The potential of nanophotonic lab-on-chip biosensors for high-value diagnostics

Summary form only given. Portable lab-on-chip (LOC) devices for clinical diagnostics will be a milestone for the achievement of universal healthcare and environmental protection. Motivated by potential benefits such as sensor miniaturisation, multiplexing capabilities and relevant sensitivities in a label-free scheme, Silicon photonics based-biosensors are the most suitable candidates to achieve such portable devices [1]. These photonic biosensors consist of compact waveguides contained on chips which can be easily miniaturized and fabricated in arrays of identical sensors for multiplexed analysis. We introduced several years ago an innovative photonic sensor design based on a bimodal waveguide (BiMW) interferometer [1], a single channel Si3N4 waveguide which mechanism is based on the interference of two waveguide modes of the same polarization, operating at visible wavelengths with monochromatic and polarized (TE or TM) light. The simplicity of our BiMW design is quite attractive while its sensitivity of around 1x10-7 RIU in bulk [1] is comparable to more complex interferometric schemes. We have been working in the full integration of the BiMW technology in a LOC platform. For the achievement of the complete platform, several units need to be incorporated, including the BiMW sensors, the microfluidics and the flow delivery system, the multiplexed in and out-coupling of the light and the light read-out. Moreover, a specific and custom-designed biofunctionalization protocol must be developed depending of the targeted application. In order to improve the integration and cost of the final device, we have introduced a new all-optical wavelength modulation system where the emission wavelength of a low-cost commercial laser diode was modulated a few nms by controlling its output power. After a Fast Fourier Transform deconvolution, the linear response of the BiMW sensor is obtained [2]. For the fabrication of the microfluidics channels we employ several routes, including polydimethylsiloxane (PDMS) channels fabricated by soft lithography or SU-8 microfluidics delivery channels fabricated at wafer level by standard lithography. We recently have proposed the integration of a fully automated and active PDMS optofluidic system with the BiMW technology [3]. One main challenge for the BiMW POC sensing technology is the demonstration of its utility in the clinical practise being able to handle and directly analyse minimum amounts of body fluids without previous labeling, detecting biomarkers in their natural form. We have demonstrated the suitability of our BiMW nanophotonic platform for the real clinical diagnostics, as for example: (i) quantitative detection of Escherichia coli in undiluted human ascitic fluid from cirrhotic patients at very low concentration (40 cfu·mL-1) [5] (iii) detection and quantification of miR-181a at attomolar concentrations (LOD = 23 aM) directly, and for the first time, in human urine samples of bladder cancer patients with no need for prior sample purification or amplification steps [6]. In all cases, the BiMW nanosensor has shown excellent robustness with high reproducibility and sensitivity, rendering in a valuable tool for fast diagnostics of bodily fluids samples.