Biology and Solid Surfaces
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00:00
SemiconductorSuperconductivitySensorElectricityBoatFischer, ErnstYearAngeregter ZustandLimiterUninterruptible power supplyHot workingFlightBlackFinger protocolWater vaporVideoSpare partWeather frontSuperconductivityThin filmCocktail party effectSizingRutschungCell (biology)MetalRadiationLeadKopfstützePhysicistLecture/ConferenceMeeting/Interview
02:46
SemiconductorSuperconductivitySensorElectricityBoatFischer, ErnstThin filmLastLinearpolarisationMeasuring instrumentLightWavelengthBuick CenturyRutschungSemiconductorPhysicistWater vaporRefractive indexSurfingAM-Herculis-SternFullingStriking clockIceNuclear reactorWeekWalletMental disorderLightningHourPlane (tool)OpticsLecture/ConferenceMeeting/Interview
05:06
Interplanetary magnetic fieldSemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstAbsorbanceMetalHydrogen atomFlashlightAlbumen printRutschungConcentratorMinuteLightMechanicDyeingVideoDiffuser (automotive)Automated teller machineHot workingAtmosphere of EarthLecture/ConferenceMeeting/Interview
07:26
SemiconductorSuperconductivitySensorElectricityBoatFischer, ErnstElectron microscopeFood storageAlcohol proofPhysicistRutschungAlbumen printBarometerWater vaporShot peeningBauxitbergbauDrehmasseFlightVideoYearDampfbügeleisenAtmospheric pressureTemperatureRoll formingFlugbahnGameLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivitySensorElectricityBoatFischer, ErnstImage projectorMetalRutschungLightElectronVideoParticleMicroscope slideCrystallizationDampfbügeleisenElectron microscopeGentlemanNegativer WiderstandFlightGlassNanotechnologyCartridge (firearms)PhotographyLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstBird vocalizationWavelengthParticleMicrowaveScatteringAbsorbanceGentlemanDurchstrahlungselektronenmikroskopieScale (map)GlassLightMetalField-effect transistorBook designNanotechnologyOrder and disorder (physics)RutschungDecemberSizingImage projectorRoll formingGeokoronaPhysicistLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstGeokoronaHochfrequenzübertragungScatteringRoman calendarEffects unitHourHot workingCut (gems)Diaphragm (optics)Kette <Zugmittel>Shortwave radioDVD playerLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstFlightBuick CenturyCell (biology)MachineField-effect transistorTypesettingSunriseKey (engineering)WoodGround stationBurst (band)Acoustic membraneYearPhysicistRutschungReaction (physics)Lecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstField-effect transistorSurfingReaction (physics)RulerAnalog signalYearRoman calendarVideoFlightSpecific weightElektrische DoppelschichtWind waveLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstRutschungRoman calendarBund Schweizer ArchitektenUniverseVolkswagen GolfReaction (physics)Cell (biology)Elektrische DoppelschichtRegentropfenCogenerationYearScanning acoustic microscopeGameWatercraft rowingOrbitLightDishwasherSpace probeQuality (business)Lecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstDual in-line packageRutschungBund Schweizer ArchitektenCocktail party effectYearBelt (mechanical)FlightAnalog signalVolkswagen GolfTrade windSoundGloss (material appearance)FACTS (newspaper)Lecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstSpray paintingLubricationOzone layerWire bondingElektrische DoppelschichtParticleMicroscope slideSteckverbinderTin canWhiteRutschungGlassCogenerationBund Schweizer ArchitektenElectricityEnergy levelLightFiling (metalworking)NanotechnologyLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstCell (biology)TrainGentlemanRutschungHot workingTissue paperFlugbahnElektrische DoppelschichtGlassMetalCogenerationRoll formingMicroscopeYearDie proof (philately)FlightParticleCouchMicroscope slideHeatLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstCell (biology)Tissue paperMetalGlassRutschungYearCogenerationMobile