Lec 1 | MIT Introduction to Bioengineering, Spring 2006

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PAUL MATSUDAIRA: What I'd like to do now is to introduce to you our first speaker, Professor Doug Lauffenburger. He's the head of Biological Engineering. And what he'll do is introduce us into, what is bioengineering? Doug. [APPLAUSE] [LAUGHS] DOUG LAUFFENBURGER: Thank you. Can I ask just first, how many of you are freshmen? Raise your hands. OK, good. For those who aren't, today can be a bonus lecture, but then henceforth we really do want to focus this on the freshmen as they start to look at their MIT educational careers. So it's a pleasure to do this. I will introduce you to the world of bioengineering as a whole, as we see it at MIT, to the different facets. We'll delve into a little bit about biological engineering per se as a discipline within the world of bioengineering overall. And, I hope, set the stage for most of the rest of the lectures that you'll be seeing. OK. Well, let me begin by just talking about what engineering is at all, OK? Because we can talk about bioengineering. It's nice to have a concept for what engineering is. And for those of you who are freshmen, chances are very few of you took a course in engineering in high school. How many of you took an engineering course in high school? They really don't exist, do they? So you come here and you think about majoring in engineering. Well, do I really know what it is? So let me start there. This is one way of looking at it. Engineering comprises two aspects. There's a science aspect of it. Engineers are scientists. They learn about the world around us. The second aspect is technology. Engineers are technologists. They make things that haven't existed before. So if the science is studying the things that exist and technology is making things that don't exist, engineers actually do both. OK, so there's two pieces. The formal words might be analysis. Analysis has to do with the science. We're going to study systems of interest. They're usually complicated, and there's usually many, many components to them. Hierarchical means there's details, and they come together to create something in an integrative way, and then they're put together to create something yet that now all turns into one kind of an operating system. The other word is synthesis, and that's building, and that's making technologies using these many, many components put together in complicated ways. So the science is kind of the analysis part and the technology's kind of the synthesis part. All right. In engineering, though, the one-- you say, well, how does this distinguish from science? Because scientists can also create new technologies, and scientists certainly study how the world works. One of the crucial aspects is that engineers tend to emphasize design both in the study and the building. Not only you want to see what is all there and how it works together, you want to see if there's design principles that help us understand the relationship between how they're put together and how the system as a whole operates. Because to build a technology, if you can't think about designing it from putting pieces together in order to accomplish something, it's really going to be trial and error, and that's not a very effective way to build technology. So this is something that really is an important facet of engineering, and that is design, thinking about how things get put together in order to accomplish some kind of a desired task. Now within engineering, each of the engineering disciplines you can think of focus on a particular science base for the components that it wants to study and build things from and the mechanisms it wants to study and build things from. You can't know all the science in the world. So if you're going to major in some kind of engineering, you usually pick some aspect of science that's going to be your focus. So for instance, civil engineering, mechanical engineering, electrical engineering tend to focus on particular branches of physics. That's the science they study the most. All engineers study mathematics. That's clear. But then if you're in civil engineering, mechanical engineering, electrical engineering, you really go in depth on a lot of the physics, because the components you're going to be putting together are physical components. The mechanisms are going to be the physics of how these things interact. Quantum physics, solid state physics, Newtonian physics, so forth. People who major in, let's say, chemical engineering or nuclear engineering or materials science and engineering, they learn math. They learned some physics. But then they tend to focus on some branches of chemistry. Maybe organic chemistry, maybe physical chemistry, maybe inorganic chemistry. And that's the kind of science they'll study most, because those are the-- they're going to study how chemical components work together and how chemical mechanisms operate. You notice I haven't written biology here yet, OK? That's going to come later. But if you look at the traditional engineering disciplines that have been around, they've been based on some branches of physics or some branches of chemistry, by and large. But in all of these, there's a very interesting paradigm. You can use different words for it, but here's one set of words that's easy enough to remember. Measure, model, manipulate, make. You need to measure things to quantify what's there and how it works. You need to model it. You need to describe it in mathematical terms because it's so complicated your intuition can't do it, so you need mathematical models to represent how the system operates in ways that your intuition just can't grasp. Manipulate. You need to go in and change things. Change one component. Change its properties in order to make the system behave differently. And then if you're good at all that, if you now can measure what's there and know how it