Immunomagnetic diffractometry for detection of diagnostic serum markers

We describe an integrated approach for detection of diagnostic markers using in situ assembled optical diffraction gratings in combination with immunomagnetic capture. Folate receptor (FR), a serum protein indicative of various cancers, was chosen as a model system to demonstrate the potential of the method. Magnetic beads coupled to FR antibody were used to capture FR from serum. The FR-bound magnetic beads self-assembled onto microcontact-printed folate-coupled BSA (F-BSA) patterns to form diffraction gratings which served to detect FR by measuring the diffraction intensities caused by laser illumination. The FR-containing beads, upon binding to the F-BSA surface, served as intrinsic signal enhancement agents, circumventing the need for additional enzymatic signal amplification or fluorescent labeling steps. With this approach, a detection sensitivity of 700 fM (20 pg/mL) was achieved. The potential use of this approach in clinical diagnostics was demonstrated by measuring FR concentration in blood samples obtained from cancer patients.