A Solution to the Sample Management Bottleneck

With genomics discovery and the potential of genomic medicine, both the importance and need to store biological DNA samples as a research and clinical resource have grown considerably. Researchers and physicians are striving to improve healthcare by making correlations between genetics and the environment with disease as well as between genetics and drug response.

Medical centers, academic institutions, pharmaceutical companies, and law enforcement agencies too are rapidly collecting tissue libraries containing large volumes of biosamples. A RAND study has conservatively estimated that there were more than 307 million tissue specimens from more than 178 million cases stored in the United States, accumulating at a rate of more than 20 million specimens per year. These samples are collected in large and small repositories, for example, the Armed Forces Institute of Pathology (AFIP) National Pathology Repository, one of the largest tissue repository in the world, stores more than 92 million specimens. On the other end of the spectrum, individual researchers in laboratories worldwide collected tens to hundreds of samples specific to their focused area of study. Biosamples in all types of repositories are generated, analyzed, and exchanged around the world each day as people utilize them in research and investigation.

Conventional Methods Will Not Scale to Meet Demand

Much attention has been paid to the downstream genomic analytical tools, but little attention has been paid to the upstream management of biosamples, which feed the analytical pipeline. Current methods of storing biosamples are generally limited to cryogenics, depositing a labeled test tube holding a DNA-containing biosample such as blood or extracted DNA into a freezer or nitrogen tank. Many times these freezers and nitrogen tanks are part of a scattered network of several freezers or tanks spanning several locations within a company or organization, whereby additional freezers are added as space permits and repositories grow.

Alternatively, biosamples are stored on Guthrie cards, sometimes in the cold and sometimes at room temperature. While biosamples can be stored in this manner, it is not an operationally efficient or reliable system, nor does it scale well to the levels required.

This relatively unorganized system creates a logistical challenge and limits the ability of organizations to effectively access and share critical samples and data. If biosamples must be accessed at a remote location from the actual storage site, retrieval time can be extended by days or even weeks. In addition, biosamples needing to be shipped are considered biohazardous material, require costly special handling and could be compromised or degraded if shipments are delayed en route.

Costs for extraction kits, continuously running freezers, monitoring systems, and backup generators in case of power outages can also be significant. Currently, biosample labeling is also unreliable as labels can be difficult to read, fade over time, fall off storage tubes, or placed on the wrong sample. In addition, with current labeling methods, it is impossible to identify a biosample that has been separated from its carrying container.

A Faster, Cheaper, and Better Solution

GenVault Corporation was founded to provide DNA sample accessibility for genomic medicine and identification. Supported by top-tier investors, GenVault is now installing room temperature biosample management systems at top-tier academic and industry sites around the world.

GenVault offers an alternative to expensive cryogenic sample storage that can be fully integrated into any organization’s workflow, costs less to operate, saves space and is better for the environment (Figure 1). This alternative includes: a dry-state media with which to store biosamples; a reliable, permanent and tamper-free labeling system; reagent kits for subsequent DNA recovery; software to request or track individual biosamples and their information and several secure methods of physical storage from stand-alone benchtop storage units for several hundred to a thousand samples up to completely automated storage and retrieval systems for tens to hundreds of thousands of samples which free lab workers and avoid human error.

Figure 1: An example workflow of GenVault’s sample management system, showing the progression of a sample through the system from sample and data collection through archiving to DNA recovery for genetic analysis.

The core of this system is GenVault’s GenPlate (Figure 2).. GenPlates are standard multiwell plates that contain disks of Whatman FTA® paper within each well. FTA paper is a derivative of the Guthrie card and neonatal screening cards. A variety of sample types such as blood, buffy coat or even already purified genomic DNA can by stably stored upon each disk. Because the amount of sample and the future use of sample aliquots can vary, GenPlates are available in multiple configurations to maximize storage density and use, while minimizing cost.

Figure 2. GenVault’s GenPlate standardizes FTA paper punches into an automatable format. Each well within the 384 multiwell plate contains a disk of storage media that can store blood, buffy coat, clones, or purified DNA in the dried state at room temperature.

Each aliquot within every GenPlate is embedded with an unique biological barcode, GenCode. An innovative biological tag, GenCode, permanently identifies each biosample following sample removal and recovery. GenCode is composes of a simple combination of non-human sequence oligonucleotides and is easily resolved either via genotyping or a few simple PCR reactions.

