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Robot Brings Patch-Clamping To the Masses

Unknown Lamer posted about 2 years ago | from the cat-translator-coming-soon dept.

Robotics 59

scibri writes about robots helping neuroscientists dig into the brains of (animal) test subjects. From the article: "Robots designed to perform whole-cell patch-clamping, a difficult but powerful method that allows neuroscientists to access neurons' internal electrical workings, could make the tricky technique commonplace. Scientists from MIT have designed a robot that can record electrical currents in up to 4 neurons in the brains of anesthetized mice (abstract) at once, and they hope to extend it to up to 100 at a time. The robot finds its target on the basis of characteristic changes in the electrical environment near neurons. Then, the device nicks the cell's membrane and seals itself around the tiny hole to access the neuron's contents."

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one step closer (5, Funny)

P-niiice (1703362) | about 2 years ago | (#41168515)

one step closer to recording myself into a body not ravaged by television and cheetos

Re:one step closer (0)

Anonymous Coward | about 2 years ago | (#41168587)

Still would not be you. It would be an identical copy to you, and he would probably think that hi is you, with your memories and experiences, but *you*, the original, would forever be ravaged by television and cheetos.

Die and leave a copy, or die and don't. (4, Insightful)

jeffb (2.718) (1189693) | about 2 years ago | (#41168707)

Yeah, there are two of me, briefly -- but one of me never wakes up after the transfer, and the other wakes up healthy.

I'm actually completely OK with this. Maybe it has something to do with a lifetime of going to sleep every night, and never failing to wake up the next day. Discontinuity of experience is nothing new.

Re:Die and leave a copy, or die and don't. (4, Interesting)

TooMuchToDo (882796) | about 2 years ago | (#41168955)

It doesn't have to be that way. You would slowly replace parts of your brain with wetware until it was all artificial.

http://www.extremetech.com/extreme/135207-harvard-creates-cyborg-flesh-thats-half-man-half-machine [extremetech.com]

You would then still be "you", and not two of you.

http://en.wikipedia.org/wiki/Ship_of_Theseus [wikipedia.org]

"Plutarch thus questions whether the ship would remain the same if it were entirely replaced, piece by piece. Centuries later, the philosopher Thomas Hobbes introduced a further puzzle, wondering: what would happen if the original planks were gathered up after they were replaced, and used to build a second ship.[3] Which ship, if either, is the original Ship of Theseus?"

Re:Die and leave a copy, or die and don't. (1)

Anonymous Coward | about 2 years ago | (#41169373)

I have an axe like that. Its been in the family for three generations.

Re:Die and leave a copy, or die and don't. (1)

TheLink (130905) | about 2 years ago | (#41169437)

It's the one with the legal documents stating it's the original ship. ;)

Re:Die and leave a copy, or die and don't. (0)

Anonymous Coward | about 2 years ago | (#41171111)

AKA: "The Franklin Mint Certificate of Authenticity". I can just see it, limited collectors editions of popular slashdot members, every copy guaranteed to be the one true original*

*guarantee void in R.I., US Virgin islands, Alaska and where prohibited by law.

Re:Die and leave a copy, or die and don't. (1)

jeffb (2.718) (1189693) | about 2 years ago | (#41169609)

It doesn't have to be that way. You would slowly replace parts of your brain with wetware until it was all artificial.

Well, yeah, given the choice, I would prefer that. But once you're "all artificial", I'm betting it'll still be relatively easy to make copies of yourself, and we'll still have to deal with all the existential paradoxes that result.

"On the charge of murder, first-degree, we find the defendant guilty, and sentence it to six months subjective of isolation. On the charge of attempted extermination of backups, we find the defendant guilty, and sentence it to corrective editing (removal of aggressive proclivities, augmentation of inhibitions against irrevocable harm), concurrent with the previous sentence."

Re:Die and leave a copy, or die and don't. (1)

TooMuchToDo (882796) | about 2 years ago | (#41169789)

"On the charge of murder, first-degree, we find the defendant guilty, and sentence it to six months subjective of isolation. On the charge of attempted extermination of backups, we find the defendant guilty, and sentence it to corrective editing (removal of aggressive proclivities, augmentation of inhibitions against irrevocable harm), concurrent with the previous sentence."

