Translational Opportunities for Microfluidic Technologies to Enable Precision Epigenomics

Abstract

Personalizing health care by taking genetic, environmental, and lifestyle factors into account is central to modern medicine. The crucial and pervasive roles epigenetic factors play in shaping gene−environment interactions are now well recognized. However, identifying robust epigenetic biomarkers and translating them to clinical tests has been difficult due in part to limitations of available platforms to detect epigenetic features genome-wide (epigenomic assays). This Feature introduces several important prospects for precision epigenomics, highlights capabilities and limitations of current laboratory technologies, and emphasizes opportunities for microfluidic tools to facilitate translation of epigenetic analyses to the clinic, with a particular focus on methods to profile gene-associated histone modifications and their impacts on chromatin structure and gene expression.

Isolation and Quantification of Methylated Cell-Free DNA in Plasma on an Integrated Microfluidic System

“…Experimental results show that the integration of MBD beads and the vortex-type micromixer (capture rate of 72%) could significantly lower the amount of the input cfDNA sample (20 μL) while comparing to the bisulfite-based system (>1 mL) . Also, previous studies involved sophisticated manual operations that reduced the throughput and made the assay labor intensive. − Although the bisulfite-based assay could be integrated on the droplet-based microfluidic system with a minimum DNA concentration of 500 pg/μL, the redundancy of sequence was still unavoidable, nor was the cfDNA extraction module integrated. On the other hand, the MBD-based assay was utilized in the microfluidic chip previously. ,, Even though the system has obtained an acceptable LOQ of 1 pg/μL, yet no epigenetic profiling module was integrated in one single system .…”

“…28 Also, previous studies involved sophisticated manual operations that reduced the throughput and made the assay labor intensive. 18−20 Although the bisulfite-based assay could be integrated on the droplet-based microfluidic system 33 with a minimum DNA concentration of 500 pg/μL, the redundancy of sequence was still unavoidable, nor was the cfDNA extraction module integrated. On the other hand, the MBD-based assay was utilized in the microfluidic chip previously.…”

“…In order to tackle the high false-positive/false-negative issue of the bisulfite-based assays, bisulfite-free methods have been reported as an alternative solution. − Methylation-sensitive enzymes that cleaved only the unmethylated DNA and chip-based digital PCR (dPCR) were integrated to quantify the methylated DNA . Though the detection limit could reach 0.52% methylation level, off-chip DNA extraction and 100 ng of DNA input were still required.…”

Multiplexed fluorescence and scatter detection with single cell resolution using on-chip fiber optics for droplet microfluidic applications

“…Droplet-based microfluidic technologies provide a variety of solutions for high-throughput single-cell analysis 1 , 2 at the genomic 3 , epigenomic 4 , transcriptomic 5 – 7 , proteomic 8 , 9 and metabolomic 10 levels, with increasing applications in the fields of immunotherapies 11 , 12 , precision medicine 13 , regenerative medicine 14 , drug development 11 , 15 and diagnostics 10 , 16 . The successful translation of several such droplet-based techniques into commercial assays (e.g., ddPCR by Bio-Rad and Chromium by 10X Genomics) has led to the unprecedented adoption of microfluidic technologies in the commercial sector.…”

Nutriepigenomics in Environmental-Associated Oxidative Stress

“…The epigenome encompasses multiple interacting regulatory elements that define phenotypic variation beyond what the DNA sequence encodes [ 1 , 2 , 3 ]. In addition to their roles in development and differentiation, epigenetic mechanisms play a fundamental role in transcriptional regulation during disease progression, further underscoring the importance of understanding their molecular bases [ 4 , 5 ].…”