phoneSurfingPhysicistEnergy levelStream bedLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityElectricitySensorBoatFischer, ErnstCell (biology)CogenerationKataklysmischer DoppelsternSpecific weightLightCartridge (firearms)Energy levelAbsorbanceTurningFACTS (newspaper)Scanning acoustic microscopeCommand-line interfaceRutschungBund Schweizer ArchitektenCut (gems)Lecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityCash registerElectricitySensorBoatFischer, ErnstAbsorption (electromagnetic radiation)Mechanical engineeringPufferlagerCogenerationHot workingFACTS (newspaper)Separation processVideoDayCartridge (firearms)Cell (biology)RulerRegentropfenFlightLastMechanicLecture/ConferenceMeeting/Interview
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SemiconductorSuperconductivityRegentropfenDishwasherElectricityHot workingPlatingAngeregter ZustandMeeting/Interview
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VideoMaterialNanotechnologyElectric power distributionComputer animation
Transcript: English(auto-generated)
00:24
the introduction. I'm a little bit different from most of the physicists here because I work for a large company in the United States, General Electric Company, and the kind of physics I try to do is a little bit different from the kind of physics you've heard about before because what I really
00:40
try to do is applied physics, and not because I really have to do applied physics but because I really like it. And I wouldn't give you the impression that everybody at General Electric Company is going to do applied physics. There is possible to do basic physics as well. For example, Ralph Alpher, who was one of the originators of the black water radiation in outer space, worked for
01:02
General Electric Company. Now, I'm going to also try to do a little bit different than the rest of the people. I'm going to try to tell you what I actually do, not what I hope to do or what I'm going to do or what I hope is there, but let me actually tell you and show you what I do
01:21
in this talk, and if I could start with the first slide. As you see, I am an optimist, I have a past, I have a present, but I also think I have a future. I hope that would be true. In the past, I worked with thin films, and particularly metal films and oxide films, and I worked with
01:42
superconductivity. At a present time, I have branched out, and now I work with protein films, and in particular, I work with protein interaction with surfaces. In the future and in the latter part of my talk, I'm going to tell you what I plan to do and what I'm actually doing. I'm not worrying about how cells interact with surfaces. So this is really what my interests
02:05
are at the present time, and you see it goes through at the lead line, and really, what I work with, it films. That's really what I do, right, with thin layers of stuff on surfaces. Now, if I could have the next slide. Here is shown a protein molecule, and Professor Glaser
02:25
told you all about protein molecules before lunch today, and so you'll learn everything from that from him. I also learned something from him. I have to go to more cocktail parties, but really, what you should look at here is the size of the protein molecule,
02:43
and the protein molecule is very large. It's about this particular one is hemoglobin, and it's 64 angstrom in diameter, and if you compare that with water, which is only 4 angstrom, benzene, which is 6 angstrom, and so on, you see a protein molecule is much larger than the
03:00
kind of molecules that physicists are used to deal with, and my interest really is to try and find out how these molecules react or interact with surfaces, and to do that, of course, you need an instrument. On the next slide is shown the principle of an optical instrument called the ellipsometer, and this instrument is a very elegant instrument.
