MIT scientists have developed a new technique that measures growth of many individual cells simultaneously, an advance that could lead to rapid tests for antibiotics and other drugs.
The technique offers new insights into growth variation across single cells within larger populations, and helps track the dynamic growth of cells to changing environmental conditions, researchers said.
It uses an array of suspended microchannel resonators (SMR), a type of microfluidic device that measures the mass of individual cells as they flow through tiny channels.
A novel design has increased throughput of the device by nearly two orders of magnitude, while retaining precision, said professor Scott Manalis from Massachusetts Institute of Technology (MIT) in the US.
The researchers used the device to observe the effects of antibiotics and antimicrobial peptides on bacteria, and to pinpoint growth variations of single cells among populations, which has important clinical applications.
Slower-growing bacteria, for instance, can sometimes be more resistant to antibiotics and may lead to recurrent infections, researchers said.
“The device provides new insights into how cells grow and respond to drugs,” said Manalis.
Manalis and colleagues first developed the SMR in 2007 and have since introduced multiple innovations for different purposes, including to track single cell growth over time, measure cell density, weigh cell-secreted nanovesicles, and, most recently, measure the short-term growth response of cells in changing nutrient conditions.
All of these techniques have relied on a crucial scheme: One fluid-filled microchannel is etched in a tiny silicon cantilever sensor that vibrates inside a vacuum cavity.
When a cell enters the cantilever, it slightly alters the sensor’s vibration frequency, and this signal can be used to determine the cell’s weight.
To measure a cell’s growth rate, researchers could pass an individual cell through the channel repeatedly, back and forth, over a period of about 20 minutes.
During that time, a cell can accumulate mass that is measurable by the SMR.
However, while the SMR weighs cells 10 to 100 times more accurately than any other method, it has been limited to one cell at a time, meaning it could take many hours, or even days, to measure enough cells.
The key to the new technology was designing and controlling an array of 10 to 12 cantilever sensors that act like weigh stations, recording the mass of a cell as it flows through the postage-stamp-sized device.
Between each sensor are winding “delay channels,” each about five centimetres in length, through which the cells flow for about two minutes, giving them time to grow before reaching the next sensor.
The research was published in the journal Nature Biotechnology.