# A Single Entity Method for Controlled Nucleation and Crystal Growth

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2023 · $364,499

## Abstract

The structures of biomacromolecules at atomic resolution (< 2.0-2.5 Å) are of enormous importance to
understand their physiological functions and roles in diseases. An exemplary critical need of high atomic
resolution is to resolve the location of proton/hydrogen which plays vital roles in various biological processes.
Deuteration renders neutron scattering techniques unique advantages in high contrast (signal/background) to
locate D/H. Like X-ray crystallography which has contributed majority of known biomolecule structures, high
quality single crystals are the prerequisites for both X-ray and neutron data collection. It is worth mentioning that
despite the recent progresses in electron microscopy techniques, true atomic resolution remains a formidable
challenge to achieve. Lower resolution structures are associated with ambiguity and could mislead basic
biomedical research as well as drug design/development applications. With the understanding on the
fundamental limitations and technical hurdles associated with currently adopted ensemble-based methods, we
propose to develop a single-entity method (named NanoAC) which will offer unprecedented capability to
synthesize crystals one at a time, under real-time monitoring and with predictive crystal quality. A single nanotip
will be employed to spatially confine supersaturation as the sole nucleation site. Electroanalytical and optical
methods will monitor the whole crystallization process in real-time to capture quantitative signatures for the
nucleation and crystal growth at single entity resolutions. Those signatures will enable active controls in kinetic
transitions, and be quantitatively correlated with its diffraction quality and/or crystal habits. The insights will inform
crystal synthesis such that nucleation kinetics and growth rates of each individual crystal will be finetune to
improve crystal quality and to tune crystal size/habits. Prototype soluble proteins, nucleic acids and membrane
proteins will be used as defined in this early-stage technology development program. The new toolbox, once
established, will provide paradigm-shift capabilities to improve the crystal quality in diffraction and size/habit
controls, to tackle challenging material systems currently not-crystallizable, and also feature high efficiency in
time and/or materials. The overarching goal will be pursued through three interrelated aims. Aim 1 will establish
real-time monitoring signatures for the generalization of NanoAC to crystallize soluble biomacromolecules and
complexes. Aim 2 will correlate diffraction quality and crystal habits with monitoring signatures. Aim 3 will further
develop single nanopipettes as ‘magic wand’ to crystallize membrane proteins.

## Key facts

- **NIH application ID:** 10720470
- **Project number:** 1R01GM151275-01
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Gangli Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $364,499
- **Award type:** 1
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720470

## Citation

> US National Institutes of Health, RePORTER application 10720470, A Single Entity Method for Controlled Nucleation and Crystal Growth (1R01GM151275-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10720470. Licensed CC0.

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