Quantum Sensing Integrated with Ultrasound for Precise Drug Screening

Summary The goal of this proposal is to develop a quantum sensing device to accelerate drug development process and increase its success rate. The proposed device is based on the super-resolution force spectroscopy (SURFS) technique invented by the PI and co-PI. SURFS offers a force resolution of below one piconewton which is sufficient to distinguish the binding strengths between drug molecules with similar structures and between nucleic acids with only a single nucleotide difference. Compared to other force-based techniques, SURFS has twenty times better resolution and approximately five orders of magnitude higher detection efficiency. Therefore, if successfully commercialized, SURFS may be a revolutionary technique to benefit drug development with unprecedented data. This STTR proposal will implement several strategies to achieve this goal. The first is to integrate a commercial optically pumped magnetometer with an array of piezo disks for force generation. This combination will make the device easy to use and much cheaper than the current competing devices. The second is to resolve the multiple samples located on a standard multi-well plate, with unique methods to resolve these samples. This will dramatically improve the detection efficiency, as no magnetic device can detect multiple samples at this moment. The outcome of this proposal will be a unique apparatus that will be an important asset towards precision medicine. The proposed activities will also produce the much desired but currently unavailable data regarding the selectivity of chemotherapy drugs. Despite the variety of drug combinations currently being used, it remains unclear on how strong the selectivity is, especially for drugs with highly similar structures. Therefore, the data will contribute towards filling the knowledge gap between drug structures and their preferred target sequences. This proposal focuses on the chirality and excess hydroxyl groups of the drug molecules and the methylation of the DNA sequences, which are major factors at the molecular level for drug design. Potentially, the high- resolution force measurements for drug binding with their biomolecular targets obtained with the proposed SURFS device, can serve as a new parameter to guide the optimization process of drug development, which will shorten the process, reduce the cost, and increase the success rate.