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Making the Micropipette
- bschne 3y agoFor a semi-related case study of entrepreneurial tool-building in science, I also liked this: http://milan.cvitkovic.net/writing/neuropixels/ http://milan.cvitkovic.net/writing/neuropixels/
- aaron695 3y ago[dead]
- IggleSniggle 3y ago> What is something you do, day after day, that is arduous or bothersome? Do you have a subtle itch or a pressing need to make it easier? If the answer is yes, consider spending a couple of days making improvements to the process, as a frustrated Schnitger did in 1957. Simple solutions to widespread problems can alter the course of scientific history. -- sigh I guess it's the season for mucking around with my shell again
- gpderetta 3y agoNow I continue hacking at my .emacs without guilt and just need to wait for the day I'll alter the course of history.
- throwup238 3y agoIs your Emacs Evil though? We might not want its course altered.
- fuzzfactor 3y agoTis always the season. >> What is something you do, day after day, that is arduous or bothersome? Do you have a subtle itch or a pressing need to make it easier? This is what I faced for well over 45 years of deep exposure to lab bench work from many different positions from student to grunt to leadership. Chemical commodities, not biochemical research though. However as expected there is a certain amount of similarity in some of the laboratory tasks regardless of the diversity of scientific objectives. I'm still willing to grab dangerous chemicals & apparatus by the throat with my own bare hands if necessary for valuable clients. Just not wanting to use my own throat, so I never wanted to pipet by mouth either. The vintage photo of Dr. Verder looks like she is filling a measuring pipet, before capping the glass tube with a fingertip then precisely dispensing manually as many scientists at the time would do.[0] Now it's fire-retardant lab coats and respirator-ready facial hair as table stakes. In my lab I had a vintage picture of Edison holding up a chemical solution above eye level, observing it carefully without safety glasses or PPE of any kind. His lab in the background was "a little bit" cluttered with chemicals and stuff. I didn't draw attenton to this kind of artwork, it was hanging off to the side in the front office, I figured it spoke for itself. Plus I had more types of PPE than most are familiar with, which I used carefully as needed. But that's not what I'm focusing on right now. Mouth pipetting was still common when I was getting started 30 years later than 1938, as a student so this is what had been taught for many decades but you were supposed to be a realistic judge about what risk there could be depending on what you were pipetting. The rubber bulbs which can substitute for mouth pipetting can be clumsy and not as precise and each person was expected to draw the line at what laboratory solutions they were going to avoid inhaling. These were often referred to as Pasteur pipets and were still all-glass everywhere, even thin disposable ones mostly until the 1980's when plastic disposables took over. But by the 70's there was growing interest in safety and "rules" against mouth-pipetting were getting more widespread, but it just made people look the other way when desperate workers did it a little bit anyway, there was not usually an effective formal replacement. Ripe for disruption by mechanical means I would guess. Maybe with increasing complexity to the mechanism I would say it's mainly worthwhile for quite repetitive work. Regular glass pipets are still everywhere and I was just lucky to become a professional not long before a simple precision pipet bulb was invented having little plugged vents in the rubber that are controlled by careful squeezing.[1] People from the chemical plants and refineries had never seen this, it was only available from one company until 20 years later when the patent expired. It was good for major company chemists and engineers to be able to see me manually doing NBS-traceable (now NIST-traceable) work with obvious clarity when stakes were highest. They knew their own laboratories, which supported the process units that actually made the chemicals, were way more expensively built but still somewhat embarrassing sometimes when it came to absolute certainty. Now decades later I'm not alone, "everyone" claims to be NIST-traceable, I still say not so fast. When I came to my employer almost a decade ago I had to kick out the mechanical pipets and replace them with serialized traceable manual traditional glass type, with major retraining for this exact reason. [2] Expert witnessing is more critical than routine work. I always liked the Gilson salesman, and Ranin too but I never bought anything since the stakes are so high with the big ships, and your ship doesn't come in every day anyway so there's not that kind of repitition. But a couple barges aren't too bad either. So I've got a lifetime of ideas that other people could use where I didn't go far enough to actually even flush out a prototype since I didn't need it for myself at the time. Over the decades I've watched some of the things I had come up with, be recognized and commercialized by capable operators much later. Some of the most obvious things are the most commercializable and it was going to happen anyway. Every milestone or breakthrough doesn't have to be that elusive to be good. It doesn't bother me to be late to market when I'm not in the market to begin with. It's a good feeling knowing there's more where that came from all the time, and early ideas that nobody else has touched have now stood the test of time without competition developing. Plus if I had patented everything most of it would