03:22
If you have light and shine it onto a surface, light is reflected, but if you have plain polarized light and shine it onto a surface, the light is reflected at elliptically polarized light. Now, from this ellipticity and that angle, you can get the index of a fraction of the metal, but of course, we're not going to be interested in that. We're going to be
03:44
interested in films on the surface, so if you put a thin film here of an oxide, for example, or in this particular talk, we're going to talk about films or protein, then the ellipticity will change quite a bit, and from that change, you can calculate the film
04:03
thickness, and while the amazing thing is that this instrument uses optical light, I mean, ordinary light, but you can get to a wavelength of 5,000 angstrom or so, but you can measure the accuracy of the film thickness to less than one angstrom, because you rely on polarization of light. So I sort of jokingly refer to this instrument as the instrument of the
04:25
sensory, and basically, it's true, it was invented the last century by Drude, invented in 1880, but it really hasn't been used very much because it's so sensitive, and it's so difficult to get clean surfaces, and now it's used very extensively in the semiconductor
04:41
industry. Now, the basic experimental condition I deal with is shown on the next slide. What I have is a small bucket of salt water, and actually, all biologists use the salt water. You could use distilled water if you wanted to, maybe even water coming out from Berkeley,
05:04
I don't know. Experiments work equally well, but if you don't use salt water, biologists will get mad at you, so you better try to do what they want to do. And now, what I want to find out, I want to drop some protein, and this is the protein which is equivalent to the
05:23
hydrogen atom, is known as bovine serum albumin. It's the main protein in the blood of a cow. I want to drop some of that pure protein into this bucket, and I want to find out whether this protein will diffuse, actually, it's a stirring mechanism here, but a pure protein will go over and absorb itself on the metal surface. That's what I'm concerned with. And
05:46
of course, the way I do this is to mount this thing in the ellipsometer. And so the ellipsometer shines light in here and light out, which I can detect, and then by asking the ellipsometer, I can tell whether these protein molecules diffuse over and attach themselves
06:03
to the metal surface. That's what I want to find out. And on the next slide, shows that that does indeed happen. Here is time on this axis, and here is photo current, which is equivalent to thickness. This is not a very accurate measurement, but if you don't require accuracy of an angstrom or so, this is perfectly all
06:23
right. So really, what you have here is thickness versus time. And you see there's some wiggles here, and this is really historical slides. And when I started out this work, I had to borrow an ellipsometer. And this ellipsometer did not work in a room light, so I had to work in a dark room. Now, when you work in a dark room, and you
06:44
want to drop protein in a bucket, you miss all the time. So what I had to do is hold a flashlight in my left arm. And this is the wiggles from the flashlight, so these are purely experimental wiggles. What you find is that as soon as you drop the protein in,
07:01
protein absorb on the nickel surface, and you end up with a thickness of approximately 30 angstrom, which is equivalent to a monolayer of protein on the surface. And this is time here. This is approximately one minute when you use that concentration over there. So indeed, protein, this particular experiment, indeed, the protein sticks to the
07:24
surface. And it's important to recognize it only sticks in a single layer. Now, Professor Glaser tried to point out to you today the difference between biologists and physicists. Let me try to do that too. If a biologist had done this particular experiment, what he would have said
07:41
is that if you drop bovine serum albumin into a bucket at 25 degrees C into salt water at temperature, at barometric pressure, one atmosphere, and with my hands, if you want to have that, then the protein will stick in a monolayer. What the physicist says is shown on the next slide. And you see, the object of physics, of course, is to generalize.
08:12
And this is an awful general statement based on a very little experimental evidence. But as far as I'm concerned, and as far as this talk is concerned, this is really true,
08:22
protein will stick to everything except itself. That's why it only form a single layer. And I think that biologists in general would gain by a little, be a little more brave, and I agree with Professor Glaser, physicists will gain by being a little more humble than they normally are. Now, the question we asked of ourselves is how did the protein go down on
08:46
the surface? And what we decided that it does is it's similar to throwing pennies on the surface. It goes down at random, and we then made a computer simulation, which is shown on the next slide. And what you see here is this is actually done by a colleague of mine, Jens Sveder,
09:04
who is with me from Oslo from a year. And here we have had the computer throw pennies on the surface in a random fashion. And you see you have really plenty of open spaces left, but this is really a filled surface. And the amount of protein you get there is approximately half full coverage. So we recognized when we saw it and measured it, it really averages over
09:24
this thickness. Now, unfortunately, it is very difficult to see serum protein, which I am interested in, in the electron microscope. But there are particular kind of proteins which you can see, and one protein is called ferritin. And ferritin is a protein that stores iron in
09:42
your spleen. And since it contains a lot of iron, it's easy to see in the electron microscope. And the next picture, which is done by a man named Easterbrook, you see that indeed you can see protein absorbed on the surface. Each of these is a protein molecule containing a lot of iron. And you see, by and large, it looks like a random picture, which I showed you before.
10:06
But of course, it is very difficult to recognize something which is random. You think you know what random is, but it's very hard to do. So you had to make a test, and the test you do, you focus yourself on one molecule, and you try to find out what
10:21
we call the pair correlation function, where the next molecule will be. And if you have a crystal lattice, of course, the pair correlation function would oscillate. If you have a random thing, it will not. On the next slide, shows such a thing. The solid line here is the pair correlation function, which you get from the computer simulation. And we know that that is random.