Its shit like this that scares me, even as a very progressive futurist. Stay the hell away from my brain with a hex editor sort of thing.

Re:Die and leave a copy, or die and don't. (0)

mcgrew (92797) | about 2 years ago | (#41170725)

Which happens anyway. I doubt you have any of your cells you had when you were a child.

Re:Die and leave a copy, or die and don't. (1)

TooMuchToDo (882796) | about 2 years ago | (#41170843)

Completely agree. My original post suggests using artificial methods to integrate and slowly replace human tissue with an alternative that can last longer.

I.E. I have no intention of going through the messy process called death.

Re:Die and leave a copy, or die and don't. (2)

MindlessAutomata (1282944) | about 2 years ago | (#41170017)

Absolutely nonsense. Asking which one is the real "you" is presumptive since there is no "real you." there is no soul, no vital essence, no metaphysical, ontological chain of identity that exists as any discrete, singular being separable from the functional state and operations of your physical makeup. The outcome is two yous, both perceiving themselves as the real McCoy.

You guys are operating on naive philosophical assumptions best left in the bronze age with its cosmology. Your intuitions rely on extra material baggage whether you recognize or will admit to it or not.

Re:Die and leave a copy, or die and don't. (0)

Anonymous Coward | about 2 years ago | (#41173539)

This is also a pretty good setup for some lulz. Wait until somebody goes unconscious for the transfer... Then swap out the expected replacement body with an attractive one of the opposite gender.

Discontinuity of experience indeed.

Re:one step closer (0)

Anonymous Coward | about 2 years ago | (#41168597)

to the BORG!

Re:one step closer (3, Funny)

davester666 (731373) | about 2 years ago | (#41168605)

I'm not sure I want to know how your TV has ravaged you...I hope for your personal safety it's unplugged when it ravages you in the future.

Re:one step closer (0)

Anonymous Coward | about 2 years ago | (#41168963)

>one step closer to recording myself into a body not ravaged by television and cheetos

One step closer to nerve stapling [wikia.com] .

I'll leave you to guess which of the two technologies gets developed first.

Re:one step closer (1)

macraig (621737) | about 2 years ago | (#41169153)

Don't they have fat-free diet cheetos now?

Re:one step closer (0)

Anonymous Coward | about 2 years ago | (#41186723)

I've had those - they came in a box of hardware I ordered and they tasted like styrofoam.

Yeah, but the addiction (1)

liquidweaver (1988660) | about 2 years ago | (#41168585)

to neuropyzine is going to suck.

Seriously (1)

HangingChad (677530) | about 2 years ago | (#41168633)

Who thinks this shit up? We'll just design this little nanobot that seeks out a neuron, cuts a hole in it and welds itself into place and then it will start injecting shit into your thought patterns. Like it's no problem.

Just amazing.

Re:Seriously (2)

gstoddart (321705) | about 2 years ago | (#41168719)

Who thinks this shit up?

In all honesty, my first thought was of William Gibson's Neuromancer [wikipedia.org] and Razorgirl.

Re:Seriously (0)

Anonymous Coward | about 2 years ago | (#41168825)

My first thought was tcpdump for your brain.

Re:Seriously (2)

Nethemas the Great (909900) | about 2 years ago | (#41169163)

My first thought was Peter Hamilton's "Commonwealth Saga", or Richard Morgan's "Takeshi Kovacs" series. My second thought was "hurry the hell up".

Re:Seriously (1)

aristotle-dude (626586) | about 2 years ago | (#41170247)

My first thought was Peter Hamilton's "Commonwealth Saga", or Richard Morgan's "Takeshi Kovacs" series. My second thought was "hurry the hell up".

So you support fascism? Do you really want to be a drone?

Re:Seriously (1)

Nethemas the Great (909900) | about 2 years ago | (#41170561)

I think either you read different books than I, or you're focused on the politics not the technology proper. The notion of dispensing with physical peripherals for mental visualization and control, wetware augmentation, the "stack" as a means of enabling conscience (or self) to be communicated from body to body even over interstellar distances are all very intriguing prospects.

