Led by Dr Scott Manalis, researchers from the Massachusetts Institute of Technology (MIT) in the US, developed a device that can weigh cells at resolutions six orders of magnitude more sensitive than commercial methods.
The tool, described in the latest issue of Nature, incorporates a cantilever that changes resonance frequency as cells pass through a microfluidic channels.
Dr Ken Babcock, co-author of the article and CEO of Affinity Biosensors is currently commercialising the sensor.
There are examples of using chip-based mass sensors to detect the presence of a single virus weighing as little as 9.5 femtograms (9.5x10-15g) in air or a cluster of 30 xenon atoms 7 attograms (7x10-21g) in a vacuum.
However, if the particles to be weighed are in solution the viscosity of the fluid damps the callipers resonance, leading to a loss in sensitivity .
By incorporating a channel into the device through which the cells can flow, the device can be isolated in a vacuum and this loss of sensitivity avoided, enabling the measurement of particle masses to an accuracy of 300 attograms (300x10-18g)
Central to the researcher's results was the observation that the viscous resonance damping due to the fluid in the device, was negligible compared to the intrinsic damping caused by the silicon crystal resonator itself.
"The resonator is sealed in a tiny vacuum cavity inside the chip, so there is virtually no resistance to the vibration, This lets us measure a mass change, say 10 parts in a billion, of the already very light microcantilever " said co-author Dr Thomas Burg.
This method has the advantage of allowing biomaterials to be weighed in a more natural environment, allowing the analysis of cells that would not survive in a high vacuum.
The device can be used in two ways, the first of which involves simply flowing particles through the sensor with the height of the signal depending on the position of the particles along the channel.
According to the researchers, the exact mass of a particle can be quantified by the peak frequency shift as the particle passes the apex of the resonator.
The researchers used a low flow rate of less than 10pl per second to maximise particle transit time and enable higher-resolution frequency measurements.
The other method involves using selective binding agents to adhere cells or biomolecules to the channel wall and by measuring the change in mass of the accumulated particles, the number of particles can be counted.
This method was used to calculate the concentration of goat anti-mouse immunoglobulin-gamma (IgG) molecules in a sample by immobilising anti-goat IgG antibodies on the channel walls and the researchers believe that this could be used to achieve a detection limit of 1pM for a 1 nM solution of a 30kDalton analyte.
In comparison enzyme-linked immunosorbent assays (ELISA) have detection limits down to 0.1pM but cannot provide a quantitative real-time readout of antigen binding.
They believe that the detection limit could be improved to femtomolar sensitivity by mass-labelling the adhered-particles.
The researchers believe that by labelling biomolecules with nanoparticles a variety of interesting protocols for highly specific and sensitive detection of molecules, cells, and viruses could be designed.
Immune system CD4 cells are routinely counted to monitor AIDS progression, and could be labelled in this manner to distinguish them from other cells present in a blood sample.
This could provide a cheap solution to help sufferers in developing countries where flow cytometry is not routinely available.
