SealSAFE is the world’s first automatic system that fills dedicated bags containing biospecimens with the required fixative (i.e. formalin) in a standardized and documented way.
This innovative and patented technology allows operators in surgery rooms and in pathology laboratories to handle histology specimens in complete safety.
Needle Biopsies are small and are fixed rapidly when placed in neutral buffered formalin (4% formaldehyde), but larger surgical specimens require controlled conditions and fixation. Nonetheless, lab administrators have to pay special attention to limiting personnel exposure to the dangerous formaldehyde. For the best results outcome, it is optimal for the fixation process to be controlled by the pathology laboratory so, SealSAFE can also be used for specimen collection transport & storage without fixative. This may involve fresh specimen collection and transport to the pathology laboratory, under vacuum and refrigerated for the optimal tissue microscopy & macro molecules preservation.
Fresh tumour samples may be taken in the operating theatre and transported to the laboratory for pathologist evaluation, molecular analysis or tissue banking, according to defined protocols.
Many groups have shown the damaging effect on nucleic acids and proteins from cold ischemia time. Cold ischemia occurs between removal of tissue and its fixation and is a problem for large surgical specimens. Cold ischemia alters levels of gene expression (at the RNA and protein level) and is a major consideration for molecular pathology. Control of specimen collection transport & storage is recommended for molecular analysis of proteins such as ERBB2 (HER2) or for the analysis of gene expression. Vacuum packing of tissue and transfer to the laboratory at 4°C (TissueSAFE – SealSAFE) can be very useful for sites distant to the hospital laboratory.
Cooling should be as rapid as possible and cold fixation preserves RNA well, though cold shock-induced changes can be a consideration for some biomarkers.
This innovative specimen collection transport & storage technology, allows operators at surgery rooms and at pathology laboratories, to handle histology specimens in full safety. Today’s manual operation to prepare, transport and stock histology specimens, can be drastically improved with SealSAFE technology.
The traditional procedures of specimen collection, transport and archiving of pathology specimens are specific at each institution. The introduction of SealSAFE technology at the starting point of sample generation (the surgery room), pathology accessioning, and in the grossing area provides a dynamic and flexible solution with benefits to all involved departments.
Such a procedure enables close monitoring of fixation time and yields fresh (not fixed) tissues for biobanking and cell culture or xenografts, while preserving nucleic acids and proteins.
In the dirty room of a surgery department, the SealSAFE is used to vacuum seal biospecimens for being transported to the laboratory. The operator can select the desired procedure for specimen management: fixative-free vacuum sealing with no transport medium and transported to laboratory immediately or automated filling of fixative plus vacuum sealing with specimens kept even at room temperature.
Large specimens like stomach and bowel specimens are advised to be cut open to allow the penetration of fixative.
Time and temperature conditions during transportation are monitored with a dedicated electronic data-logger, activated by operator at the SealSAFE starting point. In case of vacuum sealing without fixative, collection and transport storage at +4°C are required. In this modality, optimal preservation of the molecular material of the specimen is guaranteed up to 72 hours, covering Friday to Monday operations.
Installing a SealSAFE unit in the pathology laboratory enables maximum flexibility for specimen collection. In addition, SealSAFE reusable vacuum storage bags allow for multiple opening and sealing events. Those can accommodate status pre-examination of large case specimen fixation/hardening; receipt, grossing, and final storage of medium-sized specimens; well-fixed tissues can be sealed with minimal amounts of formalin or simply with vacuum to achieve drastic cost and space savings.
As specimens arrive into pathology and are processed through accessioning, relevant data can be downloaded and saved for future use. A detailed profile of temperature conditions, duration of storage, and additional specimen collection transport & storage information is viewable and easily associated with patient cases.
In addition to the above facts, formaldehyde is known to be toxic and is classified as a category 1B carcinogen and a significant association was demonstrated between formalin-fixation procedures and the generation of oxidatively damaged DNA testified also by the formation of the molecular adduct. This would justify its banning, as recently proposed by EU authorities. Formaldehyde can induce increased levels of oxidative stress and enhanced formation of ROS by different ways, including the activation of oxidases and the inhibition of scavenger systems.
However, given that to date a reagent able to guarantee the same performance in histopathology is not available, a reasonable policy is to reduce the risk during specimen collection transport & storage, by creating working conditions in which the exposure of the personnel involved is limited to an acceptable minimum.
The adoption of the Vacuum system procedure for surgical specimens transported to the laboratory results in a sharp decline in the exposure of nurses to formaldehyde. In fact, evidence of the reduction of oxidative stress in nurses adopting the Vacuum technique as an alternative to the use of formaldehyde in operating theatres was given. This data adds to the already acquired experience on the advantages offered by the Vacuum system procedure in specimen collection, in terms of improved tissue preservation for diagnosis and research, and appreciation of the operational feasibility of the process, by the nursing staff. The major source of exposure to formaldehyde is not its use in pre-filled vials for fixing small biopsies, since in fact this procedure was carried out in both types of surgical theatres, while the bulk of exposure is related to the habit of pouring liquid formaldehyde (3-5 liters at a time) in large containers. In conclusion: With SealSAFE Milestone offers an innovative, scientific publications proved method for a better and safer specimen collection transport & storage.
In the Operation Theatre site, nurses or surgeons’ assistant vacuum pack specimens in an automated way, standardized and tissue are ready to be transported to the laboratory in vacuum sealed bags with or without transport medium.
