Liquid crystals (LCs) with stimuli-responsive configuration transition and optical anisotropic properties have attracted enormous interest in the development of simple and label-free biosensors. The combination of microfluidics and the LCs offers great advantages over traditional LC-based biosensors including small sample consumption, fast analysis and low cost. Moreover, microfluidic techniques provide a promising tool to fabricate uniform and reproducible LC-based sensing platforms. In this review, we emphasize the recent development of microfluidics in the fabrication and integration of LC-based biosensors, including LC planar sensing platforms and LC droplets. Fabrication and integration of LC-based planar platforms with microfluidics for biosensing applications are first introduced. The generation and entrapment of monodisperse LC droplets with different microfluidic structures, as well as their applications in the detection of chemical and biological species, are then summarized. Finally, the challenges and future perspectives of the development of LC-based microfluidic biosensors are proposed. This review will promote the understanding of microfluidic techniques in LC-based biosensors and facilitate the development of LC-based microfluidic biosensing devices with high performance.

A microfluidic device integrated with 3D thin film microelectrode arrays wrapped around serpentine-shaped microchannel walls has been designed, fabricated and tested for cell electrofusion. Each microelectrode array has 1015 discrete microelectrodes patterned on each side wall, and the adjacent microelectrodes are separated by coplanar dielectric channel wall. The device was tested to electrofuse K562 cells under a relatively low voltage. Under an AC electric field applied between the pair of the microelectrode arrays, cells are paired at the edge of each discrete microelectrode due to the induced positive dielectrophoresis. Subsequently, electric pulse signals are sequentially applied between the microelectrode arrays to induce electroporation and electrofusion. Compared to the design with thin film microelectrode arrays deposited at the bottom of the side walls, the 3D thin film microelectrode array could induce electroporation and electrofusion under a lower voltage. The staggered electrode arrays on opposing side walls induce inhomogeneous electric field distribution, which could avoid multi-cell fusion. The alignment and pairing efficiencies of K562 cells in this device were 99% and 70.7%, respectively. The electric pulse of low voltage (∼9 V) could induce electrofusion of these cells, and the fusion efficiency was about 43.1% of total cells loaded into the device, which is much higher than that of the convectional and most existing microfluidics-based electrofusion devices.

Retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) have become a promising model in vitro to recapitulate human retinal development, which can be further employed to explore the mechanisms of retinal diseases. However, the current culture systems for ROs lack physiologically relevant microenvironments, such as controllable mechano-physiological cues and dynamic feedback between cells and the extracellular matrix (ECM), which limits the accurate control of RO development. Therefore, we designed a controllable perfusion microfluidic chip (CPMC) with the advantages of precisely controlling fluidic shear stress (FSS) and oxygen concentration distribution in a human embryonic stem cell (hESC)-derived RO culture system. We found that ROs cultured under this system allow for expanding the retinal progenitor cell (RPC) pool, orchestrating the retinal ganglion cell (RGC) specification, and axon growth without disturbing the spatial and temporal patterning events at the early stage of RO development. Furthermore, RNA sequencing data revealed that the activation of voltage-gated ion channels and the increased expression of ECM components synergistically improve the growth of ROs and facilitate the differentiation of RGCs. This study elaborates on the advantages of the designed CPMC to promote RO growth and provide a controllable and reliable platform for the efficient maturity of RGCs in the ROs, promising applications in modeling RGC-related disorders, drug screening, and cell transplantation.

Integrating three-dimensional (3D) microelectrodes on microfluidic chips based on polydimethylsiloxane (PDMS) has been a challenge. This paper introduces a composite 3D electrode composed of Ag powder (particle size of 10 nm) and PDMS. Ethyl acetate is added as an auxiliary dispersant during the compounding process. A micromachining technique for processing 3D microelectrodes of any shape and size was developed to allow the electrodes to be firmly bonded to the PDMS chip. Through theoretical calculations, numerical simulations, and experimental verification, the role of the composite 3D microelectrodes in separating polystyrene particles of three different sizes via dielectrophoresis was systematically studied. This microfluidic device separated 20-, 10-, and 5-μm polystyrene particles nondestructively, efficiently, and accurately.