Automating 3-Dimensional Histology (3D Histo)




Background & Clinical Need Currently, conventional histology relies on the examination of 2-dimensional 4 µm tissue sections, which leads to limited sampling of tissue. In skin cancers, margin assessment is carried out by sampling surgical margin using 2-dimensional sections, but only a limited proportion of about 0.1% is examined. This leads to high false negative rates and a higher recurrence of cancer, with a 5-year recurrence rate of 4.1-10.1% for basal cell carcinoma, a type of skin cancer. We propose to improve the false negative rates and to disrupt current histo (pathological) approach by using tissue optical clearing and three-dimensional volumetric imaging (3D Histo) which will permit us to examine the entire specimen, minimising false negative rates. 3D Histo involves steps which can be automated, thereby reducing the need for trained manpower, improving consistency and accuracy of sample preparation process and throughput. Aim We are building a novel modular tissue processor for semi-automation of 3D Histo sample preparation processes (permeabilization, immunostaining, optical clearing). Significance We intend to introduce this novel tissue processor for Research Use Only (RUO) market in initial phase to first validate our approach; eventually implement 3D Histo within clinical setting. We anticipate the tissue processor to reduce reliance on trained manpower and improve 3D Histo sample throughput.  Prototype is in development and we intend to file a patent application for the tissue processor design, eventually licensing it to company for production. We are seeking partners who are dealing with research products (especially in equipment), that maybe interested in taking the tissue processor prototype forward for commercialization, by manufacturing and/or marketing the technology.


The tissue processor is currently in development, but it will have the following features: A processor through which different types of buffers (aqueous, organic solvents) can be pumped in and removed while leaving the tissue intact. A one-stop solvent-compatible tissue processor for the processes of fixation, permeabilization, immunostaining and optical clearing without the need for tissue transfer. Pressurisation of the tissue processor to speed up solvent infusion into tissue, improving efficiency of the 3D Histo process. A detachable portion for easy mounting onto the microscope.


Primary Application Area Research use only (RUO) market for organoids, 3D whole organ immunostaining and optical clearing. The 3D Histo technique is of great interest to many academic laboratories around the world, and start-ups have been funded overseas to pursue the development of 3D histology in internal organs using serial thick sections or whole tissue. The RUO market also has lower barriers to entry in comparison to the clinical diagnostics market, and there is potential for the tissue processor prototype to be applied and validated in preclinical studies using a wide variety of tissue types. Microscope core facilities are our potential customer target, as they will be involved in promoting and improving the uptake of whole tissue imaging techniques in research laboratories. Other Application Area Clinical histopathology laboratories to aid in disease diagnosis. Potential Products for Development Immunostaining-linked products, optical clearing linked products, imaging-linked products, image analysis products. Estimated Market Size Our target market is the global pathology market, which was valued at 16.82 billion in 2017, and is projected to reach 32.91 billion by 2025 with a compound annual growth rate of 8.53%.


Better and more accurate diagnostic tool to reduce false negative diagnoses – allow examination of the whole specimen, instead of 0.1%-0.2% (16 3µm-thick slices of 3 cm specimen) providing 100-200 times more information. Potential development of modular product pipeline – 3D Histology involves multiple steps, and products and solutions can be developed for each 3D Histology step.