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The effective analysis of the basic structure and functional information of bioparticles are of great significance for the early diagnosis of diseases. The synergism between microfluidics and particle manipulation/detection technologies offers enhanced system integration capability and test accuracy for the detection of various bioparticles. Most microfluidic detection platforms are based on optical strategies such as fluorescence, absorbance, and image recognition. Although optical microfluidic platforms have proven their capabilities in the practical clinical detection of bioparticles, shortcomings such as expensive components and whole bulky devices have limited their practicality in the development of point-of-care testing (POCT) systems to be used in remote and underdeveloped areas. Therefore, there is an urgent need to develop cost-effective non-optical microfluidic platforms for bioparticle detection that can act as alternatives to optical counterparts. In this review, we first briefly summarise passive and active methods for bioparticle manipulation in microfluidics. Then, we survey the latest progress in non-optical microfluidic strategies based on electrical, magnetic, and acoustic techniques for bioparticle detection. Finally, a perspective is offered, clarifying challenges faced by current non-optical platforms in developing practical POCT devices and clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Flow cytometry has proven its capability for rapid and quantitative analysis of individual cells and the separation of targeted biological samples from others. The emerging microfluidics technology makes it possible to develop portable microfluidic diagnostic devices for point-of-care testing (POCT) applications. Microfluidic flow cytometry (MFCM), where flow cytometry and microfluidics are combined to achieve similar or even superior functionalities on microfluidic chips, provides a powerful single-cell characterisation and sorting tool for various biological samples. In recent years, researchers have made great progress in the development of the MFCM including focusing, detecting, and sorting subsystems, and its unique capabilities have been demonstrated in various biological applications. Moreover, liquid biopsy using blood can provide various physiological and pathological information. Thus, biomarkers from blood are regarded as meaningful circulating transporters of signal molecules or particles and have great potential to be used as non (or minimally)-invasive diagnostic tools. In this review, we summarise the recent progress of the key subsystems for MFCM and its achievements in blood-based biomarker analysis. Finally, foresight is offered to highlight the research challenges faced by MFCM in expanding into blood-based POCT applications, potentially yielding commercialisation opportunities.

Microalgae cells have been recognized as a promising sustainable resource to meet worldwide growing demands for renewable energy, food, livestock feed, water, cosmetics, pharmaceuticals, and materials. In order to ensure high-efficiency and high-quality production of biomass, biofuel, or bio-based products, purification procedures prior to the storage and cultivation of the microalgae from contaminated bacteria are of great importance. The present work proposed and developed a simple, sheathless, and efficient method to separate microalgae Chlorella from bacteria Bacillus Subtilis in a straight channel using the viscoelasticity of the medium. Microalgae and bacteria migrate to different lateral positions closer to the channel centre and channel walls respectively. Fluorescent microparticles with 1 μm and 5 μm diameters were first used to mimic the behaviours of bacteria and microalgae to optimize the separating conditions. Subsequently, size-based separation in Newtonian fluid and in viscoelastic fluid in straight channels with different aspect ratios was compared and demonstrated. Under the optimal condition, the removal ratio for 1 μm microparticles and separation efficiency for 5 μm particles can reach up to 98.28% and 93.85% respectively. For bacteria and microalgae cells separation, the removal ratio for bacteria and separation efficiency for microalgae cells is 92.69% and 100% respectively. This work demonstrated the continuous and sheathless separation of microalgae from bacteria for the first time by viscoelastic microfluidics. This technique can also be applied as an efficient and user-friendly method to separate mammalian cells or other kinds of cells.

Although droplet-based microfluidics has been broadly used as a versatile tool in biology, chemistry, and nanotechnology, its rather complicated microfabrication process and the requirement of specialized hardware and operating skills hinder researchers fully unleashing the potential of this powerful platform. Here, we develop an integrated microdroplet generator enabled by a spinning conical frustum for the versatile production of near-monodisperse microdroplets in a high-throughput and off-chip manner. The construction and operation of this generator are simple and straightforward without the need of microfabrication, and we demonstrate that the generator is able to passively and actively control the size of the produced microdroplets. In addition to water microdroplets, this generator can produce microdroplets of liquid metal that would be difficult to produce in conventional microfluidic platforms as liquid metal has high surface tension. Moreover, we demonstrate that this generator can produce solid hydrogel microparticles and fibers using integrated ultraviolet (UV) light. In the end, we further explore the ability of this generator for forming double emulsions by coflowing two immiscible liquids. Given the remarkable abilities demonstrated by this platform and the tremendous potential of microdroplets, this user-friendly method may revolutionize the future of droplet-based chemical synthesis and biological analysis.

