The proposed research aims to demonstrate an ultrasensitive point of care biosensor for ongoing prostate-specific antigen (PSA) monitoring in prostate cancer patients. Early detection of the disease will help timely identification of the appropriate treatment options and improve the long-term patient outcomes. The proposed biosensor is based on detection of magnetic reporter nanoparticles on a paper strip (like a pregnancy test) and will be integrated with the readout electronics costing under $300 and disposable test chips costing under $3. Successful completion of this work would yield a point-of-care PSA device that will allow physicians to test patients in their offices during follow-up visits after surgery, or allow patients to self-monitor themselves at home and transmit results to care providers for follow-up and consultation. This research will also help establish a new general biosensor platform broadly useful in other areas of therapy monitoring, molecular diagnostics, biomarker detection, and biomedical research, which will satisfy the ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, (almost) equipment-free and deliverable to end users) criteria established by the World Health Organization for point-of-care diagnostics.
The proposed biosensor platform offers a number of technological advancements over the current state-of-the-art magnetic biosensor technologies. It enables ultrahigh sensitivity, completely electronic readout, precision and the cost advantages of high-throughput manufacturing, and simplicity of assembly. The sensors are embedded into low-cost PCB (printed circuit board) components sandwiching an lateral flow assay strip in between. Each disposable sensor chip incorporates a test line and a control line with the readout voltages proportional to the number of magnetic reporter particles captured in the respective sensing volumes and with the background (due to non-specific binding) automatically subtracted. The miniaturization of the inductive sensing design enables larger excitation fields and high-frequency operation resulting in a significantly higher sensitivity of 10 pico-emu, a 100,000 fold improvement over conventional inductive detectors. The 100-fold signal reduction in sensitivity as one moves away from conventional multi-coil AC susceptometer design operating in the sub-1000 Hz Brownian relaxation mode is offset by the 200,000-fold sensitivity increase due to radically higher operation frequency (>200 MHz) and significantly smaller, more efficient sensing and excitation elements. Specificity is achieved by a lateral flow sandwich immunoassay. The system dynamic range of the system is electronically adjustable (excitation frequency and/or field) for detection of both low and high concentrations of the analyte. The system is expected to be exceptionally robust against fabrication process variations and will not require calibration.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
