DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Lab-on-Chip (LOC) Platform for Assessment of Extracellular Matrix (ECM) Stiffness

Posted August 28, 2020

Sophie Leliѐvre, D.V.M., Ph.D., LL.M., Purdue University

Dr. Sophie Leliѐvre
Dr. Sophie Leliѐvre

The extracellular matrix (ECM) provides structural support for cells in almost all organs in the body. Increased stiffness in the breast ECM has been associated with an increased risk in the development of breast cancer, suggesting that structural changes in the breast ECM play a role in cancer development. Because standard 2D cell culture models do not allow for accurate modeling of ECM stiffness, a variety of polymer-based hydrogels have been developed for use in 3D modeling techniques. Existing technologies for measuring ECM stiffness in these 3D models are typically either destructive or expensive, making them unsuitable for use in long-term small-scale applications, such as the lab-on-chip (LOC) platform, used for measuring mechanical property changes in the microenvironment of cells in 3D culture. With Breast Cancer Research Semipostal and Breast Cancer Research Program funding, Dr. Leliѐvre and her team, including collaborator Dr. Rahim Rahimi, have developed a novel LOC platform that uses ultrasonic waves to quantify changes in ECM stiffness in real time. The device prototype has been developed, and initial cell viability assessments have been performed. Mammary stromal fibroblasts were embedded in 1.5% w/v agarose gel within the LOC and exposed to the ultrasonic wave signal over a 24-hour period. After 24 hours, there was no significant change observed in cell phenotype and no significant difference in the percentage of cells that underwent apoptosis, or cell death, compared to controls. Dr. Leliѐvre and her team also demonstrated the capacity of the device to measure dynamic changes in stiffness of the 3D polymer in a non-destructive manner, while simultaneously allowing visualization of the cultured tissue. Since cells appear to remain viable in the LOC under continuous exposure to ultrasonic waves within the platform, the team hopes to use this technology to create a risk-on-a-chip (ROC) platform that can be tailored to different risk factor(s) of interest, resulting in a personalized assessment of breast cancer risk, and to ultimately help clinicians identify potential prophylactic approaches for breast cancer patients. This novel platform also has implications for drug screening, providing a means of analyzing the impact different therapeutics have on tumor microenvironments and whether they have potential protective effects against breast cancer risk.

Zareei A, Jiang H, Chittiboyina S, et al. 2020. A lab-on-chip ultrasonic platform for real-time and nondestructive assessment of extracellular matrix stiffness. Lab Chip 20(4):778-788.

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Last updated Friday, August 28, 2020