December 1, 2010 (Vol. 30, No. 21)

Martin Frey, Ph.D.

Benefits Include Sample Integrity and Security and Labor, Maintenance, and Energy Cost Savings

The term “biobank” has broad application, and in the most basic form has existed for many years. In general terms, biobanks are cryogenic storage facilities maintained by institutions that manage a collection of biological materials such as human tissue, serum, plasma, urine, and blood, along with donors’ data, which can be used for medical research. A small collection of blood samples kept in a freezer can technically be classified as a biobank, but the term is often associated with larger facilities where hundreds of thousands of biological samples are maintained.

Biobanks are now recognized as vital tools in disease and therapeutic research as well as in drug discovery and development. To conduct large-scale studies with reliable results, bigger biobanks are being created today, along with consolidated facilities. Biobanks are maintained by pharmaceutical and biotech companies, hospitals and research organizations, and in some cases by governments.

One example is the U.K. Biobank, which in July of this year reached its goal of collecting genetic material from 500,000 individuals—a total of 15 million blood, urine, and saliva samples. Approximately 9.5 million samples are stored in a -80ºC automated archive, providing access to academic and commercial researchers in the U.K. and throughout the world. The goal is to aid in a wide range of research studies on complex conditions such as cancer, heart disease, diabetes, arthritis, and dementia in combination with epidemiological factors.

Sample Storage Challenges

As the number of samples increases and smaller biobanks consolidate, accurate tracking, storage, and retrieval become vital issues. Many organizations still store and retrieve samples manually from liquid nitrogen (LN2) tanks or -20ºC or -80ºC standalone freezers, an approach that is fraught with difficulties.

The first issue is the maintenance of sample quality because degraded samples may compromise assay results. Storage temperature should remain stable to ensure sample integrity. However, the constant opening and closing of a manual door creates continuous temperature fluctuations and freeze-thaw cycles.

A door held open on a manual freezer for even a short period of time can result in a significant temperature rise. Constant frost buildup makes samples harder to locate and must eventually be removed, which further exposes stored items to temperature fluctuations. Additionally, air expands by approximately 50% when its temperature rises from -80ºC to 20ºC. This creates an air draft in an upright freezer, which accelerates more fluctuations.

Data gathered by Hamilton Storage Technologies shows that the temperature of samples taken from -80ºC storage to ambient conditions increases at an average of 21.5ºC per minute (Figure 1). Holding a manual freezer door open for more than one minute can raise the temperature to above -60ºC. This can happen countless times over the lifetime of a sample stored and retrieved manually. Accumulated temperature rises above this level are believed to damage the integrity of many types of biospecimens.

Another notable challenge is the staff size needed to run a manual biorepository. For instance, the Rutgers University Cell and DNA Repository utilizes around 100 technicians to perform biorepository services and store samples for a fully functioning biobank that consists of 45 LN2 tanks and 90 chest freezers. The labor costs of running a manual biobank are high, and as biobanks continue to grow in size, manual access becomes increasingly more complex and difficult to manage accurately. 


Figure 1. Tube warm-up rates over time: The samples are 300 µL tubes with 40 µL 10X TBS pH 7.4 buffer solution.

Additionally, accessing samples in manual freezers can consume significant amounts of the staff’s time. The Table  shows the time required for each of the steps from storage to retrieval, comparing the use of a manual freezer to an automated storage system. Many manual biobanks encounter similar issues, according to assistant director Melissa Rawley-Payne from the CTSI Biorepository at the University of Florida. In some cases, she believes it could take hours for samples to be retrieved from freezers in some of the nonautomated tissue banks across the campus.

Sample security is another critical issue in any facility that is operating under regulatory controls, maintains potentially dangerous chemicals or infectious agents, or that maintains associated donor data with the samples.

In order to comply with various regulations, facilities must produce chain of custody reports and audit trails showing who had access to the samples and what they did with them. The lack of such security measures can even put the public at risk, as was the case in 2001 when anthrax was retrieved from an unsecured lab.

To address these challenges, many organizations are moving to biobank automation, which delivers a number of advantages. First, these automated systems are closed, so temperatures are kept more constant and moisture cannot enter the storage compartment, preventing freeze-thaw cycles and maintaining sample integrity.

Additionally, in Hamilton Storage systems, the cherry-picking process, in which individual samples are removed from racks of tubes, is carried out in a special tube-picking module where the temperature is kept at -20ºC. The remaining samples can then be transported back to -80ºC storage without being exposed to room temperature. Many automated systems also feature fail-safe mechanisms to maintain temperature such as mechanical cooling, backed up by power generators or gas-based backup systems.

Automated systems deliver big labor savings. It can take, on average, 2.5 hours to store and retrieve 100 samples manually, while an automated system such as the BiOS System from Hamilton Storage Technologies, shown in Figure 2, can retrieve up to 10,000 individual samples in a day. By spending less time retrieving samples, scientists can focus more attention on their research.

In addition to labor savings, maintenance and energy costs can be reduced with an automated sample-storage system. For example, during this year’s “International Society for Biological and Environmental Repositories” conference, the National Cancer Institute projected the cancer Human Biobank could save an estimated 83% on space and energy costs over the next 10 years by switching to an automated system.

Automated systems with password access provide security and ensure that samples are automatically tracked when they enter and exit the system. The software capabilities maintain a complete log, tracking who took out the sample, what was done with it, how long it was out, and how many times it was taken out. This provides a complete audit trail for the sample and the facility. A high-level report can be created at any time for any sample along with the entire temperature history.

The automated system’s administrator or lab manager can set thresholds and alarms for desired sample storage and handling conditions. The system can also produce a regular diagnostic report for the service administrator. Detailed and accurate chain-of-custody documents are easily produced, which can be invaluable in regulated environments and in forensics-related court testimony.

Automation eliminates most human handling steps, which are a major source of errors in sample management. Errors ranging from mislabeling to misplacing or even losing a sample can occur, which can have a disastrous impact on a research project. Removing high-risk areas of human handling increases the reliability, sample tracking, and accuracy of a working biobank. An automated storage system can also be integrated with sample preparation steps, such as DNA extraction, for further process streamlining.

As biobanks continue to grow in the research industry, many organizations are turning to automation to standardize procedures and implement best practices that ensure sample integrity and security. The results will be greater access to higher-quality samples, providing researchers with the right resources to discover the next generation of treatments for diseases.


Figure 2. BiOS is a next-generation automated mid- to large-size ultra-low temperature sample store.

Martin Frey, Ph.D. ([email protected]), is senior product manager at Hamilton Storage Technologies.

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