0:00:17.503,0:00:21.343 I want to tell you today about three areas[br]of science and engineering 0:00:21.343,0:00:24.313 that I think are converging[br]in very interesting ways. 0:00:24.844,0:00:26.597 I'm a mechanical engineer. 0:00:26.597,0:00:28.831 I've been working in robotics[br]for over 25 years. 0:00:28.831,0:00:31.828 I've been in micro/nanotechnologies[br]for over 15 years. 0:00:31.828,0:00:34.527 And over the past decade,[br]since I've been here in Zurich, 0:00:34.527,0:00:37.912 I've been working more closely[br]with biologists and with medical doctors, 0:00:37.912,0:00:40.246 and I think that the technologies[br]we're working on 0:00:40.246,0:00:43.677 and our vision of the future[br]has some very interesting implications. 0:00:43.677,0:00:45.391 But instead of telling you about it, 0:00:45.391,0:00:48.260 what I want to show you[br]is a clip from a Hollywood film 0:00:48.260,0:00:51.310 that actually happens[br]to be almost as old as I am, so ... 0:01:03.537,0:01:05.489 (Video) Man: All stations, stand by. 0:01:05.489,0:01:07.719 (On stage) (Laughter) 0:01:08.380,0:01:10.430 (Video) Man: Right. Inject. 0:01:24.823,0:01:26.966 (On stage) "Fantastic Voyage,"[br]it's a classic. 0:01:26.966,0:01:28.221 I love this movie. 0:01:28.521,0:01:32.003 Hollywood has two advantages[br]when they make movies, versus an engineer. 0:01:32.003,0:01:33.857 They don't have to worry about physics. 0:01:33.857,0:01:36.141 They don't have actually[br]have to make the things. 0:01:36.141,0:01:37.430 What I want to show you now 0:01:37.430,0:01:40.338 is an animation actually made for us[br]by the Discovery Channel. 0:01:40.338,0:01:43.019 They visited my lab[br]about a year and a half ago. 0:01:43.019,0:01:45.015 We appeared on one of their shows, 0:01:45.015,0:01:47.819 and they put together this concept[br]of where we're heading. 0:01:47.819,0:01:50.249 And what we've been working on[br]for several years now 0:01:50.249,0:01:54.230 have been little, what we call microrobots[br]that we inject into your eye - 0:01:54.230,0:01:56.149 we haven't done it on a human yet, 0:01:56.156,0:01:58.691 but we inject it into your eye - 0:01:58.691,0:02:02.325 and we use magnetic fields[br]to guide that device back to the retina 0:02:02.325,0:02:05.509 to perform certain retinal therapies,[br]for instance delivering drugs. 0:02:05.509,0:02:07.257 You saw there, over the patient, 0:02:07.257,0:02:10.725 the sequence of electromagnetic[br]coils that we use. 0:02:10.725,0:02:13.436 This is in a real pig's eye[br]that you're seeing right here. 0:02:13.436,0:02:16.153 This pig's eye came from the butcher[br]earlier that morning, 0:02:16.153,0:02:19.794 so we didn't harm any animals[br]ourselves in making this, but - 0:02:19.794,0:02:20.794 (Laughter) 0:02:20.794,0:02:24.344 What you see is that we're able[br]to very precisely control that device. 0:02:24.344,0:02:26.598 That device is about 0.5 mm in size, 0:02:26.598,0:02:29.811 about a millimeter long,[br]to give you an idea of scale. 0:02:29.811,0:02:31.678 And in this next slide, 0:02:31.678,0:02:36.208 you'll see on the left is a system[br]of electromagnetic coils we use. 0:02:36.208,0:02:38.607 We do in vivo animal trials with these. 0:02:38.607,0:02:40.108 There are eight of these coils, 0:02:40.108,0:02:41.210 we call it the OctoMag, 0:02:41.210,0:02:44.119 and we control the current[br]in each one of those very precisely 0:02:44.119,0:02:46.309 to guide this device[br]through the ocular cavity 0:02:46.309,0:02:47.480 back to the retina. 0:02:47.480,0:02:50.989 You'll see one of our most recent devices[br]on the fingertip there. 