Illinois team unveils new laser biosensor

ECE faculty members Brian T Cunningham and James Gary Eden, and Chemistry professor Paul Hergenrother, along with their graduate students Chun Ge, Meng Lu, Sherine George, Timothy Flood Jr., Clark Wagner (MS Physics '96, PhD Physics '04), Jie Zheng (MS '08, PhD '11) and Anusha Pokhriyal, designed an innovative type of biosensing laser that achieves super-high detection resolution – a “first-of-its-kind” technology.

The team collaborated to design and demonstrate the new biosensor, and recently published their results. Their article, “External cavity laser biosensor,” will be featured on the front cover of "Lab on a Chip" – a unique journal that publishes significant work applicable to the development of miniaturized bio-analysis systems. The paper was first published on the Web on February 22.

“We’re very excited about being the first team to demonstrate the first practical biosensing laser, and we’re really happy to be featured on the cover,” said Cunningham, who also is affiliated with the Beckman Institute and Micro and Nanotechnology Laboratory.

Cunningham, Eden, and Hergenrother accomplished super-high detection resolution via a fundamentally different approach that achieves high sensitivity and high resolution at the same time, delivering a system that is geared toward detection of biomaterial with low molecular weight (such as drugs) and low concentration in a sample (such as disease biomarkers in blood).

“There are various ways you can detect molecules, virus particles, and DNA by their intrinsic physical properties,” Cunningham said. “In this case, we measured them by how they can slow down the speed of light using their dielectric constant. The higher the dielectric constant of a molecule, the more it slows down the speed of light, and we’ve developed a sensor that enables light to interact with molecules and to change the wavelength of light emitted by a very narrowband, continuously running laser in the infrared.”

Lasers have a very high intensity that is emitted within an extremely narrow range of wavelengths. If a laser’s wavelength changes, even by a fraction of a picometer, the newly designed laser biosensor can quickly detect the change.

“It’s a way of detecting things that are ordinarily difficult to detect by any existing method,” Cunningham said.

The super-high detection resolution allows researchers to detect drug molecules interacting with proteins, with applications in pharmaceutical research and pathogen detection. The biosensor’s heightened sensitivity is key.

“This laser sensor is ideal for bio-applications,” Eden said. “If a cell, biomolecule, or virus attaches to the sensor, the laser registers the event as a color change. The key is that the laser allows us to measure extremely small color changes.”

Cunningham and Hergenrother received an NIH (National Institutes of Health) grant to develop high-resolution methods for measuring small molecule and protein interactions – a key capability that is used throughout pharmaceutical research.

“Effective drugs are molecules that can target a specific protein, and bind with it,” Cunningham said. “The targeted protein is a key element of a protein interaction network that results in abnormal cell behavior, and thus disease. Our goal is to find new candidate drug molecules that interact with specific protein pathways involved in Parkinson’s disease and cancer, by measuring the strength of the molecule-protein interactions. We sort through hundreds of thousands of molecules to identify a few ‘hits’ that have the right properties. Professor Hergenrother and his group can then make small changes to the molecules to make them work even better, and to study their effects on cells.”

The biosensor is prepared with a layer of proteins, which are subsequently exposed to different drugs. The wavelength shift generated by the tiny molecular weight of the drugs is difficult to detect.

“The laser biosensor provides the resolution needed to detect when tiny drug molecules attach to much larger protein molecules,” Cunningham said.

The newly developed biosensor can be extended to serve as a tool for scientists and medical professionals for detection of virus particles, bacterial pathogens, and cells. 

“In the long run, we want to provide an inexpensive diagnostic tool to quickly identify diseases and disorders, and to save lives,” Eden said. “That’s our goal.”