10:44
The dots are the experimental data from the previous picture, and you see they agree very much. So we know then that the protein really absorbed in a random fashion. Now, as I said, it's very unfortunate that you really can't see protein very well in an electron microscope.
11:01
But I have a method, which I call the indium slide method. And in which case, can I have the next slide? I'm not sure where I am. Yeah, that's what I'm going to talk about. See, I'm glad I'm in step with my slide here. You can't see the protein very well in an
11:22
electron microscope, but you can use an ellipsomer to see them. By now, I can also show you that you can use this simple indium slide to see protein molecules. And what this indium slide is, is a glass slide onto which you have evaporated indium. And indium is a metal, and it will go down on the surface. And this is actually not a photography, but it's a real slide,
11:45
which is mounted in a projector. So now you're really going to see a real experiment. And when you evaporate the indium, indium go down in little metal particles. And these metal particles will scatter the light, and that's the reason why you get less light here,
12:01
and more light where you don't have any indium particles. On the next slide, shows how it looks to your eye, and this shows how it looks to the transmission electron microscope. And you really see that you have metallic particles. And in a joking way, I'm very proud of this slide, because it shows you that I have become a bona fide biologist.
12:26
Because if you look very carefully, there are no scale on that slide. If you read books on biology, what infuriates me is there never are any scales on their pictures. Now, I thought
12:44
about that, and there's a good reason for that, is that physicists really tend to weigh things. They measure things, they weigh it, you know, they take specific gravity, whatever have you, and biology really isn't interested in that. They are interested more in the function and form.
13:00
You know, the key relationship is important in biology. The size really isn't all that important, and things are very variable sizes many times. So there is a reason why they are not particularly interested in scale, but I wasn't trying to keep anything secret. These metal particles are in the order of wavelength of light. Now, an amazing thing
13:21
happened when you dip a slide like that into a protein solution, which is shown on the next slide. Protein, as I said, will absorb on everything, and that includes these indium particles. And when the protein absorbs on them, the indium particle will scatter more light, and therefore this looks darker than that. So here you're looking at a monolayer of protein about 30 angstrom
13:44
thick, and you see you could very easily see it, and therefore you shouldn't be surprised any liposometer could do one angstrom, and you can do 30 angstrom with your naked eye with the help of a Kodak projector. And it is, if you absorb protein on glass, for example,
14:00
of course you can't see it. You have to have these, the secret is to have these metal particles. And on the next slide, shows you a theory and also an experiment by a man named Scharfmann who used microwaves. And what he really did, he had a large metal sphere in the order of a centimeter or so. He measured the scattering from that sphere, and then he
14:23
calculated the scattering from that sphere using Maxwell's equations, and that agreed very well. Then he covered his sphere with a thin dielectric layer and found that the scattering went up quite surprisingly large amount. And again, he went back and did the Maxwell's equations in spherical coordinate system, and he found that that was true. So I don't have any intuitive
14:44
feeling why this is true. I have to say it's buried someplace in the Maxwell's equation. But all I do is the same way I use just electromagnetic waves or very short wavelength, namely light, and my spheres is very much smaller, and so on. But I want to convey with this picture that the basic effect is understood. It's no mystery about it. It's a clear-cut thing.
15:07
Now, could I have the next slide, please? If you work for an industrial organization, and now you have this kind of surface which shows protein, what you then try to do, you try to exploit it. As a kid, you use it for some purpose, for some reason, whatever, and to try
15:25
to exploit it took me into the field of immunology. So knowing that you're a physicist, mainly, let me then explain to you what immunology is all about. And I have to say I agree with Professor Glaser. Immunology is a very reproducible system.
15:41
Otherwise, none of us would have been here today. And let me explain what that happened by taking an example. If you have a virus, if you get a virus, you will get sick. When you get sick, two things can happen. You can die, or you can recover. And you may think that the medical doctors can help you recover, but there's nothing they can do for you if you
16:05
have a virus. The only thing that makes you recover is your own immunology system. That's it. If your immunology system works, you will recover. If your immunology system does not work, you will die. That's as simple as this. Now, fortunately, if you recover,
16:22
the next time you get infected by the same virus, you are immune. You don't have to get sick. You pass by the sick putt, and you recover right away. And so this immunology then is an adaptive system. You adapt to the surrounding around you, and you only have to do it once.
