Streamlining High-Throughput Methods Development with the icon96 System and AutoNorm™ — From Single-Cell to Bulk Applications

Presented at Festival of Genomics Boston 2026

Dr. Aziz Al'Khafaji, who leads the Methods Development Lab at the Broad Institute, presents real-world data on how his lab has built the n6 icon96 system with AutoNorm™ into the backbone of their NGS workflows — from complex single-cell assays and isoform sequencing to large-scale bulk data generation across 150 postmortem brain samples. He demonstrates why fixed-cycle PCR is a silent data quality risk, showing how over-amplification past plateau drives recombination artifacts, barcode swapping, and jackpotting that corrupt even the most carefully designed experiments. He then shows how AutoNorm's per-well adaptive amplification stops each reaction at its individual optimum — no prior knowledge of input quality or cycle number required. The result: library prep time cut in half, zero provisional qPCRs, and data quality you can actually trust — even in single-shot single-cell workflows.

What You'll Learn

• Why PCR is a double-edged sword, and how over-amplification past plateau introduces recombination artifacts, size bias, and barcode swapping that undermine data integrity
• How AutoNorm independently controls amplification in every well, stopping each reaction at its sample-specific optimum regardless of input variability or RNA quality
• Why single-cell assays are uniquely vulnerable to PCR artifacts, and how per-well adaptive amplification is the only practical solution when you can't re-run a single-cell capture
• How advanced single-cell modalities like Perturb-seq and isoform sequencing are disproportionately impacted by over-amplification noise, and what that means for your downstream analysis
• How the Broad Institute generated clean data from 150 postmortem brain samples with highly variable RIN scores , eliminating sample dropout entirely with icon96
• How a novel siRNA single-cell detection assay was developed and validated in a single afternoon using icon96, with same-day sequencing verification
• Why fair, comparable matrix optimization across complex PCR condition spaces is now tractable, and how icon96 enables it at 96-well scale