works together and can manipulate it to make changes, then you can actually make something useful. So that's the progression. It requires design principles, design parameters, computational models. To make something, you really need to construct it for the kind of operation you want. You have to study how the overall system is behaving based on the components. So that's what these engineers do based on physics, and that's what these engineers do based on chemistry. So that's a little bit of a feel for engineering. OK. Well, now let's add this engineering to the world of biology and medicine, because you hear words like bioengineering, biomedical engineering, medical engineering, biological engineering. How can we make sense of that? Well, here's one way to look at it. First, let's start with these traditional engineerings that everybody's familiar with that are based on mathematics and some branches of physics and chemistry, depending on the discipline. Chemical engineering, electrical engineering, mechanical engineering, material science and engineering. OK. If you take any one of these disciplines and apply them to problems that arise from health care, whether it's clinical hospitals or the device or diagnostic industries, you can call yourself a biomedical engineer. You're taking the disciplinary engineering based on chemistry or physics. You're applying it to a medical problem. That's biomedical engineering. It's really not a discipline you would major in. So at MIT, we have a minor in biomedical engineering where you can major in any one of these things, take some courses that have to do with biology and medicine, and that's now an application field that applies yourself to problems. Now we also added biology, which I forgot to put here. This is plus medicine, and this is plus biology. So if you take any one of these traditional disciplines and also add some biology, that's essentially the field of biotechnology, thinking about engineering on biology. And that can be applied to health care problems in the pharmaceutical industry, say, or even the device industry. Or it's also applicable to many other kinds of industry, new kinds of materials, new kinds of manufacturing, biowarfare defense, things like that. OK? So a chemical engineer, an electrical engineer, a material-- mechanical engineer, material science engineer can apply themselves to biomedical engineering. They can apply themselves to biotechnology. So that's part of your choices. You can major in Course 10 or 6 or 2 or 3 and 1, and so forth. And depending on the choice of problems that you solve, you can also be part of the world of biomedical engineering or biotechnology. And all of this lumped together is what we would call bioengineering. Bioengineering is just a very broad umbrella that covers what any of these diverse disciplines might do that bring engineering together with the science of biology or the profession of medicine. Now in addition to the thing we've created here at MIT is another engineering discipline that's very analogous to this. You might think of it as a sister to Course 10 or Course 6 or Course 2 or Course 3. But now the science that it focuses on, it learns math, learns a little bit of physics, learns a bit of chemistry. But now its basic science is biology, the components and mechanisms by which biology works. So genetics, biochemistry, molecular biology, cell biology. It says, this is the science for biological engineering. So these people can now get a major. And I think we're a couple of weeks away from, we hope, being approved as Course 20. And you can use this major to solve medical problems that have to do with health care. You can use this major to solve biotechnology problems in other industries. So it becomes a sister discipline alongside chemical or electrical or mechanical or materials or civil. It's just based on a different science. All of these majors, whether it's biological engineering or any of these, you can be part of the whole world of bioengineering. You can do biomedical engineering work or biotechnology work. So this is a very important picture to keep in mind. Otherwise, these names just kind of go all over the place. Oh, what's the difference? Oh, they're all the same. It's not true. There really are specific differences, and it's just a matter of choice. So let's look at a little history to figure out how we got here. Bioengineering, biomedical engineering has actually been around for about more than 50 years. Back in the middle part of the 20th century, people were creating artificial kidneys and artificial hearts and things like that. They were trained as electrical engineers or chemical engineers or mechanical engineers with chemistry and physics, but they just applied it to the problem of replacing heart function or replacing kidney function. So the careers, they tended to work in the medical device field. Diagnostics, imaging, prosthetics. Those are artificial limbs, say. Implants, the artificial heart. Extracorporeal means outside the body, artificial kidney. So a lot of these folks would work in those industries. Or some of them could work in the pharmaceutical industry where you actually made a drug. So you worked in manufacturing or processing or delivery. OK. And these engineers didn't really need to be trained in the science of biology per se. They didn't really need genetics or biochemistry or molecular biology or cell biology. They could take the engineering they learned based on physics and chemistry and solve these kinds of problems very usefully. And most of the majors around the country, if you go to other universities, if you had choices to go to other universities, if they have a biomedical or bioengineering major, this is really what it's focused on. And you have that choice here. You can major in one of the other engineering disciplines and still apply yourself to medical problems. So just some examples, and I've got them