“Active Loading” Technology Speeds up Single Cell Drug Testing Devices

High-tech devices that flow cancer cells over a miniaturized “scale” to measure changes in the weight of single living cells are increasingly being used to test the susceptibility of cancer cells to different drugs. The devices are so sensitive that they can measure a change in growth rate of a cell within hours or days after it has been exposed to a drug—an indicator of the drug’s ability to slow the cancer cell’s growth.

Such devices are being developed and tested in collaborations between the MIT Department of Biological Engineering, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital. The clinical intent of these systems is to help choose effective therapies and avoid exposing patients to unnecessary drugs that will have no effect on their disease. As the devices begin to make their way into clinical use, scientists are working to improve them.

Keith Ligon, MD, PhD.
Keith Ligon, MD, PhD.

 One challenge has been that live cancer cells are often floating in a confusing mix of dead cells and debris when being measured in such devices. Previously, scientists would push cells along with the debris through the pipes of the device in order to get a measurement. But the debris often caused the system to clog, and time was wasted measuring debris instead of the cancer cells scientists intended to measure. This type of problem is more common than many engineers and researchers like to admit.

Recently, a team from Dana-Farber and MIT reported in Nature Communications on a new way to approach this problem. Their device streams living cells through fluid-filled channels in a device for weighing cells called a serial suspended microchannel resonator (sSMR). Scott Manalis, PhD, of MIT, and Keith Ligon, MD, PhD, of Dana-Farber Oncologic Pathology, term their new approach “active loading.” They explain that the advance comes from having a computer rapidly look at the size and shape of cells and other objects as they flow through the channel. When the computer sees an object that doesn’t look like a cell, it quickly spits it out and moves to the next object, saving valuable time.

In describing the advantage of the system, they said, “By applying active loading to the sSMR, we show that cancer cell growth can be measured from a dilute concentration of only a few cells per microliter in three hours. In contrast, the same number of measurements used to take us more than three days.”

They deployed the active loading method in a preclinical setting where they assessed patient samples from normal brain as well as primary and metastatic brain cancers containing difficult-to-measure mixture of cells and confounding biological debris. The new approach worked so well that they were able to get drug measurements from these complicated samples in a timeframe that suggests such devices could be used in the clinical setting for the first time.