Pathronix has developed an innovative tissue processing technology that will revolutionize the operation of pathology labs. It will provide doctors and patients with faster, more efficient, and more accurate diagnoses at unparalleled levels. Ultrapath processes fresh tissue samples from biopsies using variable microwave exposure and vacuum. Through the procedures described, tissues are treated with chemicals, heated, and embedded into wax-filled cassettes that are cut and mounted onto glass slides, ready for examination. Quicker processing promotes lab efficiency and early treatments. Having high quality specimens will lead to a better understanding of disease causes and cures, directly benefiting patients and healthcare systems everywhere. Rapid-processing technologies are changing the way pathology labs operate and are allowing for diagnoses that are faster and more accurate than ever before. Automation has become an indispensable tool to enhance diagnostic accuracy and streamline laboratory workflows.
Challenges
Tissue processing used to be a time consuming and error-prone process when done manually. Tissue processors have automated and streamlined the process, but current models still take 8-16 hours to complete the many rounds of filtration and extractions.
Turnaround Time
The time it takes for pathology labs to complete their reports is an important indicator of their performance. Only 76% of pathology cases are reported and verified within two days, which does not meet the industry standard of 90%. For cancer, early diagnoses are crucial to prevent exponential cellular growth and spreading to other organs. Increasing tissue processing efficiency would streamline lab workflows.
Environmental and Health Risks
Tissue samples decompose upon removal from the body due to lack of blood supply and oxygen, accumulation of metabolic products, autolytic enzyme activity, and bacterial putrefaction. Further, the tissue is too soft to cut, and does not have enough optical contrast for clear morphological examination. Formalin is currently the gold standard for fixative reagents. Formalin is a hazardous chemical, and its toxicity is well-documented – it triggers severe allergic reactions (difficulty breathing, asthma attacks), respiratory irritation, headaches, and burning of the eyes. It is a skin irritant, a carcinogen, and can be fatal if ingested. Formalin has negative effects on aquatic organisms and water quality.
Xylene is used as a clearing agent in tissue processing due to its chemical properties and high refractive index. Repeated short-term exposure to xylene causes cardiovascular, hepatic, respiratory and neurological effects. This compound has also been shown to cause damage to aquatic ecosystems. These compounds must be omitted from tissue processing for the safety of medical personnel and the environment.
Immunohistochemistry
Formalin fixation causes cross-linking of proteins. It also freezes cellular components in their current conformation. This prevents the cellular degradation that would ensue if processes could continue, in the absence of fixation. Immunohistochemistry (IHC) is a type of staining widely used to diagnose cancers. It identifies tumour-specific antigens in tissue. Standard tissue processing methods are known to cause inaccurate, off-target IHC staining, which leads to incorrect diagnoses. In the absence of formalin, antigen detection would be preserved, and the quality of results improved. Pathronix aims to resolve these issues with Ultrapath, a tissue processing system that uses rapid flow-through processing and embedding techniques to produce high quality tissue specimens.
Solutions
Quality
The temperature-controlled chambers of Ultrapath prevent tissue damage caused by overheating, or ‘hot spots.’ The system uses low temperatures to preserve structural integrity and prevent degradation. Ultrapath is designed to consistently use high purity paraffin for each processing run, which is conserved and cycled until it is automatically detected to be contaminated. At this point, the paraffin is discarded. A major drawback of using formalin is its interference with IHC staining because it masks epitopes. Because Ultrapath works in the absence of formalin, it eliminates the need for an antigen retrieval step prior to IHC staining. The native structure of cellular DNA and RNA will also be preserved, now allowing for a wide range of molecular-level tests post-processing to be possible. Ultrapath produces the highest quality specimens, increasing pathologist certainty in their diagnosis decisions due to high quality images. It also minimizes room for error; for example, the mislabeling of a cell block or cross contamination between samples. This standardization of cell preservation and embedding contributes to valid and replicable diagnoses and quality scientific research.
Green
Ultrapath eliminates the use of toxic xylene and formalin, which are currently the industry standard for tissue processing. Its reagents are safe, preventing health risks to the operator and alleviating environmental stress. The containers are sealed to promote user safety and avoid spills.
Efficient
Ultrapath is the most efficient tissue processor. It can process tissues ranging from thicknesses of 1x1x1 mm to 20x15x5 mm. Tissue types include fatty, kidney, brain, muscles, liver, breast, and skin. It processes all of these types and dimensions at the same time. Even fatty tissue, which has previously been a significant challenge. Ultrapath uses variable microwave power and vacuum, and is fully automated to control temperature, pressure, and fluid level. It has a user-friendly interface, archives process data, and operates by the push of a single button. The system can process pre-fixed tissue in 90 min, unfixed tissue in 120 mins, and bone in 3-48 h.