0:02:50.989,0:02:52.939 That particular, we call it a microrobot; 0:02:52.939,0:02:58.269 it's about 1/3 mm in diameter, [br]330 microns in diameter. 0:02:58.269,0:02:59.731 And our design specs - 0:02:59.731,0:03:01.712 the reason we want it to be so thin - 0:03:01.712,0:03:03.757 it's about 1.8 mm long - 0:03:03.757,0:03:06.567 is that we want it to fit[br]inside of a 23-gauge needle. 0:03:06.845,0:03:10.164 If it fits inside of a 23-gauge needle[br]and we inject it into your eye, 0:03:10.164,0:03:14.046 as we remove that, that puncture wound[br]doesn't need a suture. 0:03:14.046,0:03:16.165 It's relatively non-invasive. 0:03:16.165,0:03:18.793 You just put a little topical[br]anesthetic, and it's done. 0:03:18.793,0:03:22.762 All the time to inject drugs to treat[br]age-related macular degeneration - 0:03:22.762,0:03:24.529 that needle, not the microrobots, 0:03:24.529,0:03:25.569 I should say. 0:03:25.920,0:03:29.469 But that robot that I just showed you,[br]that you see there on the fingertip, 0:03:29.469,0:03:31.424 is the biggest robot we make. 0:03:31.424,0:03:35.195 My goal is to make robots that are[br]about 1000 times smaller than that, 0:03:35.195,0:03:38.389 something the size, for instance, [br]of these E. coli bacteria. 0:03:38.389,0:03:42.316 These little rod-shaped bacteria [br]are about a micron or two long. 0:03:42.316,0:03:44.636 That is about 1/100[br]of the width of a hair. 0:03:45.494,0:03:47.936 See those little tails coming off of them? 0:03:47.936,0:03:50.043 We'll get to that later, okay? 0:03:50.043,0:03:52.047 But before we start talking[br]about bacteria, 0:03:52.047,0:03:55.762 I want to talk a little bit about physics[br]and what these constraints put on us, 0:03:55.762,0:03:58.336 so we're going to do [br]a simple thought experiment here. 0:03:58.336,0:04:00.124 Let's take a cube, okay? 0:04:00.124,0:04:01.582 It's a meter on the side. 0:04:01.582,0:04:04.116 And I don't need my calculator[br]to do this calculation. 0:04:04.116,0:04:07.068 A meter by a meter by a meter[br]is a cubic meter, right? 0:04:07.068,0:04:10.594 But if I take that cube[br]and I shrink it to 10 cm - 0:04:10.594,0:04:12.362 I shrink it by a factor of 10 - 0:04:12.362,0:04:13.820 that calculation changes 0:04:13.820,0:04:16.250 because I'm taking a length[br]by a length by a length, 0:04:16.250,0:04:20.233 and all of a sudden, it's become[br]1/1000th of its original volume, 0:04:20.233,0:04:22.853 and so properties that depend on volume - 0:04:22.853,0:04:24.044 for instance, mass - 0:04:24.044,0:04:25.855 also go down by a factor of 1000. 0:04:25.855,0:04:29.106 Now, if I go down another[br]100 times, to a centimeter, 0:04:29.106,0:04:31.414 it's gone down, now, by a million times. 0:04:31.414,0:04:32.409 And so volume - 0:04:32.409,0:04:35.130 as I said, the weight of it[br]goes down by a million times, 0:04:35.130,0:04:39.650 but also those magnetic forces[br]we generate on it are also going down 0:04:39.650,0:04:42.182 because they scale also[br]with the mass of the object. 0:04:42.772,0:04:46.849 So you might say, "But since[br]it weighs less, what's the problem?" 0:04:46.849,0:04:50.091 But now, let's think[br]about the surface area of that cube. 0:04:50.091,0:04:52.893 It's got six sides,[br]each side is a square meter. 0:04:52.893,0:04:55.713 It's got six square meters on that cube. 0:04:55.713,0:04:57.872 Over the volume of one, ratio of six. 0:04:57.872,0:05:00.943 But as I go down, that area[br]is only a length by a length, 0:05:00.943,0:05:04.882 and so as I go down each order[br]of magnitude by a factor of 10, 0:05:04.882,0:05:08.007 the importance of surface area[br]goes up by a factor of 10. 