Researchers in academia and industry realize the importance of biospecimens not only for diagnostics but also for drug discovery and development. Unfortunately, the collection and processing of these precious assets varies from lab to lab, raising doubts about the accuracy of research data. IIR’s “Biorepositories” conference, held in Boston recently, provided information on new efforts to enhance biorepository operations and optimize biospecimen integrity.
Economic pressures are forcing companies to focus more on their biospecimen collection and to re-evaluate its management. “Pharmaceutical firms are realizing that it’s difficult to leverage the value of scattered resources,” said Cathy Michael, global head of sample management at BioStorage Technologies.
Another challenge is the question of future standards. “Activity now is sometimes constrained by an unknown future need,” she added. Michael presented information on applying conventional wisdom in innovative ways to maintain maximum efficiency for biorepository operations.
She also talked about relocation of samples and utilizing assets as a renewable sample resource. Many companies have scattered resources, she reported, and conventional wisdom says this is okay, because samples are close to the scientists at the bench. An emerging approach is to consolidate samples as a full asset collection and to catalog it, allowing scientists to make time-sensitive decisions based on annotated information (patient age, co-drugs, co-morbidity, etc.). This allows a collection to be mined, allowing scientists access to all samples.
Utilizing assets as a renewable sample resource is a new concept. Instead of using a sample one time due to freeze/thaw constraints, use only a tiny amount. “Science has caught up to the fact that most assays don’t require 4 mL,” Michael explained. The sample can be maximized with a liquid handler for precise aliquoting. Samples like whole blood can be separated and all components stored individually, with annotation to the parent and remaining stock.
Sample-protection and sample-relocation services were among the innovations discussed at the meeting. Sample protection includes sample-storage and sample-preparation services. “We want to help our clients with the renewable sample-resource concept, so we introduced these services,” explained Michael. These include sample processing within 24 hours after collection to maintain sample integrity, sample preparation into precise components (DNA, plasma, etc.), storage at the best temperature for sample type, and tracking of parent/stock sample and child/aliquot relationships via a 21 CFR-compliant database.
Sample-relocation services provide global shipment of samples through the company’s packaging and transportation suppliers and facilities. ReloFleet™ vehicles are repositories on wheels that are temperature controlled and provide door-to-door transportation of sample collections. A real-time sample-tracking database, ISISS (Intelligent Sample Inventory Storage System), provides 24/7 audit trail of sample movement from site to site. “We consolidated over a million samples over four locations and two continents for a pharmaceutical company this year, and it was completed in less than two months,” Michael stated.
Originally developed at Harvard University Medical School, Dale Larson’s automated frozen sample aliquotter drills into frozen specimens and eliminates thawing. “Every time you freeze/thaw a specimen, something happens to it in an unknown, unpredictable manner,” explained Larson, director of biomedical systems at Draper Laboratory.
When establishing a biorepository, he said there are two fundamental approaches in addition to his hybrid methodology for storing and processing samples. The first approach avoids freeze/thaw cycles and aliquots specimens into analysis-size samples for storage. Each sample is analyzed with only one freeze/thaw cycle, but plastic, real estate, and electric costs all increase.
The second approach is to store larger volume sizes, aliquot, and then refreeze after a sample is taken, this may result in a lower quantity of samples. The hybrid approach involves initial freezing in a small number of tubes. The first request thaws the sample and makes aliquots for that particular research activity and the remainder is aliquoted off into multiple tubes.
“What we’ve been able to do with our technology is to get the best of both worlds. You can freeze your sample in a smaller number of tubes initially, then when requested, our system extracts an aliquot without thawing the sample,” Larson explained.
Larson’s hybrid approach consists of a coring probe that drills into the sample and removes it. This enables about six or seven aliquots from a 1.8 mL cryovial, with only one freeze/thaw cycle. Although the robot is not high-speed, it is hands-free. In an economic and labor analysis of the technology, Larson said that out of 24 hours of sample processing at the create-and-deliver aliquot step, 21 hours were returned to the lab, freeing the technician for other tasks.
Research to date has worked with plasma and serum samples in 1.8 mL cryovials, although Larson strongly suspects the system will be able to extract from frozen cells, blood, and soft tissue, but probably not bone. The technology is being further developed by CryoXtract Instruments—a partnership between Harvard and Northeastern Universities.