Economic
Ultrapath is the most cost-effective system for tissue processing because it only uses four reagents, reduces technician labor, and has the shortest processing time. The system requires only four reagents, so the cost of replacing reagents per week will be reduced by 20%, leading to sizable savings long-term. The space saved from having fewer tanks allows laboratories to save on warehouse and shipping costs. Technician labor costs are reduced by 50% due to high-speed processing. Technician errors at the pre-analytical phase will be reduced by 70%, by eliminating the need for tissue sorting and protocol selection.
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Quality |
Temperature-Controlled |
No ‘hot spot’ effect; no tissue damage by overheating |
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Error-Free |
Standardized protocol; mis-labeling or cross-contamination does not render sample unusable |
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DNA & RNA Preservation |
Native structure preserved; allows for molecular testing |
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Antigen Retrieval not Necessary |
No formalin, so no masking of epitopes to be reversed |
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Green |
Formalin-Free |
Formalin is a skin irritant, carcinogen, triggers respiratory irritation, headaches Negative effects on aquatic organisms and water quality |
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Xylene-Free |
Xylene causes negative cardiovascular, hepatic, respiratory, and neurological effects Disrupts aquatic ecosystems |
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Sealed Chemical System |
Prevents spillage; promotes user safety and no wasted product |
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Efficient and Error-Free |
Fast |
Pre-fixed tissue: 90 minutes (incl. fatty) Unfixed tissue: 120 minutes (incl. fatty) Bone: 3-48 hours |
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Simultaneous |
Kidney, brain, liver, breast, fatty, and skin tissues Thicknesses 1 x 1 x 1 mm to 20 x 15 x 5 mm |
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Special Tissue Types |
Processes fatty tissue without formalin; previously impossible |
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Fully Automated |
Variable cold microwave power Automatically controlled temperature, pressure, vacuum, and fluid level |
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User-Friendly |
One protocol for operation Archive process data Safer, non-toxic working conditions for lab personnel |
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Economic |
Technician Cost |
70% fewer errors made by technicians 50% less laboratory downtime, workload bottlenecks |
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Fast |
85% faster than conventional processors 45% faster than rapid microwave processors |
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Cost of Reagents |
20% cheaper reagent costs Lowered disposal costs, replacement time |
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Number of Reagents |
Only four reagents required Save on warehouse storage costs |
Ultrapath Tissue Processing Steps
The following is a description of the way Ultrapath operates:
Tissue samples are placed inside a microwave chamber that is subject to cooling cycles to prevent overheating. The chamber is filled with a fixative reagent, which is heated to a specific temperature between 40-60° Celsius. The temperature is maintained at this set point by circulating the fixative through a temperature control system. The fixative is then removed, replaced with the first dehydrating reagent, which is heated to a set temperature within the same range, and it is kept constant. The process repeats; the first dehydrating reagent is drained and replaced with a second dehydrating reagent, and then by a clearing reagent. Once the tissue samples are clearant-embedded, they are transferred into the paraffin chamber. Molten paraffin (around 60° Celsius) fills the chamber, and displaces the clearing agent from the tissue, resulting in paraffin-embedded tissue samples.
Solutions
- Provide superior light microscopy image quality.
- Eliminate formalin and xylene from the tissue processing procedure.
- Process tissues of multiple types and dimensions at the same time.
- Promote user safety by using sealed reagent containers.
- Shorten tissue processing times, reducing current procedure duration by 45-85%.
- Eliminate antigen retrieval step for proper IHC staining.
- Protect tissue structure through low temperature processes.
- Increase cost efficiency by using only four reagents, reducing technician costs.
- Reduce pre-analytical errors by eliminating tissue sorting and protocol selection errors.
Patents
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Patent # |
Country |
Date |
Description |
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PCT/CA202 0/000130 |
Canada |
December 3, 2020 |
Variable Power Cold Microwave Tissue Processor |
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Reagents |
Future Direction
The growing presence of personalized medicine in the healthcare field has led to a focus on companion diagnostics. Companion diagnostics are developed with drugs to select or exclude patients for treatment with that drug, based on their biological characteristics. A patient’s molecular profile can indicate whether they will respond or not to the therapy. These concepts have been applied to cancer treatment, and will be used increasingly in the future.
Cell and tissue analysis techniques play important roles as diagnostic and research tools in the treatment of cancer. Cancer cellular analysis requires an understanding of the complex defects in communication between cells that alter normal programs of proliferation, transcription, growth, migration, differentiation, and death. Further advances toward understanding altered cancer pathways and their interconnections may accelerate the development of molecularly targeted therapies, improving diagnosis and treatment.