Mach-Zehnder interferometer (MZI) point-of-care system for rapid multiplexed detection of microRNAs in human urine specimens.

MicroRNAs have been identified as promising biomarkers for human diseases. The development of a point-of-care (POC) test for the disease-associated miRNAs would be especially beneficial, since miRNAs are unexpectedly well preserved in various human specimens, including urine. Here, we present the Mach-Zehnder interferometer-miRNA detection system capable of detecting multiple miRNAs in clinical urine samples rapidly and simultaneously in a label-free and real-time manner. Through measurement of the light phase change, the MZI sensor provides an optical platform for fast profiling of small molecules with improved accuracy. We demonstrate that this system could specifically detect target miRNAs (miR-21, and let-7a), and even identify the single nucleotide polymorphism of the let-7 family of miRNAs from synthetic and cell line samples. The clinical applicability of this system is confirmed by simultaneously detecting two types of miRNAs in urine samples of bladder cancer patients in a single reaction, with a detection time of 15 min. The POC system can be expanded to detect a number of miRNAs of different species and should be useful for a variety of clinical applications requiring at or near the site of patient care.

Thermal characterization of electrical tracing-assisted dual-microring optical sensors.

In this paper, we study the temperature sensitivity of an electrical tracing-assisted dual-microring optical sensor, which consists of a sensing ring to detect the refractive index change on its surface and a tracing ring to trace the resonance wavelength shift of the sensing ring by the thermo-optic effect with a heating electrode on it. The wavelength shift measurement is therefore changed to electrical power variation measurement. Thanks to the real-time compensation effect of the tracing ring, the temperature dependence of the sensor is found to be intrinsically low. The resonance wavelength temperature sensitivity difference between the two rings is measured to be as low as 10.1 pm/°C, showing that the temperature dependence of the sensor in terms of wavelength per degree is reduced by ~6 times compared to that of a single ring sensor. The temperature sensitivity of the sensor in terms of electrical power per degree is measured to be -0.077 mW/°C. By using tracing ring with enhanced tuning efficiency, this value can be further decreased to -0.0057 W/°C. The experimental results agree well with the expectation. This type of sensors with low temperature dependence has great potential to be deployed in various practical point-of-care diagnostic applications.

Single-channel Mach-Zehnder interferometric biochemical sensor based on two-lateral-mode spiral waveguide.

We propose and demonstrate a single-channel Mach-Zehnder interferometric (MZI) biochemical sensor consisting of two single-mode waveguides connected by a two-lateral-mode spiral sensing waveguide through two discontinuous junctions. The use of a two-lateral-mode waveguide offers the advantage of simple fabrication using single-step lithography and etching process. Meanwhile, the two-mode waveguide folded in a spiral layout can achieve high sensitivity of a long sensing waveguide while providing a compact sensing area compatible with commercial spotting machine and requiring small volume of sample. The sensor is demonstrated in silicon waveguides and the effect of the discontinuity offset distance on the interference visibility is studied. The bulk and surface sensitivity of a fabricated sensor with a 4582-µm-long two-mode spiral waveguide folded within a 185 µm diameter spot are characterized to be 461.6 π/RIU (refractive index unit) and 1.135 π/ng mm(-2), respectively. The biosensing capability of the sensor is verified by the measurement of biotin-streptavidin interaction of different concentrations.

Silicon waveguide filter based on cladding modulated anti-symmetric long-period grating.

In this paper, we demonstrate an optical filter using cladding modulated anti-symmetric long-period grating in a two-mode silicon waveguide. The filter consists of a two-mode waveguide connected with an input and output single-mode waveguide through two linear tapers. The anti-symmetric grating is formed by placing two periodic arrays of silicon squares offset by half of a grating pitch along the two-mode waveguide. Light coupling occurs between two co-propagating modes at the coupling wavelength through the grating and results in a rejection band at the output. The grating pitch, coupling coefficient, transmission spectrum and 3-dB bandwidth of the grating are investigated with the coupled-mode theory. By using a cladding modulated grating, the grating coupling strength can be controlled over a wide range by the two-mode waveguide width or separation distance between the grating and waveguide. Band-rejection filters are experimentally demonstrated in 1-µm, 0.8-µm and 0.7-µm wide two-mode silicon waveguides and rejection bands with different bandwidths and maximal attenuation contrasts larger than 15 dB (~97% coupling efficiency) have been achieved.

Silicon-based optoelectronic integrated circuit for label-free bio/chemical sensor.

We demonstrate a silicon-based optoelectronic integrated circuit (OEIC) for label-free bio/chemical sensing application. Such on-chip OEIC sensor system consists of optical grating couplers for vertical light coupling into silicon waveguides, a thermal-tunable microring as a tunable filter, an exposed microring as an optical label-free sensor, and a Ge photodetector for a direct electrical readout. Different from the conventional wavelength-scanning method, we adopt low-cost broadband ASE light source, together with the on-chip tunable filter to generate sliced light source. The effective refractive index change of the sensing microring induced by the sensing target is traced by scanning the supplied electrical power applied onto the tracing microring, and the detected electrical signal is read out by the Ge photodetector. For bulk refractive index sensing, we demonstrate using such OEIC sensing system with a sensitivity of ~15 mW/RIU and a detection limit of 3.9 µ-RIU, while for surface sensing of biotin-streptavidin, we obtain a surface mass sensitivity of S(m) = ~192 µW/ng·mm(-2) and a surface detection limit of 0.3 pg/mm(2). The presented OEIC sensing system is suitable for point-of-care applications.

Label-free, PCR-free chip-based detection of telomerase activity in bladder cancer cells.

