Microfluidic synthesis control technology and its application in drug delivery, bioimaging, biosensing, environmental analysis and cell analysis

The rapid development of metasurfaces -2D ensembles of engineered nanostructures -is presently fostering a steady drive towards the miniaturization of many optical functionalities and devices to a subwavelength size.The material platforms for optical metasurfaces are rapidly expanding and for the past few years, we are seeing a surge in establishing meta-optical elements from high-index, highly transparent materials with strong nonlinear and electro-optic properties.Crystalline lithium niobate (LN), a prime material of choice in integrated photonics, has shown great promise for future meta-optical components, thanks to its large electro-optical coefficient, second-order nonlinear response and broad transparency window ranging from the visible to the mid-infrared.Recent advances in nanofabrication technology have indeed marked a new milestone in the miniaturization of LN platforms, hence enabling the first demonstrations of LN-based metasurfaces.These seminal works set the first steppingstone towards the realization of ultra-flat monolithic nonlinear light sources with emission ranging from the visible to the infrared, efficient sources of correlated photon pairs, as well as electro-optical devices.Here, we review these recent advances, discussing potential perspectives for applications in light conversion and modulation shaping as well as quantum optics, with a critical eye on the potential setbacks and limitations of this emerging field. 

pdf/lithium-niobate-meta-optics-2or0cc8vrd.pdf

Lithium Niobate Meta-Optics

Droplet-based microfluidic systems require a precise control of droplet physical properties; hence, measuring the morphological properties of droplets is critical to obtain high sensitivity analysis. The ability to perform such measurements in real-time is another demand which has not been addressed yet. In this study, we used coplanar electrodes configured in the differential measurement mode for impedimetric measurement of size and velocity. To obtain the size of the droplets, detailed 3D finite element simulations of the system were performed. The interaction of the non-uniform electric field and the droplet was investigated. Electrode geometry optimization steps were described and design guideline rules were laid out. User-friendly software was developed for real-time observation of droplet length and velocity together with in situ statistical analysis results. A comparison between impedimetric and optical measurement tools is given. Finally, to illustrate the benefit of having real-time analysis, iDM was used to synthesize particles with a predefined monodispersity limit and to study the response times of syringe pump and pressure pump driven droplet generation devices. This analysis allows one to evaluate the ‘warm-up’ time for a droplet generator system, after which droplets reach the desired steady-state size required by the application of interest.

/pdf/real-time-impedimetric-droplet-measurement-idm-9p33f53ihg.pdf

Real-time impedimetric droplet measurement (iDM).

Single cell culture has been considered one of the fundamental tools for single cell studies. Complex biological systems evolve from single cells, and the cells within biological systems are intrinsically heterogeneous. Therefore, culturing and understanding the behaviors of single cells are of great interest for both biological research and clinical studies. In recent years, advances in microfluidics-based technologies have demonstrated unprecedented capabilities for single cell studies, and they have made high-throughput single cell cultures possible. Microfluidic systems enable precise control of the microenvironment for single cell culture and monitoring of the behavior of single cells in real time. In addition, microfluidic devices can consist of upstream cell sorting and cell isolation, and they can also be seamlessly integrated with various downstream analysis methods. Therefore, microfluidic technologies can obtain data about the performance at the single-cell level, providing information that cannot be achieved by studying the ensemble behavior of cell colonies. In this review, the recent developments in droplet-based microfluidics, microwell-based microfluidics, trap-based microfluidics and SlipChip-based microfluidics for the study of single cell culture is focused on. Perspectives on future improvement regarding single cell culture and its related research opportunities are also provided.

Advances in Microfluidics-Based Technologies for Single Cell Culture.

So far, microfluidic navigation based on space-charge modulation is limited in a two-dimensional (2D) substrate plane. In this paper, a three-dimensional (3D) photovoltaic water-microdroplet router based on a superhydrophobic LiNbO3:Fe crystal is reported. This router employs the repulsive electrostatic force induced by the positive photovoltaic charges generated under focused laser illumination and permits traveling microdroplets to be routed in both in-plane and out-of-plane ways. By analyzing the dynamic process of microdroplet routing, it is found that the microdroplets can gain positive charges through traveling on a superhydrophobic surface and that the positive photovoltaic charges exert an electrophoretic (EP) force on the microdroplets being charged and make them either routed inside the 2D substrate plane or jump out of the 2D plane through electrostatic ballistic ejection. The laser-illumination and microdroplet-size dependence of the deflecting parameters of the in-plane microdroplet routing as well as the jumping trajectory of the out-of-plane routing are investigated. An electrostatic kinetic model is established for both routing ways, and the simulation based on this model predicts well the experimental dependence. A few examples of cascaded free-space microfluidic transportation using the 3D photovoltaic router are demonstrated, showing the potential of this technique in future biological applications.

3D Photovoltaic Router of Water Microdroplets Aiming at Free-Space Microfluidic Transportation.

In this work, we realized and tested an integrated opto-microfluidics platform entirely made on lithium niobate (LiNbO3) crystals, able to detect the single droplet passage and estimate its size without the need of any imaging processing. It is based on the coupling of a self-aligned integrated optical stage, made of an array of optical waveguides, to a microfluidic circuit such as a T-junction or Cross-junction engraved in the same substrate. The platform presented high quality performances in terms of optical triggering, reproducibility and stability in time, allowing in real-time data analysis. The comparison with standard approaches using microscopes and fast camera imagining acquisition and relative post-processing, showed an increased capability better than 50%. The demonstrated feasibility of integration of these two stages will allow the realization of a Lab-On-a-Chip on a monolithic substrate of lithium niobate, exploiting its multiple applications for manipulation of droplets.

LiNbO3 integrated system for opto-microfluidic sensing

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LiNbO3 integrated system for opto-microfluidic sensing