Everything Wrong With: "Illumina: The Measurement Monopoly" Part 4/8
Century of Biology still has 10x the subscriptions I do… so I’m continuing my critical review of Elliot’s article on sequencing. Next we’re looking at this statement:
“Many people know that I’m a fan of the term TechBio. A lot of people aren’t. They view it as a superficial term coined by VCs. Why do I like it? We’re currently talking about a technology that embeds chemical beads directly onto a fiber-optic surface, making measurements only detectable by software. This represents a deep convergence between technology and biology.”
Personally, I don’t care what you call it. But I don’t see a huge difference between the bead array and anything that came before it in terms of “deep convergences”. Biotech or “life science tools” if you prefer has always been a crazy mix of Biology, Physics, Chemistry/Biochemistry, Materials Science, Electronics, Mechanical Engineering, Optics, Statistics, Data Analysis, Software Engineering and probably a bunch of other techniques I’m forgetting!
This applies to qPCR machines as much as it does to Microarrays or DNA sequencers.
Actually that would be fun! Let’s look at qPCR1 machines.
The First qPCR Machine
The first paper on qPCR was published in 1992. They took an intercalating dye. That’s a dye that likes to get in between in gaps in double stranded DNA (dsDNA) and fluoresces (lights up) brighter. So when there’s more dsDNA you get more light emitted.
They used PCR to amplify a specific DNA fragment in a tube and used an experimental setup to monitor amount of light emitted. Unfortunately they don’t show the experimental setup. But we can figure out what it might have looked like from the details provided:
While this picture looks complex, it actually hides a lot of instrumentation. The Flurometer uses a photomultiplier tube for detection. These are still some of the most sensitive detectors we have available, capable of detecting light down to single photons. They use an electron cascade reaction in a high voltage vacuum tube:
You could write a whole article about this single component, but the setup also contains:
A high voltage power supply for the PMT.
Peltier based thermocycler (and associated drive electronics, microcontroller).
Acquisition electronics.
Computer to log and process signals.
UV? Fiber cables.
Optical components: Fiber aligners, filters.
Xenon lamp excitation source.
And of course, all the molecular biology required to enable the amplification process.
Later qPCR machines were is some cases more complicated. You can see one example I disassembled here. More recently we’ve seen disposable LAMP based molecular detection systems. These put more emphasis on the molecular biology and simplify the electrical and detection system.
Conclusion
The reality is that TechBio is a somewhat superficial term. If you find it helpful that’s great. But tech development is complicated. In many cases we navigate a difficult course to product-market-fit. In different situations putting more or less emphasis on biochemistry and advanced detection techniques to try and find the best fit to address a demand.
Century of Biology still has 10x the subscribers I do. You can help remedy this injustice by subscribing.
I’m going to be using the term qPCR here, rather than real-time PCR. Mostly because rtPCR can lead to confusion with reverse transcriptase PCR.