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New Microscope Reveals Ultrastructure of Cells

An anonymous reader writes "For the first time, there is no need to chemically fix, stain or cut cells in order to study them. Instead, whole living cells are fast-frozen and studied in their natural environment. The new method delivers an immediate 3-D image, thereby closing a gap between conventional microscopic techniques. The new microscope delivers a high-resolution 3-D image of the entire cell in one step. This is an advantage over electron microscopy, in which a 3-D image is assembled out of many thin sections. This can take up to weeks for just one cell. Also, the cell need not be labeled with dyes, unlike in fluorescence microscopy, where only the labeled structures become visible. The new X-ray microscope instead exploits the natural contrast between organic material and water to form an image of all cell structures. Dr. Gerd Schneider and his microscopy team at the Institute for Soft Matter and Functional Materials have published their development in Nature Methods (abstract)."

58 comments

  1. Lemme guess.. the article has no pictures by mozumder · · Score: 4, Informative

    (checks article)

    yep.

    1. Re:Lemme guess.. the article has no pictures by Anonymous Coward · · Score: 5, Informative

      there are several pics from the article here:

      http://www.nature.com/nmeth/journal/vaop/ncurrent/fig_tab/nmeth.1533_ft.html

    2. Re:Lemme guess.. the article has no pictures by Snowgen · · Score: 5, Informative

      Call me a Karma-Whore, but here's the clickable link: http://www.nature.com/nmeth/journal/vaop/ncurrent/fig_tab/nmeth.1533_ft.html

    3. Re:Lemme guess.. the article has no pictures by mestar · · Score: 1

      Yes, it's absolutely crazy how stupid people can be.

      "We have new amazing pictures of living cells. Sorry no pictures."

    4. Re:Lemme guess.. the article has no pictures by Walzmyn · · Score: 1, Funny

      Yer a karma-Whore...
      But thank you.

    5. Re:Lemme guess.. the article has no pictures by nazsco · · Score: 1

      We on a copy-paste impaired android phones thank you, karma whore

  2. I never thought I'd say this here by dreamchaser · · Score: 1

    Pics or it didn't happen. I mean, seriously, an article about a new imaging technique without even a low resolution sample?

    Yes I actually read TFA.

    1. Re:I never thought I'd say this here by MeanMF · · Score: 5, Funny

      There are pictures, but unfortunately they're actual size.

    2. Re:I never thought I'd say this here by mozumder · · Score: 1

      It's usually the articles about some amazing new high-tech imaging breakthrough without pics.

    3. Re:I never thought I'd say this here by Anonymous Coward · · Score: 0

      I agree the article presents a novel method but does anyone have a link to some examples?

    4. Re:I never thought I'd say this here by Anonymous Coward · · Score: 1, Informative

      No, the TFA is under abstract; also no pictures but:

      To read this story in full you will need to login or make a payment (see right).

      Welcome to the wonderful world of paywalls. No $, no pix.

    5. Re:I never thought I'd say this here by countertrolling · · Score: 2, Informative

      That'll be a dollar... You can keep the points

      --
      For justice, we must go to Don Corleone
  3. No Images? by cyberoidx · · Score: 1

    Its kinda lame to have an article on 3D images without any image samples. Thanks Medical Daily!

  4. Where's the real article? by AdamHaun · · Score: 2, Interesting

    Okay, I read the press release copied and pasted onto a random blog. Is there a real article with pictures we could look at?

    --
    Visit the
    1. Re:Where's the real article? by John+Hasler · · Score: 1

      There may be pictures in the Nature article but it's behind a paywall.

      --
      Warning: this article may contain humor, sarcasm, parody, and perhaps even irony. Read at your own risk.
    2. Re:Where's the real article? by Rashdot · · Score: 3, Informative

      It seems that the images are accessible. Found these via Google:

      http://www.nature.com/nmeth/journal/vaop/ncurrent/fig_tab/nmeth.1533_F2.html

      --
      This is not the sig you're looking for.
  5. figures by Anonymous Coward · · Score: 1, Informative

    Figures:
    http://www.nature.com/nmeth/journal/vaop/ncurrent/fig_tab/nmeth.1533_ft.html

    1. Re:figures by rayharris · · Score: 1

      Now linked for your clicking pleasure:

      Images

      --
      I void warranties.
  6. So where are the pictures? by spagthorpe · · Score: 1

    Stories like this suck.

    --

    WWJD -- What Would Jimi Do?
    (Smash amp, burn guitar, take home the groupies)

  7. Group website. by gyroidben · · Score: 2, Informative

    Didn't find any relevant pics but if anyone's interested the research group's webpage is http://www.helmholtz-berlin.de/forschung/grossgeraete/mikroskopie/index_en.html.