16:41
You only get chickenpox once in your lifetime. Some unfortunate people get it more, but in general, once in your lifetime, you get chickenpox. Now, how can that be? I mean, this is a very mysterious thing, and the way it works is shown in the next slide. In a very simplified form, of course, your body, like a building, is made of bricks. Your body is
17:06
built up of cells. When a virus is presented to the right kind of cell, the virus will get inside the cell. When the virus is inside the cell, the virus will multiply and may become maybe a thousand viruses. Then the cell will burst, and these thousand viruses go around
17:27
looking for a thousand cells to get into, and next time you have a million viruses and so on, and you are on your way to certain death. Fortunately, there are some other cells in your body, in your blood, which are white blood cells referred to as B cells. When the virus
17:44
gets presented to the B cells, somehow, and I don't know how, it cannot take over the machinery, but the B cell responds to the virus by making a protein molecule called an antibody, and this antibody will go through the membranes of the B cells, and this antibody is very
18:01
specific for the virus. You know, in biology, they have a lock and key relationship, and the antibody will attach itself specifically to that particular virus, to that particular type of virus, and then the antibodies do, the virus gets inactivated and actually essentially get eaten up by the white macrophages in your blood cell, in your blood, and you will get well.
18:24
So you see that every time you get ill, you have this race between the viruses and the antibody. If the viruses win, which used to happen in the past for smallpox and so on, then you die. If the antibody system win, then you recover. Now next time you get a cold,
18:41
think about that, will you? Now on the next slide, it's showing the physicist view of the system. This could be a protein molecule, and these are the antibodies, and the antibodies are made a little, a little like lobsters with big claws, and so here they are, the antibodies, and they can attach
19:02
themselves to particular sites on the antigen, and now this particularly, this reaction is highly specific. It's an exceedingly, surprisingly specific reaction, and if you want to recognize protein in the, in your body, this is the reaction you use. Essentially, if you have
19:22
one of these antibodies by the tail, and you wave it down the soup, and if anything attached to it, you know it has to be that antigen, or if you have the antigen and wave it down there, and anything attached to it, you know it has to be that antibody. So we use one to find the other, and that's the only practical way to recognize protein.
19:46
On the next slide, shows you then what the people do in clinical immunology, but really what I have been dabbling. You can then check for antibody by using this high specific reaction, rubella, syphilis would be two examples. You can check for a virus,
20:01
and hepatitis is a typical example of that, or you can fool the immunology system, and you can actually use it to check for any protein you so choose, and so people have used it to look, for example, for insulin, or for a molecule called CA, and it just, you know, a numerable large number of molecules you can use the immunology system to look for.
20:23
On the next slide, shows our approach to that particular system. We take a surface, expose it to a pure protein, the protein will absorb on the surface in a single layer. Now we take this layer, and we have exposed it to blood, say we've had many different kind
20:43
of protein molecules on it, but one of my rules is that these molecules will not stick to this original layer. However, if the blood contains specific antibodies, the antibodies will go on and attach themselves in a double layer. And on the next slide,
21:05
is the final rules I'm going to give you with this, this one you've heard about before, and I say protein will not stick to an arbitrary protein, but if you have the proper antibody, they will indeed stick. And these three rules, I have to caution you, do not think about them
21:21
as you do Maxwell's equations. These are really rule of the thumb, there are a lot of exceptions to these rules, there are none to Maxwell's equations, at least none that I know about. If you find one, you will be standing here in a few years, I'm sure. On the next slide, it shows you that what we can do is a simplified procedure,
21:42
you take this indium slide, you dip it in a pure protein, you take it up and wash it, and you can see this protein layer. Now what you do, you can put it sideways, and you can put two drops of serum, which is really blood without the cells in them, on top of the protein. And now if one is positive, which has antibodies, and one does not,
22:04
if you then wash and rinse the slides, what you will see is a double protein layer there, and you will get left with a single layer there. And on the next slide shows your result of such an experiment. And you see, here is the naked slide, here is the single layer,
22:22
and here you see the double layer of protein, where you have a positive reaction, and you see you hardly can see anything here where you have a negative reaction. So this is then a simple way of doing immunology. And let me show you which makes a difference between people in industry
22:43
and people at universities. Once a year in industry, we have to, at least in general company, we have to tell the hiring managers what we have done that previous year. And for fun and games, I made up these slides to tell my hiring managers what I have done.
