Monolithically integrated Mach-Zehnder biosensors for real-time label-free monitoring of biomolecular reactions.

Arrays of monolithically integrated Mach-Zehnder interferometers were fabricated by standard silicon technology and applied to the label-free real-time monitoring of biomolecular interactions. Chips accommodating 10 MZIs were functionalized with recognition biomolecules and encapsulated in wafer scale. Detection is based on Frequency-Resolved Mach-Zehnder Interferometry, a new concept that takes advantage of the broad-band input spectrum by monitoring the changes for every input frequency. The sensitivity of the device in terms of refractive index changes (Δn) was calculated using isopropanol/water solutions. A detection limit of Δn = 4 × 10(-6) was calculated. The bioanalytical capabilities of the device there demonstrated through model binding assays (biotin/streptavidin) as well as the detection of total prostate specific antigen in serum samples using devices coated with antigen-specific monoclonal antibody. Detection limits at the pM range were determined.