Cell Sciences Imaging Facility Adds Resources to Help Researchers Use Bio-Atomic Force Microscopy

Atomic force microscopy (AFM), which uses a tiny, sharp probe to map surfaces down to the nanoscale, has long been a valuable tool for materials engineers to quantitively understand the surface morphology and mechanical, electrical, magnetic, and thermal properties of their samples.

More recently, that technology is increasingly being used by biologists as well, to image, characterize, and manipulate molecules, cells, biomaterials, and tissues.

To help biologists and other researchers make the best use of that technology, the Beckman Center’s Cell Sciences Imaging Facility (CSIF), with the help of several recent grants, is now providing additional staff assistance and training for researchers, including educational materials specifically for biologists, and has installed a new state-of-the-art bioatomic force microscope (bio-AFM).

Bioatomic Force Microscopy Is Fundamentally Unlike Optical Microscopy

Bioatomic force microscopy (bio-AFM), which is able to image in native environments and with correlated fluorescent-capable optics, can provide insight into the mechanics of cells and tissues, biomolecular nanostructures, cell and biomolecule interactions, and the binding force of single molecules, among other things.

But bio-AFM is fundamentally unlike optical microscopy methods and is less familiar to biologists. Moreover, finding educational materials on the technology that are geared toward biologists, rather than engineers, is difficult.

“We had a bio-AFM instrument installed in the CSIF satellite facility at the Shriram Center about eight years ago,” says CSIF director Jonathan Mulholland. “But there were several obstacles to the successful use of that instrument by biologists. We really lacked the technical expertise to leverage the bio-AFM for common use.”

CSIF, in collaboration with the Stanford Nano Shared Facilities (SNSF) and others, is now changing that.  

New Staff Member Nadia Makarova, PhD, Provides Bio-AFM Expertise and Training

With funding from the Stanford Community of Shared Research Platforms (C-ShaRP), Mulholland, working with Christina Newcomb, PhD, in the SNSF, hired Nadia Makarova, PhD, who has deep expertise in bio-AFM. While Dr. Makarova has a PhD in mechanical engineering, her graduate work at Tufts University was in cancer mechanics. She also worked at a Tufts-based startup company that aims to create the first AFM-based clinical diagnostics test—a test that focuses on characterizing the surface of cancer cells.

“I realized during that time that not only am I passionate about atomic force microscopy, but I also really like teaching people,” says Dr. Makarova, who joined CSIF in October 2023. “This opportunity to support and educate biologists in bio-AFM really appealed to me.”

Dr. Makarova is producing a series of videos, soon to be available on the Stanford edX website, that will teach scientists the basics of using AFM, including guidance specifically for biologists. She has also created a training program and materials to help those who are ready to start using the equipment, and provides one-on-one personalized training, support, and guidance to groups working on bio-AFM projects.

“Our goal is to not only make our educational resources available to the Stanford community, but to people outside of this institution as well,” says Dr. Makarova. “We want to introduce what AFM is and guide people on what it can do for them.”

Since joining Stanford, Dr. Makarova has collaborated on a wide range of AFM projects, ranging from characterizing bacteria cell membranes to the mechanics of bioink aggregates and even the fruit fly gut. 

“I believe AFM in biology holds immense potential for new discoveries, so I’m really trying to get the word out on the diverse set of things that it can do,” says Dr. Makarova.

State-of-the-Art Bio-AFM Instrument Is Installed at the Shriram Center

Danielle Mai, PhD, assistant professor of chemical engineering, secured funding—from the Office of Naval Research through the Defense University Research Instrumentation Program (DURIP)—to purchase CSIF’s newest bio-AFM. The state-of-the-art JPK NanoWizard V Bioscience AFM was installed in the CSIF satellite facility at the Shriram Center in June 2024.

The new instrument, Dr. Makarova and Mulholland say, is much more user-friendly then earlier devices, has automated features, and offers the latest advances in bio-AFM technology. Fully correlated optical images are now a matter of point-and-click in the software, and the device is the first AFM on the Stanford campus able to capture dynamic molecular processes in vivo, with new fast scan technology.

With a second C-ShaRP grant received this year, CSIF will also be adding additional features to the new instrument, such as a specialized stage to make imaging normally tricky tissue and other sticky or rough samples more robust.

“This will really let our biologists get more advanced imaging and extended capabilities,” says Mulholland.

To learn more about CSIF’s resources and how to schedule training or time on instruments, visit https://microscopy.stanford.edu.