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(697d) Microfluidic ChIP-Seq Device for Rapid and Parallel Analysis of Histone Modifications

Authors: 
Murphy, T., Virginia Tech
Ma, S., Virginia Tech
Lu, C., Virginia Tech
Epigenetic changes, such as histone modifications, have been implicated in a number of different disorders such as heart disease, cancer, and autism. Therefore, it is imperative that we develop a methodology to effectively study epigenetic modifications in an efficient and rapid manner. Furthermore, a variety of histone modifications (i.e. tens of histone marks), are routinely involved in gene regulation. This creates the need for parallel analysis of samples with high throughput in order to understand the complete picture of epigenomes. In this paper we demonstrate an automated and high throughput microfluidic platform capable of producing multiple sets of high quality ChIP-seq (Chromatin immunoprecipitation followed by next generation sequencing) data in a single run that takes as little as 1 hour.

The microfluidic system consists of 4 parallel units, which are controlled using a bank of computer controlled solenoid valves and syringe pumps. Each run generates 4 ChIP DNA samples (which can be prepared into 4 sequencing libraries). The total on-chip operation takes as little as 1 h, with a hands-on working time of less than 20 min. We demonstrate the testing of chromatin samples from as few as 100 cells per assay and there was high reproducibility among 4 datasets generated by the same device giving Pearson correlation coefficients of 0.956, 0.970 and 0.870 for 1,000, 300, and 100 cell samples respectively.

The development of this automated ChIP assay lays the groundwork for large scale multiplexing which will allow fast, simultaneous analysis of multiple samples and marks, which will aid in clinical analysis of disease progression.