We realized integrated photonics multi-waveguide devices for optical trapping and Raman spectroscopy of particles in a fluid. In these devices, multiple beams directed towards the device center lead to a local field enhancement around this center and thus counteract the effect of light concentration near the facets, which is a disadvantage of dual-waveguide traps. Thus, a trapping region is created around the center, where a single particle of a size in a wide range can be trapped and studied spectroscopically, free from the influence of surfaces. We report the design (including simulations), fabrication and performance demonstration for multi-waveguide devices, using our Si3N4 waveguiding platform as the basis. The designed ridge waveguides, optimized for trapping and Raman spectroscopy, emit narrow beams. Multiple waveguides arranged around the central microbath result from fanning out of a single input waveguide using Y-splitters. A second waveguiding layer is implemented for detection of light scattered by the trapped particle. For reliable filling of the device with sample fluid, microfluidic considerations lead to side channels of the microbath, to exploit capillary forces. The interference of the multiple beams produces an array of hot spots around the bath center, each forming a local trap. This property is clearly confirmed in the experiments and is registered in videos. We demonstrate the performance of a 2-waveguide and a 16-waveguide device, using 1 and 3 pm polystyrene beads. Study of the confined Brownian motion of the trapped beads yields experimental values of the normalized trap stiffness for the in-plane directions. The stiffness values for the 16-waveguide device are comparable to those of tightly focused Gaussian beam traps and are confirmed by our own simulations. The Raman spectra of the beads (in this work measured via an objective) show clear peaks that are characteristic of polystyrene. In the low-wavenumber range, the spectra have a background that most likely originates from the Si3N4 waveguides.@en

Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1μm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to monitor therapy effectiveness. Whereas, small tumor-derived EVs (<1μm) are likely to outnumber their larger counterparts, thereby offering better statistical significance, identification and quantification of small tdEVs are more challenging. In the blood of cancer patients, a subpopulation of EVs originate from tumor cells, but these EVs are outnumbered by non-EV particles and EVs from other origin. In the Dutch NWO Perspectief Cancer-ID program, we developed and evaluated detection and characterization techniques to distinguish EVs from non-EV particles and other EVs. Despite low signal amplitudes, we identified characteristics of these small tdEVs that may enable the enumeration of small tdEVs and extract relevant information. The insights obtained from Cancer-ID can help to explore the full potential of tdEVs in the clinic.@en

Optofluidic lab-on-a-chips (LOCs) employing a dual-waveguide trap for optical trapping and Raman spectroscopy have proven to be attractive and potent tools for high throughput chemical fingerprinting of bio-particles for disease diagnosis. Among the relevant bio-particles are extracellular vesicles (EVs) which a been proven through recent studies to be potential biomarkers for identification of diseases, such as cancer. However, EVs are small with diameters ranging between 30 and 1000 nm and present a challenge for both on-chip optical trapping and Raman Spectroscopy. The research presented in this thesis is aimed at the development of a multi-waveguide optical trap aimed at the combined on-chip optical trapping and Raman spectroscopy for biochemical characterisation of single EVs. Firstly, the capabilities and limitations of a dual-waveguide trap for stable on-chip optical trapping of EVs is investigated through an in-depth simulation study. This ultimately yields a comprehensive overview of stable trapping conditions for EVs in terms of EV diameter and refractive index, and the injected optical power. Then, novel multi-waveguide traps are designed and fabricated. These multi-waveguide traps lead to stronger light confinement in the channel, resulting in improved optical trapping and Raman signal generation. This is experimentally demonstrated through the optical trap stiffness values and the recorded Raman signal strength of polystyrene beads generated between a 2-waveguide and 16-waveguide trap. Finally, the 16-waveguide trap is used to demonstrate optical trapping of B. Subtillis spores, as an intermediate step towards EVs. Optical trapping of the spores is studied with both experiments and simulations. Special attention is paid to the effect of random phase differences between the beams exiting the waveguides on the optical trap quality. In conclusion, the results show promising prospects for the realisation of multi-waveguide traps for on-chip biochemical fingerprinting of EVs with optical trapping and Raman spectroscopy. @en

The application of on-chip optical trapping and Raman spectroscopy using a dual-waveguide trap has so far been limited to relatively big synthetic and biological particles (e.g., polystyrene beads and blood cells). Here, from simulations, we present the capabilities of dual-waveguide traps built from composite SiO2-Si3N4 waveguides for optical trapping of extracellular vesicles (EVs). EVs, tiny cell-derived particles of size in the range 30−1000 nm, strongly attract attention as potential biomarkers for cancer. EVs are hard to trap, because of their smallness and low index contract w.r.t. water. This poses a challenge for on-chip trapping. From finite-difference time-domain simulations we obtain the narrow beam emitted from the waveguide facet into water, for λ = 785 nm. For a pair of such beams, in a counter-propagating geometry and for facet separations of 5, 10 and 15 µm, we derive the inter-facet optical field, which has a characteristic interference pattern with hot spots for trapping, and calculate the optical force exerted on EVs of size in the range 50−1000 nm, as a function of EV position. We use two refractive index models for the EV optical properties. Integration of the force curves leads to the trapping potentials, which are well-shaped in the transverse and oscillatory in the longitudinal direction. By applying Ashkin’s criterion, the conditions for stable trapping are established, the central result of this work. Very small EVs can be stably trapped with the traps by applying a power also suitable for Raman spectroscopy, down to a smallest EV diameter of 115 nm. We thus argue that this dual-waveguide trap is a promising lab-on-a-chip device with clinical relevance for diagnosis of cancer.@en