Smith's quantum-dot research illuminating cancer biology
MNTL faculty researcher Andrew Smith wants to better understand the fundamentals of cancer biology, and to develop a new generation of diagnostic and prognostic tools for doctors who treat the disease. His tool of choice? Quantum dots, which are engineered nanoscale semiconductor particles that produce fluorescent light when attached to molecules and diseased cells.
“With single-molecule imaging, you can find diseased cells, understand why they’re different from normal cells, and see how they respond to drug treatment,” said Smith.
In one project, Smith and his students are collaborating with researchers at the Mayo Clinic to enhance a tissue-assessment process known as fluorescent in situ hybridization (FISH), which pathologists use to conduct clinical biopsies on potentially cancerous tissue samples.
According to Smith, the process has its limitations. “In a tumor, there can be 5-10 genetic mutations in the same cell, but [FISH] can only assess one or two of them simultaneously,” Smith explained. “It’s a big problem because you only get a small amount of tissue from a patient and there’s only so much you can do.”
Smith proposes a new approach: replace the conventional FISH probes with new probes made from quantum dots designed in his lab. If successful, the Mayo researchers may someday be able to examine multiple DNA sequences from a single tissue sample. In the process, Smith and his team hope to advance the field of quantitative pathology.
Currently, pathologists rely on qualitative measures like cell shape and patterns to diagnose cancer. “The human eye can only pick up so many sets of patterns,” Smith noted. “We want to make the pathology field quantitative by associating molecular and numerical metrics to everything.”
The quantum dots that Smith designed are made of a zinc, cadmium, and selenium alloy, giving them some unique properties. First, they can emit color independent of the size of the particle, which is not the case for conventional quantum dots. Second, they are small enough (5-10 nm) to maneuver between proteins and DNA in a cell, making them more comparable in size to the dyes used in conventional FISH probes.
“The core of the dot dictates the wavelength of emission, the first shell dictates how much light will be given off, and the outer shell dictates the efficiency of light emission,” said Smith, describing his novel design.
In another collaborative project, Smith is working with fellow MNTL faculty researcher Kris Kilian and Dr. Partha Ray, an oncologist at the Mills Breast Cancer Institute in Urbana, IL. The team is investigating the interaction between tumor cells and macrophage cells, which are a type of white blood cell that normally destroys cancer in the body.
Kilian uses a novel micropatterning technique to make complex diseased tissues that Smith probes with the quantum dots, allowing them to observe the signaling that occurs between the cells, and shedding light on how the cancer overtakes the immune system cells. The ultimate goal is to grow patient-specific tumors in the lab and accurately predict how the cancer may progress and then use that knowledge to develop a therapy to treat it.
Smith is also working with fellow bioimaging faculty on a College of Engineering Strategic Research Initiative project to develop the next-generation of single-molecule sensing tools that are inexpensive, easy to use, can have a high-throughput format, and can provide test results quickly.
On the education front, Smith is developing a new undergraduate course in molecular and cellular statistics to help students bridge the gap between statistical theory and the tools they need to use in their research. He’s participating in the Cancer Scholars Program, which is an applications-driven approach to undergraduate education. And he is a Co-PI on an NSF-fundedResearch Experience for Undergraduates (REU) Site called Discoveries in Bioimaging.