in alphabetical order of departments it might be associated with. For instance, there are astro department. There's interest in spaceflight physiology. What happens when you take humans out into low gravity? What changes about their physiology? That's something that an aerospace major interested in biomedical engineering might find a very attractive research area to be in. And that's a great research area to be in. They can major in aero astro and look into space flight physiology. Chemical engineering, bioprocessing. Chemical engineers are very well trained in process engineering, how to make things out of chemical products. So you learn how to build bioreactors, say, reactors that have cells making some useful therapeutic protein, OK? That's a very exciting type of thing to be in with a chemical engineering background. Electrical engineering. I think I've got a couple of examples here. Imaging, how to use different types of modalities where you send different types of electromagnetic waves into tissue and have them distorted in different ways by the different components of the tissue so they actually can see through tissue, OK? So electrical engineer can be very good at this sort of imaging work. They know a lot about electromagnetic physics and signal processing and so forth in order to figure out how different waves passed through tissue can end up depicting different portions of that tissue, tumors and so forth. So electrical engineering, biomedical engineering, this might be something that they would do. Image-guided surgery. I sort of have this under computer science, because then you can take those images, put them in the computer, and then say, well, where should I cut in order to miss some arteries and veins and do the most effective thing if I've got to do a surgery around somebody's knee? So you've got to be very well trained in computer science and robotic algorithms and apply them to this medical problem. Environmental remediation. This might be civil engineering, environmental engineering, Course 1, where you'd be very interested in the microbes in the outside world and how they consume toxic chemicals. They might be able to clean it up, OK? So that's an interesting application of, let's say, civil environmental engineering to bioengineering. Material science. You might be interested in drug delivery. Somebody makes a drug. How do you actually get it into the body, in the right places, and released at the right rates in the right amounts? Targeted to the brain, targeted to the liver. So you have to create the right kinds of materials to encapsulate drugs and let them diffuse out to the right places and the right time at the right pH, and so forth. So material scientists might be very good at controlled release drug delivery problems. Do I have any more? Oh, OK. Artificial heart. Mechanical engineers would learn all the things you need to know to build the pumps and study the fluid flow, the fluid mechanics of the blood, and how it doesn't get sheared so the blood cells get damaged, and have the right pressures, the right flow rates, the right pulsatile oscillations. So to study that sort of fluid physics, fluid mechanics, you could major in mechanical engineering and make very important contributions with, let's say, artificial hearts. Or hip implants, OK? You need to replace a damaged and injured hip. Mechanical engineers might be very well trained to be able to study the forces that need to be withstood and how to create the right structures of some kind of material to bear those loads and connect things in the right ways. You could get a degree in mechanical engineering and be very good at things like hip implants. OK? So you get the message. There's all sorts of things. You can major in one of these disciplines and connect that discipline to the application world of biology or the application world of medicine, but still trained in that discipline. And these would be things that you would major in Course 1 or 2 or 3 or 6 or 10, say, and then do the biomedical engineering minor to connect that major to some of the right elective courses. OK. And that's been the state of the world for about the last 50 years, OK? There's been all those majors. And as I said, if you go to some other universities and major in biomedical engineering, you really get trained to do one of those things. You specialize in electrical or mechanical or chemical, controlled release or implants, and so forth. And you notice I haven't said anything about biology. Those folks didn't really need to be educated in genetics, biochemistry, molecular biology, cell biology to solve those problems. And that's because biology as it used to be was not a science that engineers could address very well, because in order for engineers to really analyze, study quantitatively, develop models, and to build technologies, alter the parts, there's a lot of requirements on the science that really biology didn't satisfy. The actual mechanisms of function weren't understood. Yes, you could see that moving your arm required a certain force and would weigh a certain load, but you really didn't know what was going on down in the proteins and cells and tissues of the muscles and the bones. But still, you could design maybe an artificial bone to do this, an implant. You didn't really know the molecular components, so how in the world could you actually manipulate the system if you didn't even know what the molecules were that are really underlying this? You couldn't really do the chemistry on the biological molecules. It's very hard to quantify, since if you didn't even know the parts and the mechanisms, how could you get quantitative measurements for them, develop models? So there's good reason why there never really was a biological engineering until very recently, because biology wasn't a science that was really suited for engineering analysis and engineering synthesis. So therefore, the world