Label-free optical technology takes the power and efficiency of biological detection to a new level

Researchers at the University of Arizona have developed a new biological sensing method capable of detecting substances at the zeptomolar scale, a surprisingly tiny amount.

This level of detection, immediately useful for drug testing and other research, could lead to the discovery of new medicines. Ultimately, this advance could lead to wearable sensors that can detect environmental toxins or chemical weapons, monitor food quality or screen for cancer.

A paper describing the results was published in the journal Nature Communications August 28.

Judith Su, associate professor of biomedical engineering and optical sciences, led the research for the University of Alberta, in collaboration with Stephen Liggett of the University of South Florida. Their method uses the FLOWER device, invented by Su, to detect target compounds at zeptomolar concentrations and without the use of current labeling, which involves adding a fluorescent or radioactive tag to make a target compound stand out during testing.

Label-free optical technology

Detecting a particular target compound in an environment or seeing if it reacts with a particular protein is a tricky task. Su, a principal investigator at the University of Alberta’s Little Sensor Lab and a Craig M. Berge Faculty Fellow, said one of the current hurdles to biosensing is that in most common technologies, the detection compounds must be labeled.

FLOWER, an acronym for “frequency locked optical whispering evanescent resonator,” is a label-free detector. The detection substances can be used in their native state to detect a target compound.

“In some applications, it can be very difficult or impossible to place these tags, and they can increase costs. For things like small molecule drug screening, the tags can sometimes interfere with the results,” said Su, also an associate professor at the university’s BIO5 Institute.

FLOWER, which has also been used to detect diseases and toxic gases, uses optical technology. The heart of the FLOWER tool is a microtoroid, a glass ring supported by a round base. The microtoroid is coated with chemical compounds that capture targeted biochemical agents. Its edge guides light in a way similar to an optical fiber.

Light of a very specific wavelength resonates as it passes through the microtoroid. As disease biomarkers or toxic gases are captured, the resonance wavelength shifts slightly.

By comparing the light passing through the microtoroid to light coming directly from a tunable laser, and locking the wavelength of the tunable laser to that of the microtoroid’s resonance, researchers can detect ultralow concentrations of the targets.

Detection for drug research

The researchers used G-protein-coupled receptors as the detection compounds for their experiments. G-protein-coupled receptors are sometimes called “gatekeepers of the cell” and are the target of 40% of all pharmaceutical drugs. In addition to regulating cellular functions, they act as signals for cells, one reason why they are so important for drug research.

For the Nature Communications In their paper, the researchers looked at the kappa-opioid receptor.

“When something binds to one of these receptors, it triggers a signaling cascade in the cell,” Su said. “The kappa-opioid receptor is very important for pain, for example. A potential future application for such a thing could be pain relief, but without addictive side effects.”

According to Su, since FLOWER demonstrates record sensitivity in detecting concentrations, its potential use in pharmaceutical research could be a game-changer.

Liggett, Su’s collaborator and senior vice president for research at the University of South Florida’s Morsani College of Medicine, agrees with Su about FLOWER’s potential for drug testing. He said scientists could potentially find effective drugs they might have missed when testing with other methods.

“The ultimate goal of medicinal chemistry is to use all our tools to predict what might be a very good activator of a receptor and build that molecule. Zeptomolar sensitivity is an incredibly low number, and it has not been achieved by any method that we know of to date,” he said.

“If you find a drug that you think should work on a certain receptor, if it doesn’t have a particularly high affinity, then most of the time you can’t make a drug out of it because the body can’t absorb huge amounts of the drug.”

An immediate quantum leap

The work is an exciting advance, said Bruce Hay, a professor of biology at Caltech who studies cell biology and was not involved in the research. The high sensitivity of the new, label-free method makes it immediately useful for advanced drug screening and other research, Hay said.

“This represents a huge advance in our ability to probe the fundamental components and processes that make up biological systems,” he said.

“Dr. Su’s FLOWER sensor offers a leap forward in the maximum sensitivity of label-free biosensing,” said Mario Romero-Ortega, chair of the Department of Biomedical Engineering at the University of Alberta.

“This technology will enable a deeper understanding of membrane molecular events, enable early diagnostic testing and improve human health.”