Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, high-throughput and low-cost fabrication techniques are the main issues which should be addressed. In this study, chip-based nanostructures for intensity-sensitive detection were fabricated and tested using a thermal-annealing-assisted template-stripping method. Large-area uniform nanoslit arrays with a 500 nm period and various slit widths, from 30 to 165 nm, were made on plastic films. A transverse magnetic-polarized wave in these gold nanostructures generated sharp and asymmetric Fano resonances in transmission spectra. The full width at half-maximum bandwidth decreased with the decrease of the slit width. The narrowest bandwidth was smaller than 10 nm. Compared to nanoslit arrays on glass substrates using electron-beam lithography, the proposed chip has a higher intensity sensitivity up to 10367%/RIU (refractive index unit) and reaches a figure of merit up to 55. The higher intensity sensitivity for the template-stripped nanostructure is attributed to a smoother gold surface and larger grain sizes on the plastic film, which reduces the surface plasmon propagation loss.

Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, plasmonic sensors capable of highly sensitive detection with high-throughput and low-cost fabrication techniques are desirable. We show that capped gold nanoslit arrays made by thermal-embossing nanoimprint method on a polymer film can produce extremely sharp asymmetric resonances for a transverse magnetic-polarized wave. An ultrasmall linewidth is formed due to the enhanced Fano coupling between the cavity resonance mode in nanoslits and surface plasmon resonance mode on periodic metallic surface. With an optimal slit length and width, the full width at half-maximum bandwidth of the Fano mode is only 3.68 nm. The wavelength sensitivity is 926 nm/RIU for 60-nm-width and 1,000-nm-period nanoslits. The figure of merit is up to 252. The obtained value is higher than the theoretically estimated upper limits of the prism-coupling SPR sensors and the previously reported record high figure-of-merit in array sensors. In addition, the structure has an ultrahigh intensity sensitivity up to 48,117%/RIU.

Chip-based biosensors for sensitive label-free detection were fabricated and tested by using Fano-type resonant nanostructures. The sensor was composed of a 190 nm-thick gold nanoslit surrounded by 600-nm-period grooves. Transverse-magnetic polarized wave in these gold nanostructures generated asymmetrical resonant spectra due to the interference of broad-band cavity resonance in the single slit and narrow-band surface plasmon resonance on the periodic grooves. Compared to nanoslit arrays, such Fano-type sensor has a sharper resonance which yields a figure of merit up to 48. In addition, the crossed talk between sensing elements is reduced due to the Bragg reflection of the periodic grooves. A smaller detection separation down to 10 μm width was achieved. An antigen-antibody interaction experiment in aqueous environment verified the detection sensitivity in surface binding event.

A new microarray for dynamical studies of surface biomolecular interactions without fluorescent labeling is proposed. We employed gold nanostructures to excite surface plasmons on the microarray surface and detected the intensity changes in the extraordinary transmission. The calculation and measurement results indicate that the nanoslit array has an intensity sensitivity much higher than the nanohole array due to its narrower resonant bandwidth. In addition, the sensitivity is increased as the slit width decreases. For 35 nm slit width, the intensity sensitivity reaches to approximately 4000%/RIU, two times larger than the slit width larger than 150 nm. Using the intensity changes, we demonstrate a 10 x 10 microarray for real-time measurements of antigen-antibody and DNA-DNA interactions.

An optofluidic platform for real-time monitoring of live cell secretory activities is constructed via Fano resonance in a gold nanoslit array. Large-area and highly sensitive gold nanoslits with a period of 500 nm are fabricated on polycarbonate films using the thermal-annealed template-stripping method. The coupling between gap plasmon resonance in the slits and surface plasmon polariton Bloch waves forms a sharp Fano resonance with intensity sensitivity greater than 11 000% per refractive index unit. The nanoslit array is integrated with a cell-trapping microfluidic device to monitor dynamic secretion of matrix metalloproteinase 9 (MMP-9) from human acute monocytic leukemia cells in situ. Upon continuous lipopolysaccharide (LPS) stimulation, MMP-9 secretion is detected within 2 h due to ultrahigh surface sensitivity and close proximity of the sensor to the target cells. In addition to the advantage of detecting early cell responses, the sensor also allows interrogation of cell secretion dynamics. Furthermore, the average secretion per cell measured using our system well matches previous reports while it requires orders of magnitude less cells. The optofluidic platform may find applications in fundamental studies of cell functions and diagnostics based on secretion signals.