ABSTRACT
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.
Subject(s)
Biochemical Phenomena , Biosensing Techniques/instrumentation , Staining and Labeling , Animals , Biotinylation , Cattle , Fluorescent Dyes/metabolism , Humans , Microscopy, Fluorescence , Prostate-Specific Antigen/blood , Serum Albumin, Bovine/metabolism , Time FactorsABSTRACT
The application of fully monolithically-integrated Mach-Zehnder interferometer arrays fabricated by standard silicon technology to the label-free detection of analytes is introduced. Detection with the presented biosensor is based on a novel concept, the Frequency-Resolved Mach-Zehnder Interferometry (FR-MZI). In addition, a smart encapsulation based on an appropriately designed microfluidic system and performed at the wafer scale scheme for the easy delivery of the samples to be analyzed is demonstrated. Testing of the FR-MZI biosensors with model binding assays demonstrated the detection of streptavidin binding to immobilized biotin at concentrations in the sub nM range. This is the first experimental demonstration of the FR-MZI concept as well as the first demonstration of a monolithically fully-integrated MZI biosensor.
