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.
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