Biosensors Like Bloodhounds

Olfactory cells are being integrated into tiny microsystems to give them a bloodhound-like ability to sniff out hazards such as explosive materials, biological pathogens, spoiled food or impure water.

Three faculty researchers in the University of Maryland's A. James Clark School of Engineering -- Pamela Abshire, electrical and computer engineering (ECE) and Institute for Systems Research (ISR); Benjamin Shapiro, aerospace engineering and ISR; and Elisabeth Smela, mechanical engineering and ECE -- are working on the new cell-based sensors-on-a-chip technology. Their sensors, only a few millimeters in size, would function dramatically differently than current detectors.

Precise manipulation of cells on chip. Three yeast cells are being steered to an accuracy of 1 mm (1/1000th of a millimeter) each by feedback flow control. (Images courtesy Clark School/University of Maryland)

Today's biochemical detectors are slow and produce an unacceptable number of false readings. They are easily fooled because they often cannot distinguish subtle differences between deadly pathogens and harmless substances, and cannot fully monitor or interpret the different ways these substances interact with biological systems. To solve this problem, the Clark School researchers are learning how to incorporate real cells into the sensors to detect chemical and biological pathogens.

Different cells can be grown on these microchips, depending on the task at hand. Like a bloodhound hot on the trail of a scent, a chip containing a collection of olfactory cells plus sensing circuits that can interpret their behavior could detect the presence of explosives.

One potential life-saving application for the chips is in the detection of improvised explosive devices, or IEDs, through microchips mounted on an unmanned vehicle.

The researchers plan to use other specialized cells to act much like a canary, sensitive to certain gases, was used to determine air safety in a coal mine. The cells would show stress or die when exposed to certain pathogens, and the sensing circuits monitoring them would trigger a warning -- more quickly and accurately than in present systems.

Live (clear) and dead (blue) yeast cells patterned by means of alternating electric fields. Fields at different frequencies were applied between the pairs of electrodes shown in order to separate the cells.

For the chips to become a reality, first Abshire must build circuits that can interact with the cells and transmit alerts about their condition. Shapiro and Smela are working on microfluidics technology to get the cells where they need to be on the chip, and to keep them alive and healthy once they're in position. Smela is also developing packages that incorporate the kind of wet, life-sustaining environments the biological components need, while keeping the sensitive electronic parts of the sensor dry.

Current research funding for the cell-based sensor technology comes from the National Science Foundation, the Department of Homeland Security and the Defense Intelligence Agency. Potential applications for the sensors extend beyond national security, the researchers said.

Photomicrograph of human breast cancer cells cultured in vitro on top of a CMOS chip. An array of capacitance sensors on the chip are used to track the health and growth of the cells.

For example, cell-based sensors could detect the presence of harmful bacteria in ground beef or spinach, or detect the local origin of specialty foods like cheeses or wines. In the pharmaceutical industry they could identify the most promising medicines in advance of animal and human trials, increasing cost-effectiveness and speed in developing new drugs. And they could speed up research in basic science. Imagine tiny biology labs, each one on a chip, in an array of thousands of chips that could fit in the palm of your hand.

Such arrays could advance biologists' fundamental understanding about the sense of smell or help doctors better see how the immune system works. They could be placed on fish as they swim in the ocean to monitor water quality, or set on a skyscraper's roof to evaluate air pollution.

"We bring the capability to monitor many different cells in parallel on these chips," said Abshire. "You could say we're applying Moore's Law of exponentially increasing computer processing capability to cell biology."

For more information, visit: www.eng.umd.edu