The TRIzol method for RNA extraction has been the gold standard. The powerful protein denaturant effectively stabilizes RNA and inactivates RNases and infectious agents. However, the need for phase separation, precipitation, and potential phenol carryover can further complicate workflows. The magnetic bead-based Direct-zol procedure on the Hamilton Microlab STAR platform bypasses phase separation/precipitation and enables high-throughput automated magnetic bead-based purification of high-quality total RNA directly from samples treated in TRIzol or other acid-guanidinium-phenol based reagents. Direct-zol effectively isolates total RNA from a variety of sample sources including cells, tissue, serum, plasma, blood, and biological liquids for downstream applications, like miRNA profiling, RNA-seq, and viral detection.