Cell detachment model for an antibody-based microfluidic cancer screening system

In the quest to detect more types of cancers at ever earlier stages, researchers have been stymied by a lack of cell surface markers that distinguish in a clear-cut manner between healthy and malignant cells.

Often, these efforts attempt to find markers whose levels differ greatly between healthy and malignant cells, but such markers have proven elusive. Using a computer modeling approach, researchers at Texas Tech University have shown that microfluidics may be able to identify malignant cells based on different levels of given markers.

Jordan Berg, Ph.D., and his colleagues approached this problem as one of optimizing small differences in the ability of antibodies to bind to and release from cells containing varying levels of a given tumor marker on their surfaces. Presumably, cells with higher levels of the marker would bind more often to an antibody immobilized within the channels of a microfluidics device than would a cell with lower levels of the marker. As a result, cells with a higher level of the marker – malignant cells, for example – would move more slowly through the device than would healthy cells that had lower levels of the marker. These differences can be small, though, so the operating parameters of the microfluidics device would have to be near perfect to separate cells based on small differences in antibody binding.

To determine what those operating parameters should be, the investigators crafted a computer model for cell transport through a microfluidics device loaded with an antibody to a marker known as æ6 integrin, which is present in higher levels in cells infected with human papillomavirus (HPV), the cause of almost all cases of cervical cancer, as well as some other types of tumors.

The results of this modeling effort, which the investigators published in the journal Biotechnology Progress, revealed that flow rate was the critical operating parameter that needed to be carefully controlled to maximize the discrimination between healthy and malignant cells expressing this antigen on their surfaces. The researchers showed, too, that they could use the model to analyze cell movement through the device and generate a quantitative measure of HPV infection.

This work is detailed in a paper titled, “Cell detachment model for an antibody-based microfluidic cancer screening system.” This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website. View abstract.