# ClearScope

> **NIH NIH R44** · MICROBRIGHTFIELD, LLC · 2022 · $1,004,903

## Abstract

Combined in vivo and ex vivo three-dimensional (3D) whole-brain imaging of non-transgenic and
transgenic animal models holds the promise of novel insights into neural network connectivity patterns.
With regard to ex vivo light microscopic imaging of 3D whole-brain datasets, the best approach is brain
clearing followed by whole-brain light sheet microscopy (LSM) because of its unique combination of
speed, 3D resolving power, and low phototoxicity compared to confocal and multiphoton microscopy.
Unlike other methods, the combined brain clearing / LSM approach makes it possible to use intact tissue
and retain all intracellular connections within the brain structure. However, LSM systems commercially
available are not suitable for ex vivo light microscopic imaging of 3D whole-brain datasets in advanced
connectomics research. Recently, Dr. Raju Tomer (Dept. Biol. Sci., Columbia Univ., New York, NY)
developed light sheet theta microscopy (LSTM), essentially a unique arrangement of two light sheets
oblique to the specimen and one detection objective perpendicular to the specimen. This novel
microscope is the basis for a number of capabilities in LSTM that are not all available with any other
commercially available LSM systems. The LSTM technology has distinct advantages over confocal and
other light sheet microscopes, including the unmatched ability to image thicker tissue specimens over a
larger lateral area (XY) at higher optical resolutions, while maintaining fast imaging speed, high imaging
quality, and low photo-bleaching. This promising technology serves as the basis for this Lab to
Marketplace proposal to develop the ClearScope™, which refines and improves Dr. Tomer's original
LSTM system to create a successful commercial microscope for wide-spread adoption. The key technical
objectives for developing the ClearScope as a commercial product include creating and testing (i) a
ClearScope prototype based on an optimized microscope hardware design; (ii) novel microscope
hardware components for the ClearScope, comprising a novel chamber that contains the investigated
specimen and the immersion medium, and a novel detection objective changer; (iii) novel control and
image acquisition software for the ClearScope; and importantly, (iv) novel software that surpasses the
existing state-of-the-art technology to assemble acquired image stacks into large 3D image volumes
exceeding 10TB without need to downsample the image information. The production version of the
ClearScope will benefit the neuroscience research community, pharmacological and biotechnological
R&D, and society in general by improving understanding of neural network connectivity patterns as well
as the neuropathological underpinnings of the large-scale connectional alterations associated with
human neuropsychiatric and neurological conditions. In particular, this will result in an improved basis
for developing novel treatment strategies for complex brain diseases.

## Key facts

- **NIH application ID:** 10403446
- **Project number:** 5R44MH116827-05
- **Recipient organization:** MICROBRIGHTFIELD, LLC
- **Principal Investigator:** JACOB R GLASER
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,004,903
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403446

## Citation

> US National Institutes of Health, RePORTER application 10403446, ClearScope (5R44MH116827-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10403446. Licensed CC0.

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