SEP 12, 2016 11:06 AM PDT

Microchip Can Precisely Measure Growth of Single Cells in a Group

WRITTEN BY: Carmen Leitch
Researchers at MIT have created a new device that allows for the measurement of the growth rate of many individual cells at the same time. Publishing in Nature Biotechnology, the investigators have improved upon an existing device, the suspended microchannel resonator (SMR), which is a microfluidic device that measures individual cell mass as the cells migrate through small channels. The senior author of new work is MIT professor Scott Manalis, and he has been working on refining these devices for almost a decade. The last improvement increases throughput while retaining accuracy.
 

The SMR was first created in 2007, and since then has been modified for a variety of uses, such as the one seen in the video above, tracking the growth of a single cell over time. Other innovations include measuring the density of cells, seen in the video below, as well as weighing nanovesicles secreted by cells and measuring short-term growth rates in cells subjected to variable nutrient levels.
 

The latest device can be used to determine the impacts of antibiotics or antimicrobial compounds on bacteria as well as isolating variations in growth of individual cells within a larger population. That observation could translate into clinical applications; such as if slower growing bacteria indicate resistance to antibiotics and cause recurrent infections.

“The device provides new insights into how cells grow and respond to drugs,” explained Manalis, the Andrew (1956) and Erna Viterbi Professor in the MIT departments of Biological Engineering and Mechanical Engineering as well as a member of the Koch Institute for Integrative Cancer Research. Manalis continues, “In some cases, having a rapid test for selecting an antibiotic can make an important difference in the survival of a patient.”

The SMR devices are based on a design in which a silicon sensor, etched with a microchannel, vibrates within a vacuum. When a cell enters the channel, the vibration frequency of the sensor changes, and that change can be used to determine the weight of the cell. A growth rate can thus be measured by passing a cell through that microchannel over and over as the mass changes were recorded. However, the sensitivity was not perfect.

The latest technology was designed to control an array of 10 to 12 sensors, each weighing the cell as it passes by, and giving the cell enough time to grow or shrink before reaching the next sensor.
 
A schematic of the SMR is shown here / Credit: MIT

In their research, the investigators measured roughly 60 mammalian cells and 150 bacteria per hour, while single SMRs can only a few cells in that time. “Being able to rapidly measure the full distribution of growth rates shows us both how typical cells are behaving, an­­d also lets us detect outliers — which was previously very difficult with limited throughput or precision,” explained Nathan Cermak, a recent PhD graduate from MIT’s Computational and Systems Biology Program.

“We can reliably resolve changes of less than one-tenth of a percent of a cancer cell’s mass in about 20 minutes. This precision is proving to be essential for many of the clinical applications that we’re pursuing,” added Selim Olcum, a research scientist in the Koch Institute at MIT.

Currently, the scientists are collaborating with researchers at the Dana Farber Cancer Institute to determine if the device could be used to evaluate how patients might respond to therapy by measuring the weight of tumor cells after anticancer drug treatment.
 
Source: MIT News, Nature Biotechnology
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