Even if you are not a scientist or an engineer, you have probably heard of “cellular dynamics”. For a long time, scientists and bioengineers have been interested in studying cell-specific responses to different forces. Different techniques use various forces — such as mechanical force in atomic force microscopy and optical force in optical tweezers — to measure deformation of cellular structures. Combined with other diagnostic technologies, these cellular-level analyses can lead to better understanding of disease progression, such as cancer development and metastasis. But although these techniques can analyse different biophysical properties of cells, they suffer from low throughput and high cost.
Over the past decade, various research teams have demonstrated high-throughput quantification of human cancer cell deformability by exploiting developments in microfluidic systems. However, many of those studies relied on constricting microchannels in which physical contact with cells is inevitable. This in turn, can result in measurement inaccuracy arising from even minimal changes in device fabrication. In addition, a narrowing channel can be destructive to cells when they pass through. Overall, most of these systems fall short on analysing cell deformation independent of the cell size.
To enable contact-free cell manipulation and measurement of compressibility-dependent effects, some researchers have utilized a microfluidic acoustophoresis technique. In this approach, flow of cells is controlled through a microfluidic channel; the flow is then stopped and a transducer generates an acoustic field. Consequently, cell displacement influenced by the acoustic wave is recorded. While exciting, this approach is time consuming because the cells needs to be flushed in each round as they must be stationary when measuring their displacement.
Researchers in the US and China have now developed a new acoustofluidic cytometer that can measure cell deformation independent of cell size and achieve higher throughput analyses. In this continuous-flow cell mechanotyping method, cells are introduced into the acoustic field at a constant position and their movement through to the exit position is controlled by the acoustophoretic force (Lab on a Chip 10.1039/C8LC00711J).
The continuous flow and contact-free microfluidic inlets decouple the cell size-dependent effects, as cells with different sizes, densities and compressibility (i.e., different biophysical properties) experience different acoustophoretic forces. Analyses are performed using existing mathematical equations that relate acoustic radiation force to the densities of the cell and medium, as well as the compressibility of the cell.
The researchers, led by Arum Han from Texas A&M University and Han Wang from Tsinghua University, developed this label-free and non-invasive acoustofluidic cytometer to enhance single cell mechanotyping methods based on cells’ intrinsic biophysical properties. They used the device to measure the biophysical properties of different cancer cell lines under continuous flow. They then took advantage of the cells’ displacement to analyse single cell acoustophoresis-based deformation.
“The developed system can be used in a variety of applications, such as phenotyping of cancer cells with different metastatic potential based on their biophysical properties, …and even for analysing erythrocytes with regard to malaria infection,” say the authors.