23:01
You see, you have to be very simple-minded when you do that so your manager understands it, or at least such that he thinks that he understands it, which is equivalent. And so what I did, and you can barely see that now, I wrote with a protein BSA, I wrote the letters BSA on the slide, and you can see those. And now if you take a slide like that
23:28
and dip it into serum from a rabbit, in this particular case, and this is shown on the next slide, and the serum protein in the rabbit will absorb around the letters. So even though the letters BSA is still there, 30 angstrom thick, the other protein from the rabbit serum
23:46
is also 30 angstrom thick, and the letters has disappeared. But if you take this slide and dip it into the fruit, into serum from another rabbit, which has specific antibodies, what happened is shown on the next slide. The letters mysteriously come forward again,
24:05
and you can read BSA. And so this is a simple way of doing immunology. What we envision is to write on the slide with the illness you have. And you can test many illnesses at the same time, so then you dip the slide in your blood and you look it up and you read off what's wrong
24:22
with you, you see, right? Now, unfortunately, life is not as easy as it sounds like, and I'm trying to make this into a practical test. And if everything else fails, I'm going to
24:42
use this to send secret messages, because I know it works to do that. On the next slide, shows you one of the problems we have, and as in everything you do, sensitivity is important. And the most sensitive technique, and we've gotten the
25:04
belt price a few years ago, is Radium Unase. And you actually can detect a nanogram per milliliter, more or less, using Radium Unase. And unfortunately, our technique, both the lopsometer and the indium slide, is a factor of 10 away from that. And you may think
25:22
that the factor of 10 is not very much, but in immunology, that is a large factor. And it turns out that we cannot compete with Radium Unase head-on, and now we have turned our attention to more ordinary illnesses like rubella or syphilis or rheumatoid arthritis and things like that, where you don't need that sensitivity. But as you see, there are a lot of other
25:45
techniques doing immunology, so now if you can't compete sensitivity, we have to compete in price. And the marketplace is always there, and if you do something, you try to do something practical, you always have to worry about that. And I don't know which way this is going to go at the
26:01
present time. Now on the next slide, I'm going to show you a little variation on what I said, because as I said, I'm trying to be practical, and I like to try to invent things. And when I talk to biologists about this indium slide, they think it's a wonderful thing, I'm happy to say. But also, they don't know how to make indium slides. And general electric companies,
26:24
no way they will sell indium slides, and I have no time to make them indium slides. So they say, well, we can't try your technique. So I said, well, maybe you can make this technique, but you don't need any indium slides. And I came up with a following thing, where you use an ordinary glass slide. And out of that glass slide, you absorb, say, a layer of BSA.