0:05:08.007,0:05:09.600 And that causes problems, okay? 0:05:09.600,0:05:10.833 I can't make robots 0:05:10.833,0:05:14.598 and guide them with magnetic fields[br]the way I showed you in the eye - 0:05:14.598,0:05:17.418 I can't make them any smaller than I have. 0:05:17.418,0:05:19.783 So what are some of the implications? 0:05:19.783,0:05:21.922 Well, think about a fish[br]and how a fish swims. 0:05:21.922,0:05:25.316 A fish moves its tail back and forth[br]in a reciprocal motion. 0:05:25.316,0:05:29.898 It's pushing the mass of fluid back[br]and moving itself forward. 0:05:29.898,0:05:32.554 It knows Newton's first law, okay? 0:05:32.554,0:05:34.840 And so, Geoffrey Taylor, [br]professor at Cambridge, 0:05:34.840,0:05:38.272 thought about this and published[br]some very important papers in the 1950s, 0:05:38.272,0:05:41.892 and he made a little mechanical fish[br]just to show how it would work in water, 0:05:41.892,0:05:44.086 and it swims just the way[br]you'd think it would. 0:05:44.086,0:05:45.260 But if I took that fish 0:05:45.260,0:05:48.085 or I took you, and I made you[br]1,000 or 10,000 times smaller, 0:05:48.085,0:05:50.989 and I put you in water,[br]all of sudden, that water would feel - 0:05:50.989,0:05:52.798 even though it has the same viscocity, 0:05:52.798,0:05:54.893 the surface effects[br]or the drag of that water 0:05:54.893,0:05:56.825 would be much, much stronger on you. 0:05:56.825,0:05:58.509 And so what Geoffrey Taylor did - 0:05:58.509,0:06:00.830 this is a video he made in the 1960s - 0:06:00.830,0:06:04.062 is he got a vat of something very thick. 0:06:04.062,0:06:06.918 I think if you're from the UK, [br]you know Lyle's Golden Syrup, 0:06:06.918,0:06:09.725 and I think that's what[br]he must have used if you look at it. 0:06:09.725,0:06:12.008 So, he took his robot - 0:06:12.008,0:06:13.543 it's a little mechanical fish - 0:06:13.543,0:06:17.044 put it in there,[br]and it doesn't go anywhere 0:06:17.044,0:06:18.836 because the fluid drag is so strong 0:06:18.836,0:06:21.549 and the mass that's pushing back[br]is so much less than that 0:06:21.549,0:06:22.555 that it doesn't move. 0:06:22.555,0:06:24.844 And that's the problem[br]as we go down in scale, 0:06:24.844,0:06:30.144 is that we have to rethink [br]the way things swim 0:06:30.144,0:06:31.404 and the way things move. 0:06:31.869,0:06:35.160 Well, if you're an engineer[br]and you don't know how to solve a problem, 0:06:35.160,0:06:36.158 what do you do? 0:06:36.158,0:06:39.263 You look at nature and think,[br]"How did nature solve this problem?" 0:06:39.263,0:06:43.002 Nature solved this problem[br]millions, billions of years ago. 0:06:43.002,0:06:44.564 We know there's paramecia. 0:06:44.564,0:06:46.568 You see the spermatozoa[br]there on the right? 0:06:46.568,0:06:49.470 And they have these special[br]little hairs on them, these cilia, 0:06:49.470,0:06:52.063 these flagella[br]for the sperm, we call them, 0:06:52.063,0:06:53.859 that move in very interesting ways. 0:06:53.859,0:06:58.016 Now, nobody knew before 1675[br]that these things even existed. 0:06:58.016,0:07:01.622 Antonie van Leeuwenhoek, in Holland, [br]was looking in his microscope, 0:07:01.622,0:07:02.694 and he was astounded 0:07:02.694,0:07:06.028 to see a world of tens of thousands[br]of little microorganisms swimming, 0:07:06.028,0:07:08.690 and he wrote a letter[br]to the Royal Society the next year. 0:07:08.690,0:07:10.041 They verified his results. 