Proteinuria is an established risk marker for progressive renal function loss and patients would significantly benefit from a point-of-care testing. Although extensive work has been done to develop the microfluidic devices for the detection of urinary protein, they need the complicated operation and bulky peripherals. Here, we present a rapid, maskless 3D prototyping for fabrication of capillary fluidic circuits using laser engraving. The capillary circuits can be fabricated in a short amount of time (<10 min) without the requirements of clean-room facilities and photomasks. The advanced capillary components (e.g., trigger valves, retention valves and retention bursting valves) were fabricated, enabling the sequential liquid delivery and sample-reagent mixing. With the integration of smartphone-based detection platform, the microfluidic device can quantify the urinary protein via a colorimetric analysis. By eliminating the bulky and expensive equipment, this smartphone-based detection platform is portable for on-site quantitative detection., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay., Competing Interests: Conflict of interest statement: R.H.C., Z.J.G., and A.R.A. are shareholders in Scribe Biosciences, Inc., a company incorporated to commercialize the printed droplet microfluidics technology described in this paper.

Intercellular signalling has been identified as a highly complex process, responsible for orchestrating many physiological functions. While conventional methods of investigation have been useful, their limitations are impeding further development. Microfluidics offers an opportunity to overcome some of these limitations. Most notably, microfluidic systems can emulate the in-vivo environments. Further, they enable exceptionally precise control of the microenvironment, allowing complex mechanisms to be selectively isolated and studied in detail. There has thus been a growing adoption of microfluidic platforms for investigation of cell signalling mechanisms. This review provides an overview of the different signalling mechanisms and discusses the methods used to study them, with a focus on the microfluidic devices developed for this purpose., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ultrastructural analysis of cells can reveal valuable information about their morphological, physiological, and biochemical characteristics. Scanning electron microscopy (SEM) has been widely used to provide high-resolution images from the surface of biological samples. However, samples need to be dehydrated and coated with conductive materials for SEM imaging. Besides, immobilizing non-adherent cells during processing and analysis is challenging and requires complex fixation protocols. In this work, we developed a novel dielectrophoresis based microfluidic platform for interfacing non-adherent cells with high-resolution SEM at low vacuum mode. The system enables rapid immobilization and dehydration of samples without deposition of chemical residues over the cell surface. Moreover, it enables the on-chip chemical stimulation and fixation of immobilized cells with minimum dislodgement. These advantages were demonstrated for comparing the morphological changes of non-budding and budding yeast cells following Lyticase treatment.

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

For understanding cells functionalities and their communications, there is a need for highly sensitive cell analysis platforms capable of assessing non-specific chemicals on the surface and in the vicinity of cells. We report a microfluidic system integrating dielectrophoresis and surface enhanced Raman scattering (SERS) for the trapping and real time monitoring of cell functions in isolated and grouped cell clusters. Yeast cells are coated with silver nanoparticles to enable highly sensitive SERS analysis. The SERS responses of cells are examined under various conditions: live vs. dead and isolated vs. grouped. This work illustrates the feasibility of the system for in situ cell monitoring and analysis of secreted chemicals during their growth, metabolism, proliferation and apoptosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dielectrophoresis is a versatile tool for the sorting, immobilization, and characterization of cells in microfluidic systems. The performance of dielectrophoretic systems strongly relies on the configuration of microelectrodes, which produce a nonuniform electric field. However, once fabricated, the microelectrodes cannot be reconfigured to change the characteristics of the system. Here, we show that the reorientation of the microfluidic channel with respect to the microelectrodes can be readily utilized to alter the characteristics of the system. This enables us to change the location and density of immobilized viable cells across the channel, release viable cells along customized numbers of streams within the channel, change the deflection pattern of nonviable cells along the channel, and improve the sorting of viable and nonviable cells in terms of flow throughput and efficiency of the system. We demonstrate that the reorientation of the microfluidic channel is an effective tool to create versatile dielectrophoretic platforms using the same microelectrode design., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)