Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors.

Giant magnetoresistive (GMR) biosensors consisting of many rectangular stripes are being developed for high sensitivity medical diagnostics of diseases at early stages, but many aspects of the sensing mechanism remain to be clarified. Using e-beam patterned masks on the sensors, we showed that the magnetic nanoparticles with a diameter of 50 nm located between the stripes predominantly determine the sensor signals over those located on the sensor stripes. Based on computational analysis, it was confirmed that the particles in the trench, particularly those near the edges of the stripes, mainly affect the sensor signals due to additional field from the stripe under an applied field. We also demonstrated that the direction of the average magnetic field from the particles that contributes to the signal is indeed the same as that of the applied field, indicating that the particles in the trench are pivotal to produce sensor signal. Importantly, the same detection principle was validated with a duplex protein assay. Also, 8 different types of sensor stripes were fabricated and design parameters were explored. According to the detection principle uncovered, GMR biosensors can be further optimized to improve their sensitivity, which is highly desirable for early diagnosis of diseases

Matrix-insensitive protein assays push the limits of biosensors in medicine

Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense

Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation.

Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry