That said, I love Nanopores, I use them in my business, and those error rates you can hack around if you know what’s going on under the hood.
Modern scientists move small amounts of biological materials using a tool called the pipette. Pipettes can work with very small amounts of liquid- down the microliter. When you're running a delicate experiment being able to deliver the precise amount of liquid is critical.
Pipettes need to be calibrated. How do you calibrate a device that works with volumes of liquid? Volumes of liquid are hard to measure. Fortunately, water at STP (standard temp and pressure) has a known mass, so you attempt to draw 1 mL, and weigh it. 1 mL of water weighs 1 gram at STP (this is not a coincidence- it's by definition).
OK so you're weighing 1 gram of water and adjusting the pipette's calibrator knob so that 1mL on the pipette weighs 1 gram.
I guess that means your weighing scale needs to be calibrated, too. Huh. These sorts of scales aren't just "weigh some flour for baking", either. They have to be accurate to the hundredth of a gram, and have walls to avoid fluctuations due to air currents(!!!!) and minor temp changes. The scales are calibrated using calibrated test weights.
Oh dear. Calibrated test weights? If you follow the turtles all the way down, you find that there is actually a tracebility chain from your calibrated scale back to one of the defined weights held by NIST, the NIST equivalents in France and Japan (they all share their weights). So you can actually calculate- using those weird rules of error propagation you forget in high school- the error of your scale as a product of the errors in that chain (often, knowing your error bars is more important than knowing the accurate answer).
But that's not all. Those defined weights? They're obsolete. Le Grand K (the origin of the kilogram, still kept under lock and key) changed weight over time due to subtle metallurigcal details.
The new definition of the standard is created by an obscure machine at NIST, just like the time standards. https://en.wikipedia.org/wiki/Kibble_balance is the tool used to do it, and it depends on the NIST time reference.
So, turtles all the way down until you get the rubidium fountain.
there's a reason I went into automated biological robots.
Going on the same theme, what's an absolutely terrible example of technique?
Disclaimer: Co-Founder of BugSeq[0] 0: https://bugseq.com
Sounds like Elon calling biology a “software problem”.
Not saying that you’re wrong, just saying that the computational folk tend to discount the challenges and skills required in the wet lab.
That being said, we see a future where someone without advanced molecular training can put a sample (whether that's a nasal swab, concerning white powder received in the mail or lab-grown meat) in a black box and get out a meaningful report.
It's time to bring in the industrial automation folks. They probably won't invent a fancy new algorithm to reduce the time to splice the pieces together, but they'll fine tune and automate your reader to the 9's.
I just realized industrial automation sounds really interesting. What would my chances be for someone who never got the chance to study math?
(Basically in 1998 it was illegal to change schools in Australia regardless of how much of an eyebrow-raising situation you might've been in. Had to homeschool, without any resources. Only realized ~20 years on just how much opportunity I'll never get back.)
(Heh, I'm pretty much expecting the only obvious possible answer at this point, I was just curious if the answer is "yeah no" or "it depends".)
Do a thousand readings, fix the parts that don't match across the board?
That said, that’s basically how a lot of NGS works in things like cancer sequencing on Illumina platforms.
Seems to me, that stuff is getting cheaper all the time.