# A microED pipeline for the pharmaceutical and biotechnology industry

> **NIH NIH R44** · NANOIMAGING SERVICES, INC. · 2022 · $683,728

## Abstract

Project Summary/Abstract
Microcrystal electron diffraction (microED) is an emerging structure determination technique of high interest to
the pharmaceutical and biotechnology industries. MicroED can rapidly determine atomic-resolution structures
from microcrystals with minimal sample requirements. The goal of this Phase II proposal is to develop and deliver
robust service offerings for microED structure determination to the commercial sector. Improvements to critical
steps in this workflow will enable analysis for any suitable sample type while offering a level of efficiency that
meets the requirements of Structure-Based Drug Design (SBDD) and medicinal chemistry programs. The
permissive sample requirements, minimal time requirements, and high-quality structures generated make
microED an attractive structure determination technique with broad applications for small molecules, peptides,
natural products, proteins and protein-drug complexes. An efficient microED pipeline will help to reduce the cost
of drug development and reduce the time it takes a drug to make it into the clinic.
MicroED uses a transmission electron microscope (TEM) to collect diffraction data from small crystalline
samples. The steps required include transferring crystalline samples to TEM grids; collecting a series of
continuous-rotation, electron-diffraction datasets from single crystals; processing the diffraction data and refining
the atomic model. An initial development phase demonstrated collection of excellent quality diffraction datasets
for more than 20 samples, and the ability to deliver atomic resolution maps suitable for addressing the needs of
our pharmaceutical clients who took part in alpha and beta testing. New methods will be developed, and existing
approaches optimized to improve every step of this pipeline, substantially increase throughput, and improve final
maps and models. Specific aims include: (1) Optimizing TEM grid preparation to ensure the transfer of a sufficient
number of high-quality target microcrystals onto the grid substrate without damaging them or altering their
properties. (2) Developing an automated, high-throughput data collection system capable of unattended,
overnight data acquisition for multiple different samples, and of providing information to inform data scaling and
determining handedness of chiral small molecules. (3) Automating and improving data processing, phasing and
model refinement including real-time data reduction, brute force on-the-fly phasing, and investigating a wide
range of new programs and methods.
In parallel with the Phase II research plan, a full commercial service offering spanning the complete range of
microED capabilities will be developed.

## Key facts

- **NIH application ID:** 10402253
- **Project number:** 5R44GM140666-02
- **Recipient organization:** NANOIMAGING SERVICES, INC.
- **Principal Investigator:** Jessica Fox Bruhn
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $683,728
- **Award type:** 5
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402253

## Citation

> US National Institutes of Health, RePORTER application 10402253, A microED pipeline for the pharmaceutical and biotechnology industry (5R44GM140666-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10402253. Licensed CC0.

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