be expired by now. A lot of the chemical plants only make a handful of different chemicals at each location, and usually only a few of those are actually commodities. That limited number of chemicals are the ones that each of their labs is designed and built to handle 24/7, and some tasks can get pretty repetitive for them. But when you regularly work with material from all over the place you really get ideas for inventions for all kinds of different things. Especially with emerging instruments and techniques when there aren't so many worthwhile publications to go on. So it can be a slippery slope and you end up inventing something every day. Never comercialized very much yet, too busy, a lot is not worth money anyway or would require becoming a capitalist of some kind where the terms are not very attractive. I did OK getting paid for what I could do rather than how much I sold. Well I enjoyed sales starting as a teenager and eventually starting my own commercial lab, scientific instrument sales was supposed to be a future effort but I did not approach that milestone close enough with any prototype before natural disaster set it back where you can not make up for lost time. I also had a framed vintage picture of Hewlett & Packard posing with their original invention, hanging back there. The edge of the bench can be like a goal line where you can make field goals from a reasonable distance (if your desk or office is not too far from the bench) but you can only actually score a touchdown by crossing the line yourself. Extra points count for twice as much too when somebody personally carries the ball across the line rather than kicking it in "remotely". Plus in old labs there has never been enough space on the bench for PC's because they weren't built for it, they were just crammed in. I know. I did it myself. I still like to build labs from the ground up, it's a hoot. [0] In the backgroud of the photo there's a vat on a low wooden bench, that is a precision heating bath where the electronic temperature control consists of the logic necessary to turn off the heating element when the mercury in a special wired thermometer rises to make contact with a thin wire reaching into the inside of the glass from the top. The depth of the wire was adjustable with a knob at the top of the thermometer, not unlike the knob that would later appear at the top of the adjustable mechanical pipets to easily adjust their volumes. I was one of the last to use a bath of this vintage which I had gotten surplus and never thought I would ever restore. This does remind me that years later, but still before digital, when we needed a 0.001 degree tolerance for another location I rapidly designed an analog temperature controller using a solid-state sensor at the bottom of a glass tube, with the circuitry at the top in a small enclosure to run on an external bipolar power supply. I needed it to be a drop-in replacement for the glass mercury ones that were still common in the much more modern baths that were still in use. Plus it had to be built with as many parts as possible from Radio Shack, ended up the only thing I needed from elsewhere was a gigohm resistor. Another one of those everyday inventions. Once digital appeared it took years before this precision could be reached. [1] https://www.coleparmer.com/i/silicone-pipette-filler-3-way-valve-50-ml-capacity/2480520 https://www.coleparmer.com/i/silicone-pipette-filler-3-way-v... Now these are available in many polymers other than natural rubber, with openings plugged with different materials than the original stainless steel ball bearings. [2] Also kicked out IT since they weren't very good with chemicals (or even electronics) but that's a different story altogether.
- zabzonk 3y agospeaking as an ex microbiology/immunology technician, these things are brilliant - i really can't imagine doing the job without them.
- bentobean 3y ago> “… it is oddly fitting that a man best known for creating a device to move around small volumes of liquid died unable to manage large ones.“ Ouch. This felt… a bit unnecessary and out of place.
- bschne 3y agoyeah they missed the tone a bit there, tripped over it too
- op00to 3y agoI came here to post that. Totally uncalled for and not funny in the least. It is also not fitting at all.
- stronglikedan 3y agoIt was funny and an appropriate levity break. I laughed out loud. I hope they leave it in, despite the author's request to have it removed. The editors knew best in this case.
- op00to 3y agoCan you explain what you found funny? Everyone is entitled to their own sense of humor, but I don't see how a drowning death is funny because it happened to a scientist that invented a tool.
- riversflow 3y agoNot OP, but I’ll take a stab. > funny because it happened to a scientist that invented a tool. ..for transferring fluids. I don’t think much of Freudian psychology as a whole, but he’s got a relevant quote that is pretty good on Gallows humor, from Der Humor 1927: > "The ego refuses to be distressed by the provocations of reality, to let itself be compelled to suffer. It insists that it cannot be affected by the traumas of the external world; it shows, in fact, that such traumas are no more than occasions for it to gain pleasure." The comedy, in this light, is a result of the dissonance that someone smart and savvy enough to invent an extremely useful tool for moving liquids died in a large body of liquids not long after said invention. My guess is that people who find the humor here relate more to the drowning scientist directly. Dying from drowning in an Alpine lake, or just drowning, isn’t that common of a risk, but if it is a risk you are familiar with you’re more likely to find the humor. At least thats the case for me.