26:45
Then you expose this to serum, which contain antibodies. And what will happen is that the serum protein will absorb around the protein layer, and the antibodies will absorb specifically on top. So now you have this double layer of protein here on the glass slide. Of course,
27:04
you can't see it, but I know it's there. Then what you do, you go down and you get a can of plastic particles, which they use to grease doors and things. But I quite know what I use it for, but we have it in the stockroom. And I think you grease doors and electrical contact to wear what it is. Anyway, you take one of these plastic particles, and this can of
27:25
plastic particles, you shake it up. And if you're not afraid of ruining the ozone layer up there, you spray it onto your film. And so you get here a layer of white plastic particles. And then come the final step, you take this and put it into an acid. And immunologists know
27:43
that the acid would cleave the bond between the antibody and the antigen. And what happened then is that the antibody will go off and take the plastic particles with them. And you get left with a clear space here. And on the next slide shows you how these things look like
28:00
in real life. And you start out, and here is your glass slide. And whether you have protein or antibody ending on it, you just simply don't know because you can't see it. Now, if you spray it with the plastic particles, it become white like that. You can easily see that. This is where I held it in the tweezer. Now, if you dip this into acid, and if you have a double layer of protein there, it comes up looking like that. It goes off, and you get a clear spot
28:25
in the middle. If you don't have a double layer of protein there, it looked just the way it did. And this shows you some experimental difficulties because I really don't want to comment on it right here. So this is a different way of doing it when you don't
28:40
need these particles. Now, let me see the next slide. Yeah, now I would like to go in. This is the work I'm going to start doing, and I have done a little bit of it already. I like to look at the—I talked about the interaction of cells of protein with surfaces. Now, I want to talk about the interactions of cell with surfaces. And what I've illustrated
29:02
here is almost truth. It's not—I have to save it, Professor Glaser. You can never say anything exact in biology, but this is almost true. If you grow cells in a tissue culture, and if you grow normal cells, what they have to do, they will have to grow on the surface.
29:22
They always do. You cannot make them divide or do anything unless they grow on the surface. And what they will do, they will multiply and grow and form a monolayer all over the surface. That's what normal cells will do, and actually crawl along and find its neighbor and so on. Now, if you grow cancer cells on the surface, cancer cells won't do that. They tend to
29:45
climb on top of each other and form funny-looking layers. And you can look in the microscope, and if you're real good, you can tell the cancer cells from a normal cell, but it requires a large amount of training. And for example, it's a sort of frightening thing is that if you have a biopsy and you're going to find out whether you have cancer or not,
30:05
the only way people can tell is by looking. You have a trained person looking through a microscope, and he decides whether you have cancer or whether you don't. There's no, as to my knowledge, scientific test with an impractical value anyway, which can determine cancer cells from
30:22
normal cells. It's simply by looking. Well, the reason I got interested in how cells interact with the surface is shown on the next slide. And these are slides done by, this is a work done by a man named Harris, and what he did is something that I sort of like to do. He evaporated metal squares onto a glass
30:45
slide, and these are palladium. And what he found out is it's not, it's hard to see, but these are cells here, and he found out that the cells simply did not want to grow on the metal spheres. They just preferred the glass. Then he did the same thing, but now he put
31:02
the metal spheres on the plastic. And now, you see, the cells chose to be on the metal spheres, and they did not want to be on the plastic. So, you see, cells crawl around, and they try to find out, you know, where they are happiest. And I, when I learned, when I found this experiment, I was very disturbed, because I spent my last few years worrying about protein
31:25
layers. And while Harris did this experiment, he did not know that his surfaces were covered in protein anyway. So, I would like to know why the cell recognizes what's underneath the protein layer. This is shown maybe better in the next slide. When you grow molecules,
31:47
you need to feed them something. You grow cells, rather. You need to feed them something, and you have a surface, and you put what they call tissue culture medium, which the cells grow in, and the tissue culture medium contains everything you can think of. I mean, there are
32:02
and the cells then should grow in the tissue culture medium. And fortunately, they don't. What you have to do in addition, you have to add a little bit of blood, and only then will the cell grow in vitro. Why you got to add this little bit of blood? Nobody knows. And as a physicist, it's very disturbing to think about. I always thought that people knew
32:24
what was in your blood, but they don't. They only know, you know, the few basic molecules and stuff, but a lot of stuff in your blood, people don't have the faintest idea why it's there and what it does. Now, since you have all these protein in the blood, what will happen right away is that you get a layer of protein on the surface, and the cells never see the
32:44
naked surface. They always grow on top of this protein layer, and so that's why I got interested in the problem, because I knew about protein layers, and I said, well, maybe I can go in and find out what the cells like, and I said maybe I could then pick certain pure proteins, see if they like those or not. And on the next slide, shows a typical or the
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basic experiment, which we said some are doing now and going to continue to do, is say, for example, I take a protein like trypsin and cover half the surface with it, and then let the other half of the surface have serum protein. Now, trypsin is an enzyme,
33:24
and is an enzyme which is known to cut protein molecules, and actually is used to harvest cells and a priori, you would say that cells could not grow on top of trypsin molecules. That's the reason why I did this experiment, but when you grow the cells, they couldn't care less.
