Sample Identification

Discover solutions to persistent issues with sample collection and biorepository work

Flaws in the identity and quality of biorepository specimens produce misleading data that cost research labs millions of dollars in wasted resources, and in some cases lead to erroneous publications that damage reputations. Given the high price of research and the current funding challenges facing many laboratories, there is greater demand on biorepositories to ensure sample integrity. Yet the biobanking process is prone to error.

In his December 2012 article in Nature, John R. Masters estimated that 15% of cell lines acquired from biorepositories are not derived from the claimed source. According to a 2011 survey published in National Cancer Institute Monograph, almost 50% of participating cancer researchers reported difficulty in obtaining quality biospecimens, resulting in 60% questioning their findings and 81% limiting the scope of their work. And non-standardized biobanking practices are believed to be a major contributor to the 65% inconsistency rate in data obtained by independent investigators, according to a March 2014 study published in Clinical Biochemistry.

Biobanks continue to make strides toward addressing these critical issues by developing standardized quality control protocols and adopting technologies that allow efficient and cost-effective sample verification. Fluidigm provides a solution with the SNP TraceTM panel (formerly SNPtrace), one component of its comprehensive DNA fingerprinting platform.

Biorepositories are vital partners of the scientific community, providing the nucleic acid, cell and tissue specimens that allow for the advancement of basic, translational and clinical research. Unsurprisingly, biobanking is one of the fastest-growing industries in biotechnology services, with an estimated 9 million samples collected globally in 2012, according to Andy Brooks, COO of Rutgers University's RUCDR® Infinite Biologics, the world's largest university-based biorepository. A typical large biobank might hold millions of nucleic acid samples and cell lines and distribute 1 million samples a year. That volume presents many opportunities for quality and identity problems. Understanding their origin requires careful examination of a sample's itinerary through the biobank process.

Biobank samples go through five main operations: acquisition, processing, storage, distribution and analysis. Although stringent protocols are in place to control for sample integrity, each step is subject to potential mismanagement. Thanks to improved oversight in the last decade, sample errors rarely occur during the biobanking process at accredited institutions. However, this oversight does not reach the thousands of collection sites worldwide, which operate without a standardized protocol for collecting, processing and shipping specimens.

According to the Clinical Biochemistry article, a single specimen may pass through as many as 20 hands en route to a biobank. An alarming 98% of errors originate at sample collection, according to Brooks. Without a stringent quality control protocol at the banking stage, poor-quality or mislabeled samples often slip through the cracks and reach laboratories, where they can affect experimental outcomes.

As gatekeepers for what arrives at the research bench, biorepositories bear great responsibility. A mislabeled sample compromises not only the experimental data but all downstream analyses. After publication, the cycle of damage continues when other investigators attempt to reproduce or expand upon erroneous findings. Given those costly consequences as well as tougher submission guidelines from top-tier journals and the risk of paper retractions, academic and biopharmaceutical institutions are more vigilant of biobank quality controls.

In response to such demands, best practices and formal certification and accreditation are being developed to standardize quality control and quality assurance. The College of American Pathologists; the European, Middle Eastern & African Society for Biopreservation & Biobanking; the International Society for Biological and Environmental Repositories and other organizations have spearheaded the movement toward standardized guidelines for specimen handling and processing and for instrumentation.

In addition, new technologies have enabled biobanks to carry out analytical and functional testing of incoming samples in an automated, high-throughput and cost-effective manner. Most notably, samples can now be verified within two weeks of deposition, allowing biobanks to detect collection errors almost immediately.

A key challenge in functional testing of incoming samples is the variability in sample types such as blood, saliva and degraded specimens like formalin-fixed, paraffin-embedded (FFPE) samples. The ideal solution must allow seamless and cost-effective genotyping of every sample, cell line or tissue that enters the repository.

As an established partner with core genomic facilities and biorepository programs, Fluidigm is at the forefront of efforts to provide a complete solution for sample fingerprinting. The simple and cost-effective Fluidigm DNA fingerprinting platform includes the Biomark™ HD system, the 96.96 Genotyping IFC and the SNP Trace panel. This platform is superior to other existing technologies in its vastly simplified protocol, handling time and cost per reaction (less than $10 per sample).

The SNP Trace panel consists of 96 SNPs chosen or confirmed by Brooks and uses Fluidigm SNP TypeTM assay chemistry. The SNPs in the panel are selected for specific attributes around gender, ancestry or polymorphism across populations. As demonstrated in a poster at the American Society of Human Genetics meeting in November 2013, SNP Trace is able to uniquely identify individuals, detect sample contamination and verify gender.

Biobanks striving to build a reputation for quality specimens can now attain this goal by adopting both available guidelines and new technologies that allow rapid sample verification. By improving sample quality control and assurance, biobanks ensure and enhance their contributions to translational research and the advancement of human health.