[HN Gopher] Making the Micropipette
___________________________________________________________________
Making the Micropipette
Author : bschne
Score : 132 points
Date : 2024-01-03 10:32 UTC (12 hours ago)
(HTM) web link (press.asimov.com)
(TXT) w3m dump (press.asimov.com)
| bschne wrote:
| For a semi-related case study of entrepreneurial tool-building in
| science, I also liked this:
| http://milan.cvitkovic.net/writing/neuropixels/
| IggleSniggle wrote:
| > 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 wrote:
| Now I continue hacking at my .emacs without guilt and just need
| to wait for the day I'll alter the course of history.
| throwup238 wrote:
| Is your Emacs Evil though? We might not want its course
| altered.
| fuzzfactor wrote:
| Tis 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-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 wrote:
| speaking as an ex microbiology/immunology technician, these
| things are brilliant - i really can't imagine doing the job
| without them.
| bentobean wrote:
| > "... 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 wrote:
| yeah they missed the tone a bit there, tripped over it too
| op00to wrote:
| I came here to post that. Totally uncalled for and not funny in
| the least. It is also not fitting at all.
| stronglikedan wrote:
| It 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 wrote:
| Can 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 wrote:
| Not 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.
| op00to wrote:
| Just so I follow, if the inventor of the ez bake oven
| died in a home gas explosion, that's sort of the same
| concept at play?
|
| Thank you for the explanation.
| Metacelsus wrote:
| You're right, this was rather tone-deaf. It wasn't in my
| original draft and was added by an Asimov editor in an attempt
| to make the piece more interesting. Although I did review the
| final article proof, so it's my responsibility too. I've made a
| request for Asimov to edit it.
| BiteCode_dev wrote:
| For the record, I find it achieves the editor's goal for me.
|
| A bit of dark humor can be a nice touch.
|
| The problem is rather if you are ok with the fact a part of
| your audience will be offended with it.
| Metacelsus wrote:
| You know, this might be a classic case of "Your Incentives
| Are Not The Same As Media Companies'"
|
| https://www.astralcodexten.com/p/your-incentives-are-not-
| the...
| jsight wrote:
| It seems like slightly different wording would have fixed
| it. "Oddly fitting"? We don't usually describe untimely
| deaths as "fitting". Perhaps "ironic" or something along
| those lines would fit the tone better.
| op00to wrote:
| If the pipette dude would have died of drowning by
| pipetting, that would be ironic. If he drowned from a
| microlitre of water, that'd be ironic. But saying he
| couldn't handle large amounts of water is weird. The
| dude's unfortunate drowning death really doesn't add much
| to the story.
| bobmaxup wrote:
| I thought these devices were called pipettors not strictly
| micropipettes?
| kortex wrote:
| A 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 wrote:
| Everything 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/li
| quid-h...
| fuzzfactor wrote:
| It'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 wrote:
| Author here. I'm happy to answer any questions.
| seanc wrote:
| Thanks! 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 wrote:
| Even today mouth pipettes are still used occasionally (in
| embryology, for example).
| dekhn wrote:
| I 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 wrote:
| I 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 wrote:
| it's all about control. You get a lot more feedback and
| accuracy with your mouth.
| sopchi wrote:
| OK, I see. I still find that surprising because I would
| imagine having the pipette hanging from your mouth doesn't
| allow ou to really see what is going on if you are really
| trying to hit a target volume. I would have thought the
| feedback you need is visual.
| function_seven wrote:
| I just looked up photos of people pipetting by mouth.
| They use tubes.
| dekhn wrote:
| Oh. I'm actually looking at the pipette tip under a
| microscope (in my case it's clear glass that I pulled to
| a fine tip using heat) and I can see the tardigrade get
| sucked into the tip when I gently pull with my mouth. And
| then I can see it whoosh back out when I push. The actual
| volume doesn't matter, just that I pick a single
| tardigrade and place it where it needs to go.
|
| The other folks pipetting by mouth are actually looking
| down at the tube and see the fluid volume reaches a
| particular well-defined line on the glass pipette. If you
| can taste the fluid, you've gone too far.
| dmd wrote:
| > 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.
| bschne wrote:
| was wondering the same thing!
| BiteCode_dev wrote:
| You 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 wrote:
| Even 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 wrote:
| Multi-pipettes are made, as well, here's a 64-channel one:
| 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.
| Metacelsus wrote:
| >Is that really the life?
|
| Yes it is! For example, a simple 96-well plate qPCR experiment
| can use 192 tips. It's easier with multichannel pipettes
| though.
|
| So it's more like: use 200 tips in the morning, then do reading
| and meetings the rest of the day.
| kortex wrote:
| I've gone through a box a day at peak just doing regular
| chemistry (biochem uses way more) so I completely believe it.
|
| It's not like one pipet tip a minute. It's more like, you have
| N source vials and M destination vials/wells/rows, and you'll
| do that several times a day, interspersed with other processes.
| A cycle goes like:
|
| 10 New tip
|
| 20 Suck up sample from source n
|
| 30 Dispense into m-sub-i
|
| 40 while you still have destinations for the current solution,
| goto 20
|
| 50 eject tip
|
| 60 goto 10
|
| This cycle takes maybe a few seconds to half a minute. Also
| multiply number of tips by P if you have a multi-tip pipette.
| flobosg wrote:
| > a new tip about every 3-4 minutes nonstop
|
| Pipetting and changing tips are a matter of seconds, not
| minutes.
| SAI_Peregrinus wrote:
| > 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 wrote:
| I 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://en.wikipedia.org/wiki/Lateral_thinking
| robocat wrote:
| What 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 wrote:
| One 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 wrote:
| This just hurts one's ego, try that with acids/bases or highly
| toxic compounds.
| HeyLaughingBoy wrote:
| One 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 wrote:
| Interesting, 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 wrote:
| > 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 wrote:
| The 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.
| kragen wrote:
| that sounds pretty safe; hiv and cmv don't infect cows. what
| are the dangers?
| analog31 wrote:
| My mom pipetted by mouth in grad school in the 50s, doing
| radiochemistry.
| bell-cot wrote:
| A bit further back -
| https://en.wikipedia.org/wiki/Radium_dial
|
| > Radium dials were typically painted by young women, who
| used to 'point' their brushes by licking and shaping the
| bristles prior to painting the fine lines and numbers on the
| dials. This practice resulted in the ingestion of radium,
| which caused serious jaw-bone degeneration and malignancy and
| other dental diseases. The disease, radium-induced
| osteonecrosis, was recognized as an occupational disease in
| 1925 after a group of radium painters, known as the Radium
| Girls, from the United States Radium Corporation sued. By
| 1930, all dial painters stopped pointing their brushes by
| mouth. Stopping this practice drastically reduced the amount
| of radium ingested and therefore, the incidence of
| malignancy.
| pugworthy wrote:
| There 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 wrote:
| picoliter 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 wrote:
| Not 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 wrote:
| HP as in Agilent or as in HP printer division?
| pugworthy wrote:
| HP printer. Based in Corvallis.
| dekhn wrote:
| Speaking 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(!)
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