# "Grid-Tape": A High-Throughput Platform for Brain Connectomics and Nanoscale Structural Analysis

> **NIH NIH R44** · LUXEL CORPORATION · 2021 · $477,629

## Abstract

The wiring diagram of brain circuits is one of the foundational and fundamental questions of modern
neuroscience. Since the connectivity of these circuits critically influences their function, understanding the
structure of these networks will have a major impact on understanding their role in health and disease. The
primary challenge is extracting a circuit-sized volume at synaptic resolution, which requires large-scale electron
microscopy imaging of thousands of sections of brain tissue. Until now, the slow speed of tissue sectioning and
imaging has been a major limitation to the field of connectomics, requiring many years to acquire a dataset of
this size. GridTape™, developed in Phase I, removes this bottleneck by allowing fast automated imaging of
thousands of sections on a continuous tape inside a transmission electron microscope (TEM). This new reel-
to-reel sample substrate leverages inherent speed and resolution advantages of camera-based TEM to provide
higher data acquisition rates with lower cost than scanning electron microscope (SEM) alternatives. In Phase I,
GridTape™ achieved a longstanding goal for connectomics with the successful acquisition of a cubic mm
volume at 4 nm resolution, yielding a dataset of more than 2 petabytes. The data spanned 26,500 serial
sections split between seven reels of GridTape™, and was imaged with five TEM microscopes running in
parallel for six months at an effective imaging rate of 500 Mpixel/s. While the best multi-beam SEM alternative
can achieve 3X the imaging rate of a single TEM with GridTape™, the cost is roughly 20X higher ($4-6M) and
only a few multi-beam SEMs currently exist in the world; this drives the economics of volume-EM heavily in
favor of an approach using multiple cheaper TEMs in parallel with GridTape™. With feasibility clearly
demonstrated, Luxel will partner with Harvard in Phase II to improve a number of data quality issues for
GridTape™. The technical challenges include reducing the background image noise from intrinsic structure in
the support films, reducing costs for the thin film coating, mitigating image artifacts that arise from tissue cracks
and folds, and expanding the film-covered slot areas to allow larger tissue samples without breakage. We plan
to achieve these goals by developing alternative low-noise polymer films that also offer manufacturing
scalability benefits including faster substrate removal. We will partner with connectomics researchers at
Harvard and the Allen Institute to determine optimal tissue block preparation formulas and methods to maintain
film tension that mitigate tissue cracks and folds.

## Key facts

- **NIH application ID:** 10219050
- **Project number:** 5R44MH112349-04
- **Recipient organization:** LUXEL CORPORATION
- **Principal Investigator:** Ryan M Smith
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $477,629
- **Award type:** 5
- **Project period:** 2017-06-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219050

## Citation

> US National Institutes of Health, RePORTER application 10219050, "Grid-Tape": A High-Throughput Platform for Brain Connectomics and Nanoscale Structural Analysis (5R44MH112349-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10219050. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*