# Ultra-stable, photon-efficient cryogenic super-resolution fluorescence imaging for visualizing vitrified biological samples with molecular-scale resolution

> **NIH NIH R21** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $215,825

## Abstract

ABSTRACT
Cryogenic electron microscopy (CryoEM) and cryo-electron tomography (CryoET) are powerful
techniques for visualizing macromolecular assemblies at a near-native state and in their
functional context inside cells; however the undiscriminating/non-specific contrast of such
techniques often complicates identifying regions of interest and specific molecular targets in
high-resolution cryoEM/cryoET datasets. Super-resolution (SR) fluorescence methods have
exquisite molecular specificity, but SR techniques have only achieved limited spatial resolutions
(~20-60 nm FWHM) when imaging vitrified biological samples at cryogenic temperatures. The
proposed project will create new ultra-stable, photon efficient cryogenic SR methods for imaging
vitrified biological specimens with true molecular-scale resolution (<2-3 nm FWHM), closing the
gap towards the (sub-)nanometer resolution of cryoEM/cryoET. The increased spatial resolution
will be leveraged for further development of powerful correlative light-electron microscopy
(CLEM) approaches that will ultimately enable elucidating the structural basis for many critical
macromolecular processes inside cells.

## Key facts

- **NIH application ID:** 10510195
- **Project number:** 1R21GM147769-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alexandros Pertsinidis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $215,825
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510195

## Citation

> US National Institutes of Health, RePORTER application 10510195, Ultra-stable, photon-efficient cryogenic super-resolution fluorescence imaging for visualizing vitrified biological samples with molecular-scale resolution (1R21GM147769-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10510195. Licensed CC0.

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