  8. Picture is worth 1000 words by Andy+Smith · · Score: 1

    As a news photographer, who naturally believes that pictures are very important in news coverage, it blows my mind that a story about a new imaging technique would run without one single illustration.

    1. Re:Picture is worth 1000 words by Anonymous Coward · · Score: 2, Funny

      Maybe they're just respecting the copyright of the cells.

    2. Re:Picture is worth 1000 words by K.+S.+Kyosuke · · Score: 1

      In this case, it's more like "a picture is worth 1000 US cents" or something. (Anyway, all the possible thousands of words associated with pictures form a rather limited subset of the set of all conceivable thousands of words, which seriously limits the applicability of pictures.)

      --
      Ezekiel 23:20
    3. Re:Picture is worth 1000 words by vlm · · Score: 1

      Maybe they're just respecting the copyright of the cells.

      As far as I can tell its a tomographic tech, so the output is a 3D model. I would guess it is in fact copyrighted.

      The killer is you can get better res from other techs if you're willing to wait. The story is you can get useful data quicker than say, electron microscope slices.

      It would be like posting a pic from my backyard telescope with the announcement that it is 10 times better than the average cheap backyard scope, to a generation that is used to billion dollar Voyager probe probe photos. No one outside of a lab is going to be impressed.

      --
      "Science flies us to the moon. Religion flies us into buildings." - Victor Stenger
  9. ...a little googling, and I found these by Anonymous Coward · · Score: 1, Informative

    http://www.helmholtz-berlin.de/pubbin/news_seite?nid=13186;sprache=en;typoid=3228

  10. natural environment? by jc42 · · Score: 2, Insightful

    ... whole living cells are fast-frozen and studied in their natural environment.

    Um, unless we're talking about species native to Antarctica, I wouldn't think that frozen would be their "natural environment".

    Freezing is known (and not just by the State of California ;-) to do damage to many cell structures. For example, they no longer qualify as "living".

    Somehow, I think this could have been better expressed with different words.

    --
    Those who do study history are doomed to stand helplessly by while everyone else repeats it.
    1. Re:natural environment? by vlm · · Score: 1

      I also laughed at "The new X-ray microscope instead exploits the natural contrast between organic material and water to form an image of all cell structures."

      As if not using a stain/dye is a new concept in the microscopy arena.

      Standard slashdot car analogy would be pimping my new car engine for using the new "naturally aspirated" technology instead of one of those old fashioned turbocharger gimmicks.

      --
      "Science flies us to the moon. Religion flies us into buildings." - Victor Stenger
    2. Re:natural environment? by SEWilco · · Score: 1

      p>Standard slashdot car analogy would be pimping my new car engine for using the new "naturally aspirated" technology instead of one of those old fashioned turbocharger gimmicks.

      Except this "naturally aspirated" technology requires all the engine's air to be bottled and frozen.

    3. Re:natural environment? by jc42 · · Score: 1

      As if not using a stain/dye is a new concept in the microscopy arena.

      Whaddaya wanna bet that someone will soon patent the concept?

      --
      Those who do study history are doomed to stand helplessly by while everyone else repeats it.
    4. Re:natural environment? by HomelessInLaJolla · · Score: 0, Offtopic

      Indeed. Fast freezing has advantages in that, theoretically, a sufficiently instantaneous freeze could preserve tertiary and quaternary structures. In practice the laboratory technique is no where near that good.

      Similar concepts apply to pharmaceutical development based upon data gleaned from enzymatic assay or even cell cultures of only one cell type. There is a whole lot that goes on in the surrounding environment that makes a heckuvalot more difference than just the one thing under the microscope.

      Take creamer in coffee, real cream. Do not add it to hot coffee or the coffee will taste burnt and, likely, you will have gas from it. Hot coffee denatures cream. Allow the coffee to cool before adding cream. Cold is no different. When enzymes and proteins go from normal temperature to super-frozen they constrict and often fold differently.

      Still... interesting technique and I am positive there will be good applications in the future.

      --
      the NPG electrode was replaced with carbon blac
    5. Re:natural environment? by interkin3tic · · Score: 3, Informative

      Natural environment meaning microenvironment, or rather, with other cells.

      A lot of cell biology is done on cells which have been mechanically or chemically separated, or cells grown in a single layer on a dish. That's okay for some studies, but if you want to study, for example, the stem cells of the intenstine, that's not much good. When you dissociate cells, they change shape which makes some of the microscopy you'd want to do on them pointless right off, and many if not most cells will start changing in other ways when you dissociate them. For many cells, being attached to other cells is a sign they're doing what they're supposed to, if they lose contact they'll start to kill themselves. It's a safeguard against metastasis of cancer cells. If you were looking at cells you isolated from the intestine after you'd dissociated them, you wouldn't be studying intestinal stem cells anymore, you'd be studying cells that were starting to commit suicide.

