Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development We believe this review will promote communications among biology, chemistry, physics, and materials science

Emerging Droplet Microfluidics

Microdroplets in microfluidics offer a great number of opportunities in chemical and biological research. They provide a compartment in which species or reactions can be isolated, they are monodisperse and therefore suitable for quantitative studies, they offer the possibility to work with extremely small volumes, single cells, or single molecules, and are suitable for high-throughput experiments. The aim of this Review is to show the importance of these features in enabling new experiments in biology and chemistry. The recent advances in device fabrication are highlighted as are the remaining technological challenges. Examples are presented to show how compartmentalization, monodispersity, single-molecule sensitivity, and high throughput have been exploited in experiments that would have been extremely difficult outside the microfluidics platform.

/pdf/microdroplets-in-microfluidics-an-evolving-platform-for-2cv0bnf850.pdf

Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology

This Review summarizes recent developments in the field of responsive photonic crystal structures, including principles for design and fabrication and many strategies for applications, for example as optical switches or chemical and biological sensors. A number of fabrication methods are now available to realize responsive photonic structures, the majority of which rely on self-assembly processes to achieve ordering. Compared with microfabrication techniques, self-assembly approaches have lower processing costs and higher production efficiency, however, major efforts are still needed to further develop such approaches. In fact, some emerging techniques such as spin coating, magnetic assembly, and flow-induced self-assembly have already shown great promise in overcoming current challenges. When designing new systems with improved performance, it is always helpful to bear in mind the lessons learnt from natural photonic structures.

Responsive photonic crystals.

Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

https://iopscience.iop.org/article/10.1088/0034-4885/75/1/016601/pdf

Droplet based microfluidics

Natural structural color materials, especially those that can undergo reversible changes, are attracting increasing interest in a wide variety of research fields. Inspired by the natural creatures, many elaborately nanostructured photonic materials with variable structural colors were developed. These materials have found important applications in switches, display devices, sensors, and so on. In this critical review, we will provide up-to-date research concerning the natural and bio-inspired photonic materials with variable structural colors. After introducing the variable structural colors in natural creatures, we will focus on the studies of artificial variable structural color photonic materials, including their bio-inspired designs, fabrications and applications. The prospects for the future development of these fantastic variable structural color materials will also be presented. We believe this review will promote the communications among biology, bionics, chemistry, optical physics, and material science (196 references).

Bio-inspired variable structural color materials

In recent years, suspension arrays, which use self-encoded microcarriers as elements, are attracting increasing interest in the field of drug discovery, gene-function analysis, clinical diagnosis, and so on. Compared with the conventional microarrays on a plate, suspension arrays may offer greater flexibility in the preparation of new assays, higher diffusional flux of analytes due to the radial diffusion, less consumption of sample and reagents, and higher sensitivity. One of the key techniques of suspension arrays is encoding. Spectrum is a wellused encoding approach, due to its simplicity both in encoding and decoding. Fluorescent dyes and quantum dots are the main spectrum-encoding elements, and the beads encoded by fluorescence have been commercialized by Luminex and other companies. However, fluorescence dyes tend to be quenched or bleached, and the quantum dots are usually biotoxic. Also, the fluorescence of the carriers can interfere with the signal from the labeling molecules, and as a result affect the detection limit. Photonic crystals have been suggested as a new type of spectrum-encoding carrier, whose code is the characteristic reflection peak originated from the stop-band. As the peak position is based on their periodical structure, the code is very stable, and the fluorescent background is low. These properties render photonic crystals suitable for highly sensitive detection. Conventional planar photonic-crystal carriers have to be properly dispersed and correctly orientated to avoid stacking or standing of the flakes during the decoding process. Recently, we found that these problems might be solved with the use of photonic beads with a 3D structure. Unlike planar photonic-crystal carriers, the photonic beads retain their reflection spectra when the crystals are rotated under light impinging on the crystal surface at a fixed incident angle. This indicates the accurate encoding character of photonic beads. Another key technique for using suspension arrays is target analysis, which is generally realized by detecting the labels attached to the biomolecules. In addition to the high cost imposed by reagents and instruments, the labels, or labeling itself, will hinder the interactions and the activity of biomolecules. Therefore, label-free detection is anticipated. In this paper, we proposed the use of inverse-opaline photonic beads as carriers for suspension arrays. The beads showed large encoding capacity by changing their lattice constant. A label-free multiplex detection of tumor markers, Human CA125, CA19-9, and CEA, which showed great significance in early screening and clinical diagnosis of some tumor diseases including colorectal cancer, gastric cancer, and lung cancer, show the flexibility and feasibility of our suspension array in clinical applications. In addition, both the decoding and bioreaction detection were measurements of the characteristic reflection peak, which rendered the detection and the analyzing apparatus extremely simple. Up to now, attention was devoted to the fabrication of inverseopaline photonic films, and only a few reports on the formation of inverse-opaline photonic beads are available. Template replication and spray-drying with colloidal templates are examples of methods that showed the difficulty in preparing beads with smooth edges and long-range-ordering porous surfaces, due to low surface tension and too fast assembly. Herein, we produced inverse-opaline photonic beads by colloidal crystallization in droplet templates. First, an aqueous suspension containing monodisperse polystyrene spheres and ultrafine silica particles was broken into droplets by oil flows in a microfluidic device, and the droplets were taken into a collection container that was also filled with silicon oil. Then, the polystyrene spheres self-assembled into ordered lattices, and the ultrafine silica particles infiltrated into the interstitial sites between the spheres during the evaporation of water in the droplets. After solidification, the hybrid beads were thoroughly washed with hexane to remove silicon oil. Finally, the hybrid beads were calcined, to remove the polystyrene spheres and improve the mechanical strength of the inverseopaline photonic beads. Generally, the long-range ordering of pores on bead surfaces was important for the optical performance of the inverse-opaline photonic beads. To optimize this performance, change of pore arrangement on the bead surface with varying polystyrene spheres to silica particles volume ratios in the droplet template were investigated. Theoretically, when the polystyrene spheres packed closely to a bead in a face-centered cubic arrangement, and the ultrafine silica particles infiltrated all the interstitial sites between the polystyrene spheres, the volume ratio was about 3.85. In our experiment, however, we found that during the evaporation of water the polystyrene spheres escaped more easily from the droplet templates than silica particles; also, after solidification the silica particles could not infiltrate into all the interstitial sites

