Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment At last, some advanced system-level complementary metal-oxide semiconductor (CMOS) chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes

Silicon Photonic Biosensors Using Label-Free Detection.

We demonstrate a highly sensitive label-free Mach–Zehnder interferometer (MZI) biosensor based on silicon nitride slot waveguide. Unlike the conventional MZI sensors, the sensing arm of the sensor consists of a slot waveguide while the reference arm consists of a strip waveguide. Thanks to the slot waveguide's property to provide high optical intensity in a subwavelength-size low refractive index region (slot region), which allows high light–analyte interaction, higher sensitivity can be obtained as compared to conventional waveguides using the slot waveguide as sensing region. The bulk refractive index sensitivity of the slot waveguide MZI sensor was found to be 1864 π /RIU (refractive index unit) with 7 mm long slot waveguide sensing arm, which shows higher sensitivity compared to the conventional MZI device based on silicon nitride. The biosensing capability of the developed slot waveguide MZI was investigated using biotin–streptavidin binding as a model system. The sensitivity of the system was demonstrated down to 18.9 fM or 1 pg/ml of streptavidin solution and to the best of our knowledge, it is the best reported experimental value for the limit of detection of a MZI sensor. Furthermore, we investigated the specific detection and quantification of the methylation of DAPK ( Death-associated protein kinase ) gene, which is a widely used biomarker for human cancers. We have shown that methylation sequences of DAPK gene of various methylation densities (100%, 50%, and 0% of methylation sites) can be quantified and discriminated even at a concentration as low as 1 fmol/μl or 1 nM.

Highly sensitive Mach–Zehnder interferometer biosensor based on silicon nitride slot waveguide

Label-free optical resonant sensors for biochemical applications

Nowadays, optical devices and circuits are becoming fundamental components in several application fields such as medicine, biotechnology, automotive, aerospace, food quality control, chemistry, to name a few. In this context, we propose a complete review on integrated photonic sensors, with specific attention to materials, technologies, architectures and optical sensing principles. To this aim, sensing principles commonly used in optical detection are presented, focusing on sensor performance features such as sensitivity, selectivity and rangeability. Since photonic sensors provide substantial benefits regarding compatibility with CMOS technology and integration on chips characterized by micrometric footprints, design and optimization strategies of photonic devices are widely discussed for sensing applications. In addition, several numerical methods employed in photonic circuits and devices, simulations and design are presented, focusing on their advantages and drawbacks. Finally, recent developments in the field of photonic sensing are reviewed, considering advanced photonic sensor architectures based on linear and non-linear optical effects and to be employed in chemical/biochemical sensing, angular velocity and electric field detection.

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Recent advances in integrated photonic sensors.

Resistance thermometry provides a time-tested method for taking temperature measurements. However, fundamental limits to resistance-based approaches has produced considerable interest in developing photonic temperature sensors to leverage advances in frequency metrology and to achieve greater mechanical and environmental stability. Here we show that silicon-based optical ring resonator devices can resolve temperature differences of 1 mK using the traditional wavelength scanning methodology. An even lower noise floor of 80 μK for measuring temperature difference is achieved in the side-of-fringe, constant power mode measurement.

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Ultra-sensitive chip-based photonic temperature sensor using ring resonator structures.

As the sensitivity and detection limit of photonic refractive index (RI) biosensor increases, the temperature dependence becomes a major challenge. In this paper, we present a Mach-Zehnder Interferometer (MZI) biosensor based on silicon nitride slot waveguides. The biosensor is designed for minimal temperature dependence without compromising the performance in terms of sensitivity and detection limit. With air cladding, the measured surface sensitivity and detection limit of MZI biosensor reach 7.16 nm/ (ngmm−2) and 1.30 (pgmm−2), while achieving a low temperature dependence is 5.0 pm/o C. With water cladding, the measured bulk sensitivity and detection limit reach 1730(2π)/RIU and 1.29 × 10−5 RIU respectively. By utilizing Vernier effect through cascaded MZI structures, the measured sensitivity enhancement factor is 8.38, which results in a surface detection limit of 0.155 (pgmm−2).

Thermal independent silicon-nitride slot waveguide biosensor with high sensitivity.

We present a label-free aptamer sensor based on an array of silicon micro-ring resonators. An array of sensors consists of three sensor rings and a reference ring was fabricated and its surface sensitivity and the limit of detection was obtained using polyelectrolyte multilayer. The mass sensitivity and the limit of detection of the fabricated sensor ring is 0.35 nm/ng mm−2 and 42.8 pg/mm2 in air and 0.24 nm/ngmm−2 and 62.5 pg/mm2 in water, respectively. We successfully demonstrated the binding assay over a broad range of protein concentrations using a model system with human thrombin as the analyte and DNA aptamers as immobilized ligands.

Jessie Quah Yiying

Papers

Thermal independent silicon-nitride slot waveguide biosensor with high sensitivity.

Silicon micro-ring resonators for label-free aptamer-based biosensing