Re:Seriously (0)

Anonymous Coward | about 2 years ago | (#41169069)

Who thinks this shit up? We'll just design this little computer that seeks out an internet connection, connects with other computers, makes a network of computers, that will then become self aware and take over all the ICBMs. Like it's no problem.

Just amazing.

Re:Seriously (1)

Eponymous Hero (2090636) | about 2 years ago | (#41171653)

"Can I just come home and think I've been fishing all day or something?"

"That's really not what I do, Peter."

Actually... (1)

macbeth66 (204889) | about 2 years ago | (#41168701)

It's a good thing that I renewed my Old Glory Robot Insurance.

Re:Actually... (0)

Anonymous Coward | about 2 years ago | (#41168817)

Are you ready to release all that pressure backed up in your Robot. You've come to the right place, is the answer is yes. These horny Robots love nothing more then for you to shoot your neurons on their pretty face. This commentary is packed with loads of Robots.

Eeek (0)

Anonymous Coward | about 2 years ago | (#41168807)

I don't want my brain patch clamped, thx

Re:Eeek (2, Funny)

Anonymous Coward | about 2 years ago | (#41168877)

You're getting your brain clamped. Deal with it.

Re:Eeek (1)

Anonymous Coward | about 2 years ago | (#41169039)

Just like on TV

http://futurama.wikia.com/wiki/Francis_X._Clampazzo

Brings patch-clamp to nobody new. (1, Informative)

lcampagn (842601) | about 2 years ago | (#41168971)

This is cool, but alone it does not bring electrophysiology to anybody who did not already have it. The robot only handles the easiest part of the experiment--putting an electrode into a brain and sealing onto neurons is standard practice that most electrophysiologists learn with a few days of practice.
Generally the most difficult parts of these experiments are 1) surgery / dissection, 2) keeping your animal / slice alive, 3) _keeping_ the electrode attached to the cell, and 4) managing racks full of complex, noisy, temperamental equipment. It would probably speed up the process, particularly since the experimenter is free to do other things while the robot patches cells (like prepare new electrodes for the robot).

Re:Brings patch-clamp to nobody new. (1)

Niedi (1335165) | about 2 years ago | (#41176435)

Mod parent up, it's spot on! The actual patching is not really hard, especially since it only seems to do "blind" patching (just guided by the electrical response).

The only things to add are
- Fighting with your pipette puller to deliver constant results, because either you have your own crappy little puller that is hideously unreliable or you have a fancy one which is shared, meaning there is a high risk of someone messing with the filament and/or settings. And if your pipettes are crap, neither you nor the robot are going to succeed...
- Finding out why you suddenly have massive noise in your recordings
- Not freaking out after matlab, igor et al crash halfway through your recording session taking all your data with it.

Patch-Clamping To the Masses (3, Interesting)

Un pobre guey (593801) | about 2 years ago | (#41168977)

Patch-Clamping To the Masses

1) Almost nobody on /. knows about or will ever see this technique practiced
2) BTW, it is done in vitro or in instrumented animal models, not in your head. At least not with any reasonable expectation of safety in the hands of "the masses."
3) At the moment there are essentially no practical applications of patch clamping "for the masses"

If I am mistaken, then boy are we in deep shit now.

Re:Patch-Clamping To the Masses (4, Insightful)

Hatta (162192) | about 2 years ago | (#41169021)

1) Almost nobody on /. knows about or will ever see this technique practiced

Almost nobody who knows about patch clamping practices it. It's that hard. "The masses" in this case refers to the 90% of neuroscience labs who don't have a patch clamp apparatus because it's an incredibly difficult technique. Putting an automatic patch clamp machine on every lab bench would be a huge boon to neuroscience.

