A platform developed nearly 20 years ago previously used to detect protein interactions with DNA and conduct accurate COVID-19 testing has been repurposed to create a highly sensitive water contamination detection tool.
The technology merges two exciting fields - synthetic biology and nanotechnology - to create a new platform for chemical monitoring. When tuned to detect different contaminants, the technology - which was developed by a cross-disciplinary team of Northwestern University researchers from the Center for Synthetic Biology and the Scanning Probe Instrumentation and Development (SPID) facility of the Northwestern University Atomic and Nanoscale Characterization (NUANCE) Center - could detect the metals lead and cadmium at concentrations down to two and one parts per billion, respectively, in a matter of minutes.
The paper was published this week in the journal American Chemical Society Nano and represents research from multiple disciplines within Northwestern's McCormick School of Engineering.
The test was created by interfacing nanomechanical microcantilevers with synthetic biology biosensors. The tiny cantilevers are made of silicon and easily reproducible. When they are coated with specially designed DNA molecules, biosensing molecules called transcription factors bind to the DNA causing the cantilevers to bend. When exposed to target chemicals, the transcription factor biosensors unbind, causing the cantilever to "debend," which can be measured precisely to detect the chemicals.
The microcantilever technology was combined with that of Northwestern synthetic biologist Julius Lucks, who has built and grown a cell-free biosensor called ROSALIND (short for "RNA output sensors activated by ligand induction"). Its first model could sense 17 different contaminants using only a single drop of water, glowing green when a contaminant exceeded the U.S. Environmental Protection Agency's standards. The ROSALIND technology is based off the same transcription factor biosensors, which were configured to control gene expression in a cell-free reaction by binding and unbinding DNA.
During the coronavirus pandemic, Lucks saw the microcantilever technology at work when it was adapted by professors Vinayak P. Dravid and Gajendra Shekhawat to accurately detect SARS-Cov-2. Impressed, Lucks thought maybe by coating these cantilevers with Lucks Lab-engineered DNA, he could trigger the cantilevers to detect chemical toxins. By combining components of the two tools, the McCormick duo - along with first author and post-doc Dilip Agarwal and graduate student Tyler Lucci -created an ultrasensitive test for water contaminants.
"These are micro- and nanosystems that don't need a lot of viral material to make a difference," said Northwestern nanotechnology expert Dravid. "Microcantilevers can give you a faster turnaround, within two or three minutes, because they leverage specific affinity surface binding. And unlike most sensors available that rely on just one protein, we can look at multiple targets at the same time."
Dravid is the Abraham Harris Professor of Materials Science and Engineering at Northwestern's McCormick School of Engineering and a faculty affiliate of the Paula M. Trienens Institute for Sustainability and Energy. He is the founding director of the NUANCE Center as well as the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource and serves as the associate director for global programs at the International Institute of Nanotechnology.
Lucks is a professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and a co-director of the Center for Synthetic Biology.
The team started by testing tetracycline because the frequency with which it is used in synthetic biology has allowed for a deep knowledge base to develop about how tetracycline behaves, then moved on to sense lead and cadmium down to just a few parts per billion, a record for biosensor detection approaches.
The teams hope to further simplify the technology, which right now requires specialized equipment to visualize the microscopic bending movements. Ultimately, they think the device could be generalized for use in human health monitoring for toxins in the body and environmental contexts, such as raising standards for drinking water safety. The tech becomes part of a thriving, interdisciplinary ecosystem of Northwestern research making waves solving worldwide challenges as complex as water systems.
This work was supported by the Northwestern McCormick Catalyst Award, National Science Foundation (grant no. 2319427) and the Northwestern University Synthesizing Biology Across Scales National Research Training Program (grant no. 2021900).