33:40
They grow exceedingly well on trypsin, as well as they do on the regular serum protein. A matter of fact, we have tried, I don't know how many proteins by now, but maybe not more than 10 or 15 maybe, and in most of the cases, the cells don't care. They grow equally well on all different kind of proteins, which is not so surprising. There are, however, one exception, and this deals with the antibody I already talked about,
34:05
and this is shown on the next slide. This is cells which have been stained. That's why they look so skinny. Really, in real life, they sort of all butt together, and this is, on this half of the surface, I have antibodies, this molecule I just talked about.
34:22
On this half of the surface, I have BSA, and you see cells really prefer the BSA, and they don't like to grow on antibodies. Now, why that is, I don't know. You can take this experiment one step further, and as shown on the next slide, you can absorb, see these antibodies I said were shaped like a lobster.
34:43
If you absorb them at random, you may think they sort of will absorb in a fashion like that. What we also can do, we can absorb them specifically to the molecule on the surface, and then they all will have their tail up. So let's find out whether the cell wants to grow on the tail which is pointing up, and this is the basic, the next slide, please.
35:07
Here's the basic, this is the dirt down here, but here's the basic thing. You put BSA here, and you put the antibodies up here, which is specifically absorbed, and what we're going to look at now is the circle here to find out where the cells like to grow, and on the next slide, shows you what will happen. These are the cells,
35:27
and you see where we have the antibody, the cells simply do not grow, and that is really a general observation in biology because we have tried several different cell lines, several different antibodies, several different anything, and cells never grow on
35:41
there. I, of course, was hoping that cancer cells would grow there, normal cells would not, but no such. Look, cells simply do not grow on top of the antibody layer, and you see this is a beautiful answer, but I really haven't discovered what the question is, and I don't know, I'm interested in why this is the case, and it must have some biological
36:02
significance, except I haven't the faintest idea what it is, and I hope that I will be able to discover that in the next few years. Finally then, I like to, I like to stop with a story. It's always nice to stop with a story in particular because it's true, and when I started this work and got interested in protein absorption on surfaces, I didn't know
36:26
anything about biochemistry, and actually I still don't know anything about biochemistry. Anyway, I told some biochemists working at General Electric Research Laboratory, you know, presented my work to them what they thought, and the work was not in such a good shape then, but what they said, you know, what kind of buffer did you use,
36:45
and I said buffer, buffer, I tried to gain some time, because I'm really a mechanical engineer, and buffer is something that keeps trains apart. Well, in biochemistry, buffer is something by which you regulate the pH of the solution,
37:05
and it's very important that protein molecules deal with pH around seven or so, so cleverly I said to the person, what kind of buffer do you use, and he said phosphate, so I said, well, let me give, give me some phosphate, and I'll go back, and I'll do it over again, and keep the pH constant, then would you believe
37:24
me, and so on and so forth, so I got some phosphate, and I repeated my experiments, and surprisingly enough, in phosphate, protein does not stick to a surface, so my, my basic rule is violated, protein do not stick to a surface when you use a phosphate solution, matter of fact, in the last slide, shows you a, this is some dirt again here,
37:46
but this is a protein layer of BSA, here I put two drops of phosphate at various pH's, I think seven and eight, and you see the phosphate actually removes the protein from the surface, and I got this wonderful idea that we're going to make the general electric dishwashing
38:01
detergent, and little did I know that all dishwashing detergents in the United States at least contain 30% phosphate, so the people who make dishwashing detergents know very well that phosphate take protein or take egg off your plates, but the biologists do not, not because they are dumber, but because they have no need to know, you see, right,
38:24
and therefore the moral of my story really is that, is that the important thing, if you're going to be in science, is to do something, don't worry about that you don't know everything before you start, you know, the important thing is to go in the laboratory, get your hands dirty, and maybe you are the person who have the golden hands
38:42
who can make this experiment work, thank you.