0:07:10.041,0:07:12.013 People were astounded, what was going on. 0:07:12.013,0:07:16.244 And what van Leeuwenhoek[br]saw in his microscope 0:07:16.244,0:07:20.384 was the first time[br]anybody had ever seen bacteria. 0:07:21.072,0:07:24.972 This is a graphic[br]of one of the rod-shaped ones. 0:07:24.972,0:07:26.512 It's about a micron or two long. 0:07:27.702,0:07:30.154 And as you look at these[br]under a microscope - 0:07:30.154,0:07:32.326 you saw the one I showed of the E.coli - 0:07:32.326,0:07:34.417 you'll notice it has[br]a little flagella on it. 0:07:34.417,0:07:36.373 And as you look at it under a microscope, 0:07:36.373,0:07:39.695 what you see is this flagella[br]seems to be wiggling back and forth, 0:07:39.695,0:07:42.403 but if you were able to look at it[br]from another direction, 0:07:42.403,0:07:45.643 you realize it's not wiggling[br]back and forth; it's actually rotating. 0:07:46.398,0:07:47.396 And Howard Berg, 0:07:47.396,0:07:51.542 when he was at University of Colorado[br]in the early 1970s, discovered this, 0:07:51.542,0:07:54.166 and what he discovered was astounding: 0:07:54.166,0:07:56.472 nature has invented a rotary motor. 0:07:56.472,0:07:57.468 Think about it. 0:07:57.468,0:08:00.152 Where else in nature[br]is there a rotary motor? 0:08:00.152,0:08:05.912 And Howard has been to our lab[br]and given us some advice on what to do. 0:08:05.912,0:08:08.999 He calls these things[br]nature's microrobots, okay? 0:08:08.999,0:08:14.079 So the body of the bacteria[br]has sensors on it, chemoreceptors. 0:08:14.079,0:08:17.169 Those chemoreceptors communicate[br]with the motor in the back of it, 0:08:17.169,0:08:18.327 to drive it. 0:08:18.327,0:08:19.856 That also has software in there. 0:08:19.856,0:08:22.187 The software is the chunks[br]of DNA floating around. 0:08:22.187,0:08:24.295 They're just telling it[br]what parts to make 0:08:24.295,0:08:27.723 to keep building the sensors it needs,[br]the motors it needs, and all that. 0:08:27.723,0:08:29.940 And the motor is a fascinating structure. 0:08:29.940,0:08:34.291 Since Howard discovered[br]these bacterial motors in 1973 - 0:08:34.291,0:08:37.970 which, by the way some people believe[br]is evidence of an intelligent designer, 0:08:37.970,0:08:41.430 but I don't think[br]most biologists believe that. 0:08:43.518,0:08:47.828 These motors are made[br]from about 30 to 40 proteins. 0:08:48.188,0:08:50.651 They assemble into this structure 0:08:50.651,0:08:54.106 that spins up to[br]160 revolutions per second. 0:08:54.106,0:08:56.806 And you see on the right here,[br]a video from Howard's lab 0:08:56.806,0:09:00.658 of fluorescent bacteria[br]swimming at these speeds. 0:09:00.658,0:09:03.238 Remember that the size of these[br]is a micron or two. 0:09:04.663,0:09:07.378 So we looked at this, [br]and we were thinking, 0:09:07.378,0:09:08.762 "What can we learn from this? 0:09:08.762,0:09:10.432 How can we take advantage of this?" 0:09:10.432,0:09:15.442 So we leveraged some[br]of our nanotechnology experience 0:09:15.442,0:09:18.641 to build something we called [br]an artificial bacterial flagella. 0:09:18.641,0:09:20.253 Now, I can't make that motor yet. 0:09:20.253,0:09:22.702 That motor's about[br]45 nanometers in diameter. 