Stiffness-dependent separation of cells

Gautam Rangavajla

Early diagnosis of disease is always a priority in medical treatment. In general, the earlier a disease is detected and treated, the greater the patient's chance of recovery. Many diseases including cancer and pathogenic conditions such as malaria result in disease-affected cells (e.g. cancer cells or malaria-infected red blood cells) in the blood. The ablility to rapidly detect these cells can lead to better diagnoses and treatments and an improved outcome for patients. Recent research from a Georgia Tech lab has developed an innovative technique that could isolate disease cells in a fluid medium, which may lead to new tools for detecting disease cells and studying disease.

The lab of Dr. Todd Sulchek, an assistant professor in the George W. Wodruff School of Mechanical Engineering, has recently developed a new technique for separating cells based on their stiffness. A 5 mm-long device utilizing stiffness-dependent separation was designed and constructed, and is capable of continually processing 250 cells per second.

The onset of disease induces changes in various aspects of cell mechanics, such as the stiffness of the cell, or its ability to resist deformation from an external force. Stiffness-dependent separation derives from exploiting this difference in cell stiffness to isolate the cells of interest. Cancer, for example, can prompt cell remodeling into a less rigid form. By processing a quantity of a fluid (such as blood) that contains cancer cells, stiffness-dependent separation will yield a concentrated solution of the cells, known as enriched cells, which is of interest to researchers seeking to study cancer or develop new treatment methods.

Dr. Sulchek sought to develop a device capable of continuously processing and separating cells based on differences in stiffness (Fig. 1). The device consists of an input for the cell sample, two outputs for the stiff and soft cells, and the separation channel, which has numerous diagonal ridges. As the fluid containing the cell sample flows from the input through the separation channel, the diagonal ridges deform the cells as they flow across.

As a result of the deformation, the cells experience a transverse force rel- ative to their stiffness. The stiffer cells therefore experience a greater transverse force that pushes them upward in the channel. The softer channels more easily pass through the ridges, but are influenced by fluid flow patterns between the ridges, which lead to their transverse migration in the opposite direction. The outflows of the device are situated alongside the transverse edges (Fig. 1), and thus are able to selectively collect either stiff or soft cells.

Dr. Sulchek believes the advantages over current enrichment methods provided by this device can at present greatly aid researchers as a lab technique for isolating disease cells of interest prior to study. As a tool, the separation device can hasten the rate of research and potentially assist in the development of new treatments. He also hopes that this technology can soon play a role in diagnosis by lowering detection thresholds for disease as an enriched sample of cells can provide early notification that can lead to better treatment options for patients.