A Study of 3D Microenvironments Provides Physicians with More Complete Information
From a patient’s perspective, when a doctor orders a biopsy of a tumor, the more information that a single sample can provide, the easier it is on the patient. And when that data comes from a sample analyzed in 3-D rather than 2-D, the information about the tumor and its microenvironment will be much more complete, providing the doctor with a bigger picture. An interdisciplinary Notre Dame team has recently developed a microfluidic device that will, as Jeremiah Zartman, assistant professor of chemical and biomolecular engineering, points out, “take diagnosis to a higher dimension,” providing a three-dimensional view of the distribution of cells and proteins in the sample.
Traditional methods for testing biopsies use a slice of sample tissue thin enough for light to pass through — effectively two dimensional — so that once stains are applied it can be examined with a conventional microscope. A few markers can be studied for a single sample, and additional biopsies are necessary to test for more markers. The new device encapsulates a 3-D block of sample tissue, roughly twenty times the thickness of a conventional slice. Clearing the stain from a 2-D sample is time consuming; the device allows the 3-D sample to remain in place and be cleared quickly and restained multiple times—offering the advantage of using the same sample for repeated tests and thus avoiding challenges related to using different samples for each test. A detailed picture of the sample evolves, using material from a single biopsy rather than several. More complete information is expected to translate into a more effective treatment plan for the patient.
The project, “Microplex-Lab-on-a-Chip: High-Throughput Characterization of Breast Tumors and the 3D Microenvironment In Situ,” was recently submitted to the Research Like a Champion student competition at the Mike and Josie Harper Cancer Research Institute where it received an award of $12,500. Graduate student Cody Narciso and undergraduate Kyle Cowdrick, both chemical and biomolecular engineering students, submitted the project, and Zartman and Siyuan Zhang, the Nancy Dee Assistant Professor of Cancer Research, are the project’s co-mentors. Work on the device and its system of processing samples brings together the collaborative efforts of three labs, those of Zartman, Zhang, and David Hoelzle, assistant professor of aerospace and mechanical engineering. Additional seed funding was recently awarded through Notre Dame’s Advanced Diagnostics and Therapeutics Initiative in a project entitled: “3D Reconstruction of Tumor Biopsies: an Nth-Dimensional Imaging Approach for Next Generation Diagnostics.”
Involved in fabricating and testing the devices, Narciso points out that chemical and biomolecular engineering functions like a bridge, translating the toolkit of skills possessed by chemical and biomolecular engineering students and applying them to solve outstanding research questions in biology in new ways. This is one example of how chemical and biomolecular engineers shine in collaborative and interdisciplinary research, bringing a fresh perspective to the problems at hand. In addition to the benefit of 3-D analysis, because the project’s microfluidic device uses smaller quantities of expensive reagents, it can provide abundant data at a lower cost than the traditional method which require large amounts of reagent.
Still in its early stages, theoretically the device could be used in testing any type of tissue biopsy, not only those involving cancer. In more immediate terms, the automated staining system that is used in processing the tissue samples can be applied in working with other lab samples. This collaborative project, one of many within chemical and biomolecular engineering, brings together faculty, researchers, and students from different disciplines to apply traditional engineering approaches in new ways to solve critical problems that affect people everywhere.