Biobanking provides exciting opportunities to recapitulate the in vivo molecular architecture using patient material. Repositories of human biological specimens serve to inform genomics, proteomics, drug investigations, and preclinical analysis. They can be population-focused with an emphasis on genetic susceptibility and serve to inform pleiotropic disease research; disease-focused biobanks focus specifically on a disease of interest such as cancer or AIDS.
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A major concern is the standardization of processing and storage of these samples to ensure homogeneity, especially for older samples. The bioethics of retaining human biological samples remains an ethical concern, warranting dynamic approaches to balance participation consent and the advance of biological understanding.
Sample preparation
Preparation of the sample is critical to maintaining integrity and homogeneity. the introduction of artifacts may jeopardize any downstream data. Human samples include tissue and cells, blood, DNA/RNA, bodily fluids, etc. Human tissues are typically obtained post-mortem or after surgery.
In the past formalin-fixed paraffin-embedded tissue was the gold standard to facilitate the storage of these specimens. FPPE has now been shown to fail to recapitulate the molecular structure. Fresh or frozen tissue is now preferred: it produces better quality RNA and DNA. This is especially critical for genetic studies such as genome sequencing. Tissue blocks maintain protein integrity, but these samples are often further manipulated to generate slides for immunohistochemistry; these slides suffer from decreased antigen detection over time.
A concern with fresh or frozen samples is the period between extraction and storage. In surgical procedures, the extraction of tissue for biobanking is not a priority so the sample may experience warm ischemia for an unmonitored period. This can be mitigated by the intervention of technicians to rapidly freeze the samples. Most samples were typically stored at -20°C.
Nowadays, most are stored at -80 or -150 to maintain integrity. Cryoprotectants are often included to prevent damage to the specimens. DMSO, glycerol, and 1,2-propanediol are often used. The inclusion of carbohydrates serves to moderate cytotoxicity. Fetal Bovine Serum is discouraged due to the inclusion of growth factors and cytokines in the media.
Quality Control
A major issue in repositories of biological material is the heterogeneity in sample processing and storage, as discussed above. The extent of qualification depends on the downstream analysis. This depends on whether the biobank is population-based or disease-oriented. There are two methods of quality control.
The collection of bio-samples with careful pre-analytical annotation (SPREC) involves a series of parameters that prevent the introduction of significant variants in downstream analysis. These include reagents used, conditions during processing, and storage conditions.
Alternatively, individual samples/collections are retroactively analyzed and stratified using internal factors (e.g., protein content) or external factors (e.g., centrifugation conditions). These entirely depend on the sample(s) being investigated and the downstream assays conducted will reflect that. In recent years there has been a shift to harmonize procedures between biobanks and bring them to International Organisation for Standardization standards.
In 2012, the first SOPs for biobanking were introduced by the US National Cancer Human Biobank (http://biospecimens.cancer.gov/resources/SOPs). This has presented a reference to inform and standardize all steps in the biobanking process to prevent artifacts from being introduced that slow the progress of research. Concurrently, a working committee has been established to provide quality control to the field of biobanking (the ISO/Technical Committee (TC) 2761/Working Group (WG) 2 Biobanks and Bioresources).
Journey of a cancer biobank blood sample
Consent and bioethics
Lessons learned from the misappropriation of cells taken from Henrietta Lacks in the mid-20th century have demanded better legislation regarding patient consent. Informed consent remains the cornerstone for the collection of human biological material. There is no international consensus for consent.
General Data Protection Regulation (GDPR) served to inform consent in the European Union. Different strategies are utilized by different institutions to overcome the issue of ensuring the relevant parties remain informed. The “broad consent” model allows different investigations to be conducted on the samples; it is implied that the patient will not receive information about these. An alternative model involves a more “dynamic” approach.
Improvements in information technology allow patients to be informed as to the applications of their samples. Several biobanks refer to themselves as custodians of the samples, issues around the ownership of samples by principal investigators continue to pose a concern.
Management of Biobanks
The sustainability of biobanks is often dependent on the funding of researchers and clinicians who utilize the facilities. The safe and effective biobanking of samples warrants trained technical staff and effective liaison with research/clinical institutions. Most researchers are allocated funding from grants to access biobanks, usually with a defined time span.
Biobanks, however, observe a more longitudinal existence due to their nature. Many larger biobanks are funded by funding bodies such as the UK biobank. Others involve a charge-based system to recoup costs of consumables and staffing such as the Wales Cancer Bank, the Ontario Tumor Bank.
The management and governance of biobanks pose considerable challenges in terms of logistics and standardization of protocols. The International Society for Biological and Environmental Repositories was established in 2000 to address the issues surrounding biological samples including consent, logistics, standardization of procedures.
In Europe, the European Biobanking and BioMolecular resources Research Infrastructure (BBMRI)-European Research Infrastructure Consortium (ERIC) was activated in 2011. Both organizations strive to improve liaison between different biobanking centers, ensure ongoing concerns about consent are addressed, and act as a nexus between the pharmaceutical industry, participants, investigators, and clinicians.
Applications
Biobanks present exciting new opportunities in terms of Genome-Wide Association studies, drug sensitivity investigations, pre-clinical analysis, and oncology (pre-and post-exposure to therapeutics). The UK biobank has obtained whole-genome sequencing for 500,000 people. This is critical for investigating genetic polymorphisms (SNPs, indels, etc) associated with drug sensitivity and toxicity. This population-wide genetic analysis also investigated allelic variations in the HLA genes associated with numerous diseases.
Trastuzumab, the front-line treatment for HER2-positive breast cancer, started from the analysis of breast cancer tissue at NIH. Biobanks have played an influential role in the development of The Cancer Genome Atlas. This provides genomic data for numerous cancer types (and subtypes), informing ongoing investigations.
Sources:
- Bycroft, C. et al. (2018) ‘The UK Biobank resource with deep phenotyping and genomic data’, Nature. 2018/10/10, 562(7726), pp. 203–209. doi: 10.1038/s41586-018-0579-z.
- Coppola, L. et al. (2019) ‘Biobanking in health care: evolution and future directions’, Journal of Translational Medicine, 17(1), p. 172. doi: 10.1186/s12967-019-1922-3.
- Lehmann, S. et al. (2012) ‘Standard preanalytical coding for biospecimens: review and implementation of the Sample PREanalytical Code (SPREC)’, Biopreservation and biobanking, 10(4), pp. 366–374. doi: 10.1089/bio.2012.0012.
- Simeon-Dubach, D., Zeisberger, S. M. and Hoerstrup, S. P. (2016) ‘Quality Assurance in Biobanking for Pre-Clinical Research’, Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2016/09/17, 43(5), pp. 353–357. doi: 10.1159/000448254.
Further Reading