# Non-cleaved Electro-Mechanical Expansion (NEME) technology for super-resolution imaging of biological samples with conventional optical microscopes

> **NIH NIH R00** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $249,000

## Abstract

Abstract
Understanding the nanoscale organizations of biomolecules in complex biological systems such as the brain, can not only
provide fundamental biological insights but also help in the discovery of new targets and technologies for treating
diseases. Optical microscopy provides a convenient way for imaging biological samples using readily available
dyes/antibodies. However, the spatial resolution of conventional optical microscopes is limited to 300 nm due to the
diffraction of light waves. On the other hand, existing super-resolution optical techniques, face challenges in scalability to
thick tissues and require extremely expensive hardware, which limits their application. Recently discovered expansion
microscopy (ExM), which is based on physically expanding the sample (embedded in a swellable gel) by about 4.5 x and
thus, achieving an effective resolution of 70 nm, is scalable and compatible with conventional optical hardware. But, its
resolution of 70 nm is not sufficient for observing subcellular structures. Though the resolution can be improved through
iterated ExM (iExM), it results in low biomolecular yield as it requires transfer of biomolecules from one gel to another,
with the cleaving of the first gel. The proposed work aims to develop a technology for expansion, where gel cleaving or
transfer of biomolecules is not required, resulting in high biomolecular yields. This technology utilizes both electrostatic
and mechanical forces for expansion to achieve high expansion factors (20x to 100x), thus leading to 300 / 20 ≈ 15 nm to
300 / 100 ≈ 3 nm resolution. This technology, which I termed non-cleaved electro-mechanical expansion (NEME) is
different from previous expansion technologies which utilizes only electrostatic forces for expansion. The mentored phase
of the proposed work will involve the development and characterization of the NEME technology while in the
independent phase, NEME will be extended for imaging of dense protein complexes as well as RNA and DNA. NEME
technology can lead to super-resolution imaging without any specialized or expensive hardware and can also provide high
biomolecular yields and scalability to thick tissues. Thus, it can greatly benefit simultaneous characterization of super-fine
biomolecular structures and large 3D biological systems.

## Key facts

- **NIH application ID:** 10176530
- **Project number:** 5R00GM126277-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Deblina Sarkar
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-04-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176530

## Citation

> US National Institutes of Health, RePORTER application 10176530, Non-cleaved Electro-Mechanical Expansion (NEME) technology for super-resolution imaging of biological samples with conventional optical microscopes (5R00GM126277-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176530. Licensed CC0.

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