0:09:22.702,0:09:24.475 But what I can make is the flagella 0:09:24.475,0:09:27.162 of a similar size and shape[br]that a bacteria has. 0:09:27.162,0:09:30.738 And on the front of it there on the left,[br]you'll see what looks like a head, 0:09:30.738,0:09:33.265 and what that is is actually[br]a little piece of magnet, 0:09:33.265,0:09:35.142 and what I can do with that magnet 0:09:35.142,0:09:38.685 is I can generate a torque on it[br]with a magnetic field, 0:09:38.685,0:09:40.068 and as I rotate that field - 0:09:40.068,0:09:41.787 and these are very, very low fields; 0:09:41.787,0:09:44.073 they're about 1000 times[br]less than an MRI field - 0:09:44.073,0:09:45.507 they start to get it to twist, 0:09:45.507,0:09:47.761 and as it twists,[br]it propels itself forward, 0:09:47.761,0:09:49.551 just like E. coli do. 0:09:50.217,0:09:52.688 To give you an idea of the scale[br]we're talking about, 0:09:52.688,0:09:55.286 here's a scanning electron[br]micrograph of a human hair; 0:09:55.286,0:09:57.661 it's about 100 microns or so in diameter. 0:09:58.191,0:10:00.477 There is the size of our smallest ABFs. 0:10:00.477,0:10:03.406 They're about 10 microns,[br]these particular ones. 0:10:03.406,0:10:05.610 And this is the size[br]of a red blood cell, okay? 0:10:05.610,0:10:06.710 So we're about double. 0:10:06.710,0:10:09.664 Our smallest ones are[br]about twice the size of a red blood cell. 0:10:09.664,0:10:13.481 And here are three of them swimming[br]together in a sort of swarm behavior. 0:10:13.481,0:10:14.719 To me, they look alive. 0:10:14.719,0:10:16.921 I get excited when we do this, you know? 0:10:16.921,0:10:17.915 (Laughter) 0:10:17.915,0:10:19.107 That's why I do robotics. 0:10:19.107,0:10:22.464 There's nothing more fun than building[br]a machine and watching it move. 0:10:22.464,0:10:24.905 Now, you'll notice[br]these will start to go backwards. 0:10:24.905,0:10:27.431 I didn't reverse the video;[br]I just reversed the field. 0:10:27.431,0:10:30.569 There's some really interesting[br]fluid dynamics to be explored here, 0:10:30.569,0:10:32.006 and that's pretty interesting. 0:10:32.006,0:10:35.284 One exciting thing for us this year[br]was when we were in the bookstore, 0:10:35.284,0:10:38.265 we picked up a copy of[br]the 2012 Guinness Book of World Records 0:10:38.265,0:10:41.317 and discovered that we were[br]in the Guinness Book of World Records 0:10:41.317,0:10:43.003 for the smallest medical robot. 0:10:43.003,0:10:44.003 (Audience) Whoo! 0:10:44.003,0:10:47.242 Bradley Nelson: Being in the[br]Guinness Book of World Records is great, 0:10:47.242,0:10:48.908 but what I'm really gunning for is, 0:10:48.908,0:10:50.983 I want to win a medal[br]in the next Olympics, 0:10:50.983,0:10:53.129 and so we're developing[br]synchronized swimmers. 0:10:53.129,0:10:54.131 (Laughter) 0:10:54.681,0:10:55.781 These are interesting - 0:10:55.781,0:10:58.373 What's particularly interesting[br]about these guys 0:10:58.373,0:11:00.278 is that they're made out of a polymer. 0:11:00.278,0:11:01.548 They're noncytotoxic. 0:11:01.548,0:11:02.635 They don't kill cells; 0:11:02.635,0:11:04.363 in fact, cells like to grow on them. 0:11:04.363,0:11:06.083 And we've developed a new technology 0:11:06.083,0:11:08.747 that allows us to make[br]some fairly arbitrary shapes here. 0:11:08.747,0:11:11.080 So in this next little video[br]I want to show you 0:11:11.080,0:11:12.826 is one of our devices. 0:11:12.826,0:11:14.156 We put a claw on it, 0:11:14.156,0:11:17.718 and so what it can do is go around[br]and grab these little - 0:11:17.718,0:11:19.343 these are 6-micron diameter beads, 0:11:19.343,0:11:21.679 so they're about the size[br]of that red blood cell - 0:11:21.679,0:11:25.260 grab those, move them up in 3D, [br]move them up and down, 0:11:25.260,0:11:28.860 and then eventually release them[br]using these fluidic forces. 