GenConnect is GenVault’s sample management software and database which allows users to track their samples from GenPlate application to DNA recovery. GenConnect organizes data by study, subject and samples. Users can design dynamic form templates to customize their demographic or phenotypic annotation to any and all of these three levels. GenVault’s February 2007 release of GenConnect will allow users to track not only their samples stored within GenVault’s hardware solutions, but also samples stored in altnerative containers such as freezers or liquid nitrogen tanks.

GenVault provides an array of solutions for organizing and storing GenPlates. At the smallest end of the spectrum is the Desktop Archive, a stand-alone storage module for 100 GenPlates that has a capacity of 38,400 aliquots, essentially comparable to a standard upright freezer, but in 1/10th the space. The Desktop Archive requires no electricity to operate for a substantial operational savings over traditional freezers. GenVault offers a larger manual storage module, the Personal Archive. This cabinet is about the size of a large freezer, but holds up to 400,000 aliquots or 10 times the amount of a traditional freezer in that same space.

Additionally, for users with large sample collections, GenVault offers the Dynamic Archive. This fully automated solution is scalable and designed in modules which can be added as a user’s collection grows. The Dynamic Archive requires only a fraction of the space and energy needed to operate a traditional freezer farm. For example, 153 million aliquots can fit into the space of a two-car garage.

Finally, GenSolve is GenVault’s reagent kit for recovering high-quality double-stranded DNA from GenPlate aliquots, FTA paper and Guthrie cards. The protocol requires no special equipment, simply an incubation at 56°C with GenSolve reagents removes DNA, cellular debris and proteins from the paper. The DNA is then ready for purification with a typical DNA purification kit.

Grow a Sample Collection while Saving Energy and Space

Among the many benefits of GenVault’s sample storage systems is the immediate reduction in energy usage. In many laboratories and clinics, cryostorage is a significant portion of operating costs. Just the electricity costs of directly operating a single -80°C freezer for one year can far exceed $1,000. Additionally, rooms that have a large number of freezers may require additional air conditioning that can further increase the electrical costs of operating a frozen archive. Even if researchers are not individually aware of their electric bills, this cost may be charged indirectly in the form of overhead that is deducted from research budgets.

GenPlates enable GenVault to utilize hardware with little or no power requirements for sample storage. For example, our Desktop Archive is a 2 cubic foot storage module that holds a maximum of 38,400 aliquots. Also the Desktop Archive requires no power to operate, for a yearly savings of greater than $1,000 in electricity costs (Table 1). For large sample collections, our Personal Archive holds 403,200 aliquots and only requires 3 kWh/day to operate compared to >20 kWh/day for a -80°C freezer.

Table 1: Savings in capital and energy costs by purchasing one Desktop Archive instead of one ultralow freezer.

Adoption of GenVault’s system results in more than just monetary savings. Reducing the number of ultralow freezers in operation can have a significant impact on the environment as well. Table 2 summarizes the environmental impact of replacing one ultralow freezer with a Desktop Archive.

Table 2: Environmental impact in replacing one ultralow freezer with a single Desktop
Archive from GenVault.

An additional benefit of the GenVault system is a substantial savings in space allocated to sample storage. A Desktop Archive is about 2 cubic feet and requires only about 2 additional square feet of door clearance, yet holds about the same amount of samples as a traditional -80°C freezer which requires a total of 30 square feet including door clearance and space for heat dissipation. Similarly, a Personal Archive requires about 28 square feet yet holds 10 times the amount of samples as a traditional -80°C freezer. With rent ranging anywhere from one to several dollars a square foot, immediate operational savings of hundreds to thousands of dollars per year can be achieved utilizing GenVault’s more efficient storage design.

While the space and energy savings with the GenVault system can be easily calculated, GenVault also provides more intangible benefits to researchers:

• Because GenPlates inactivate biohazards such as viral and bacterial pathogens, they can be easily shipped without biohazard labeling or dry-ice. Not only does this result in monetary savings by lowering shipping costs, but it provides peace of mind knowing that when shipments are delayed, the sample integrity will be maintained.
• Additionally, GenCode, provides a tracking mechanism to identify samples even after they are removed from their physical containers. This mechanism allows researchers to determine the true identity of a sample even if a lab mixup has occurred.

In conclusion, GenVault’s room temperature DNA sample storage system, will result in substantial cost savings over traditional cryostorage, while providing a more robust system that keeps samples stable even in complete absence of power, providing conclusive sample tracking and providing an alternative that will easily integrate within any organization’s workflow. The infrastructure for genomic medicine and identification DNA accessibility is GenVault.