Magnetically Functionalized Hydrogels for High-Throughput Genomic Applications

Single-cell genomics has revolutionized tissue analysis by revealing the genetic program of individual cells. The key aspect of the technology is the use of barcoded beads to unambiguously tag sequences originating from a single cell. The generation of unique barcodes on beads is mainly achieved by split-pooling methods, which are labor-intensive due to repeated washing steps. Toward the automation of the split-pooling method, a simple method to magnetize hydrogel beads is developed. It is shown that these hydrogel beads provide increased yields and washing efficiencies for purification procedures. They are also fully compatible with single-cell sequencing using the BAG-seq workflow. The work opens the automation of the split-pooling technique, which will improve single-cell genomic workflows. Split-pooling is critical to single-cell genomics but remains tedious and labor-intensive. In this report, a method that opens the way to its automation by creating magnetic hydrogel beads, which enables simple bulk separation is demonstrated. The approach uses commercially available paramagnetic microbeads and is simple and cost-effective. The compatibility of magnetic hydrogels with single-cell genomics is also shown.image