Biospecimens are indisputably the lifeblood of both basic and clinical research; thus, preserving the integrity of solid as well as liquid samples is a mission critical function. Whether you work with a biobanking partner or handle biomaterials within your own organization, there is likely room for improvement in your processes. Here we talk to experts in collection, processing, preservation, and distribution of human biomaterials for insights on how to determine the best biobanking service partner or to implement an automated workflow, if that is the path that makes the most sense for your organization’s research needs.
A bonus feature at the end of the article includes five ATCC tips for ensuring sample integrity.
Our commentators—Alissa Resch, Ph.D., CSO at Coriell Institute for Medical Research, Maryellen de Mars, Ph.D., vice president, Standards Resource Center at ATCC, and Matt Hamilton, president, Hamilton Storage—share their knowledge and recommendations for best practices.
What are the most important considerations when choosing a biobank?
Dr. Resch: Evidence of a quality management system is an important consideration when choosing a biobank. Most reputable biobanks adhere to stringent quality control measures and undergo external audits to ensure best practices are followed. Quality management guidelines ensure that standard operating procedures are in place for collection, receipt, processing, storage, and distribution of samples. Because biobank samples are often used to develop new technologies, assays, and therapeutics, strict quality measures are critical for ensuring the production of reproducible, high-quality specimens.
It is also important to evaluate domain expertise when choosing a service provider—the expertise of the biobank should align with the customers’ needs. For example, if a customer is interested in establishing an induced pluripotent stem cell (iPSC) distribution bank, the biobank should have demonstrated expertise in stem cell reprogramming and an established quality control pipeline for assessing the quality of newly developed iPSC lines. If a customer is interested in setting up a clinical research study, the biobank should be well versed in human subjects research and have the capability to coordinate with clinical sites, process samples, and manage associated clinical and genomic datasets.
Dr. de Mars: When searching for a biobanking service provider, there are several important factors to consider—quality, temperature control, inventory management, and security.
Quality is an important feature in biomaterials management. The processing, storage, and shipment of biomaterials should be carried out under a quality management system that is supported by standard operating procedures, quality control procedures, and risk management. Furthermore, those standard operating procedures should comply with regulatory requirements and industry best practices.
Ensuring that biomaterials are maintained at an appropriate temperature is critical for downstream applications. When looking for a biobanking service provider, you should look for biorepositories that offer temperature-controlled units that are supported by 24-hour temperature-monitoring systems. This guarantees that samples are maintained at the desired temperature during storage and throughout all steps of the logistics process, thus helping to ensure the shelf life and integrity of biological materials.
Biobanking service providers should also have an inventory management system in place that enables the secure and confidential storage of materials and data. This ensures that inventory is properly tracked and can be accessed when needed.
Finally, a comprehensive security system is an important consideration when selecting a biorepository. Restricted-access facilities that have around-the-clock surveillance systems ensure that biomaterials are properly protected and are handled only by certified and trained staff. Biobanking facilities should also be equipped with automated security alarms, multiple power systems, back-up units, and on-call personnel to continuously monitor equipment functionality and so ensure that biomaterials are protected in case of power outages or equipment failure.
Mr. Hamilton: Regardless of whether researchers outsource their samples to a biobank or invest in internal means such as an automated system, they should consider examining the entire process. Once these broad considerations are clarified, it’s easier to navigate capabilities and details of the necessary process tools. I agree that the incorporation of a quality management system, especially in context of automation, is absolutely critical, because data is meaningless if it’s derived from poor quality samples.
With that said, quality systems can be complex and time-consuming to manually manage and are still prone to sources of human error. For example, every time a manual freezer is opened, samples are exposed to rapid temperature fluctuations that can compromise integrity. Is this documented manually? While rummaging through freezer contents, researchers could dislodge samples, replace them to the wrong location, or forget to document the activity. How are these issues captured? Multiply these risks over the short-, mid-, and long-term, and it’s easy to understand how seemingly small issues can grow exponentially into significant quality problems.
On the other hand, quality systems are easy to adopt and enable through automated technologies. Not only can automated systems integrate with upstream and downstream processes for seamless workflows and audit trails, they significantly reduce the burden on users. An automated system provides a consistent storage environment without risking sample integrity, full sample tracking to eliminate human errors, and capabilities to move samples from storage through processing steps without human intervention. In the automated system, all sample locations, environmental conditions, equipment maintenance, derived data and more can be accessed at the touch of a button instead of manually compiled from different sources.
Why should organizations/companies work with a biobanking service instead of handling samples on their own?
Dr. Resch: There are several advantages to working with a biobanking service. First, biobanks offer a variety of services that are sometimes difficult to find under a single roof. Biobanks specialize in the receipt, processing, and storage of samples, but they also provide services that involve project management and information technology (IT) support. In addition to maintaining cryogenic storage facilities, most biobanks are equipped with laboratories to support their molecular biology, cell culture, cytogenomic, and sequencing needs.