Re:Patch-Clamping To the Masses (3, Informative)

Un pobre guey (593801) | about 2 years ago | (#41169151)

I saw it done in grad school, in Mexico. It definitely looked like it required serious ninja lab skills. On a grander scale, automating such tricky and delicate maneuvers will revolutionize all of the sciences. The great 20th century scientific techniques will be subsumed to an invisible stratum hidden inside machines. 21st century scientists will use those as building blocks and tools. They will each be standing on the shoulders of several generations of scientists. Unbelievably scary, unbelievably cool.

Re:Patch-Clamping To the Masses (1)

tgibbs (83782) | about 2 years ago | (#41169635)

Patch clamping isolated cells is not all that hard. It has become the standard method of single-cell recording, and automated devices to do it have been available for years. This device automatically patch clamps neurons in brain slices, which is trickier because it's harder to see what you are doing.

Re:Patch-Clamping To the Masses (1)

Monkey-Man2000 (603495) | about 2 years ago | (#41169941)

1) Almost nobody on /. knows about or will ever see this technique practiced

Almost nobody who knows about patch clamping practices it. It's that hard. "The masses" in this case refers to the 90% of neuroscience labs who don't have a patch clamp apparatus because it's an incredibly difficult technique. Putting an automatic patch clamp machine on every lab bench would be a huge boon to neuroscience.

Neurophysiologist here: patching isn't nearly as hard as it looks and is quite fun. Now-a-days investigators don't even need to build their own amplifiers like in the old days. However, that said, it does take practice and as I like to say, "I've never met anyone who learned how to patch-clamp after getting a Ph.D." Only undergraduates and graduate students have the time and dedication to learn it.

I should also point out there have been automatic patching machines that cater to high-throughput drug discovery on cultures (big pharmas like these). However, the novelty for this paper is that the patching is for live animals.

Another point I should make is that in the last 5 or so years the number of high-profile papers that just (or mostly) rely on patching are becoming exceedingly rare. It still has it's place, but we now know a great deal about the properties of ionic currents and their channel proteins and these properties are conserved across many subsystems. Now people are off working on complementary things...

Re:Patch-Clamping To the Masses (1)

bitingduck (810730) | about 2 years ago | (#41180131)

However, that said, it does take practice and as I like to say, "I've never met anyone who learned how to patch-clamp after getting a Ph.D."

I know quite a few (including me) but most of them got their PhDs in physics, EE, or something non-biological before learning to poke at wet things. It didn't take long-- I was doing sharp electrode in about 2 hours, and getting gigaohm seals and action potentials within a few sessions.

Re:Patch-Clamping To the Masses (1)

Monkey-Man2000 (603495) | about 2 years ago | (#41191807)

Actually, you probably have a point because I know a couple bioengineering-related people that probably picked it up after a Ph.D. So, maybe the better distinction is that most 'biologists' won't learn it after a Ph.D. IMO. The people you describe are probably more likely to tinker with a new skill compared to the people I work around who already have the cookbook of experimental techniques they use everyday and don't need/want to devote a lot of time to something new.

Re:Patch-Clamping To the Masses (2)

bitingduck (810730) | about 2 years ago | (#41169997)

I got pretty good at it as a hobby trying to work on multi-electrode array stuff with neurons. It's not that hard if you're patient and have a light touch on the controls and can read an oscilloscope. I could do two mouse hippocampal neurons (in a dish) at once pretty reliably, and I tried did 3 a couple of times just to show off. The limiting factor on how many you can do at once is generally the size of the manipulators and amplifiers. Getting 4 in is possible but tricky, more than that starts to get really hard, which is part of why we were working on using electrode arrays for talking to neurons. I was visiting a lab about a year ago and could still do it, even after a break of 5+ years.

Re:Patch-Clamping To the Masses (0)

Anonymous Coward | about 2 years ago | (#41175327)

Good job! You really have a pair of dexterous hands. Could you tell me what amplifier you were using when you did 2 mouse hippocampal neurons at once? EPC series? or AXON series? How about getting 4? Could you describe for me a little more about the scene getting 4 in your lab? I'm really curious about that!!! Thank you in advance!

