Evaluation of the Droplet-Microarray Platform for High-Throughput Screening of Suspension Cells

Abstract

Phenotypic cell-based high-throughput screenings play a central role in drug discovery and toxicology. The main tendency in cell screenings is the increase of the throughput and decrease of reaction volume in order to accelerate the experiments, reduce the costs, and enable screenings of rare cells. Conventionally, cell-based assays are performed in microtiter plates, which exist in 96- to 1536-wells formats and cannot be further miniaturized. In addition, performing screenings of suspension cells is associated with risk of losing cell content during the staining procedures and incompatibility with high-content microscopy. Here, we evaluate the Droplet-Microarray screening platform for culturing, screening, and imaging of suspension cells. We demonstrate pipetting-free cell seeding and proliferation of cells in individual droplets of 3-80 nL in volume. We developed a methodology to perform parallel treatment, staining, and fixation of suspension cells in individual droplets. Automated imaging of live suspension cells directly in the droplets combined with algorithms for pattern recognition for image analysis is demonstrated. We evaluated the developed methodology by performing a dose-response study with antineoplastic drugs. We believe that the DMA screening platform carries great potential to be adopted for broad spectrum of screenings of suspension cells.

Facile One Step Formation and Screening of Tumor Spheroids Using Droplet‐Microarray Platform

“…DMA slide consists of a glass slide patterned with an array of hydrophilic spots (water contact angle (WCA) ≤ 10°, sliding angle (SA) > 90°) separated by superhydrophobic borders (WCA = 154 ± 1.5°, SA = 2.4 ± 0.5°) (Figure a). In this work we used DMA slides with dimension of 25 × 75 mm containing 588 square hydrophilic spots with side length of 1 mm (Figure a,b).…”

“…Droplet‐Microarrays : Two types of DMA slides were used for the experiments. First type of DMA slides was coated with hydroxyethyl‐methacrylate (HEMA)–ethylenedimethacrylate (EDMA) and prepared as described previously . All the experiments except drug treatment were performed on HEMA–EDMA coated DMA slides (Figures a,d (manual seeding of cells), , and ; Figures S1–S3 and Tables S1–S3, Supporting Information).…”

Micro‐/Nanostructured Interface for Liquid Manipulation and Its Applications

“…SPW had also been widely adopted in cell culture, analysis, and related drug screening . Levkin group conducted many related researches . For example, they proposed a droplet‐array sandwich chip based on superhydrophobic–superhydrophilic micropatterning .…”

Nanomolar Synthesis in Droplet Microarrays with UV‐Triggered On‐Chip Cell Screening

“…Directly after dispensing, the array was sandwiched onto an indium tin oxide (ITO)‐coated glass slide with the same size as the DMA. The design of the sandwiching device that helps to align two slides over each other was reported previously . After contact of the droplets from the DMA with the ITO slide, the slides were separated again, leaving part of the droplets containing both synthesized compounds and matrix solution attached to the ITO surface in the array format mirroring the DMA slide.…”

“…The droplet microarray (DMA) is a platform for miniaturized high‐throughput cell screening in volumes down to several nanoliters, which has been exploited in diverse biological applications . It is usually based on a support substrate (e.g., glass) coated with a thin nanoporous polymer layer, which is spatially modified via UV‐induced thiol‐yne reactions to yield hydrophilic (HL) spots on a superhydrophobic (SH) background.…”