The process of formalin-fixed paraffin-embedding (FFPE) emerged in the late 19th century as a valuable histological method for stabilizing and preserving the morphology and cellular details of tissue samples. Additional advantages of preserving tissues using the FFPE technique included long term room temperature storage without fear of degradation, and if tissues were correctly preserved, FFPE blocks could be used over decades to prepare additional slides for microscopic analysis (as long as there was remaining tissue in the paraffin block) with little or no tissue degradation. Significant advances in protein and nucleic acid isolation techniques from FFPE tissues have yielded sufficient amounts of material for a wide range of analytical techniques to determine structure and function of these key biological molecules.
FFPE tissue preservation has become a reliable tool for histological research and analysis; protein harvesting and analysis techniques such as MALDI (matrix assisted laser desorption /ionization Mass Spectrometry), LC-MS analysis (Liquid Chromatography-Mass Spectrometry), Western Blotting, IHC (Immunohistochemical analysis for antigen retrieval) were subsequently applied and have yielded valuable molecular weight information on a wide range of protein species.
Since then, techniques have also been developed for the isolation of RNA and DNA not only from an FFPE tissue section but also from subsections harvested by LCM (Laser Capture Microdissection). Although the DNA is fragmented as a consequence of the formalin preservation, the advent of PCR, whole genome amplification and similar techniques have made it possible to obtain a wealth of genetic data from FFPE tissue blocks.
From a historical perspective, there are millions of FFPE tissue blocks in storage and in use today; these range in age from being generated several decades ago to blocks prepared at the time of this writing. Block storage methodologies have typically been comprised of the following, although there are variations on the theme:
- Each FFPE Block is identified by applying handwritten or printed labels to the block /cassette based on patient information.
- Blocks are sorted numerically. As blocks from additional tissues for the same patient are generated at a later time, grouped blocks are re-sorted to accommodate the nested blocks.
- Blocks are archived on-site for a length of time until storage space becomes an issue.
- Blocks are routinely retrieved when slides need to be made. Delays in returning these blocks to the archive can cause blocks to be placed in the wrong location, resulting in delays when trying to locate blocks in this situation. Often, the entire archive needs to be searched manually to locate the missing block.
- Blocks are stored off-site after on-site storage capacity is exceeded, using the same numerical storage method.
This storage process works well for small numbers of samples, but is quickly overrun when thousands of blocks begin to accumulate. The retrieval and return process can be error prone, leading to potential specimen loss, delays in retrieval, and excessive time spent re-cataloging and locating blocks, all translating to patient impacting events. Given today’s patient health care requirements, many FFPE blocks need to be retrieved daily; with the legacy systems described above, biospecimens are not always archived on the same day. Coupled with the constant demand for block retrieval there are cases in which sporadic, manual record keeping is maintained of who a block was sent to or when a block is due to return. In addition, many blocks sent out for clinical trial use can lack traceability for the same reasons.
Recently, an end to end system (ARCOS™ Block Management System, Thermo Fisher Scientific Kalamazoo, MI) was developed and implemented in several locations worldwide to address the issues encountered with FFPE block storage, retrieval and restocking. The ARCOS system is primarily designed to accurately store, catalog and track FFPE blocks, minimizing/eliminating potential patient impacting events caused by delayed FFPE retrieval and re-archiving events, is 21 CFR Part 11 compliant and eliminates the need to catalog blocks in numerical or similar order.
The following figure outlines the ARCOS process:
With the ARCOS system, requesting the retrieval of one to many blocks is simply accomplished by selecting a ‘pick list’ of the required block IDs in the ARCOS database. This action allows the handheld mobile scanner to ‘see’ the picklist and aid in the verification of the correct blocks being ‘pulled’ from storage as well as identifying the user performing the retrieval information along with the time and date of each event, essentially maintaining chain of custody for each FFPE block.
A few key features of the ARCOS system include:
- Database contains a list of all blocks in the system, along with chain of custody information (storage location, retrieval, restocking) as well as date and time stamps for all events, humidity and temperature data, and identification of who performed any actions to the blocks.
- No need to sort blocks into any kind of sequence.
- No need to leave spaces for delayed or shipped blocks.
In summary, the installed ARCOS systems to date have been shown to significantly improve FFPE data documentation, storage and retrieval; and in conjunction with off-site biobank storage have significantly improved chain of custody and turnaround time for short and long term FFPE block retrieval and storage.
Choosing an off-site storage provider means asking the right questions to determine if the provider has the appropriate risk mitigation infrastructure in place. Fisher BioServices’ biobanking & biorepository services offer a global network of facilities for off-site storage, supported by validated procedures and an integrated quality management system, to ensure optimal storage methods for downstream research. We provide a complete range of temperature options, from ambient to cryogenic, to support the management of critical biological materials, including FFPE tissue blocks
In additional to the ARCOS systems and off-site storage solutions, there are even more tips and technologies that can be used to improve the management of all types of inventory. Download your free copy of InsideAccess: Maintaining Inventory Accuracy to learn about some other tools we use in working towards our goal of absolute, 100% accuracy in our operations.
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Zhang et al. The utilization of formalin fixed paraffin embedded specimens in high throughput genomic studies. International Journal of Genomics Vol 2017, Article ID 1926304.
Kokkat et al. Archived formalin fixed paraffin embedded blocks: a valuable underexploited resource for extraction of DNA, RNA, and protein. Biopreservation & Biobanking Vol. 11 (2) 2013.
Grizzle et al. Issues in collecting, processing and storing human tissues and associated information to support biomedical research. Cancer Biomark. 2010 Vol 9 (1-6) pp 531-546.