# Development of 3D interferometric super-resolution methods for imaging dynamic, multi-component molecular systems, in single cells and in multi-cellular environments

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $377,972

## Abstract

ABSTRACT
Understanding how cell-cell communication and collective cell phenomena shape cell function and cell fate
decisions requires the ability to follow the detailed molecular processes as they take place inside live cells, with
the cell remaining embedded in its natural setting of the tissue and organism of origin. Although tremendous
progress has been made in imaging of single isolated cells, the requirements for probing crowded multi-cellular
systems with high spatio-temporal resolution and down to single-molecule sensitivity present an enormous
challenge for optical microscopy. Here we propose to tackle this challenge, using recent breakthroughs to i)
increase the capability of extracting high-resolution information from weak fluorescence signals – using 3D
interferometry; ii) image fragile/delicate biological samples using optimized configurations - based on selective-
plan illumination; iii) maintain/recover high resolution information through optically inhomogenous samples –
using adaptive optics. We hypothesize that successful synthesis of these three key technologies will create
new approaches that cross into previously uncharted realms of combined spatio-temporal resolution, detection
sensitivity, non-invasiveness and penetration depth. Based on these ideas we propose the following two
specific aims: (1) To develop multi-color volumetric 3D interferometric imaging, based on reliable, artifact-free
optical reconstructions, for increasing the ability to extract high-resolution information from weak fluorescence
signals; (2) To achieve non-invasive, background-free, long-term 4D imaging, at ~100nm near-isotropic 3D
spatial resolution, at millisecond acquisition times and over large and highly crowded (multi)cellular volumes.
The new techniques will significantly increase our abilities to interrogate dynamic biological processes with
molecular detail, in single isolated cells as well as in intact complex multi-cellular systems, thus having
widespread and immediate impact across biomedical disciplines.

## Key facts

- **NIH application ID:** 10022131
- **Project number:** 5R01GM135545-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alexandros Pertsinidis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,972
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022131

## Citation

> US National Institutes of Health, RePORTER application 10022131, Development of 3D interferometric super-resolution methods for imaging dynamic, multi-component molecular systems, in single cells and in multi-cellular environments (5R01GM135545-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022131. Licensed CC0.

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