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Researchers at Brown University and their collaborators have developed a new method for measuring cellular properties. The research team notes that this advancement holds significant importance, as accurately measuring changes in cell elasticity can help deepen understanding of disease mechanisms, aid in patient diagnosis, and provide more precise prognostic assessments.<\/span><\/p>\n In the case of tumors, for example, cancer cells typically become softer as malignancy increases and metastatic risk rises. Meanwhile, blood disorders such as malaria and sickle cell anemia cause red blood cells to become stiffer. Additionally, mechanical changes at the cellular level are also observed in neurodegenerative diseases, cardiovascular conditions, and chronic inflammatory diseases.<\/span><\/p>\n According to a study published in the journal\u00a0<\/span>Lab on a Chip<\/span><\/em>, the researchers have introduced a microfluidic device called a “mechanical phenotype cytometer,” designed to measure the physical size and softness of cells\u2014that is, their mechanical phenotype.<\/span><\/p>\n Graylen Chickering, a doctoral candidate in biomedical engineering at Brown University and the study’s lead author, points out that mechanical phenotyping is currently underutilized, mainly because relevant measurement techniques lag behind other methods for analyzing cellular properties.<\/span><\/p>\n Chickering explains that the “gold standard” for measuring cell softness or stiffness is atomic force microscopy. This method requires adhering cells to a surface and then testing them one by one with a tiny indenter.<\/span><\/p>\n “It’s essentially poking the cell to measure it,” Chickering says. “Imagine looking at a water balloon. If you poke the edge rather than the center, it feels different. This method is also quite slow, making it difficult to study large numbers of cells within a reasonable timeframe.”<\/span><\/p>\n In developing the new technique, scientists turned to a measurement known as “time-of-flight”\u2014the time it takes for a cell to travel through a liquid-filled microchannel.<\/span><\/p>\n “The cell essentially moves from one checkpoint to another, and we obtain timestamps at each checkpoint to determine the time-of-flight,” Chickering explains.<\/span><\/p>\n The researchers used the existing fluorescence signals from a flow cytometer (an instrument for counting and measuring cells) to determine cell size, then combined that with time-of-flight to determine cell stiffness. Softer cells migrate toward the center of the channel, where fluid flows fastest, while stiffer cells remain near the edges, where fluid flows more slowly.<\/span><\/p>\n Chickering notes that while an experienced scientist using atomic force microscopy can measure about one cell every 30 seconds, her new method can observe 60 to 100 cells per second\u2014with the potential to reach hundreds or even thousands of cells per second.<\/span><\/p>\n “Graylen’s data validate this concept, showing that cell-sized particles of different stiffnesses and sizes exhibit different time-of-flight values, which aligns with our theoretical expectations,” says study co-author Eric Darling, an associate professor at Brown University. “Compared with previous methods, this approach is remarkably clean and reproducible. Traditional methods often yield different measurements depending on how they’re performed.”<\/span><\/p>\n This achievement is the result of years of collaboration between researchers at Brown University’s Institute for Biology, Engineering, and Medicine and a team at the National Institute of Standards and Technology (NIST) in Maryland. Darling notes that Brown University provided synthetic cell-like particles well-suited for experiments, while NIST scientists designed the cytometer’s foundational structure.<\/span><\/p>\nMechanical Phenotyping: An Underutilized Tool<\/span><\/h2>\n
Cell Transit Time: A Key Measurement Metric<\/span><\/h2>\n
Cross-Institutional Collaboration and Future Applications<\/span><\/h2>\n