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German Researchers Awarded €2M to Develop 'Suprasensors' for Use in Clinical Diagnostics


NEW YORK – Researchers at the Karlsruhe Institute of Technology in Germany have been awarded €2 million ($2.1 million) to develop a new sensor technology that could find use in a multitude of molecular diagnostic applications.

Frank Biedermann, a group leader in KIT's Institute of Nanotechnology, received the European Research Council consolidator grant last month. Called SupraSense, the effort will run through 2028. The ERC awarded €657 million in such grants to 321 researchers at the end of January.

Biederman and his team have been developing supramolecular assays based on chemiluminescent chemosensors, or "suprasensors," that can detect metabolites in saliva, blood, and urine.

Although the current ERC-funded project is for fundamental research, Biedermann said the long-term goal is to develop the suprasensors for clinical use.

"In five years, we should have a library of important biomarkers and sensor molecules that can be cheaply prepared," Biedermann said. To make use of such molecules, however, will require additional work. "We would consider making a startup, and I want to," he said. "I would say that it's my dream, but it's a dream, not a promise."

Biedermann noted that conventional biosensors rely on proteins or nucleic acids to detect the presence of target analytes in a sample. "In essence, one uses what nature is providing," he said. However, such approaches often require multiple steps to modify the affinity and selectivity of the receptors. While scientists have been working to create molecules that could serve the same purposes in a biosensor, these have failed to reach the selectivity and affinity of natural receptors.

"There is hardly any product of supramolecular chemistry in diagnostic applications because performance parameters were not reached," remarked Biedermann.

Chemists in the 1960s were able to engineer such supramolecules already, said Biedermann, but it has taken decades to improve on these issues. To overcome them, Biedermann's group has devised an indicator displacement assay that relies on a supramolecular host-guest complex of chemiluminescent phenoxy 1,2-dioxetane as a "guest" or indicator and a macrocyclic molecule called cucurbituril that serves as a synthetic receptor or "host." In the presence of a target analyte, the indicator is dislodged from the host, resulting in a detectable change in optical signal.

In August, the researchers published a paper in ACS Sensors describing the use of their approach to enable low-micromolar detection of drugs in human urine and serum, using nuclear magnetic resonance spectroscopy. In December, they further described the general chemistry and methodology behind the supramolecular assays in the journal Chemical Communications.

Fraser Hof, a professor of chemistry and associate VP of research at the University of Victoria in Canada, said in an email that he is "excited about the potential" of KIT's work. Hof is not taking part in the project, but his research concerns supramolecular and medicinal chemistry.

According to Hof, supramolecular sensors, like those being developed at KIT, have some properties that could make them suitable for diagnostic applications. For example, they can give "on-the-spot readouts without needing time- and labor-intensive sample-processing steps," he said. They also help to avoid the need for expensive instrumentation, Hof said. However, the uptake of supramolecular sensors in clinical settings has to date been hindered because of a lack of specificity for any particular analyte.

According to Hof, the approaches being developed in the Biedermann lab at KIT could change this dynamic, as they rely on new supramolecular sensors that have "improved selectivity, and also harness new informatics approaches that turn sensor signals into useful readouts of medically important analytes."

Backed with the new ERC funding, Biedermann's group now aims to develop new sensors by applying the same binding principles to new materials. "We can take a different design approach to sensors, because we are not only relying on a lock-and-key principle, but employ a hydrophobic effect," he said.

Most of the €2 million in financing will support work of postdoctoral and Ph.D. students beginning this summer, as well as the purchase of lab consumables. Partners at Jena University Hospital and Heidelberg University Hospital in Germany will supply the KIT researchers with patient samples from their biobanks to help validate assays run using their technology.

The new sensors, Biedermann said, will be constructed from microporous materials that can be shaped into selective molecular binding units that can be read out using a variety of approaches, including fluorescence and chemiluminescence, and absorption and optical spectroscopy. This will result in arrays of sensor molecules targeted toward a range of metabolites. As part of the project, the researchers will also study the binding process to improve future generations of the technology. Here machine-learning tools will be involved, as the researchers can run computer simulations to predict the binding properties of new molecules.

"We would like to have a binding model to predict new sensor materials," said Biedermann.

Once the team has an array of sensors, it can approach potential diagnostics collaborators. The researchers have noted in a statement that their artificial receptors could eventually be used to monitor metabolites and improve early detection of cardiovascular diseases, inflammation, sepsis, and other metabolic or age-related diseases.

"In the end, once you can detect biomarkers, you can hook up with engineers, and make at-home tests and other devices that have an optical readout," said Biedermann. "We mainly are working on the materials and assay formats, so it's up to others to make it into a device," he commented.