During specimens’ transportation, there is not risk of transport medium (typically formaldehyde, if present) spillage and fumes’ leakages.
Once in the Pathology lab, specimens are immediately accessioned and cut up for different use like for biobanking, cell culture, nucleic acids and proteins detection. At the end of the procedure, specimens are safely collected & storage in vacuum sealed bags, saving both storage space and disposal costs.
Publications document the scientific validation of placental tissue for pathologic examination using TissueSAFE formalin-free vacuum sealing system has been performed and published. The study was conducted to document the safety, quality, and cost of SealSAFE for transportation of placenta. While most placentas are normal and do not require pathological examination they still require a safe system for storage and disposal. Placentas that require pathologic evaluation present numerous challenges of non-standardized ex vivo time, tissue preservation conditions, and timed exposure to formalin-fixation. The consumption of high volumes of formalin for proper fixation, and the sometimes inadequate volume of formalin also creates challenges. Eventually expensive disposal of the specimen and associated bloody container and formalin as hazardous waste is required. To address all of these issues a study was performed to look at a vacuum-sealed, formalin-free tissue handling system designed to originate in Labour and delivery with the intent to control placental preservation and transport to pathology for histological evaluation.
Study design: Eight placentas were vacuum sealed and transported fresh from Labour and Delivery to the Pathology laboratory. Each was dissected according to protocols with three standard sections submitted for immediate formalin fixation. Placentas were then sealed under low vacuum with the Tissue SAFE system and stored at 4C for 24 hours. (8 cases) 48 hours (4 cases) and 72 hours (4 cases). H&E stained slides were independently accessed by two placental pathologists using a three part scheme of: 1) adequate, 2) less than optimal or 3) inadequate for histologic evaluation.
Results: all of the 102 H&E slides were accessed adequate for histologic evaluation. No degradation of histologic detail was noted between fresh, formalin fixed to delayed fixation after 72 hours of vacuum sealed cold storage.
Conclusion: The histologic validation of vacuum sealed human placenta allows consideration of differently designed process for tissue handling by care givers and pathologist. Potential advantages are controlled preanalytic placenta preservation up to three days at refrigerator temperature. Controlled fixation of fresh sections from each preserved placenta markedly reduces the amount of formalin (approximately one gallon /placenta) ordinarily used to fix the entire placenta before gross examination. Reduction of formalin at the front-end process of initial fixations translates to reduced back-end disposal of formalin as expensive hazardous waste. Both reductions translate to financial savings to the healthcare system. In Labour and delivery practices, this may eliminate formalin and formalin exposure from the unit. Additionally most placentas require disposal and vacuum-sealing of individual specimens provides for a safe isolation and disposal avoiding a fetid waste disposal receptacle be maintained in the Labour and Delivery unit.
The use of vacuum sealing and cold preservation of Human placentas in Labour and Delivery is a disruptive technology that advances three improvement opportunities.
a. No formalin in L&D is required to transport placentas to lab
b. Safe isolation of remaining placentas in sealed bags for waste disposal or return to patient (if requested)
a. Controlled pre-analytic specimen preservation variables
b. Controlled formalin fixation times in lab
Avoidance of formalin disposal as expensive formalin hazardous waste
Additional publications cite the preservation of Nucleic acid in Vacuum sealed surgical pathology specimens. The study was developed to understand impact of transportation of specimens using vacuum sealed and refrigerated specimens. Formalin is a universal fixative in surgical pathology however it is highly toxic and 1B carcinogen. Use requires diligent care to protect staff from unnecessary exposure. The concern with eliminating formalin from the surgical suite is the ultimate impact on the ability to perform all needed pathological studies. The study cited was developed to address this concern.
Design: 15 surgically resected specimens from colon, lung and uterus were selected for the study. Specimens were sealed in plastic bag under vacuum and transported at 4C. These were compared to samples that were collected and snap frozen at -80C and samples that were prepared as Formalin fixed paraffin embedded tissues.
Results: H&E stained sections from all samples showed optimal histologic preservation. The yield of extracted DNA and RNA was adequate with good purity for both the fresh and FFPE tissues.
H&E stained sections form all the FFPE samples showed no significant morphologic artifacts with optimal histologic preservation.
Data suggests that the DNA integrity is very well preserved even after 3 hours of vacuum sealing of the surgical specimens without formalin fixation. RNA integrity was marginal in the FFPE with the delay in fixation while there was no significant decline in the fresh specimen cohort at any time point. Vacuum-based preservation of surgical specimens is a viable, molecular friendly and environmentally -safe option for tissue transport to the laboratory.
The numerous experimental and clinical studies of formaldehyde exposure has convinced governmental organizations and institutional facilities to implement measures for monitoring formaldehyde exposure. While there are calls to restrict or even eliminate use of formaldehyde use, the value of formaldehyde as the universal fixative in anatomic pathology suggests that it will continue to be in use for the immediate future. The value of SealSAFE and TissueSAFE to both Histology and Surgical staff is an effective and immediate solution to address and reduce formalin exposure.
Formalin spills that can occur when transporting specimens in plastic containers that leak or break will result in increasing the surface area of the formalin. Formalin gas evaporation depends more on square surface area than the volume of formalin spilled. This means a small spill can result in a higher exposure than normally occurs under normal handling. Exposure levels of exceeding the short term exposure limit of 2ppm for a 15 -minute exposure can easily occur with comparatively small volumes requiring clean up by trained personnel and evacuation of patients and staff while clean up occurs.