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Biosensor Acts as Modern-Day Canary in the Coal Mine

Toxicity of Nanoparticles Assessed in Real Time

The nanocanary sensor uses a quartz crystal (thin disk mounted on the metal base) to detect changes in the health of cells living in a solution of nutrients above the crystal (clear cylinder attached to the quartz).

By Edwin L. Aguirre

In the old days, canaries in cages were used in coal mines as a visual and audible early-warning system, alerting miners to dangerous buildups of toxic gases such as carbon monoxide and methane in the mine shaft. These gases would kill the bird first before affecting the miners.

A team of UMass Lowell researchers has developed a modern, high-tech equivalent of this canary warning system for use in the nanomanufacturing industry.

Called the “nanocanary,” the new ultra-sensitive biosensor is designed to assess the toxicity of engineered nanomaterials, such as carbon nanotubes (CNTs), on living cells. This is important in studying how nano-size particles affect human health and the environment as well as in the safe development of commercial nano products.

The research team includes Asst. Prof. Dhimiter Bello in Work Environment, Prof. Kenneth Marx in Chemistry, Prof. Susan Braunhut in Biology and Asst. Prof. Joel Therrien in Electrical and Computer Engineering, along with postdoctoral student Gang Wang, staff scientist Jianping Zhang and graduate students Abiche Dewilde, Anoop Pal and Malavika Vashist.

“With the nanocanary, we have demonstrated the ability to monitor the cells’ response to nanomaterials in real time,” says Therrien. “In doing so, we now have the ability to see changes in the cells that might otherwise have been missed.”

The team’s findings were published online in February in the journal Particle and Fibre Toxicology.

Sensor Uses Quartz-Crystal Technology

The sensor uses a quartz-crystal microbalance to monitor the health of cells attached to the surface of an oscillating quartz crystal. Physical changes in the cells resulting from exposure to a toxic environment are converted to an electrical signal via the piezoelectric properties of the crystal.

“Changes that are considered abnormal can be identified and used as a diagnostic tool,” says Therrien. “They often indicate the onset of cellular changes such as apoptosis, or programmed cell death, many hours before there are visible signs that can be measured by current assays. In contrast to current assays, the nanocanary’s output is continuous and in real-time.”

He says the nanocanary has a distinct advantage over other biological/chemical sensors in that it is capable of directly sensing toxicity.

“The direct sensing of toxins is arguably one of the largest unfulfilled needs that the sensor community faces,” says Bello. “Because the nanocanary monitors the overall health of a population of representative cells, it measures an effect rather than an agent concentration. As such, the nanocanary is better able to respond to complex exposure environments — chemical, biological, radiation, etc. — and sense interactive effects of toxins, including those not previously known. This property is particularly important for homeland-security applications.”

In its paper, the team reported its work involving lung macrophages, cells specifically known to be sensitive to fibrous materials such as asbestos. The team added the macrophages to the sensor and subsequently exposed them to various low doses of carbon nanotubes.

“The sensor was able to predict the death of the cells, before conventional detection methods did, by up to 24 to 48 hours in advance, as well as document a dose-dependent recovery,” Therrien says. “Due to the real-time nature of the data, the sensor was able to identify responses of the macrophages to low CNT doses that standard assays might have missed.”

The results indicate that low doses of CNTs do induce a biological response and that the sensor can be used to study more realistic exposure models where repetitive exposures occur.

“The nanocanary biosensor is expected to have uses in environmental monitoring, testing for toxicity in nanomanufacturing, drug development and customized cancer therapeutics,” he says.
Transmission-electron micrograph of the carbon nanotubes (long fibrous material) used in the team's study and the metal catalyst particles (dark circles) from which the nanotubes were grown. The white scale bar is 100 nanometers long. (A nanometer is a billionth of a meter.)