of biomedical engineering mainly involved all these application problems that I've just talked about that didn't necessarily require biology per se. But that's changed, OK? The good news for you folks is biology has changed. It's now a science that engineers can, in fact, connect to very well. It was very different when I was your age. When I was your age and a freshman in college, biology was just starting to be on the verge of becoming a quantitative, mechanistic component. Manipulable, designable, modelable science. And when I sat in your chair, it wasn't that way. I envy you all. Two revolutions happened. One was the molecular revolution about molecular biology. At one point in time, that was a revolution. It didn't exist. The identification of the actual components involved. So if we just look at bone, you may think, well, it's just this mechanical material tissue. Well, no. Underneath it is cells that build up polymers and degrade them, and they have little motors that move them around and machinery that pulls on the tissues, and factories inside that create the molecules and degrade them. And that's all governed by specific networks and machines that we'll talk about in a minute. And molecular biology allowed all these pieces, these components underneath just this big, macroscopic structure to now start to be identified. Only when you could identify the actual molecular components could you really start to do engineering on it, could you really decide what they were, measure them, and then change them, say, genetically. The second revolution was the genomic revolution. And that was really important, because even though molecular biology existed and you could identify these components and study their properties and manipulate them, it was very painstaking. You kind of have to do it one at a time. And it might take a decade to really learn about one particular gene or one particular protein. The nice thing about the genomic revolution is it just accelerated this immensely. You can now learn about the parts in a very comprehensive way, hundreds at a time, thousands at a time. And the technologies that exist now to study these now allow us to get many, many more components understood, identified, measured, and so forth. So we can now identify the parts, manipulate them, and do this actually in a very fast way. So biology is at the point where getting the parts and manipulating them is now relatively easy. Now the hard part is, how do they work? Now that you know what the components are, how do they work? Well, interestingly enough, they work as machines. If you look at a picture of a cell here migrating across a surface and you want to know how to make that cell migrate faster to colonize a biomaterial or slower to prevent a tumor from metastasizing, you have to look inside the cell for how the molecular components work together as a machine to transmit forces to the environment, pull on the environment, pull the rest of the cell along. So there's actin cytoskeleton and all sorts of proteins that link the actin cytoskeleton to receptors that cross the cell membrane, and they bind to proteins in the extracellular matrix. And these all work as an exquisite, many, many, many, many, many molecule machine to decide what forces to generate and where and how strong, OK? So just knowing that all these parts exist and their properties is crucial, but then you have to put them all together to study them as a machine. The other aspect is these machines are not autonomous. They're not just sitting there, working constantly at the same rates and the same powers. They're regulated. So those machines might be tuned to generate more force or less force, or force at one side of the cell instead of the other. Well, who regulates them? Well, there's whole other sets of molecules that actually work as information processing circuits. And you can draw them as signal transduction cascades where signals come in from the environment and they set off enzymatic reactions that change what genes are expressed and the forces at which cytoskeleton pools and the rates at which enzymes perform metabolic reactions. And people draw them then schematically as circuits where you would take all the molecules that might be in this kind of biological cartoon and just draw them here in some kind of archaic electrical circuit, because the cells are-- they have machines that carry out function and they have circuits that govern how those machines work. So these are very appealing metaphors, and this is engineering language. So all this is saying, biology, now that we have the components and we can do something with them, it actually needs to be studied, the way engineers look at things in terms of machines, circuits, systems, and so forth. So the point is biology is now very different. The biology of 30 years ago didn't allow biological engineering. Biology now does, OK? So the bioengineering world that's existed for 50 years that has chemical engineering, electrical engineering, mechanical engineering, material science aimed at medical problems without really studying biology in depth, that's been around for 50 years because it didn't need biology. It still exists. But now that biology can be accessed by engineers, this new thing shows up beside them. And now there is a biological engineering that you can study if you learn genetics, biochemistry, molecular biology, cell biology as your basic science. Because now, biology can be analyzed and it can be synthesized. And actually, it benefits from this engineering approach, because these machines then-- circuits are complex. So the components can now be identified and the mechanisms can now be studied. You can now quantify them. Genetic engineering means you can very easily manipulate these. If there's a protein that has a critical function, you can mutate it, make it express at higher levels or lower levels, or move it to different places in the