      By freezing it and then leaving the tissue intact, you'd be able to study those cells as they are supposed to exist: attached to other cells and not undergoing apoptosis (assuming you did it right). There are ways of freezing tissues to prevent the formation of damaging ice crystals. They won't be alive, but they'll make a good snapshot.

  11. Everybody here is from Missouri by Anonymous Coward · · Score: 0

    The "show me" state.

  12. Old technique by vlm · · Score: 4, Informative

    Terrible misleading article. Maybe its the first time the journalist heard about it, but its hardly the first time this has ever been done.

    Despite a desperate attempt by the journalist filter to avoid "science-y words" I've figured out the technique they're talking about is xray microtomography. Basically yet another tomography tech (make a 3 d model in a computer out of a crapload of 2 d pix and lots of processing and memory) but applied to little things.

    "The first X-ray microtomography system was conceived and built by Jim Elliott in the early 1980s" Back then 50 nm was considered pretty good resolution, and thirty years later these dudes are down to 30 nm. A slight improvement on the past, and it is cool, but its not like they are "the first", like being the first men to step onto the moons surface or something.

    http://en.wikipedia.org/wiki/X-ray_microtomography

    Saying these guys are the first, is kind of like saying I'm the first human being to see the moons of jupiter thru a telescope, with the footnote that I'm defining telescope today as being home made using these exact lenses from Edmund Optics and these specific (empty) toilet paper tubes with these somewhat unique specific optical parameters, and no one has ever used that exact tech. Or I'm the first to have ever driven my car to work, while burning these specific individual hydrocarbon molecules.

    --
    "Science flies us to the moon. Religion flies us into buildings." - Victor Stenger
    1. Re:Old technique by fjanss · · Score: 4, Informative
      X-ray_microtomography is not new. What is new is :

      "using partially coherent object illumination instead of previously used quasi-incoherent illumination"

      which led to :

      "We obtained three-dimensional reconstructions of mouse adenocarcinoma cells at ~36-nm (Rayleigh) and ~70-nm (Fourier ring correlation) resolution, which allowed us to visualize the double nuclear membrane, nuclear pores, nuclear membrane channels, mitochondrial cristae and lysosomal inclusions."

    2. Re:Old technique by Anonymous Coward · · Score: 4, Informative

      Coherence-based imaging (e.g. coherent diffractive imaging) is also not new. What these researchers have done is to push the envelope of what can be done by perfecting known imaging principles. They have not invented something drastically new.

      But I'm not trying to downplay their achievement in saying that their work is not without precedent. Frankly the media is over-obsessed with novelty. They only want to report on things from a "first of its kind" perspective, but that's fundamentally disconnected from the way science is done. All advancements build on previous work. Truly new and different things are rare--and they typically don't make much of a splash when they are first tried because the initial work is esoteric, crude, and primitive.

      What these scientists have done is really amazing. The images are fantastic and this will no doubt add to researchers' toolkit for analyzing materials in fine detail. I really wish that people could appreciate the quality of this work without it having to be exaggerated or its novelty mis-represented.

    3. Re:Old technique by Thing+1 · · Score: 1

      Despite a desperate attempt by the journalist filter to avoid "science-y words"

      Interesting. The fourth estate is helping to create a second class of citizens.

      --
      I feel fantastic, and I'm still alive.
    4. Re:Old technique by vlm · · Score: 1

      Interesting. The fourth estate is helping to create a second class of citizens.

      Not so much second class. The market has been engineered to be too small for multiple classes. Instead, its a well known narrowcasting thing. Peaking out a non-global local max on a graph.

      So, two newspapers, both appealing to B.S. degree holders. Lightbulb on MBAs head appears, I can increase circulation by appealing to B.S. degree minus one year folks. Repeat on both sides a couple dozen times, you end up with modern american corporate media, which no one beyond the (mental or physical) grade school level finds informative. The market is too small to support multiple corporate news suppliers so don't count on the dead hand of the market competition to "fix things". Its quasi-stable.

      --
      "Science flies us to the moon. Religion flies us into buildings." - Victor Stenger
  13. Royal Rife by brirus · · Score: 1
    Royal Raymond Rife had a better microscope in the 30's. He took pictures and film... he still had to stain, but he was able to view living bacteria.
    • http://www.rife.de/what_has_become_of_the_rife_microscope.html
    • http://video.google.com/videoplay?docid=-661201775015095955#

    Suppressed technology or conspiracy theory? You decide.

    1. Re:Royal Rife by intellitech · · Score: 1

      Possibly, but I'd like to see the 3D technology he used in the 30's.

