The Problem

Current gold standard techniques are 100 years old and rely on the analysis of 2D thin section FFPE (~5-10 micron). Spatial and morphological analysis of the tissue microenvironment is highly limited. 2D is destructive, slide-based, non-digital, is variable, and highly manual and does not represent the entire biology.

A Single City Block vs. All of Manhattan

The Solution

See more biology in 3D. Bringing CLARITY to the complexity of your 3D histopathology models.

CLARITY

 

CLARITY is an acronym for Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging / Immunostaining / in situ-hybridization-compatible Tissue hYdrogel)

CLARITY tissue clearing embeds tissue in a hydrogel matrix. Lipids are cleared to create an optically transparent hybrid that is transparent to light and permeable to molecules. Scientists can then add molecular markers to highlight specific features for further imaging and analysis.

 

  • Compatible with previously frozen, fresh, formalin-fixed, and FFPE embedded tissue
  • Compatible with traditional pathology work flow methods
  • Non-destructive, fewer samples, allowing recapitulation of spatial heterogeneity without laborious sectioning and registering
  • No dehydration/rehydration steps involved as with FFPE samples, or other clearing technologies
  • Compatible with standard nucleic acid and antibody interrogation techniques
  • Allows multiple interrogations of a single sample to increase 3D biomarker information
  • Samples can be stored for future biomarker analysis
  • Imaging compatibilities include: Confocal, Light Sheet, SPIM

The CLARITY Tissue Processing Work Flow is Simple

Input Tissue

Mouse, Rat, Human
Fixed • Fresh • Frozen • FFPE

Hydrogel Embedding
Hydrogel Embedding a Tissue using CLARITY tissue clearing method - ClearLight Biotechnologies
Tissue Clearing Fluorescent multiplexing
3d Image Analysis

Machine Learning/AI

Publications

  1. 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. Nature: Scientific Reports, (2019)
    9:5624.
  2. Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, Vesuna S, Evans K, Liu C,   Ramakrishnan C, Liu J, Nolan GP, Bava FA, Deisseroth K. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science. 2018 Jul 27;361(6400)
  3. Gradinaru V, Treweek J, Overton K, Deisseroth K. Hydrogel-tissue chemistry: principles and applications. Annual Review of Biophysics, 2018 May 20;47:355-376.
  4. Hsueh B, Burns VM, Pauerstein P, Holzem K, Ye L, Engberg K, Wang A-C, Gu X, Chakravarthy H, Arda HE, Charville G, Vogel H, E mov IR, Kim S, Deisseroth K. Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease. Sci Rep. 2017 Jul 19;7(1):5899.
  5. Deisseroth K. A look inside the brain. Scientific American, 2016 Sep 20;315(4):30-37
  6. Sylwestrak EL, Rajasethupathy P, Wright MA, Jaffe A, Deisseroth K. Multiplexed intact-tissue transcriptional analysis at cellular resolution. Cell. 2016 Feb 11;164(4):792-804
  7. Chung K, Deisseroth K. CLARITY for mapping the nervous system. Nature Methods. June 2013. 10(6):508-13.
  8. Structural and molecular interrogation of intact biological systems. Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AJ, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, and K Deisseroth. Nature 497, 332–337 (16 May 2013).

Posters

Abstract #4690: Sharla L. White, Yi Chen, Qi Shen, Laurie J. Goodman. Multi-sample automation of the
CLARITY technology for the processing of 3D volumes of tissue. AACR Annual Meeting, March 29-April 3,
2019, Atlanta, GA. [Download] [PDF]

Abstract #351: Three-dimensional (3D) Imaging of Biomarkers in Human Core Needle Biopsies of Normal and Cancerous Breast Tissue. Yi Chen, Qi Shen, Laurie J. Goodman, Yesim Gokmen-Polar, Sunil Badve. SABCS Annual Meeting, Dec 4-8, 2018, San Antonio, TX.  [Download] [PDF]

Abstract 5915: Three-dimensional, 3-D, multiplex imaging of biomarkers in tumor tissue. Sharla L. White, Sarah McCurdy and Laurie J. Goodman. AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  [Download] [PDF] 

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