For the first time, researchers at the Massachusetts Institute of Technology (MIT) have found a way to measure the mass of single cells with high accuracy. The new technique, which uses microfluidics and a nanoscale device known as a cantilever, could allow researchers to develop inexpensive, portable diagnostic devices and might also offer a unique glimpse into how cells change as they undergo cell division.
Unlike conventional methods, the MIT technique allows cells to remain in fluid while they are being measured, opening up a new realm of possible applications, says Scott Manalis, Ph.D., who led the team of investigators that built this nanosize scale and published its results in the journal Nature.
In addition to weighing cells, the technology can be used to weigh nanoparticles or biomolecules. Current mass measurement methods achieve a resolution down to a zeptogram (10-21 grams) but only work with nonliving things because the procedure must be performed inside a vacuum. So, the MIT researchers decided to turn the conventional system inside out.
In the traditional method, the molecules to be weighed are placed on top of a tiny slab, or cantilever, made of silicon. The slab vibrates at its resonant frequency (the frequency at which the material naturally tends to vibrate) inside a vacuum. When a molecule sits on the slab, the frequency changes slightly, and the mass of the molecule can be calculated by measuring that change. This measurement must be performed in a vacuum to prevent air (or fluid) from interfering with the frequency of oscillation. However, cells cannot survive in a vacuum, so they must be measured in fluid, which diminishes the accuracy of the measurement.
The researchers solved this dilemma by placing the fluid containing the sample inside the silicon slab, which still oscillates within a vacuum surrounding it. The biological sample is pumped through a microchannel that runs across the slab, without impairing its ability to vibrate.
So far, the researchers have weighed particles with a resolution down to slightly below a femtogram (10-15 grams), but Manalis believes that, with refinements, the sensitivity could potentially be lowered by several orders of magnitude within a few years. "Every step along the way will open up new possibilities," he said.
Manalis is planning a collaboration with MIT colleague Angelika Amon, Ph.D., who is interested in studying how the mass density of a single cell changes as it goes through cell division. Using the new method, scientists can ultimately trap a single cell and observe it over a long period of time. Changes in mass could correlate to production of proteins, offering a new way to study what the cell does during division, Manalis said, and perhaps during uncontrolled cell division, the hallmark of cancer.
Another application of the new technology is to measure small particles, or beads. "It is important to know the size of particles used in paint, drug delivery devices, coatings, and nanocomposite materials," said Manalis, who added that the new technology could become the "gold standard" to measure these particles one by one.
This work is detailed in the paper "Weighing of biomolecules, single cells and single nanoparticles in fluid." Investigators from Innovative Micro Technology and Affinity Biosensors, both in Santa Barbara, CA, also participated in this study. An abstract of this paper is available through PubMed.