- bobmaxup 3y agoI thought these devices were called pipettors not strictly micropipettes?
- kortex 3y agoA pipettor is an agent which does the pipetting, usually this is the scientist when manually pipetting, but there are autopipettors which are robots. Pipettes are originally the glass tubes of fixed or graduated volume, but the definition has expanded to include air displacement pipettes aka "micropipettes" (even when the volume is measured in milliliters not microliters, they are still colloquially micropipettes).
- dekhn 3y agoEverything I've ever seen says that pipettor is in fact the pipette with additional components, not the scientist or the robot. https://www.sigmaaldrich.com/US/en/products/labware/liquid-handling-and-dispensing/pipettors#pipettor https://www.sigmaaldrich.com/US/en/products/labware/liquid-h...
- fuzzfactor 3y agoIt's just terminology, "regular" pipets dispense mainly in milliliters, micropipets dispense in microliters. The pipet is considered the tube, the pipettor is the mechanical attachment, I would say that is whether the attachment is with lips & tongue or not.
- Metacelsus 3y agoAuthor here. I'm happy to answer any questions.
- seanc 3y agoThanks! My daughter works with pipettes all day long, and this is fascinating. One of her favorite aphorisms is "Don't lick the science!" and today I learned that apparently we used to lick the science.
- Metacelsus 3y agoEven today mouth pipettes are still used occasionally (in embryology, for example).
- dekhn 3y agoI use a mouth pipette (really just a small piece of glass and some rubber tubing with a filter to transfer tardigrades to my microscope slide. This was recommended to me by a tardigrade expert. I had previously used bulb for large glass pipette (my high school lab had a big sign "DO NOT PIPETTE BY MOUTH") and micropipettes for decades, and I was blown away with the level of control you get from mouth pipetting. I'm not that bothered by inhaling some tardigrades. But being lazy one of my side projects is to make an automatical tardigrade pipettor (ML-based with motors and stuff).
- sopchi 3y agoI am surprised there is on mention of rubber bulbs. If the main concern is safety, as the beginning of the article seems to imply, the rubber bulb would have been enough of a solution. The micropipette solves mostly all the other concerns: speed, repeatability, avoidance of contamination, ease of use one-handed. A great invention for sure. Why would they even mouth pipette if they can use a rubber bulb? Is it that the rubber bulb was somehow invented later? Did you encounter anything about that when researching this topic?
- dekhn 3y ago
- dmd 3y ago> A typical PhD student in the biosciences will use about 200,000 pipette tips over the course of their research. (An estimated ten boxes of 96 tips per week, with 50 working weeks per year over a 5-year period, comes out to 240,000 tips. And five years is a generous estimate for completion of a PhD in the biosciences.) This seems ridiculously high to me. If the student works 6 days a week, 10 hours a day, they would be using a new tip about every 3-4 minutes nonstop, every single hour of those 10 hours a day 6 days a week for 5 years. No reading, no writing, no meetings - just pipette tips every 4 minutes, 10 hours a day for 5 years. Is that really the life? edit: Oh. Machines. Right.
- AlgorithmicTime 3y ago[dead]
- bschne 3y agowas wondering the same thing!
- BiteCode_dev 3y agoYou assume they do it manually. Today we have machines that can batch processes using pipettes, and they can burn them at a fast rate.
- gipp 3y agoEven when done by hand, you're also generally going to use a large batch all at once to create a panel of different tests under varying conditions. So it's more like you're using a new tip about every 5-10 seconds for 15 minutes or so, twice a day.
- margalabargala 3y agoMulti-pipettes are made, as well, here's a 64-channel one: https://bioventures.com/products/capp%C2%AE-64-channel-pipette-0-5-10ul https://bioventures.com/products/capp%C2%AE-64-channel-pipet... When you're using 64 tips at a time, it's easy to imagine using ten boxes of 96 tips per week. Ten boxes of tips will fill that pipette only 15 times. So you're using your multipipette twice a day.
