal store™ (Nexus) and the Agilent BioCel System.
One key element for sample storage is the need to store samples safely and securely, yet ensure they remain easily accessible by end users. By embracing 2D bar code technology, TTP LabTech made it possible to achieve 100 percent verification of samples on a tube-pertube basis, enabling rapid and error free storage and retrieval.
Traditional manual storage methods pose disadvantages in that, during the placement and removal of samples, there is a risk of exposure to significant temperature fluctuations while the fridge or freezer door is open and racks are removed. Automated storage and retrieval using internal robotic or pneumatic handling devices reduces exposure of samples to unnecessary freeze/thaw cycles. Integration of additional intelligent software to enable cherry picking of individual samples from storage also eliminates disturbance of surrounding tubes, thereby maximising sample integrity.
The maintenance of sample integrity is an essential requirement for any long-term store. To minimise the risks of sample degradation, scientific evidence suggests samples should be kept in dry, dark, cold, and inert conditions. During the development of comPOUND, it was decided individual samples should be stored under nitrogen or dry air in hermetically sealed chambers. Similar conditions are used by other storage management facilities.
Often, sample submission into existing compound libraries is a protracted process and selection of individual samples or screening subsets can be difficult. Storage systems coupled with intelligent software, which are easily integrated into lab information management systems (LIMS), provide a secure and error-free solution for sample management. Also, the ability to link automated storage to automated stacking systems, such as TTP LabTech’s comSTACKER or comMOTION, enables the user to log and place samples to be stored in racks and walk away, resulting in significant time savings.
Since the launch of comPOUND, many similar modular storage systems have become available for both tube and plate storage from ambient to -20°C. Plate storage modules offer high-density storage of low-volume samples proving ideal for the storage of “ready to assay” plates. In these systems, however, plates can be cherry picked but individual samples cannot. For larger sample volumes and for the ability to select individual samples, tube storage becomes the best method of sample storage and the ability to link tube selection to automated plate processing technology overcomes the need for plate storage. Some storage systems have been designed to provide automated storage of plates and tubes simultaneously but are generally larger and involve slower processing times for sample input and retrieval.
Many systems allow automated storage management to go beyond simple storage and retrieval, linking compound storage to sample processing robots. Hamilton features an integrated active thaw, tube decapping system with a robotic arm linking to third-party devices. TTP LabTech’s comPILER similarly transports microtubes, thaws, centrifuges and decaps the tubes. The tubes are then purged with Argon, to provide an inert barrier air or water ingress and presented to a third party liquid handling robot. When sample processing is completed, comPILER re-gasses, re-caps and returns the microtubes to store.
Additional technology such as TTP LabTech’s comPANION 121 and 124 enables pneumatic transportation of samples from storage to a remote laboratory which can then be passed to a variety of robotic liquid handling devices. Such a system also enables the placement of storage modules in rooms or areas distant from the main research lab.
The recent design of TTP LabTech’s automated sample transport management system, LAB2LAB, which transports samples from remote laboratories and connects them directly to analytical instrumentation, shows a potential for fully automated workflows in pharmaceutical research. Using this system, the sample is placed in a bar-coded tube and sent to the analytical laboratory. The sample is held in a buffer and when the selected instrument is available, the system presents the microtube to the injection position in the autosampler of the instrument where analysis takes place. The results of analysis are rapidly returned to the originator’s electronic lab notebook, and the sample can either be sent back to store, to waste, or returned to the buffer for further analysis.
The use of sample management and storage systems has many advantages including increased health and safety and allows scientists to concentrate on science rather than manually storing and retrieving samples, preparing and transporting them and queuing for instrument time. This vision of a fully automated system from sample synthesis, analysis, storage and biological testing is not far away, enhancing interactions between chemists and biologists which are crucial for success in modern drug discovery programs.