Fish Capsules: A System for High‐Throughput Screening of Combinatorial Drugs

Abstract

Large‐scale screening of molecules heavily relies on phenotyping of small living organisms during preclinical development. However, deep profiling candidate therapeutics on whole animals typically requires laborious manipulations and anesthetic treatment using traditional techniques or automated tools. Here, a novel fish capsule system that combines automated zebrafish encapsulating technology and droplet microarray strategy for in vivo functional screening of mono/polytherapies is described. This platform enables automated, rapid zebrafish orientation and immobilization in agarose to generate large‐scale fish capsules by using a microfluidic device. Based on the effect of discontinuous dewetting, the prompt trapping of fish capsules in the aqueous arrays is successfully demonstrate. This system provides the capability to integrate pharmaceutical treatments with real‐time multispectral microscopic imaging in a simple, pipetting‐free and highly parallel manner. Coupling with machine learning algorithms, a small library of compounds is screened and analyzed, and clues about how to exploit compound combinations as therapeutic candidates are obtained. It is believed that this proposed strategy can be readily applied to multiple fields and is especially useful in the exploration of combinatorial drugs with limited amounts of samples and resources to accelerate the identification of novel therapeutics for precision medicines.

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics

“…However, deep profiling candidate therapeutics typically requires laborious manipulations. Tang et al combined automated zebrafish encapsulating technology and a droplet microarray strategy for in vivo functional screening of mono/polytherapies . First, zebrafish larvae are oriented and immobilized in agarose devices that generate large-scale fish capsules.…”

“…Tang et al combined automated zebrafish encapsulating technology and a droplet microarray strategy for in vivo functional screening of mono/polytherapies. 157 First, zebrafish larvae are oriented and immobilized in agarose devices that generate large-scale fish capsules. Second, these capsules are distributed in an aqueous array for large-scale imaging.…”

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

“…However, poor correlation between in vivo and in vitro delivery outcomes suggests that flow cytometry and image cytometry must be restricted to ex vivo therapeutic applications. Small in vivo models, such as Caenorhabditis elegans, , zebrafishes, and the chicken egg chorioallantoic membrane (CAM) model could be applied in tandem with high-content analysis platforms to screen out toxic formulations prior to testing in primate/murine models. While Caenorhabditis elegans and zebrafishes will not recapitulate human physiology, they combine several interesting features for high-throughput screening of toxic formulations.…”

Femtosecond laser-scribed superhydrophilic/superhydrophobic self-splitting patterns for one droplet multi-detection

“…Droplet manipulation is fundamental for a wide range of applications, including combinatorial analysis, [1][2][3] high-sensitivity detection, [4][5][6] and biological screening. [7][8][9] Various strategies have been developed to regulate droplet movement, such as external field stimulation, [10][11][12][13][14][15][16][17] which controls droplet dynamics by applying specific forces such as light, heat, magnetism, and electricity.…”