Plastic-Based Distributed Feedback Laser Biosensors in Microplate Format

A process that combines polymer nanoreplica molding with horizontal dipping was used to fabricate large area (~ 3 × 5 inch²) distributed feedback laser biosensors (DFBLB) on flexible plastic substrates, which were subsequently incorporated into standard format 96-well microplates. A room temperature nanoreplica molding process was used to create subwavelength periodic grating structures, while a horizontal dipping process was used to apply a ~ 300 nm, dye-doped polymer film. In this work, the DFBLB emission wavelength, used to characterize the device uniformity, demonstrated a coefficient of variation (CV) of 0.41% over the fabricated device area, representing a thickness standard deviation of only ~ 35 nm for the horizontal dipping process. The fabricated sensors were further characterized for sensitivity uniformity by measuring the bulk refractive index of the media exposed to the sensor surface and by measuring adsorption of biomolecular layers. An assay for detection of the cytokine Tumor Necrosis Factor-alpha (TNF-α) was used to demonstrate the operation of the sensor in the context of label-free detection of a disease biomarker. The demonstrated capability represents an important step towards roll-to-roll manufacturability for this biosensor that simultaneously incorporates high sensitivity with excellent wavelength shift resolution, and adaptability to the microplate format that is ubiquitous in pharmaceutical research.