ClearLight Biotechnologies, Sunnyvale, Calif, has announced publication of the first peer-reviewed manuscript describing the efficacy of the company’s Clarity lipid-clearing technique for tissue specimens.1 The company is developing an automated instrumentation platform based on the Clarity technology, which was originated by company founder Karl Deisseroth, MD, PhD, a professor of bioengineering and of psychiatry and behavioral sciences at Stanford University.
The Clarity technique enables the transformation of a tissue specimen into a nanoporous, hydrogel-hybridized form that is crosslinked to a three-dimensional (3-D) network of hydrophilic polymers. The process produces a fully assembled, intact tissue that is permeable to macromolecules and optically transparent, thus allowing for robust 3-D imaging of subcellular components (DNA, RNA, and proteins) and analysis of heterogeneous cellular interactions within the microenvironment of the tissue. Paired with proprietary 3-D image analysis software, the technology will enable more-accurate analysis and assessment of normal and diseased tissue.
Current technologies used for preclinical research and clinical drug development in cancer are largely dependent upon two-dimensional (2-D) analysis of thin sections (5–10 µm) of formalin-fixed, paraffin-embedded (FFPE) tissue. To accurately predict the outcomes of immunotherapy drugs, however, it is important for researchers to understand cellular phenotypic information in combination with the 3-D spatial analysis of tissues. The recently published study describes the use of the novel Clarity method to process and immunolabel breast cancer core needle biopsies, followed by 3-D quantitative analysis of a nuclear proliferation marker, Ki67.
While the study found overall concordance with the gold standard technique, the 3-D tissue specimens processed using the Clarity technology revealed variation in intratumoral Ki67 expression that was not evident in individual 2-D FFPE sections. The team also demonstrated the compatibility of the Clarity method with archived FFPE samples, establishing early feasibility for use in processing retrospective clinical samples with associated clinical outcome data. The work provides a foundation for future large-scale clinical sample processing and nondestructive 3-D analysis of tumor tissue by the Clarity method.
“The currently commercially available techniques provide limited spatial data by the multiplexed analyses of a thin (5 µm) section of tissue,” explains Sunil Badve, MBBS, professor of pathology and laboratory medicine and director of the translational genomics core at the Indiana University School of Medicine. “The Clarity technology holds promise to revolutionize spatial analysis by enabling 3-D analysis of thick (up to 1000 µm) tumors, to achieve more biologically relevant information regarding tumor heterogeneity and key spatial relationships in the tumor microenvironment.”
“By partnering with the team at Indiana University’s Melvin and Bren Simon Cancer Center, we have been able to work with world-renowned experts in the clinical and translational field, while greatly advancing our platform development program,” adds Laurie Goodman, PhD, CEO of ClearLight Biotechnologies. “We look forward to future collaborative work to establish the clinical utility of the technology.”
For further information, visit Clearlight Biotechnologies.
- Chen Y, Shen Q, White SL, Gokmen-Polar Y, Badve S, Goodman LJ. Three-dimensional imaging and quantitative analysis in Clarity processed breast cancer tissues. Sci Rep. 2019;9(1):5624; doi: 10.1038/s41598-019-41957-w.