Collaboration to manufacture high-sensitivity biosensors for food and clinical samples


By Bruce Flickinger

A new mass-detection system utilizing microelectromechanical systems (MEMS) and a unique resonating sensor is being developed by a collaboration of academic, industrial and government groups, and initially promises several performance improvements over existing technologies in the detection of foodborne pathogens, infectious diseases and cancer.

The technology is based upon a device called a suspended microchannel resonator (SMR), which consists of a cantilevered microchannel with a resonator that vibrates in a vacuum. The interior surface of this channel can be functionalized for a number of target analytes, so that when a sample is introduced and the target molecule is present, the mass of the resonator starts to rise.

“We can detect this oscillation with good precision, better than one part per million,” says Dr. Ken Babcock, who is president of the newly formed Silicon Biosensor Division at Innovative Micro Technology (IMT, Santa Barbara, Calif.), a MEMS manufacturing company collaborating on the SMR project along with Professor Scott Manalis’s research group at the Massachusetts Institute of Technology (MIT, Cambridge, Mass.).

Mass detectors essentially detect small changes in sample mass, which then is correlated to a number of molecules. However, SMR differs from quartz crystal microbalance (QCM) and standard cantilevered mass detectors, which are heavily damped in fluid. “The fluid damping reduces the quality factor of the resonator, which, in turn, reduces the ability to resolve the resonance frequency, and hence the mass you are trying to detect,” Babcock says.

Basic SMR capability has been validated by the Manalis Lab at MIT in published demonstrations of specific biomolecular detection. IMT is building second-generation units, to be completed this spring, using MEMS silicon microfabrication in a project being funded by a $2 million grant from the Institute for Collaborative Biotechnologies (ICB), a partnership among universities, industrial partners and the U.S. Army. The three-year project will focus on detecting pathogens at extremely high sensitivities for food-safety applications, in collaboration with Dr. Andre Senecal, a senior food technologist at the Army’s Natick Soldier Center. Botulism toxin is the initial food-safety focus.

Suspended microchannel resonator device showing cantilevered microchannel with resonator.
Click here to enlarge image

In addition to the ICB program, SMR as a cancer diagnostic is the aim of a $2.3 million NIH grant awarded to the Manalis Lab at MIT. Babcock and Manalis also are planning to test SMR for detection of anthrax spores and viruses, and for rapid diagnosis of malaria. “Our goal is to detect a single bacterium or infected red blood cell, without the need for time-consuming cultures,” says Babcock. In terms of actual specifications, detailed tests won’t be done until the devices are fabricated at IMT. But we anticipate that SMR has the potential to be ‘real time’-a few minutes at most to detection-which is critical for rapid response.”

The units being made by IMT initially will be housed in a benchtop platform, Babcock says, with the ultimate goal of a “very robust” handheld device for point-of-care diagnostic or field screening for food pathogens. Work currently is focused upon removing the optical lever so that it is an entirely electrical system.

“Besides the compelling aspects of the technology, I think the fact that commercial-grade sensors are being fabricated at IMT is the main factor that makes success of SMR likely,” Babcock says. “These devices push the state of the MEMS art, and IMT has been impressive in its ability to make them a reality.”