A new technique invented at MIT can precisely measure the growth of many individual cells simultaneously. The advance holds promise for fast drug tests, offers new insights into growth variation across single cells within larger populations, and helps track the dynamic growth of cells to changing environmental conditions.
The technique, described in a paper published in Nature Biotechnology
, 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.
‘The reduced recording time, at which the device measures cell growth is critical in testing antibiotics or antimicrobial peptides against bacterial infections in clinical settings as that makes an important difference in the survival of patients.’
The paper's senior author, MIT professor Scott Manalis, and other researchers have been developing SMRs for nearly a decade.
In the new study, 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.
"The device provides new insights into how cells grow and respond to drugs," says Manalis, the Andrew (1956) and Erna Viterbi Professor in the MIT departments of Biological Engineering and Mechanical Engineering and a member of the Koch Institute for Integrative Cancer Research.
In one experiment using the device, the researchers observed the effects of an antibiotic, called kanamycin, on E. coli. Kanamycin inhibits protein synthesis in bacteria, eventually stopping their growth and killing the cells.
Traditional antibiotic tests require growing a culture of bacteria, which could take a day or more. Using the new device, within an hour the researchers recorded a change in rate in which the cells accumulate mass. The reduced recording time is critical in testing drugs against bacterial infections in clinical settings, Manalis says: "In some cases, having a rapid test for selecting an antibiotic can make an important difference in the survival of a patient."
Similarly, the researchers used the device to observe the effects of an antimicrobial peptide called CM15, a relatively new protein-based candidate for fighting bacteria. Such candidates are increasingly important as bacteria strains become resistant to common antibiotics. CM15 makes microscopic holes in bacteria cell walls, such that the cell's contents gradually leak out, eventually killing the cell.
However, because only the mass of the cell changes and not its size, the effects may be missed by traditional microscopy techniques. Indeed, the researchers observed the E. coli cells rapidly losing mass immediately following exposure to CM15. Such results could lend validation to the peptide and other novel drugs by providing some insight into the mechanism.
The researchers are currently working with members of the Dana Farber Cancer Institute, through the MIT/DFCI Bridge program, to determine if the device could be used to predict patient response to therapy by weighing tumor cells in the presence of anticancer drugs.