      --
      vos nescitis quicquam, nec cogitatis quia expedit nobis ut unus moriatur homo pro populo et non tota gens pereat.
    2. Re:Royal Rife by brantondaveperson · · Score: 1

      What he saw convinced him that germs could be not the cause, but the result of disease; that depending on its state, the body could convert a harmless bacterium into a lethal pathogen

      Perhaps because he was a loon?

  14. Opt-Out? by Garrett+Fox · · Score: 1

    What about the cells that opt out of this intrusive screening?

    --
    Revive the Constitution.
    1. Re:Opt-Out? by ilsaloving · · Score: 1

      They're taken aside and intrusively penetrated by a security virus.

  15. Freely available article link by Anonymous Coward · · Score: 1, Informative

    The article is freely available here or using wget:
    wget --referer="http://www.nature.com/regions/germany/" http://www.nature.com/nmeth/journal/vaop/ncurrent/pdf/nmeth.1533.pdf

  16. Of course by Anonymous Coward · · Score: 0

    Its only a matter of time before the TSA starts using this at airports...

    1. Re:Of course by Anonymous Coward · · Score: 0

      Likewise, it's only a matter of time before the TSA bans passengers from aircraft because they will discover that the average human body is composed of 60% water - and you know water can be used as a bomb component!

  17. no replacement for fluorescence by Anonymous Coward · · Score: 1

    Traditional fluorescent microscopy isn't going away anytime soon. While immunohistochemistry is fairly "low resolution" optically, it does give you the ability to image individual protein targets (even if they do show up as big green and red blobs). This x-ray scope has no where close to that kind of "resolution." For the most part we already know what the insides of cells "look like." What is interesting is what the individual molecules are up to.

    1. Re:no replacement for fluorescence by zalas · · Score: 1

      Furthermore, you don't need to kill the target for fluorescent microscopy. While attaching labels may affect some of the chemistry in the organism, you can at least still observe biological behavior.

  18. *not* immediate by zalas · · Score: 3, Insightful

    Here's the relevant passage from the article with the juicy bits:

    We acquired X-ray microscope images of these vitrified mammalian cells at tilt angles from 60 to +60 in increments of 1 at a pixel size of either 9.8 nm (25-nm zone plate objective) or 15.6 nm (40-nm zone plate objective). Exposure times for each tilt angle were 224 s. The total X-ray exposure (~109 Gy) produced negligible radiation damage, as we detected no difference in image quality between images acquired at the beginning and end of the tilt series (Supplementary Fig. 3). We processed the images using a reciprocal space algorithm11 to generate a 3D tomogram composed of cubic voxels whose side lengths were either 9.8 nm (25-nm zone plate objective) or 15.6 nm (40-nm zone plate objective).

    So they took 121 x-ray images of the specimen, with each image taking 2-24 seconds, and then stitched them together using a tomography technique to obtain their 3D volume. It's certainly faster than a few weeks, but this is not what I would consider "immediate". The article also points out that poor cryopreservation led to some artifacts and that the resolution in this technique was still not as good as the TEM; not having an entire 180 degree rotation of the object led to artifacts as well:

    We did not detect some structures by X-ray tomography that we detected by TEM, such as ribosomes and the double membrane of the mitochondrial cristae. These probably fall below the current resolution limit (see below). An additional limitation was the restricted tilt angle range (±60) used in these experiments. This led to poorer resolution in the z dimension, as indicated by a distortion in the 3D shape of some organelles, which appeared more cylindrical in x-z views (Fig. 3b) as well as an inability to obtain face-on views of the nuclear pores (data not shown) or follow the complete circumference of the nuclear membrane (Supplementary Fig. 5b).

    1. Re:*not* immediate by Anonymous Coward · · Score: 0

      The total X-ray exposure (~109 Gy)

      Sweet Jesus! That's more than most cancer patients are given in two months.

  19. Great News! by digitalPhant0m · · Score: 1

    On a side note, they'll be tasty and fresh in a jiff too!

  20. Yet another link spam to an SEO website... by RocketRabbit · · Score: 0, Troll

    Medical Daily is a linkfarm, and Slashdot is linkspamming the world. It was shocking to see a link to the Nature abstract, though - normally I would have to Google that up for myself.

    Verdict? Slashdot still sucks, but samzenpus is at least a notch above Timothy.

  21. CellCraft by Danny+Rathjens · · Score: 1

    If you don't the difference between a lysosome and the endoplasmic reticulum, this is a great way to learn that I encountered the other day. :)
    CellCraft

  22. Lame imaging by Anonymous Coward · · Score: 0

    The Nature Methods paper in question is pretty lame. Its difficult to see why it merited publication, since there is nothing new in the paper. Other groups have been doing this kind of imaging routinely for years (and doing so without the artifacts caused by only being able to collect a relatively restricted tilt series).

    Probably they needed some hype prior to submitting a funding proposal.