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Tracking antibodies: BU microsensor research could bring cancer detection to the bedside

Handheld computers made possible by tiny electronic circuits have brought mobility to functions once tied to the desktop. Harold Ackler’s work takes aim at a similar goal: creating microsensors that can be built into portable systems and take measurements once restricted to the lab. His research could bring cancer detection to the bedside and make it easier to monitor streams for pollution or test for biohazards at the scene of a terrorist attack.

An assistant professor of mechanical engineering in the Thomas J. Watson School of Engineering and Applied Science, Ackler came to Binghamton University in August 2003. Together with mechanical engineer Timothy Singler, Ackler is beginning a project to develop a micro-scale cell analysis device. The project builds upon Ackler’s earlier work, at the Lawrence Livermore National Laboratory, on a device to separate and identify cells in a fluid.

Ackler and Singler are talking with oncologists at Philadelphia’s Fox Chase Cancer Center and Thomas Jefferson Medical College “about developing sensors to detect small numbers of cancer cells in blood,” Ackler said. “These could be used for very early detection of cancer or monitoring patients after cancer treatment.”

The device relies on the fact that certain fluorescent chemicals can be bound to antibodies, and specific antibodies bind to specific cancer cells. “The oncologists have determined that, for at least one particular colorectal cancer, there are cells that have a very specific protein on their membrane surface,” Ackler said. Adding the right fluorophor to a blood sample “tags” the cells to which this antibody clings. “After the cells are tagged, you run the blood through a device that will excite them with light that causes the fluorescent molecules to glow,” he said. When a photo detector registers a set of glowing molecules, that identifies a cancer cell.

A portable system based on this technology would make it possible to diagnose a patient for cancer soon after taking a blood sample. “You can get results faster than if you had to take it out to a lab,” Ackler said.

Much of the fundamental technology needed for this device is already known. “The problem is integrating a variety of different functions into one device and one system, so it will enable you to process enough blood” to find very small numbers of cancer cells. The channel through which the blood passes is so small, one microsensor can process only minute volumes. Ackler and his partners are trying to create an array of sensors, “so you can run larger volumes of blood through in a reasonable time.”

The sensor array will be packaged in a system that also contains a mechanism for delivering blood to the microfluidic chips, plus electronics for controlling the process and processing data from the sensors. “It’s very much an interdisciplinary effort,” Ackler observed.

The principle of diagnosis on the spot also applies to another project on Ackler’s agenda. Together with electrical engineer Qing Wu, chemist Wayne Jones and environmental scientists Joe Graney and Siddartha Mitra, Ackler has applied to the National Science Foundation for a grant to develop a chemical sensor for environmental applications. Scientists could use the sensor to monitor water for heavy metals, transitional metals, endocrine-disrupting chemicals and other pollutants.

One technique the partners might employ takes advantage of fluorescent polymers that grow more intense in color when they come in contact with metal ions. Specific polymers react to specific ions. A waveguide coated with one of these polymers will direct light at water as it is pumped through the sensor. If the polymer changes intensity, a photodetector registers that fact, indicating that the water contains the metal in question.

Today, environmentalists generally monitor streams and wells by testing water in the lab. “That means they have people out in the field, collecting samples all over the place, all the time, and bringing them back. The costs of doing that are very high,” Ackler said. A device containing an array of microsensors, each testing for a different pollutant, could sit in the water, take measurements and periodically transmit data back to the lab via a wireless network.

One major challenge in developing micro-scale devices is figuring how to build them. Engineers working in this field borrow techniques from microelectronics but must adapt them for three-dimensional fabrication. Then they have to refine their techniques to make them robust enough for commercial production. “If it takes a PhD to make the device, it’s not a very good process,” Ackler said.

Another challenge is getting multiple microdevices to work with one another, and with other components, in a system built for use in the real world. When developing a microdevice, it’s important to consider from the start how it will be packaged, Ackler said. “If you don’t, you end up with a chip you can’t work with.” Ackler is lending his expertise in this area to BU’s Small Scale Systems Packaging Center, which works with other Centers of Advanced Technology throughout New York to incorporate micro- and nanoscale devices into integrated systems.

“Most academics are concerned with just the chip, which is fine, because it’s very challenging,” Ackler said. “But someone’s got to think about how to put those chips into an operating system.”

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