Droplet Microfluidics for High-Resolution Virology

Abstract

Microfluidics has enabled a new era of cellular and molecular assays due to the small length scales, parallelization, and the modularity of various analysis and actuation functions. Droplet microfluidics, in particular, has been instrumental in providing new tools for biology with its ability to quickly and reproducibly generate drops that act as individual reactors. A notable beneficiary of this technology has been single-cell RNA sequencing, which has revealed new heterogeneities and interactions for the fundamental unit of life. However, viruses far surpass the diversity of cellular life, affect the dynamics of all ecosystems, and are a chronic source of global health crises. Despite their impact on the world, high-throughput and high-resolution viral profiling has been difficult, with conventional methods being limited to population-level averaging, large sample volumes, and few cultivable hosts. Consequently, most viruses have not been identified and studied. Droplet microfluidics holds the potential to address many of these limitations and offers new levels of sensitivity and throughput for virology. This Feature highlights recent efforts that have applied droplet microfluidics to the detection and study of viruses, including for diagnostics, virus−host interactions, and cell-independent virus assays. In combination with traditional virology methods, droplet microfluidics should prove a potent tool toward achieving a better understanding of the most abundant biological species on Earth.

The development of droplet-based microfluidic virus detection technology for human infectious diseases

“…Microuidics has proven to be a useful tool when used in conjunction with conventional virological methods to more successfully detect viruses early. 51 There are microuidic systems that can categorize millions of HIV-1 particles with >99% accuracy based on the expression of an epitope recognized by broadly neutralizing antibodies. 52 The investigation of individual viral particle surface epitopes holds enormous promise for the creation of vaccine candidates.…”

“…Microfluidics has proven to be a useful tool when used in conjunction with conventional virological methods to more successfully detect viruses early. 51…”

Sequentially Selective Coalescence of Binary Self-Propelled Droplets upon Collective Motion

“…Droplet-based synthesis and subsequent detection have shown promise in the development of novel functional materials and drugs because droplets could be used as microreactors for small-scale synthesis and detection of covalent/non-covalent molecular interactions. , However, the sequentiality and selectivity of microreactor coalescence require expensive devices and elaborate technologies, such as spatiotemporal control of droplet arrangement in manners of geometry, gravity, , magnetic field, electronic field, , acoustic wave, − thermal control, and optical manipulation. − Therefore, the self-organization exhibited by autonomous droplets under non-equilibrium conditions must bring innovation to manipulating sequential and selective droplet coalescence because the manipulation based on the autonomy of droplets does not require expensive devices and elaborate technologies.…”

Machine Learning-Aided Microdroplets Breakup Characteristic Prediction in Flow-Focusing Microdevices by Incorporating Variations of Cross-Flow Tilt Angles

“…18,19 Microdroplets with diverse morphologies and behavior are widely used in numerous fields, such as the controlled release of drugs, 20,21 biopharmaceuticals, 22,23 synthetic particulate materials, 24 and molecular analysis. 25,26 Due to the complexity of two-phase flow in droplet generation processes, developing a forecasting platform that provides a comprehensive overview of the size, frequency, regime, and quality of the produced droplets enormously aids researchers in cutting off the trialand-error expenses for acquiring the required droplet size and morphology. A few recent studies have been conducted to develop microfluidic devices for size-specific production of droplets.…”

“…One of the main hurdles in the microencapsulation of synthesized hydrogels for cell analysis, culture, and protein therapeutics is the lack of efficient methods for generating tunable capsule sizes . Besides, monodispersed droplets are required for interdisciplinary studies, such as particle synthesis, cell detection and separation, chemical reactions, and experiments in which each droplet is tested per second. , Microdroplets with diverse morphologies and behavior are widely used in numerous fields, such as the controlled release of drugs, , biopharmaceuticals, , synthetic particulate materials, and molecular analysis. , Due to the complexity of two-phase flow in droplet generation processes, developing a forecasting platform that provides a comprehensive overview of the size, frequency, regime, and quality of the produced droplets enormously aids researchers in cutting off the trial-and-error expenses for acquiring the required droplet size and morphology. A few recent studies have been conducted to develop microfluidic devices for size-specific production of droplets.…”