What factors are contributing to the unexpected 30% increase in synthesis failure rates for Integrated DNA Technologies's custom oligonucleotides in the past month?

Introduction

The unexpected 30% increase in synthesis failure rates for Integrated DNA Technologies's custom oligonucleotides over the past month is a critical issue that demands immediate attention. This problem directly impacts our core product offering and could have far-reaching consequences for our customers and business. I'll approach this analysis systematically, focusing on identifying potential root causes, validating hypotheses, and developing both short-term fixes and long-term solutions.

Step 1

Clarifying Questions (3 minutes)

• Looking at the timing, I'm thinking there might be a recent change in our production process. Have we implemented any new equipment or procedures in the oligonucleotide synthesis workflow in the last 1-2 months?

Why it matters: Recent changes often correlate with sudden performance shifts. Expected answer: Yes, a new automated synthesizer was introduced. Impact on approach: If confirmed, we'd focus on the new equipment's calibration and integration.

• Considering the scale of the issue, I'm wondering about our quality control measures. Has there been any change in our QC protocols or the team performing these checks?

Why it matters: QC changes could lead to different failure detection rates. Expected answer: No changes in QC protocols or team. Impact on approach: If unchanged, we'd look more closely at the synthesis process itself.

• Given the specificity of the problem, I'm curious about the affected oligonucleotides. Is this increase uniform across all types of oligos, or are certain lengths or sequences more affected?

Why it matters: Pattern recognition could point to specific synthesis steps or chemical interactions. Expected answer: Longer oligos (>50 bases) are more affected. Impact on approach: We'd investigate factors that specifically impact longer sequence synthesis.

• Thinking about external factors, I'm considering our raw materials. Have we changed any suppliers or received any new batches of key reagents in the past month?

Why it matters: Raw material quality can significantly impact synthesis success. Expected answer: A new phosphoramidite supplier was introduced last month. Impact on approach: We'd scrutinize the new supplier's quality and compare with previous batches.