0:11:33.396,0:11:37.047 We've also been thinking about other,[br]more serious applications as well. 0:11:37.047,0:11:38.391 Here's one of our devices. 0:11:38.391,0:11:41.448 We coated it with[br]a fluorescent molecule called calcein. 0:11:41.448,0:11:45.441 This molecule, you're looking at it [br]in a fluorescent microscope there. 0:11:46.101,0:11:48.201 This molecule, actually, 0:11:48.201,0:11:51.011 is the same molecular weight[br]as a lot of chemotherapy drugs. 0:11:51.011,0:11:57.551 And on the left, you'll see [br]some red cells that are stained red. 0:11:57.979,0:12:02.239 We discovered as we moved this bacteria[br]near those cells and touched them with it, 0:12:02.247,0:12:04.743 the calcein actually[br]gets taken up by the cells. 0:12:04.743,0:12:09.573 So this allows us, now, to potentially[br]deliver drugs into individual cells 0:12:09.573,0:12:12.357 and target individual cells[br]with this kind of technology. 0:12:12.357,0:12:13.738 The other thing that's cool - 0:12:13.738,0:12:16.548 I've only shown you a few, [br]but we can make armies of these. 0:12:16.548,0:12:18.168 We can make them by the thousands. 0:12:18.168,0:12:19.718 We can make about one a second. 0:12:19.718,0:12:22.097 We make tens of thousands, [br]put them in suspension. 0:12:22.097,0:12:24.621 So I think there's some interesting[br]possibilities here 0:12:24.621,0:12:28.441 for the future of where this can go. 0:12:29.068,0:12:30.985 So let's go back to the bacterial motor. 0:12:30.985,0:12:34.286 This is a video from[br]Keiichi Namba's lab at Osaka University. 0:12:34.286,0:12:35.856 He and his group have spent years 0:12:35.856,0:12:38.288 trying to understand[br]the exact sequence of proteins, 0:12:38.288,0:12:40.240 how they assemble into this rotary motor. 0:12:40.240,0:12:43.102 And while I'm not at the point[br]where I can develop the motor, 0:12:43.102,0:12:45.564 I can develop some of these[br]parts of this device, 0:12:45.564,0:12:49.325 and so what we're hoping as we move into[br]the future and keep going in this area, 0:12:49.325,0:12:52.279 we'll learn more and more from nature[br]at these molecular scales 0:12:52.279,0:12:54.999 and be able to build machines[br]that operate in similar ways 0:12:54.999,0:12:56.382 and under similar principles. 0:12:57.032,0:13:00.037 I've been very fortunate[br]to work with some brilliant scientists, 0:13:00.037,0:13:02.296 brilliant medical doctors, 0:13:02.296,0:13:03.586 and when you're at the ETH, 0:13:03.586,0:13:05.830 the Swiss Federal Institute[br]of Technology here - 0:13:05.830,0:13:07.326 you know, I'm an engineer. 0:13:07.326,0:13:12.276 I walk the hallways where people[br]like Conrad Röntgen, who invented X-rays, 0:13:12.276,0:13:14.296 Wolfgang Pauli or Albert Einstein were. 0:13:14.296,0:13:16.058 It's a humbling experience. 0:13:16.058,0:13:19.724 So I take a little bit of comfort 0:13:19.724,0:13:23.315 in a quote from a famous[br]aeronautical engineer from Caltech, 0:13:23.315,0:13:25.036 Theodore von Karman, 0:13:25.036,0:13:26.839 and von Karman said, 0:13:26.839,0:13:31.099 "The scientist describes what is; [br]the engineer creates what never was." 0:13:31.099,0:13:32.097 (Laughter) 0:13:32.097,0:13:33.387 Okay. So. 0:13:34.304,0:13:36.491 I want to leave you[br]with one last thought here. 0:13:36.491,0:13:39.496 This is from Richard Feynman,[br]the famous physicist from Caltech, 0:13:39.496,0:13:41.978 who said, "What I cannot make, [br]I do not understand." 0:13:41.978,0:13:42.977 (Laughter) 0:13:42.977,0:13:44.357 Okay. So thank you very much. 0:13:44.357,0:13:45.364 (Applause)