In 2016, two graduate students, one in aerospace engineering and the other in medical engineering, joined a Caltech effort to invent a new approach to cancer treatment. Over the next four years, with faculty support, they modeled and tested the approach, called oncotripsy, and proved and improved its ability to kill cancer cells in petri dishes.
Before joining Caltech as a Keck Institute for Space Studies fellow, Schibber works as an aerospace engineer in Argentina. Knowing that satellites can break apart if launches rattle them at the same rates at which they naturally vibrate, she makes models to find their resonant frequencies.
Mittelstein, who is pursuing an MD/PhD degree, wants to see a project through from idea to implementation. At first, with support from Caltech’s Andrew and Peggy Cherng Department of Medical Engineering, the biomechanical engineering student works on an ongoing prosthetic heart valve project in the lab of Mory Gharib (PhD '83), Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering.
Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering Michael Ortiz and graduate student Stefanie Heyden (PhD ’14) theorize that, because cancer cells differ in shape, size, and stiffness from healthy cells, their resonant frequency differs, too. So, precisely tuned pulses of ultrasound might shake them until they catastrophically break, while leaving nearby cells healthy.
Schibber’s vibration-stress research applies so well to oncotripsy that she pivots from aerospace to biomedicine, eager to see what she can add. Gharib joins the project and recalls that Mittelstein wanted an idea-to-implementation opportunity. Mittelstein jumps at the chance and soon invites one of his professors, ultrasound innovator and professor of chemical engineering Mikhail Shapiro, to the group.
A grant from what is now the Rothenberg Innovation Initiative (RI2) enables both Mittelstein and Schibber to focus on the project. As the research begins to show promise, it gains further funding from Amgen and the Caltech–City of Hope Biomedical Research Initiative.
In Shapiro’s lab, and with Gharib’s guidance, Mittelstein develops a strategy and an experimental setup to target individual cells in petri dishes with controlled pulses of ultrasound. When City of Hope investigators join the project, he builds a testing instrument for them too. Together, they bring practical experimental and medical insight to the project.
Schibber models ultrasound frequencies, intensities, and pulse rates to find combinations that could kill cancer cells. Mittelstein provides feedback on the clinical practicality of the proposed combinations and conducts experiments to see how they actually affect cells. To enable faster iterations of experiments, Schibber invents and validates a vastly streamlined model.
All three professors—Gharib, Shapiro, and Ortiz— meet with the students often to analyze results. The students discover that the ultrasound kills cancer cells by wearing down their repair mechanisms, not by causing acute failure. The team publish results showing that oncotripsy can destroy leukemia, lymphoma, and breast- and colon-cancer cells floating in petri dishes.
All three professors—Gharib, Shapiro, and Ortiz—meet with the students often to analyze results. The students discover that the ultrasound kills cancer cells by wearing down their repair mechanisms, not by causing acute failure. The team publishes results showing that oncotripsy can destroy leukemia, lymphoma, and breast cancer and colon cancer cells floating in petri dishes.
Now beginning her engineering career at Saint-Gobain Research North America, Schibber believes her versatility helped her stand out to a company that addresses problems across aerospace, the life sciences, medicine, construction, and energy.
When he leaves Caltech to finish his MD degree, Mittelstein remains close to the project as the Caltech–City of Hope team advances oncotripsy into solid tumors and beyond the petri dish.