ABI SOLiD Sequencing (Historical)

What Was SOLiD?

SOLiD (Sequencing by Oligonucleotide Ligation and Detection) was a next-generation sequencing platform developed by Applied Biosystems (later acquired by Life Technologies, then Thermo Fisher).

Status: Essentially discontinued. Replaced by Ion Torrent and other technologies.

The Key Difference: Ligation Instead of Synthesis

Unlike other NGS platforms:

  • Illumina: Sequencing by synthesis (polymerase adds nucleotides)
  • Ion Torrent: Sequencing by synthesis (polymerase adds nucleotides)
  • SOLiD: Sequencing by ligation (ligase joins short probes)

How It Worked (Simplified)

  1. DNA fragments attached to beads (emulsion PCR, like Ion Torrent)
  2. Fluorescent probes (short 8-base oligonucleotides) compete to bind
  3. DNA ligase joins the matching probe to the primer
  4. Detect fluorescence to identify which probe bound
  5. Cleave probe, move to next position
  6. Repeat with different primers to read the sequence

Key concept: Instead of building a complementary strand one nucleotide at a time, SOLiD interrogated the sequence using short probes that bind and get ligated.

Why It's Dead (or Nearly Dead)

Advantages that didn't matter enough:

  • Very high accuracy (>99.9% after two-base encoding)
  • Error detection built into chemistry

Fatal disadvantages:

  1. Complex bioinformatics - two-base encoding required specialized tools
  2. Long run times - 7-14 days per run (vs. hours for Ion Torrent, 1-2 days for Illumina)
  3. Expensive - high cost per base
  4. Company pivot - Life Technologies acquired Ion Torrent and shifted focus there

The market chose: Illumina won on simplicity and throughput, Ion Torrent won on speed.

What You Should Remember

1. Different chemistry - Ligation-based, not synthesis-based

2. Two-base encoding - Clever error-checking mechanism, but added complexity

3. Historical importance - Showed alternative approaches to NGS were possible

4. Why it failed - Too slow, too complex, company shifted to Ion Torrent

5. Legacy - Some older papers used SOLiD data; understanding the platform helps interpret those results

The Bottom Line

SOLiD was an interesting experiment in using ligation chemistry for sequencing. It achieved high accuracy through two-base encoding but couldn't compete with faster, simpler platforms.

Why learn about it?

  • Understand the diversity of approaches to NGS
  • Interpret older literature that used SOLiD
  • Appreciate why chemistry simplicity matters (Illumina's success)

You won't use it, but knowing it existed helps you understand the evolution of sequencing technologies and why certain platforms won the market.