Biobank Sample Collection
Sample Collection
As you are planning your resource, you will to need determine if your collection will include biologic samples now or in the future. Collecting biological samples is important if adequate samples do not currently exist, or if current collections are fragmented and not shared. Advocacy organizations can also leverage their biobank sample collections to direct the research being done on their disease or condition of interest.
Well-characterized biological samples are a very valuable research tool. However, sample collection is not a trivial undertaking, and proper planning is required. Advocacy organizations will need to work with their medical and scientific advisors to determine what is appropriate to collect. There are also technical considerations and resource considerations.
Some basic questions to consider include:
- What types of samples will you collect?
- From whom will you collect samples?
- Where will samples be collected?
- When will samples be collected?
- Who will collect the samples?
- How often will you collect samples?
- Do other similar sample collections exist?
OBBR has developed a brochure on the importance of high quality biospecimens.
Biological Samples and Derivatives
It is vital to anticipate how samples will be used prior to collecting them, so they can be collected and processed appropriately. For example, different vacutainer tubes are used for blood collection, depending on how the blood will be processed in the lab.
Many biobanks collect blood and/or tissue. Blood is a robust source for DNA, as all cells in the body generally have identical DNA signatures. Blood can also be used to isolate PBMCs (peripheral blood mononuclear cells), study biomarkers, or make EBV-transformed cell lines (although this is not as common today since smaller amounts of DNA are needed for experiments). Blood is usually processed (e.g. DNA isolated) prior to being sent to researchers.
Tissue is often used to study changes in gene expression (RNA) and can be a source for cell line generation. Tissue samples can be processed prior to being sent to researchers, or sent to researchers directly as frozen pieces of tissue. Representative pieces of tissue may also be embedded in paraffin, sectioned, and stained to see the characteristics of the tissue (histology and pathology). Generally, tissue is much more complex to collect and process than blood, and the more complex the processing, the higher the cost.
As you are planning your collection, you will need to understand what biological materials and derivatives are needed from the research community. There are many options to consider, and below is a list of biological samples and common derivatives. While not comprehensive, this is a starting place for the discussion.
Blood
- DNA
- RNA
- Protein
- PBMCs
- Cell lines
- Serum
- Plasma
Tissue
- DNA
- RNA
- Protein
- Cell lines
- Cell blocks
- Paraffin sections
- Frozen sections
- Frozen pieces of tissue
- Whole tissue from autopsy
Mechanisms for Sample Collection
Once you have decided what biological samples you will collect, you must then determine how you will collect them. Blood and tissue are the most commonly collected sample types. Blood collections are relatively straightforward, and can occur in collaboration with a healthcare provider or by non-traditional mechanisms, such as sending kits directly to participants or at outreach events. Outreach events are an excellent opportunity to bring your community together, educate about the importance of research, and collect samples. Tissue is collected exclusively at point of care with the collaboration of the provider. For all collections, it is important to include materials required for collection and instructions on how samples should be collected, stored, and shipped to the lab.
Below are common ways to collect blood and tissue:
Blood
- Collection at point of care with provider
- Sample donation kit mailed directly to participant
- Collection at outreach events
Tissue
- Collection at point of care with provider
- Collection at autopsy (special arrangements required)
Sample Processing and Storage
As we discussed, sample collection is not a trivial undertaking, and proper planning is required. In addition to deciding what to collect, you will need to determine how the samples will be processed and stored. Since most organizations do not have laboratory space, you will likely need to work with a vendor or partner for processing and storage.
Some basic questions to consider include:
- Where will samples be processed?
- How will samples be processed?
- Where will samples be stored?
- How will samples be stored?
- How will samples be accessed?
- For what types of experiments will samples be used?
Pre-analytical Variation
Procedures for biospecimen collection, processing and storage can lead to a wide variation in quality of specimens and data. For example, changes in specific transcript levels may be based on the ischemic time and not the disease. Pre-analytical variation includes both pre-acquisition and post-acquisition factors. (Pre-acquisition factors can include presence of antibiotics or other drugs, type and duration of anesthesia, and time of arterial clamp time. Post-acquisition factors include time at room temperature, temperature of the room, type of and time in fixative, and aliquot size to name a few.)
Ideally, every piece of relevant data should be collected to support future users who may have no connections to or understanding of the biospecimen collection protocols. Research is also needed to better understand how these variables affect molecular integrity, as some variables will have great influence on molecular pathways and others will not.
A number of initiatives are underway to better understand pre-analytical variation and biospecimen science:
- The Office of Biospecimen and Biorepositories Research (OBBR) has developed Biospecimen Reporting for Improved Study Quality (BRISQ ) to guide researchers to capture information about the source and handling of biospecimens.
- The ISBER Biospecimen Science Working Group has developed the Standard PRE-analytical Coding for biospecimens (SPREC) to improve biospecimen research experimental protocols and to provide information about the biomolecular quality of samples.
- The Standardisation and Improvement of Generic Pre-Analytical Tools and Procedures for In Vitro Diagnostics consortium, better known as SPIDIA, has developed pan-European quality assurance schemes and guidelines for pre-analytical procedures, including sample collection, handling, transportation, processing, and storage of clinical samples.
Best Practices
When working in any area, including registries and biobanks, it’s important to know where to find trusted information. What are the best practices, and who are the key organizations in the field?
In biobanking, best practices are needed to provide state-of-the-science guidance and to harmonize procedures for collection, processing, storage, and distribution of data and samples. While multiple best practices exist, there is not yet uniform adoption of these protocols. Three useful resources are listed below.
- The Department of Health & Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ) released a handbook, Registries for Evaluating Patient Outcomes: A User's Guide, that provides guidance for establishing, managing, and analyzing patient registries.
- The International Society for Biologic and Environmental Repositories (ISBER) has developed Best Practices for Repositories, focusing on the collection, storage, retrieval and distribution of biological materials for research.
- The National Cancer Institute (NCI) has developed NCI Best Practices that examine the scientific evidence for collection, annotation, processing, and storage of biospecimens.
Insuring your biobank samples
Biobank collections are precious and in many instances not replaceable. The samples are priceless, with immense scientific value. It is possible to insure the facility and equipment, but insurance for loss of samples is almost always cost prohibitive. If you do insure your collection, it is important to assess the cost of obtaining similar samples, including labor and all logistics for acquiring and storing the replacement samples. It is very challenging to assign a value to the collection itself.
Instead of focusing on insurance, a better strategy may be to focus on risk management and preventing loss in the first place. This can be accomplished by:
- Storing samples in multiple freezers and routinely splitting samples from the same case into separate freezers.
- Separating critical batches of samples to different sites. If offsite storage is not possible, store samples in different tanks or freezers in different rooms.
- Utilizing higher floors to decrease flood risk.
- Using internal controls, automated monitoring, routine maintenance and staff training to minimize risk of loss.
