Microfluidic Low-Input Fluidized-Bed Enabled ChIP-seq Device for Automated and Parallel Analysis of Histone Modifications

Abstract

Genome-wide epigenetic changes, such as histone modifications, form a critical layer of gene regulations and have been implicated in a number of different disorders such as cancer and inflammation. Progress has been made to decrease the input required by gold-standard genome-wide profiling tools like chromatin immunoprecipitation followed by sequencing (i.e., ChIP-seq) to allow scarce primary tissues of a specific type from patients and lab animals to be tested. However, there has been practically no effort to rapidly increase the throughput of these low-input tools. In this report, we demonstrate LIFE-ChIP-seq (low-input fluidized-bed enabled chromatin immunoprecipitation followed by sequencing), an automated and high-throughput microfluidic platform capable of running multiple sets of ChIP assays on multiple histone marks in as little as 1 h with as few as 50 cells per assay. Our technology will enable testing of a large number of samples and replicates with low-abundance primary samples in the context of precision medicine.