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###### Department of Health and Human Services

###### National Institutes of Health

# AGENCY:

National Institutes of Health, HHS.

# ACTION:

Notice.

# SUMMARY:

The invention listed below is owned by an agency of the U.S. Government and is available for licensing to achieve expeditious commercialization of results of federally-funded research and development.

# FOR FURTHER INFORMATION CONTACT:

                        Licensing information may be obtained by communicating with Vidita Choudhry, Ph.D., Office of Technology Transfer and Development, National Heart, Lung, and Blood Institute, 31 Center Drive Room 4A29, MSC2479, Bethesda, MD 20892-2479; telephone: 301-594-4095; email:                         *vidita.choudhry@nih.gov.*                         A signed Confidential Disclosure Agreement may be required to receive any unpublished information.                    

# SUPPLEMENTARY INFORMATION:

Technology description follows.

## Apparatus for Cryogenic-Electron Microscopy Sample Preparation

Cryo-Electron Microscopy (cryo-EM) is used to obtain high-resolution structural images of macromolecular structures. Samples must be purified and loaded onto cryo-EM grids before imaging. The ideal cryo-EM grid consists of particles that are evenly and richly distributed in a broad distribution of orientations throughout the holes of the support film. Current techniques to prepare cryo-EM grids are performed manually and require trial and error, resulting in a bottleneck in cryo-EM workflows.

Researchers have developed a device and method for time-resolved preparation of liquid samples for cryo-EM experiments. In particular, the mixing and dispensation of liquid samples is achieved by electrical signals that are transduced into specific acoustic frequencies to mix the liquid samples (low frequency) and then dispense the mixture (high frequency) in small, nanoliter volumes onto a cryo-EM grid. This novel apparatus and method provides more precise control over liquid sample mixing and dispensing, and improved dispensation of the mixture onto the EM grid. Also, the improved quality of captured images of homogeneous macromolecular structures is achieved due to a uniformly mixed and dispensed sample on the EM grid. This allows electrons to be transmitted through the very thin liquid film in the holes of the cryo-EM grid to form an image.

### Potential Commercial Applications

    - Automation of cryo-EM experiments aimed at Structure-based Drug Design by examining macromolecular structure and its interactions with ligands.
    - Kits with hardware and software components to setup robotic automation of cryo-EM sample preparation, dispensation, plunging and storage.

### Competitive Advantages

    - Automated workflow eliminates the guesswork out of cryo-EM sample preparation.
    - Increases sample prep success rate and decreases the need to screen repeated trials.
    - Using acoustic-based, multiple-sample mixing enables homogeneous mixing and facilitates the observation of transient molecular interactions with high time resolution.
    - Python code is available for command and control of a robot that manipulates the cryo-EM grid.       ( print page 58591)      

### Development Stage

    - Prototype.

### Inventors

Venkata M. Dandey (NIEHS), Mario J. Borgnia (NIEHS), Wyatt Peele (NIEHS), Tony J. Huang (Duke), and Kaichun Yang (Duke).

### Intellectual Property 

HHS Reference No. E-184-2023-0; U.S Provisional Patent Application 63/472,113 filed June 09, 2023.

### Licensing Contact 

                    Vidita Choudhry, Ph.D.; 301-594-4095;                     *vidita.choudhry@nih.gov. This notice is made in accordance with 35 U.S.C. 209 and 37 CFR part 404.*

Dated: August 22, 2023.

Vidita Choudhry,

Senior Technology Transfer Manager, National Heart, Lung, and Blood Institute, Office of Technology Transfer and Development.

[FR Doc. 2023-18438 Filed 8-25-23; 8:45 am]

BILLING CODE 4140-01-P