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UIC publishes first review of novel graphene-based liquid cell electron microscopy

Photo of PhD candidate Seyed Ghodsi and Professor Tolou Shokuhfar

Researchers at the University of Illinois Chicago have put together the first comprehensive review article of a novel imagining technique that they say could be a key to unlocking new discoveries in life and material sciences.

Seyed Ghodsi, a Richard and Loan Hill Department of Bioengineering Ph.D. candidate in Associate Professor Tolou Shokuhfar’s In Situ Nanomedicine Laboratory at UIC, is the first author on the Small Methods article, which looks at the working principals, opportunities and challenges surrounding graphene-based liquid cell electron microscopy.

Transmission electron microscopy (TEM), which uses a beam of electrons sent through a thin specimen to form an image, has been around for decades. But as Ghodsi points out, the traditional TEM technique requires the sample material to be in an ultrahigh vacuum within a microscope column. This made it extremely difficult for researchers to image materials and biological structures in a liquid environment because the vacuum causes liquids to boil.

To get around this challenge, and to help prevent the electrons from damaging biological tissue, researchers designed a graphene-based liquid cell (GLC) technique. This technique involves sealing the liquid inside the TEM microscope in a capsule made with an extremely thin layer of graphene. The graphene sheets are made up of a few layers of graphene with an overall thickness of less than 1 nanometer. For scale, Ghodsi noted a human hair is approximately 100,000 nanometers wide.

“This is the first time scientists can look into the live cell with an atom-resolution microscope,” Ghodsi said.

In addition to the high resolution, TEMs also use spectroscopy, the study of the interaction between matter and electromagnetic radiation, to see a more complete picture of what is being imaged.

“The JEOL ARM-200F is equipped with ultra-high energy, resolution spectroscopy tools, which gives you the capability to see spot by spot, atom by atom, what elements you have in the sample and what is the composition of the sample in that specific point,” Ghodsi said.

The GLC technique was first described in a paper in 2012 by material scientists who were looking at how the nucleation and growth of materials happens within a solution, according to Shokuhfar. After reading about the initial research, she had the revelation that the new technology could be used to study minerals in the human body. The GLC’s ability to protect liquid samples has opened a wide range of medical research opportunities.

“My aim was to now look into the human body, which does have a lot of minerals in it,” Shokuhfar said. “We are made of Earth elements a little bit, with most elements being very essential to our bodies. But even those that are essential can become toxic if they are accumulated or not reserved or formed in a physiology condition.”

Shokuhfar’s research team has already investigated the development of kidney stones within similar conditions to what is found in the human body. She noted this research could be used to develop preventions that stop the process before it needs to be treated with medical procedures or drugs. Her lab is also looking into how the body stores and uses iron, which has been implicated in neurological disorders such as Alzheimer’s and Parkinson’s disease, and the mineralization processes associated with cholesterol in the body.

“Not many people have looked into these diseases from the angle we are looking at,” Shokuhfar said. “From the very fundamental understanding of how these minerals in the human body are formed and what is their role in certain types of diseases. It has been said we are from Earth, and nobody has really looked at that nonorganic matter and these minerals really do play an excessive role in those diseases.”

In addition to summarizing the current GLC research landscape, Ghodsi and his co-authors also offer up potential avenues for future research into the technology. His recommendations include studying the behavior of electrodes during battery cycling to help improve their performance, developing a GLC apparatus capable of housing liquids that can flow, and increasing the understanding of how confining samples inside the GLC impacts their behavior.

“This whole GLC concept is very new, it’s still in its embryonic stage,” Ghodsi said. “It is going to bloom much more than it is now.”

The other authors of this review article include Constantine Megaridis, distinguished professor with the Department of Mechanical and Industrial Engineering at UIC, and Reza Shahbazian‐Yassar, an associate professor with the Department of Mechanical and Industrial Engineering at UIC.

Learn more about Shokuhfar’s research at

By David Brazy, UIC