Bladder cancer is one of the most common cancers in Worldwide. The determination of urinary telomerase activity is a promising tool for the diagnosis of bladder carcinoma owing to the high rate of expression of telomerase in cancer cells. Typical assay for telomerase activity is the telomeric repeat amplification protocol (TRAP) based on polymerase chain reaction (PCR) amplification. However, TRAP assay is susceptible to PCR-derived artifacts and requires time-consuming procedure, expensive equipments and reagents. To develop a new method for telomerase activity assay that is fast, simple, and cost-effective, we have examined a silicon-based microring resonator biosensor to detect label-free, PCR-free telomerase activity using telomerase extracted from two bladder cancer cell lines, J-82 and HT-1376, in a buffer solution and spiked urine. With telomerase primer immobilized microring resonator sensor system, we successfully demonstrate the detection of telomerse extracted from as little as 10 cells/µL and 100 cells/µL in buffer and urine, respectively. Especially, the results represented here is the first demonstration of the detection of telomerase activity in human urine on the chip-based system. From the results, we expect that the silicon photonic microring resonator system can provide a powerful tool for cost-effective and sensitive telomerase activity detection in urinary bladder cancer.

A refractive index sensor design based on grating-assisted coupling between a strip waveguide and a slot waveguide.

In this paper, we present a design of a refractive index sensor based on grating-assisted light coupling between a strip waveguide and a slot waveguide. The slot waveguide serves as the sensing waveguide while the strip waveguide is used for light launching and detection. The wavelength at which the light is coupled from the strip waveguide to the slot waveguide serves as a measure of the refractive index of the external medium. The sensitivity of the sensor is ~1.46 × 10(3) nm/RIU (refractive index unit) and can be almost doubled by isolating the strip waveguide from the external medium. The effects of the slot-waveguide parameters on the sensitivity have also been investigated. In particular, it is found that the sensor can achieve extraordinarily high sensitivity (on the order of 10(5) nm/RIU) when the group indices of two waveguides are close. The temperature dependence of the sensor is also investigated and a sensor with very low temperature dependence can be achieved with a polymer isolation layer.

Label-free biosensor based on an electrical tracing-assisted silicon microring resonator with a low-cost broadband source.

We present a novel biosensor based on an electrical tracing-assisted silicon dual-microring resonator sensor system. The dual-microring system comprises one microring resonator as a sensing element and the other microring resonator integrated with an electrical controller as a tracing element. The resonance wavelength shift of the sensing microring induced by the refractive index change due to antigen-ligand bindings is traced and determined by direct voltage applied to the electrical tunable tracing microring. The sensor system enables the use of a low-cost broadband light source instead of a bulky and expensive tunable laser, which allows the development of cost-effective point-of-care diagnostic devices by significantly reducing the device cost and increasing its portability. The sensing capability of the developed dual-microring sensor was investigated using biotin-streptavidin binding as a model system. We have demonstrated the quantitative detection of streptavidin over a broad range of concentrations down to 190 pM by monitoring the electrical power applied to the tracing ring. We have also validated the sensing principle of the dual-microring system by a direct comparison between the calculated and measured values for the resonance wavelength shift of the sensing microring. Furthermore, we have shown the quantitative and specific detection of a well-known breast cancer biomarker, human epidermal growth factor receptor 2 (HER2), in a bovine serum albumin solution using the antibody-modified dual-microring sensor system.

Electrical tracing-assisted dual-microring label­free optical bio/chemical sensors.

We propose and demonstrate a novel electrical tracing-assisted dual-microring resonator-based optical sensor system in silicon-on-insulator substrate. The system comprises one microring resonator-based sensing element and another microring resonator-based tracing element integrated with electrical controller. The resonance wavelength shift of sensing microring induced by the refractive index change is traced and determined by direct voltage supply of the electrical tunable tracing microring. Such optical sensing system eliminates the traditional wavelength-scanning method thus provide a cost effective sensing scheme. Proof-of-principle demonstration by testing polyelectrolyte multilayer shows the sensitivity of ~4.0 mW/ng∙mm-2 and the detection limit of ~5.35 pg/mm2.

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

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/(ng mm(-2)) and 1.30 (pg mm(-2)), while achieving a low temperature dependence is 5.0 pm/° 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 (pg mm(-2)).

Design and fabrication of Poly(dimethylsiloxane) arrayed waveguide grating.

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) arrayed waveguide grating (AWG) with four-channel output for operation in the visible light wavelength range. The PDMS AWG was realized based on the single-mode PDMS rib waveguide. The device was designed for 1 nm channel spacing with the wavelength ranging from 639 to 644 nm. The measured insertion loss is 11.4 dB at the peak transmission spectrum and the adjacent crosstalk is less than -16 dB. The AWG device occupies an area of 7.5 × 15 mm(2). PDMS AWG has the potential for integration with microfluidics in a monolithic PDMS lab-on-a-chip device for visible light spectroscopy applications.

Design and fabrication of poly(dimethylsiloxane) single-mode rib waveguide.

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) single-mode rib waveguides. PDMS was chosen specifically for the core and cladding. Combined with the soft lithography fabrication techniques, it enables an easy integration of microoptical components for lab-on-a-chip systems. The refractive index contrast, of 0.07% between the core and cladding for single-mode propagation was achieved by modifying the properties of the same base material. Alternatively, a higher refractive index contrast, of 1.18% was shown by using PDMS materials from two different manufacturers. The fabricated rib waveguides were characterized for mode profile characteristics and confirmed the excitation of the fundamental mode of the waveguide. The propagation loss of the single-mode rib waveguide was characterized using the cutback measurement method at a wavelength of 635 nm and found to be 0.48 dB/cm for of 0.07% and 0.20 dB/cm for of 1.18%. Y-branch splitter of PDMS single-mode rib waveguide was further demonstrated.