Re:Patch-Clamping To the Masses (1)

bitingduck (810730) | about 2 years ago | (#41180083)

It was homemade amplifiers that Jerry Pine had made (probably published somewhere). I don't think we had enough manipulators to get 4, but there was room-- to do 3 it was 2 on one side of the scope, and one on the other. 4 would have been the same, but two on each side. There wouldn't have been room for 5. The manipulators were just micrometer style-- no piezo, but they were very smooth and could sit on a cell for a couple hours without slipping. Data storage for a while was with an analog storage scope and a polaroid scope camera (for real!).

Re:Patch-Clamping To the Masses (3, Insightful)

damn_registrars (1103043) | about 2 years ago | (#41169347)

Don't forget though that patch clamping is useful to a lot of biological sciences beyond neuroscience. Pretty well every cell in a higher eukaryote uses voltage-gated channels for something; I've seen cardiology research groups use it to monitor Na+ ion currents for one but it goes much further than that. As someone already pointed out a big part of what restricts the adoption of patch clamping in other disciplines isn't that it doesn't have an application but rather that it is so immensely difficult to master. If it can be automated that not only makes it available for more types of work but it also increases the confidence on the measurements by making it easier to do a lot of them.

Re:Patch-Clamping To the Masses (1)

gatesstillborg (2633899) | about 2 years ago | (#41171033)

It doesn't appear to be actual patch clamping the researchers are referring to. As the wikipedia page states, this seems to be more of a form of (whole) intracellular recording. (See my detail below.) Good for characterizing neural networks and behaviors vs. rigorous ion current measurement.

Re:Patch-Clamping To the Masses (1)

autonomouse (1203262) | about 2 years ago | (#41170217)

I used to do this for a living, does that mean I'm finally almost somebody?!

Re:Patch-Clamping To the Masses (1)

interkin3tic (1469267) | about 2 years ago | (#41170301)

3) At the moment there are essentially no practical applications of patch clamping "for the masses"

Maybe because other types garage research into cell biology are still not happening. At home PCR machines are feasible, at this point you can build one for around $500. I heard of a relatively cheap desktop electron microscope not too long ago. The price of DNA sequencing is falling fast. Microscopes are getting cheaper and more powerful. All the tools seem to be headed in the direction of home experimentation.

Maybe someone in their garage will harvest some of their own fibroblasts, make their own culture media, transfect in the four necessary genes for induced pluripotence, harvest pluripotent colonies, direct differentiation to neurons, and will start making neruonal computers, using patch clamps to check the output. That's feasible, it would still be too rich for me to do in my apartment, but give me a few years to start making more than a postdoc salary, a few years for IPSC efficiency to increase and for culture media to come down in price.

Re:Patch-Clamping To the Masses (0)

Anonymous Coward | about 2 years ago | (#41175337)

Yeah~~! I also believe some researchers are reducing the price and size of the patch clamp equipment! Let's keep an eye on it!

What I immediately thought of (3, Funny)

Anonymous Coward | about 2 years ago | (#41168997)

Thank you to Unknown Lamer (1, Insightful)

damn_registrars (1103043) | about 2 years ago | (#41169283)

I frequently bash the slahdot editors for terrible choices in front page articles (Timothy for one pro-republican posting after another, samzenpus for conservative spin that makes me want to vomit, etc), this time I'd like to extend a big thank-you to "Unknown Lamer" for his postings. Recently he posted the article on NEMS mass spec as well, so it is nice to see some science coverage on the front page. Heck, "Unknown Lamer" even posted some actual computer hardware stories recently, too - what a concept!

So thank you, Unknown Lamer. It's nice to see something that actually is news for nerds and not just politics as usual on the front page.

Working for the Borg (0)

Anonymous Coward | about 2 years ago | (#41170681)

Hmm, sounds like someone is working for the Borg.
We got to listen and talk to individual neurons, to link to the Collective.
Prepare to be assimilated!

Certainly this robotic manipulation system (1)

gatesstillborg (2633899) | about 2 years ago | (#41170741)

sounds like quite an achievement, but I was similarly interested by the way the term "patch clamp", and, specifically, the "clamp" part appears to have diverged from its original meaning.

