April 15, 2014 (Vol. 34, No. 8)
Strategies for Safely Transferring Legacy Samples to Modular, Automated, and Secure Biobanks
Biobanks are a key resource for storing important biological material such as DNA, RNA, tissue samples, blood, and cells, all of which are widely used for biomedical research, drug discovery, and the development of new diagnostic tests. Prior to the 1990s, labs created their own collections of specimens using regular freezers, with each employing individual methodologies to label, store, track, and reuse their samples. However, modern labs now collect and store more samples than ever before, putting a growing strain on these homegrown solutions.
Much of this pressure has been fuelled by the revolution in genome and biomarker analysis, with researchers now routinely studying samples from tens of thousands of individuals in one experiment, all in the hope of better resolving the importance of disease-specific biomarkers. As such, providing access to viable, high-quality tissues is now considered essential to improving the success rate of drug discovery, guiding diagnostic development and linking specific patient subsets with the best possible treatment.
In order to obtain access to large enough sample collections, modern researchers routinely share specimens with other laboratories around the world. At the same time, dedicated institutional and national biobanks have gained increasing importance, supplying a multitude of research groups working across a diverse range of fields. These can include anything from blue sky academic research through to personalized medicine, pharmaceutical development, diagnostic advancement, food and agriculture use, and even the preservation of natural and cultural heritage. Given this increase in demand, biobanks are experiencing a significant growth in global market value.
Planning for Future Growth
One of the main advantages of a well-managed biobank is that it allows researchers to analyze samples in retrospect. The ability to tap into a portfolio of archived patient samples can be invaluable when validating newly discovered biomarkers and correlating their incidence with disease outcome. Biobanks of samples collected over long time periods are also especially useful when working to understand orphan diseases, as it can take many years to collect enough samples to generate statistically relevant data.
Biobanks increase in value every time a new sample is added. However, this growth also increases the complexity of storing and utilizing the samples they contain. In order to make the most effective use of these growing collections, samples must be processed, stored, maintained, and tracked using highly organized systems and procedures, future-proofed to ensure error-free sample safety, integrity, and accessibility.
Unfortunately, biobank growth has not always been managed with the future in mind. Many collections routinely incorporate a variety of different sample types and formats, thereby making their use and management more complex, while in the process risking long-term sample availability and quality. In addition, a significant number do not conform to current legal and regulatory requirements, as they were created before the International Society for Biological and Environmental Repositories (ISBER) issued its best practice guidelines for specimen storage, access, handling, culling, and repository termination. In other cases, biobanks designed to hold a finite number of samples are now outgrowing their storage space, with no strategic expansion plans in place to manage the overflow. Such haphazard growth is rarely cost- or time-effective.
The Impact of Freeze-Thaw
As well as the need to store large numbers of samples, biobanks suffer from a series of unique challenges presented by biological specimens, which tend to be very sensitive to temperature changes. Any access to the store creates an opportunity for temperature change such as frequently opening and closing freezer doors, allowing an influx of warm air and leading to partial thawing of samples and potential frost build-up. This jeopardizes sample integrity, while frost can mask or partially erode sample labels, increasing the chances of error. These problems are exacerbated when users search large collections for samples manually, which can take significant amounts of time.
Most assays also require very small sample volumes, such that fractionating samples into multiple small aliquots for one-time use is preferred. However, this is not always possible, as it requires the use of an efficient fractionating system, more storage space, and good automated tracking systems. For this reason, samples tend to be stored in larger volumes, which are then accessed multiple times across many years to draw small aliquots. With every freeze-thaw cycle, the risk of sample damage increases.
Sample Transfer without Freeze-Thawing
Minimizing the impact of freeze-thaw cycles is just one of many reasons to transition to automated biobanking systems (Figure 1). By moving samples from older legacy hardware to new automated sample management systems, it is possible to improve storage accuracy and sample integrity, increasing the long-term value of a biobank while simultaneously reducing personnel costs.
Many technological solutions are available to help streamline the otherwise tedious process of transferring legacy samples from manual archives to automated storage systems, while also maintaining sample integrity. One such technology is the CryoXtract proprietary coring system, which can be used to automatically re-aliquot thousands of samples quickly and easily. Perhaps just as importantly, it avoids the need for freeze-thawing by effectively functioning at -80ºC, removing sections of the parent sample as frozen cores without thawing ever needing to take place.
In one recent study to assess the effectiveness of the method, researchers at AIT Bioscience tested the stability of re-aliquoted plasma samples containing the inherently labile and thermal sensitive pro-inflammatory cytokine TNFalpha using ELISA, comparing them to the original parental sample. The aliquoted samples generated the same results as the parental sample, confirming the effectiveness of the CryoXract CXT 750 when paired with an appropriate automated -80ºC freezer storage system such as TTP Labtech’s arktic. This advanced sample store uses a rotary and pneumatic mechanism to avoid the use of internal robot arms and reduce the risk of mechanical failure in the cold zone.
Samples in arktic are stored in bar-coded microtubes (Figure 2), such that an electronic database is automatically updated whenever a sample is accessed. As well as precisely tracking the location of each sample, the database also includes useful information such as the age of the specimen, the exact donor of the sample and details around consent, the likes of which are often required for legal and regulatory reasons. This workflow eliminates the risk of mislabeling or misplacing samples and increases the reliability of the biobank.
For ensuring sample integrity and security, samples in arktic are stored in an extremely low humidity controlled freezer in individual pipes with the system providing sample retrieval in less than eight minutes (based on accessing 96 cherry-picked samples from different areas of the store, Figure 3). It would take as long as two hours to carry out this operation manually, putting both the samples of interest and those in adjacent compartments at risk of temperature fluctuations and partial thawing. Instead, arktic only removes the samples of interest via a cherry-picking system, leaving all others undisturbed. With just 0.8 m(d) x 2.0 m(h) x 1.3 m(w) dimensions, arktic is also compact, capable of storing up to five times the number of samples that can be held by a standard laboratory -80°C freezer, thereby facilitating scale up without sacrificing laboratory space.
The modular format of the arktic also fits both short- and long-term expansion strategies, future proofing any investment in an automated sample store. In comparison the purchase and installation of a large storage facility can be costly with a large degree of redundancy, carrying significant service and maintenance costs as the biobank grows and reaches full capacity. A modular store, however, can be easily expanded while the self-contained units can be relocated as the storage requirements change.