- SAI_Peregrinus 3y ago> Interestingly, Suovaniemi didn’t attribute his inventions to diligence or tireless ambition, but quite the opposite. “I’m extremely lazy by nature,” Suovaniemi once told an interviewer, so “I created a pipette with nine channels.” Engineering is all about laziness. The whole field is about making devices & structures to reduce overall labor required. Engineers need a certain sort of laziness, a willingness to work now in order to work less later (or to help others work less later). Tireless ambition rarely leads to good engineering, it leads to continued drudgery.
- adolph 3y agoI think 1319 better represents this comment than 1205. In addition to laziness/efficiency, curiosity and lateral thinking are helpful qualities. https://xkcd.com/1319/ https://xkcd.com/1319/ https://en.wikipedia.org/wiki/Lateral_thinking https://en.wikipedia.org/wiki/Lateral_thinking
- robocat 3y agoWhat is the law of engineering that causes an abundance of complexity? There's some entropy law of abstraction that is the opposite of Occam's razor: take a simple idea and embellish it until it is sophistimicated enough to require total reengineering to decomplexify it.
- gertrunde 3y agoOne feels compelled to mention the family member who learned the hard way of the dangers of mouth pipetting... while working in a bovine sperm collection facility....
- ta988 3y agoThis just hurts one's ego, try that with acids/bases or highly toxic compounds.
- HeyLaughingBoy 3y agoOne of the first medical instruments I developed code for featured automated precision pipettes (precision measured in single microliters) for sampling reagents and human body fluids. We had a guest once who used to be a lab nurse and mentioned using mouth pipettes. The looks of horror on the scientists in the room was palpable!
- waltbosz 3y agoInteresting, I too heard of mouth pipetting via an antidote about a modern day bovine sperm collection facility. I was surprised that anyone still did it given the availability of the micropipett. Also, I wonder why the scientists of the past didn't obtain the liquid samples by simply sticking their thumb over one end of a straw dipped in the liquid.
- adolph 3y ago> sticking their thumb over one end of a straw dipped in the liquid Brings back memories of learning how to do that with my siblings. Every chance we got, we would scrunch up straw wrappers and then use the method to animate the wrapper with liquid. Not certain if I should show my kids how to do that.
- seanc 3y agoThe pipettes I worked with in school 30 years ago were effectively glass straws with a mark for the designated volume. One dipped it in the solution over the mark, used the thumb to seal it, and then carefully let tiny amounts of air in to drop the bottom of the miniscus down to the line. It was terrible and nothing ever worked and my thumbs hurt.
- pugworthy 3y agoThere are some pretty nifty modern replacements for the pipette for automated well plate work specifically. HP has one such product, which I work on. It is a "digital dispenser" that leverages inkjet technology to dispense complex, multi-fluid protocols with picoliter to microliter accuracy over about any type of well plate quite quickly and effectively. The basis of the product is a one-time-use cassette that incorporates dispense heads and fluid reservoirs which the user fills with their own fluids. Depending on the model, the cassette can work with 1, 4, or 8 fluids at a time. The latest new cassette type can sense and dispense single cells into wells with a high level of occupancy and viability. I know this comes off as a bit of a sales pitch, but it's a product I'm genuinely excited to work on and our customers seem quite pleased with it as well. If you search for "hp digital dispenser" you'll find more info on it.
- HeyLaughingBoy 3y agopicoliter accuracy is impressive!!! What's your precision (dispense coefficient of variation) like? When I was working with automated pipettes, we found that in order get down to single-microliter precision we had to "touch off" on the dispensing surface to use surface tension to pull the last drop off consistently. However, our aspirate/dispense ranges were pretty wide -- around 15uL to about 50mL from the same device.
- pugworthy 3y agoNot sure the exact numbers, but the fluid is jetted so there is not really an issue with surface tension. It’s also no problem to do 1536 plates and even some nano-well setups using custom well plate definitions.
- varjag 3y agoHP as in Agilent or as in HP printer division?
- pugworthy 3y agoHP printer. Based in Corvallis.
- dekhn 3y agoSpeaking of science tools, one of my favorite is the Worm Pick. Researchers working with C.Elegans (one of those most common model organisms) use worm picks to pick up and transfer worms from one plate to another. The pick is made out of a metal that can be heated up (to sterilize) many times. Such as platinum or kanthal. Often, new researchers will craft their own worm pick rather than purchase it. Originally, reseachers used eyelashes as worm picks(!)