When I first learned about neural "voltage clamp" in college, it was a way to maintain a constant voltage across a neural membrane, which is otherwise normally altered by a trans-membrane conduction event. That is, a current is passed in/out of the cell during a conduction event to compensate for it, thus maintaining or "clamping" the voltage constant. This allows for more rigorous quantification of ion channel currents than is possible under varying voltage conditions. As applied by these researchers, the term must refer to the phenomenon of the membrane patch being "clamped" to the pipette tip (ie. via suction), which, though perhaps of some interest is not as interesting, I think, as the original meaning.

The linked wikipedia article, referring to "whole cell recording" or "whole cell patch" (as a form of simple intracellular recording with its advantages and disadvantages over same) seems fundamentally accurate, whereas the abstract referencing "whole cell patch clamping" seems somewhat misleading. Intracellular recording is about events at the cell level (eg. action potential), whereas (patch) voltage clamp is about ion currents, whether at the single or multiple (ie. membrane) channel level . And I did the intracellular recording in college under a dissection scope with a pulled glass electrode in a micro-manipulator, and I can attest to its difficulties.

Re:Certainly this robotic manipulation system (0)

Anonymous Coward | about 2 years ago | (#41176839)

sounds like quite an achievement, but I was similarly interested by the way the term "patch clamp", and, specifically, the "clamp" part appears to have diverged from its original meaning.

When I first learned about neural "voltage clamp" in college, it was a way to maintain a constant voltage across a neural membrane, which is otherwise normally altered by a trans-membrane conduction event. That is, a current is passed in/out of the cell during a conduction event to compensate for it, thus maintaining or "clamping" the voltage constant. This allows for more rigorous quantification of ion channel currents than is possible under varying voltage conditions. As applied by these researchers, the term must refer to the phenomenon of the membrane patch being "clamped" to the pipette tip (ie. via suction), which, though perhaps of some interest is not as interesting, I think, as the original meaning.

Actually to clamp the cell (ie. maintaining the current or the voltage across the membrane constant. What you are referring to as the "original meaning" is voltage clamp) you need to suck its membrane and then make a tiny hole in it. The suction assures you have what is called a "giga seal" which just means you have a high resistance (in the giga ohms range) between your pipette and the outside world. Without this high resistance you have no chance of voltage (or current) clamping your cell. So the researchers in TFA are actually referring to clamping the cell in the electrical meaning if you wish, which requires a physical clamping by suction anyway.

The linked wikipedia article, referring to "whole cell recording" or "whole cell patch" (as a form of simple intracellular recording with its advantages and disadvantages over same) seems fundamentally accurate, whereas the abstract referencing "whole cell patch clamping" seems somewhat misleading. Intracellular recording is about events at the cell level (eg. action potential), whereas (patch) voltage clamp is about ion currents, whether at the single or multiple (ie. membrane) channel level . And I did the intracellular recording in college under a dissection scope with a pulled glass electrode in a micro-manipulator, and I can attest to its difficulties.

"whole cell recording" "whole cell patch" and "whole cell patch clamping" are all referring to the same technique where you are imposing a constant voltage (or current) to the whole cell after making a hole in its membrane.
Intracellular recording (what you did in college) is a different technique where you insert a tiny (an order of magnitude smaller) electrode inside the cell. This way you can record spikes but not small ion currents as you are not able to patch the cell. On the contrary when you patch a cell you can record both big events as action potentials and small ones like tiny ion currents. But, you are using a huge pipette and making a pretty big hole in the membrane...

Sunflower Society Press Release (0)

Anonymous Coward | about 2 years ago | (#41173493)

Robotic patch clamping is the leading cause of cyber-brain sclerosis.

Call me... (1)

OhSoLaMeow (2536022) | about 2 years ago | (#41173681)

... when they get a robot to perform nipple clamping.

I've read the paper, and sth's different. (0)

Anonymous Coward | about 2 years ago | (#41175219)

I didn't find the author claim, no matter in the article or in the supplementary files, that they can record 4 neurons at once. Where does this information come from?

Robot (0)

Anonymous Coward | about 2 years ago | (#41176617)

Robotics is what we need

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