cell, or have it interact with different molecules or with different affinities. You can now change any component you want. So the hard part is predicting what's going to happen when you do. OK. So this is where engineers now come in. So added then to the traditional engineering disciplines that can be applied to solving medical problems, there is this new discipline now that MIT has created that's called biological engineering, because it's rooted in biology, just like chemical engineering's rooted in chemistry. Electrical engineering's rooted in-- well, electrons, but that's a branch of physics, and so forth. So it's hard to call everything physical engineering. That's why we have the different branches. But there's an analogy to 100 years ago, electrical engineering was invented here. You may not know this. There was no such thing as electrical engineering until the 1890s. MIT invented it. It's like, you know what? There's all these advances in physics, and we ought to train engineers to study it better and build things on it. So MIT created electrical engineering. In the 1930s, up till then, there was no such thing as chemical engineering. MIT invented it and said, you know what? There's all these advances and chemistry. In the early part of the 20th century, chemistry became mechanistic and quantifiable. And MIT said, you know what? We ought to train people who think like engineers to study it and build things on it, and they created chemical engineering. Well, now we're in roughly 2000-plus, and MIT's doing the same thing with biological engineering, saying, you know what? There's been these revolutions in biology, and it's now mechanistic and quantifiable and desirable and manipulatable. Let's create this too. So it doesn't take place that frequently. Every few decades, there's a new kind of engineering. So this is the newest one. So it's got both the technology facets and science facets. Biological engineers want to create new technologies, new things that are built from biological components. And there's also the science facet. We want to analyze and understand better the way biological systems work as these machines and circuits, and so forth. So you can be interested in understanding. You can be interested in building. Both are facets. So it looks just like all the other engineering science technology. There's analysis of these complicated, many component systems. There's synthesis, which is building new things based on these systems. There's measure, model, manipulate, and make. The only difference is instead of doing these on the basis of physical components and inorganic or organic chemistry components, you're doing it on genes, proteins, and cells. That's the science of which you analyze and build. All right. Let me just give you a few examples of the sorts of things that are being done in the labs of some of the biological engineering faculty that will give you a flavor of this, of what happens when you think like an engineer in terms of analysis and synthesis of complicated things in quantitative, integrative, design-based ways, but you're doing it on the substrate of the mechanisms of biology. So one aspect is, are there new methods to really manipulate biological systems? Maybe for studying them better. Professor Bevin Engelward has a new kind of genetic construct that she's made. I won't go into it in detail. But in the genes of a cell, if you think about, how do you get mutations, you may get bombarded by radiation, toxic chemicals, chemicals in your inflammatory response. Those chemicals can interact with the DNA in your chromosomes and cause little mutations in the chromosomes. They just change the basis in the DNA, and that changes the way the genes turn into proteins and can mutate the cells. How can you watch that happen. How could you actually see that happen? She's created a way to do it by taking a gene that will make a protein that's yellow, fluorescent yellow, but only when there's been a damage event in that particular piece of the DNA. So my mouse might normally be whatever color it is, white or brown. If every one of its cells was expressing this yellow protein, the mouse would be green. That wouldn't help you much. What you really want is to be able to see a green or a yellow cell only when there's been a damage mutation there that might lead to cancer. So she's created that. And what you can see here, this is actually the pancreas of a mouse. And the mouse is just about all white or brown. But every now and then, the pancreas, let's say, you can see one cell or two cells that now light up yellow. It's because their chromosomes have been damaged in this place by some radiation or chemical or some kind of an event. So she's created a new way to manipulate the biology inside a living animal to study these mutation events. That's biological engineering. It's manipulated a system by biological components in order to study them better. Another type of biological measurement method, this is Professor Scott Manalis. And you might want to be able to have better ways of studying how DNA interacts with RNA, or how proteins interact with DNA, or how proteins interact with each other. But you really want to measure them in cells at very low levels and without having to add extra labels like fluorescence or radioactivity, just intact. So he's created this new device where he can put one kind of molecule on these tiny little of cantilevers that are only a few hundred microns long and very, very thin. And then if he takes some sample from blood or tissues or cells, if they bind to these molecules in a very selective way, it'll bend. You can scan a laser across it and watch little tiny bends and measure tens or hundreds or thousands of these things simultaneously. So it's a new measurement method aimed at understanding the molecular components inside cells. You may create entirely new systems in which to study biology Professor Linda