Second, biobanks are often equipped with state-of-the-art technology. The automation they offer is important for standardizing workflows, minimizing human error, and reducing costs. Also, their well-established quality control pipelines ensure high-quality products.
Last, biobanks house diverse sample collections annotated with rich clinical, genomic, and phenotypic data. These collections are often well characterized and they provide valuable resources to the research community. Their sample collections may include many different types of samples and may be collected from human or non-human species.
Dr. de Mars: There are several reasons why an organization should work with a biobanking service provider instead of handling their own materials. First and foremost, biorepositories specialize in the maintenance of biological specimens and associated data; as such, they can assure the quality, accessibility, security, and safe distribution of valuable materials. In addition, biobanking service providers can often offer specialized services that address customer-specific needs.
Biorepositories also offer dedicated storage facilities that are overseen by personnel with expertise in biomaterials management. Biorepositories are able to offer security and 24/7 temperature monitoring of the facility and the equipment, ensuring that materials are kept at the correct temperature at all times. Because biobanking requires a significant amount of space and funding to support equipment, instrumentation, and security, many biorepositories are able to provide biobanking services more efficiently than an organization could achieve in house.
How can institutions qualify legacy samples and bring them into an active biobanking library?
Mr. Hamilton: Often, they need to ask tough questions. “What is the quality of the samples manually stored over decades, and what value will it bring to future research and to the business? What supporting documentation is available for the sample throughout its lifespan, which could be decades?” If the sample is of poor quality—some samples may have incomplete information or an unknown history—it just doesn’t make sense to pull it into an automated system.
Once the quality and value are established, they can look at the physical transition in context of the intended use. If samples require full or immediate accessibility, we may recommend incorporating a liquid handler to aliquot them into automation-friendly tubes prior to storage or evaluating other labware solutions that could help bridge the automation gap. Conversely, if samples are intended for long-term storage, or are in a container that is not automation friendly, we have methods to transition them in their original box or rack to minimize disturbance.
Recommendations for Ensuring Sample Integrity
1. Make sure that the sample is pure and authenticated prior to preservation and storage. Skipping this essential first step can lead to lost time, money, and publications owing to cross-contamination and misidentification. By implementing a best practices approach and using a multifaceted method toward biomaterial authentication, researchers can help ensure the integrity of their samples, which in turn can improve assay reproducibility and data accuracy. Some of the methods that we recommend—and consistently use—for cell line or microbial authentication include short tandem repeat profiling, CO1 (or, cytochrome c oxidase subunit 1) barcoding, mycoplasma detection testing, next-generation sequencing, biochemical analyses, and morphological studies.
2. Use correct cryopreservation procedures when managing a biological sample. High levels of ice formation and increased solute concentration can have a negative impact on viability. Using a suitable cryoprotectant is one factor that can affect cell viability. Typical cryoprotectants include dimethyl sulfoxide (DMSO) and glycerol. The amount and type of reagent used will depend on the biomaterial being preserved and will often need to be determined empirically. Freezing cells at a cooling rate of 1°C to 3°C per minute is also essential for avoiding the formation of intracellular ice crystals that would otherwise result in structural damage. The best method of cooling involves the use of a programmable controlled-rate freezing unit that can rigorously maintain a steady cooling rate.
3. Storage temperature is an important factor to consider for ensuring sample integrity. The temperature required for long-term storage can significantly differ depending on the culture and how it is prepared. For example, animal cells may require storage in the vapor phase of liquid nitrogen, whereas bacteria may require storage at –80°C. When storing biomaterials in the liquid nitrogen vapor phase, it is essential to maintain sufficient levels of liquid nitrogen in the container so that the correct temperature is maintained. All storage containers used should be equipped with temperature-monitoring systems and alarms to ensure the proper temperature is maintained at all times.
4. Cold-chain management is essential for maintaining sample integrity when handling, processing, and shipping preserved biomaterials. Multiple rounds of freezing and thawing can significantly affect protein structures, lead to oxidative stress, and cause cell membranes to rupture. To maintain biomaterials under the correct low-temperature conditions, specialized equipment such as portable liquid nitrogen transporters, cryogenic carts, or refrigerated vehicles can be used. Another management consideration is the use of appropriate packaging. Packing materials and containers that provide insulation, temperature tracking, and a coolant can help ensure low-temperature maintenance.
5. Ensure biomaterial integrity by properly storing and maintaining your cells under optimal conditions. The methods that support this often require a significant amount of empirical testing as well as expertise in sample authentication, processing, storage, and distribution. Entrusting these critical elements to the experts can help safeguard the integrity and viability of irreplaceable biomaterials, and so ensure their use in future studies.
Recommendations submitted by ATCC.