One‐Step Generation of a Drug‐Releasing Hydrogel Microarray‐On‐A‐Chip for Large‐Scale Sequential Drug Combination Screening

Abstract

Large‐scale screening of sequential drug combinations, wherein the dynamic rewiring of intracellular pathways leads to promising therapeutic effects and improvements in quality of life, is essential for personalized medicine to ensure realistic cost and time requirements and less sample consumption. However, the large‐scale screening requires expensive and complicated liquid handling systems for automation and therefore lowers the accessibility to clinicians or biologists, limiting the full potential of sequential drug combinations in clinical applications and academic investigations. Here, a miniaturized platform for high‐throughput combinatorial drug screening that is “pipetting‐free” and scalable for the screening of sequential drug combinations is presented. The platform uses parallel and bottom‐up formation of a heterogeneous drug‐releasing hydrogel microarray by self‐assembly of drug‐laden hydrogel microparticles. This approach eliminates the need for liquid handling systems and time‐consuming operation in high‐throughput large‐scale screening. In addition, the serial replacement of the drug‐releasing microarray‐on‐a‐chip facilitates different drug exchange in each and every microwell in a simple and highly parallel manner, supporting scalable implementation of multistep combinatorial screening. The proposed strategy can be applied to various forms of combinatorial drug screening with limited amounts of samples and resources, which will broaden the use of the large‐scale screening for precision medicine.

Microspinning: Local Surface Mixing via Rotation of Magnetic Microparticles for Efficient Small-Volume Bioassays

“…In addition, these polymeric microparticles are designed to have the shape code on their surface for use in multiplexed bioassays (Supplementary Figure S2). Multiplexed bioassays using shape-encoded microparticles enable the simultaneous detection and quantitation of multiple secreted proteins in a single microwell [21][22][23]. Thus, shape-encoded microparticles with 1D chains of magnetic nanoparticles are capable of using both magnetic attraction and magnetic rotating, which can result in diverse functional advantages in comprehensive bioassays (Figure 1b).…”

Divide and conquer: A perspective on biochips for single-cell and rare-molecule analysis by next-generation sequencing

“…NGS can be used on these platforms to measure changes in gene expression profiles after treatment with the drug candidates. For example, Song et al introduced massively parallel drug screening biochips that can measure the effects of sequential drug treatments 54 . The platform is composed of a cell-biochip with multiple microwells seeded with cells.…”

Comprehensive strategies of machine-learning-based quantitative structure-activity relationship models

“…AI technologies are driven by new ML algorithms, advances in computational power, and ever-increasing experimental data ( Bazoon et al., 2002 ; Pasquier and Hamodrakas, 2009 ). Advanced biotechnologies such as next-generation sequencing ( Dijk et al., 2014 ; Kim, 2019 ), cryo-electron microscopy, high-throughput screening ( Shin et al., 2016 ), medical digitization, and internet-of-things infrastructure ( Adrian et al., 1984 ; Atzori et al., 2010 ; Cai et al., 2019 ; Dubochet et al., 1988 ; Feng et al., 2012 ; Gupta et al., 2009 ; Li et al., 2013 ; Song et al, 2019 ) provide high-quality Big Data for the application of ML-based drug development. ML algorithms can be roughly divided into three kinds: unsupervised, supervised, and reinforced ( Ertel, 2017 ; Figueiredo and Jain, 2002 ; Kaelbling et al., 1996 ; Le, 2013 ; Piotr et al., 2006 ; Radford et al., 2015 ; Sahami, 1997 ; Sasakawa et al., 2010 ; Turian et al., 2010 ; Wang et al., 2019 ; Zhu and Goldberg, 2009 ).…”