Fighting Cancer Using Graphene-based Early Detection Techniques

Spotlight on Kriti Agarwal

Meet Kriti Agarwal. Kriti is a doctoral candidate working on improving detection times and analysis of cancer-causing DNA mutations using big data and mathematical techniques. She is conducting her research under the guidance of ECE faculty Prof. Jeong-Hyun Cho.

A recipient of two fellowships and several other honors recognizing her research, Kriti’s path to excellence in research began in India. Raised by academic parents, who emphasized the value of education and exploration, Kriti earned her bachelor’s degree in electronics and communication from Manipal Institute of Technology, India. Work beckoned after graduation, and Kriti joined IBM as an engineer, quickly making her way up as project lead. But even as Kriti was rising through the ranks at IBM, she began to feel restless, and yearned for new challenges. In her search for a new path, Kriti went back to her undergraduate roots, where as a student of engineering, she was introduced to nanotechnology. And while she was always interested in the area, it now struck an exciting chord within her.

Kriti is working on developing innovative mathematical techniques that can improve cancer detection, and eventually disease prognosis.

Kriti started toying with the idea of a career in research, particularly in nanotechnology, and applied to the University of Minnesota, drawn by its reputation in nano-based research. When she arrived at the department, she sought out Prof. Cho, intrigued by his 3D micro and nano engineering research group, and requested a tour of his lab. The tour clinched it for Kriti; she had found her calling. And after careful vetting by Prof. Cho, she became a member of his research team.

Kriti’s Research

Currently, Kriti is working on developing innovative mathematical techniques that can improve cancer detection, and eventually disease prognosis. Working with other researchers in Prof. Cho’s lab, she has developed a novel liquid biopsy method that is capable of detecting DNA mutations. However, along the way, Kriti has accomplished several firsts, and introduced many innovations, starting with fabricating three-dimensional incarnations of the typically two-dimensional structure of graphene.

Why 3D Graphene?

Kriti found that when planar 2D graphene nanoribbons are curved to form 3D cylindrical graphene nanotubes, changes are introduced in the near-field enhancement.

When disease causing DNA mutations take place, there is a corresponding modification in the proteins, which makes detection and analysis of proteins critical for diagnosing diseases, as well as for predicting the prognosis. The Fourier transform infrared spectroscopy (FTIR) method can provide vital information about the structure of biological specimens, besides molecular vibrations, hydrogen bonds, chemical composition, and other characteristics that serve as disease markers. However, there is a significant mismatch between the wavelength of incident infrared light, which is on the micrometer scale, and the size of the proteins, which are on the nanometer scale. The mismatch leads to low levels of light absorption and the resulting peaks in the frequency spectrum are barely discernible. The situation presents a need for a technique that can bridge the mismatch.

Enter graphene. With its unique optical, chemical, and other properties, this wonder material is being widely used in and tested for a number of medical and biological applications. When light on the microscale wavelength falls on nanoscale graphene it causes the surface electrons in graphene to oscillate, a phenomenon called surface plasmon resonance (SPR). The graphene plasmons confine the incident light to its surface and enhance the weak energy density due to spatial constrictions. However, limiting the near field (a region of the electromagnetic field around an object) to only the surface of graphene as in the case of 2D graphene-based sensors presents a new challenge. The proteins under observation cannot retain their structure and biological functions if immobilized on 2D graphene. Also, the area of confinement of light is so small that at low molecular concentrations it can take more than twenty-four hours for the specimen to diffuse to the graphene surface.

In her search for a suitable solution, Kriti found that when planar 2D graphene nanoribbons are curved using a process much like the Japenese art of Origami to form 3D cylindrical graphene nanotubes, changes are introduced in the near-field enhancement. The SPR in the fabricated graphene nanotubes offers a stronger confinement of the incident light throughout the enclosed volume, increasing the electric field by six orders of magnitude. Thus, any molecules flowing within the tube are detected with sensitivities in the picomolar range (the concentration of a solution is conveyed by its molarity, and a picomole is a trillionth of a mole).

Kriti uses mathematical techniques for analysis of the data gathered through this liquid biopsy technique. Through methods such as finite element modeling, the spectroscopy measurements will be verified, and deconvoluted, tracking frequency changes for each cancer DNA mutation that takes place as a result of changes in the vibrations of molecular bonds within the DNA specimen.

As Kriti’s research progresses, the deliverable she seeks is a fast, real-time, highly sensitive liquid biopsy technique of circulating tumor DNA (ctDNA) that is capable of detecting multiple mutations simultaneously. Ultimately, Kriti hopes to create a library of sorts, where such changes in structure and composition, i.e. mutations, are correlated to changes in the spectrum, which can aid in accurate and faster disease diagnosis.

Recognition for her work

Kriti believes that the liquid biopsy technique she is working on, once realized, could substantially improve diagnosis, treatment options, and disease prognosis.

Kriti’s research is gaining recognition, and she is the recipient of multiple awards and honors. She recently received a UMII MnDrive graduate assistantship for 2019-2020, for her work on cancer detection via an innovative liquid biopsy technique based on big data and mathematical methods. Previously, she was the recipient of the Louise T. Dosdall fellowship (2018 – 2019). The fellowship is awarded to women graduate students in the natural or physical sciences and engineering, who hold superior academic records and show professional promise. She also received the Best Poster award at the fall 2018 meeting of the Materials Research Society for her poster, “Geometrical Modification of Hybridized Plasmon Modes in 3D Graphene Nanostructures.” She was one of twenty other recipients from the 2,640 poster entries at the meeting.

Kriti’s other awards and honors include:

Best poster award runner-up at 2018 American Vacuum Society Minnesota Chapter Annual Symposium and Vendor Exhibition.
• Best poster award (3rd place) at 2018 Annual Retreat and Conference organized by the Institute of Engineering in Medicine, University of Minnesota.
• Best poster award at Material Research Society Fall Meeting, November 2017, awarded to 20 posters out of 2500 participants.
• Best poster award at Material Research Society Spring Meeting, April 2015, awarded to 11 posters out of 1900 participants.
• Materials Research Society poster exchange fellowship, 2015 to attend International Materials Research Congress at Cancun, Mexico in August 2015.

Kriti’s research could have far reaching impact. The American Cancer Society estimated 1.7 million new cancer cases in the United States, and approximately 600,000 cancer related deaths in 2018. It is increasingly common for us to have a personal story of dealing with the disease and its aftermath. Despite advancements in treatment options, mortality rates remain high due to delayed detection of the disease owing to reasons such as poor healthcare accessibility, and complications associated with biopsies. Kriti believes that the liquid biopsy technique she is working on, once realized, could substantially improve diagnosis, treatment options, and disease prognosis, especially for people living in non-urban and remote areas. And we are rooting for Kriti all the way!

Learn more about Prof. Jeong-Hyun Cho’s research lab