Optical sensing systems for microfluidic devices: a review.

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

Ultrafast laser writing of waveguides in glasses is a very flexible and simple method for direct on-chip integration of photonic devices. In this work we present a monolithic optofluidic device in fused silica providing label-free and spatially-resolved sensing in a microfluidic channel. A Mach-Zehnder interferometer is inscribed with the sensing arm orthogonally crossing the microfluidic channel and the reference arm passing over it. The interferometer is integrated either with a microchannel fabricated by femtosecond laser technology or into a commercial lab-on-chip for capillary electrophoresis. The device layout, made possible by the unique three-dimensional capabilities of the technique, enables label-free sensing of samples flowing in the microchannel with spatial resolution of about 10 μm and limit of detection down to 10−4 RIU.

Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection

By leveraging advances in semiconductor microfabrication technologies, chip-integrated optical biosensors are poised to make an impact as scalable and multiplexable bioanalytical measurement tools for lab-on-a-chip applications. In particular, waveguide-based optical sensing technology appears to be exceptionally amenable to chip integration and miniaturization, and, as a result, the recent literature is replete with examples of chip-integrated waveguide sensing platforms developed to address a wide range of contemporary analytical challenges. As an overview of the most recent advances within this dynamic field, this review highlights work from the last 2–3 years in the areas of grating-coupled, interferometric, photonic crystal, and microresonator waveguide sensors. With a focus towards device integration, particular emphasis is placed on demonstrations of biosensing using these technologies within microfluidically controlled environments. In addition, examples of multiplexed detection and sensing within complex matrices—important features for real-world applicability—are given special attention.

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Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications

In biomolecular interaction analysis, direct optical detection is attracting increasing interest in academia and industry. Therefore, a previous review has been updated. Optical principles are given in brief, focussing especially on modern and frequently used techniques. Commercialized methods are listed with some specific applications. In addition, some of the many applications found in the literature are listed; others which have been reviewed elsewhere are cited. Overall, the growing interest in direct optical monitoring of biomolecular interaction is demonstrated and future trends are outlined. Because optical methods is a very wide field, the paper concentrates on the currently most common methods, microrefractometry and microreflectivity.

Chang Min Kim

Papers

A Mach-Zehnder interferometer based on silicon oxides for biosensor applications.