Griffith-- all of these are biological engineering professors-- is very interested in studying the onset of human disease. And it's really hard to study human patients and say, you know what? I want to treat you-- I want to give you this thing and I want to see if you get this disease. That's ethically not very good. You can do it with animals, but animal physiology isn't the same as human physiology. So how can you actually study human physiology and the onset of disease when you can't really do it in humans and you can't really do it in animals? So in the world of tissue engineering, what she's really discovered is you can create human tissues outside the body. So here, she has this tiny silicon chip. You can see how small it is relative to a penny. And in this is drilled all sorts of holes. And in these holes essentially she can build, with the right combinations of cell biology and biochemistry and biophysics, she can recreate liver tissue capillary beds where she has liver cells all branching, and she can have blood-like fluid flow through it and the cells live. And she can study this with microscopy or things like that. So she's created human tissue, liver tissue outside the body, so she can now study the onset of human liver diseases, cancers, viral infections in ways that you could never do, because you couldn't do it on human patients. This is biological engineering. She's created a new biological assay system out of biological components. New biology-based materials. Professor Angela Belcher wants to create-- it's very important to have small micro electronic circuits, let's say, or photonic displays. But what they require is to get inorganic compounds patterned in a very, very careful and very reliable way down at the nanometer scale so that the right crystal structures form, and so forth. Right now, that's done with very expensive and very toxic processes. Toxic chemicals, high pressures, things like that. Could you replace this all with a biological process that didn't require the toxic chemicals and the high pressures and temperatures and the environmental waste? And so she's taken viruses that are tiny-- they're on a nanometer scale-- and engineered them, genetically altered them so that on their tips and their sides they express specific peptide sequences that can bind to the particular inorganic materials crystals that she's interested. And the viruses will organize them into wires. She's made conducting wires. She's made batteries. And she can do this on the lab. She could do on this bench right here. No high temperature, no high pressure, no toxic chemicals. Just do it right here, or the viruses will do it if she just manipulates them correctly genetically, OK? So new kinds of materials based on biology. Professor Matsudaira, who's your instructor for this course, you might think of this as new biology-based devices. I talked about biological machines. Well, these molecules come together and they can generate forces in very clever ways. So he's studying how, for instance, in some organisms, the horseshoe crab has something called an acrosome in which you have a coiled up cytoskeletal structure. And then under the right conditions it gets released and very quickly generates a very large force that can push or penetrate, or so forth. So he's threading the structure of this molecule, how it's regulated, how it moves from a confirmation that stores energy and that can be triggered to then change its conformation and structure and generate a force. This now can create new kinds of force-generating devices based on biology. Creating whole new organisms. Some of you have heard of this field of synthetic biology. Really, what that is is genetic engineering but with an engineering design perspective rather than just trial and error. What happens if I mutate this gene? It's, OK, I'm going to have a model for gene regulation and expression and the proteins. And what are these proteins going to do in a network for metabolism or protein production or things like that? I'm going to have engineering models for this, and I'm going to say exactly what I have to do to the gene sequence in order to get the outcome that I want, OK? So that's genetic engineering with real engineering. Interestingly, it's called synthetic biology. So Drew Endy, Professor Endy in biological engineering has taken a particular virus, the bacteriophage T7 that has a very complex genome that people understand parts of it but not all of it. And he's essentially refactoring it, re-engineering it. He likes to call it refactoring, because it's like he's redoing a computer algorithm. And he's intentionally changing the genome on a base-by-base sequence, fundamental modeling understanding to say, what proteins are going to be expressed, and at what levels and in what order? And then study the various new organisms that he's made for how they can grow under different conditions, and so forth. So you can actually create new organisms or organisms with new processes, new properties. OK. So these last examples I gave you came from over here. This is what you can do if you're educated to think like an engineer in terms of the analysis and synthesis and complicated, many components, quantitative modeling design, but just on genetics, biochemistry, molecular biology, and cell biology. And that now creates this discipline that's alongside of all these others that are strongly based in chemistry and physics. And the application areas, yes.
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Channel: MIT OpenCourseWare
Views: 124,657
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Keywords: mit, opencourseware, bioengineering, engineering, biomechanical, biology, biomems, biomaterials, bioprocessing, engineers
Id: GfoM-s9ZKrI
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Length: 38min 47sec (2327 seconds)
Published: Tue Feb 05 2008
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