Encoded porous beads for label-free multiplex detection of tumor markers.

A novel hydrogel suspension array, which possesses the joint advantages of quantum-dot-encoded technology, bioresponsive hydrogels, and photonic crystal sensors with full multiplexing label-free DNA detection capability is developed. The microcarriers of the suspension array are quantum-dot-tagged DNA-responsive hydrogel photonic beads. In the case of label-free DNA detection, specific hybridization of target DNA and the crosslinked single-stranded DNA in the hydrogel grid will cause hydrogel shrinking, which can be detected as a corresponding blue shift in the Bragg diffraction peak position of the beads that can be used for quantitatively estimating the amount of target DNA. The results ofthe label-free DNA detection show that the suspension array has high selectivity and sensitivity with a detection limit of 10 ―9 M. This method has the potential to provide low cost, miniaturization, and simple and real-time monitoring of hybridization reaction platforms for detecting genetic variations and sequencing genes.

Quantum‐Dot‐Tagged Bioresponsive Hydrogel Suspension Array for Multiplex Label‐Free DNA Detection

Multiplex detection of biomolecules has facilitated clinical diagnosis, drug discovery, and environmental testing. Immunoassays using labeled antibodies are the most popular methods for the detection of biomolecules because of their sensitivity and selectivity. However, labeling protocols are time-consuming and expensive, and may alter the form or physicochemical behavior of the antibodies, which could lead to false negative results. In addition, the reagent stability, high cost, and difficulties associated with antibody production, together with the adverse action of toxic compounds or immunosuppressants on the metabolism and the immune system during the production of antibodies, are often cited as problems. Therefore, it is highly desirable to carry out multiplex label-free detection of biomolecules without using immunoassay methods. Suspension arrays, which use self-encoded microcarriers as elements, have shown obvious advantages in the multiplex detection of biomolecules. However, few of them can be used for the label-free detection of biomolecules. Moreover, these methods are still based on the use of probe antibodies. In contrast, molecularly imprinted polymers (MIPs) have unique properties as mimics of natural molecular receptors that may make them suitable for revolutionary applications in biotechnology. Recently, many kinds of MIP sensors have been developed for the detection of biomolecules based on physicochemical responses of the MIPs, such as changes in refractive index and volume. However, these sensors could respond only to single analytes, and the detection signals from the physicochemical response of the MIPs were not distinct and were difficult to measure with accuracy. Herein, we report a new type of suspension array for the multiplex label-free detection of biomolecules without using immunoassay methods. The microcarriers of our suspension array are molecularly imprinted polymer beads (MIPBs) with photonic crystal structure, which not only provide diffraction peaks for encoding but also convert the slight physicochemical response signals to the obvious changes of optical signals. This technique combines the advantages of suspension arrays, molecular imprinting, and photonic crystal sensors. As a proof of concept for the multiplex label-free detection of biomolecules not based on immunoassay methods, we constructed an imprinted suspension array with affinity for proteins. For large biomacromolecules, surface imprinting was used for the fabrication of the MIPBs with photonic crystal structure due to the easy removal and rapid rebinding characteristics during assays. Scheme 1 outlines the

Multiplex Label‐Free Detection of Biomolecules with an Imprinted Suspension Array

Multiplex detection of tumor markers with photonic suspension array.

A microfluidic device was used to generate droplets of monodispersed silica nanoparticles in poly (ethylene glycol) diacrylates (PEG-DA), which were then polymerized into hydrogel beads by UV irradiation. The nanoparticles in the beads were assembled into ordered lattices and locked in the network of the hydrogel. Therefore, the beads showed photonic crystal features, whose reflection peaks were used as the coding elements of biomolecular carriers. And huge coding capacity could be gained by changing the volume fraction of the silica nanoparticles in the droplets. The beads provided homogeneous water surroundings so that some shortcomings in bioassay introduced by the presence of solid surface of carriers could be avoided. Their application in oligonucleotide detection demonstrated potential advantages of hydrogel beads as encoded carriers in multiplex biomolecular detection.

Jing Hu

Papers

Encoded porous beads for label-free multiplex detection of tumor markers.

Quantum‐Dot‐Tagged Bioresponsive Hydrogel Suspension Array for Multiplex Label‐Free DNA Detection

Multiplex Label‐Free Detection of Biomolecules with an Imprinted Suspension Array

Multiplex detection of tumor markers with photonic suspension array.

Photonic crystal hydrogel beads used for multiplex biomolecular detection