 Good morning or good evening depending on wherever you are. I am Professor Shantanu Bhattacharya and I am an associate professor at the Department of Mechanical Engineering at the Indian Institute of Technology Kanpur. So, today I will be actually teaching you about this very fantastic area of micro systems fabrication by using advanced manufacturing process. So, to begin with I would just like to say a few lines about what really micro systems are or how this micro systems technology has emerged over the years. So, if you look at this particular slide it kind of gives you a historical perspective of micro systems research and the way it evolved and here especially this highlighted region as you can see talks about this very famous lecture by Sir Richard Feynman called there is plenty of room at the bottom. So, it all started really from this particular lecture which incidentally was presented at the annual meeting of the American Physical Society way far back in 1959. So, at this time really the research in the micro systems engineering area was fledgling at its fledgling stage and there were some very interesting ideas which were pointed out by Dr. Feynman about what can happen really when one can go smaller and smaller. For example, in one instance he really pointed out that if you can write the whole large prayer on the tip of a simple ballpoint tip or ballpoint pin how small can the letters be. So, he talked at length about different scales and how they would look at when you really do miniaturized them and some of the very fundamental concepts like scanning electron microscope, transmission electron microscope etcetera and the power of high energy beams have really emerged from this lecture. So, this really followed one of the most rapid technological developments which is also known as the miniaturization of electronics and microelectronics as we call nowadays and there was this very famous law called Moore's law which came into being from a business perspective where it was pointed out that this miniaturization density if you look at every 18 months for a period of 18 months would be essentially doubling which means that the amount of circuits that you can really print on to a small square area would go twice exactly with the passage of about 18 months or so. So, this law really also tells you about how small the miniaturization drive of electronics can take you to it kind of gives you a time scale estimate for that. So, this law when it started looked very good and you know people really had about 18 months time period for approximately doubling of the integration density. However, because of the limitations posed by photo lithography processes I am going to describe this in details little bit later what photo lithography means really. So, because of the limitations posed by this photo lithographic process of being able to go more than 100 nanometers or so this law may eventually change to doubling in every 24 months and nowadays increasingly it has been seen that instead of the 18 month period the period of integration density doubling itself has shifted to about 24 months or so. So, this is a sort of brief overview of where the micro systems drive or micro systems revolution really started from. So, you know because of this limitations posed by the Moore's law to the business of the micro electronic industry there were some processes really which fell out because they were no longer capable to handle the integration density which was offered by micro electronics. So, in the late 70s these technologies were kind of gathered together and the silicon technology was extended to what you call machined mechanical micro devices or MEMS as the term is known micro electromechanical systems which came into being because of the fallout of the processes from the micro electronic industry. So, this field really was very exciting because it had a component of mechanical motion or mechanical synthesis of small miniaturized structures or features. It also had a component of electronics where whatever signals it would be able to process can be transduced into corresponding electronic signals and then of course it was at the micro scale. So, that is the name micro electromechanical systems. So, as this field emerged micro systems technology increasingly of got applied to many fields like fluidic and optical industry or components and these sort of synergized with the MEMS technology and got integrated into this whole you know micro devices. The concept of devices actually came up where variety of techniques like fluidics, optical components, micro electronic systems, micro mechanical systems could be all integrated into one platform and together these so called micro devices were and the way that it was realized or built were known as the micro systems technology. So, our course really would focus more on this micro systems technology and some of the very state of the art processes of fabrication which should be used for realizing these systems as would see in details later on. So, let us look at little more of historical perspective as to how the MEMS or microelectromechanical systems really got integrated into biological or you know biomedical MEMS. So, really when the MEMS started in the 1970s it was dedicated mostly to physical systems like realization of temperature or measuring measurement of temperature, acceleration, velocity so on and so forth. But towards the late 1980s there were increasing amount of usages of this micro systems technology to realize micro flow sensors, micro pumps, micro valves where fluidic motion at the micro scale suddenly became very important. I would also like to point out to this one famous paper by Sir Andrews Mans which was presented at a plenary lecture on miniaturized total chemical analysis system a novel concept for chemical sensing and this was presented at the international conference on sensors and actuators which really changed the dimension for these microelectromechanical systems and slowly and increasingly the field emerged into the biomedical micro devices or biomedical MEMS systems. So, what these bio MEMS devices are or what they do really they are having relatively very high applicability to the field of life science, biotechnology and medicine and of course they are systems made up of very very small micro to nanometer size components and this is because primarily these MEMS features scale very well with some of the biological entities which are available. Therefore, this concept of MEMS which emerged from physical MEMS and went into biomedical MEMS really has taken a lot of steps and research has emerged in this particular area. So, this really shows why MEMS can be applied to the biological world and this is one slide which mentions some something about the sizes and the scales in the comparisons of the various MEMS devices with respect to the biological entities. So, here if you look really at towards this left side of the scale it starts from about 0.1 nanometers as you can see and it can go all the way to about 100 microns or so and just to give you a few examples on the size domain 100 microns typically is size of a human here and these entities here as you can see are the biological entities which are very commonly available in different forms of life in the nature. For example, most plants and animal cells if you really look at the size domain are about 10 micron plus region. This is an illustration of a red blood cell. It is like a inverted button from a shirt. It is a small sack which contains various chemicals and it is a very good oxygen transporter within the human system. This for example is E. coli. It is a small cylindrical 2 to 3 micron length about 1 to 1.5 microns diameter object and this is a bacteria and most of these bacteria are in the size range of about 1 micron to 10 microns. If you look at this particular species here it is a virus. It is a capsid made up of proteins with enclosing few genetic information of materials and most of the viruses are in the 100 plus nanometer domain size range. If you go one step further, this for example is a protein molecule and this here as you can illustrate here is a DNA deoxyribonucleic acid and one helical turn of the DNA is about 2 to 3 nanometers, 20, 30 Amstons. So, you can think of that mother nature kind of builds these systems up using a bottom of technology assembling atoms and molecules in a particular fashion. So, that you can generate these smaller entities biological entities and these together would realize one of the very highest and most complicated forms of life using bottom of fabrication technique. On the other side, on the right side you can see some of these structures and features from the common micro systems domain. This for example is a micro cantilever. You can see this lip sticking out of this structure and this whole pool here as you can see is a sort of cavity into which this lip is sticking out. So, you can recall this as a diving board in a swimming pool kind of structure. The only difference here is that because it is micro scale, this lip is about close to about tens of microns and the thickness could be about 2 to 300 nanometers and the depth into which this cavity is placed is can be close to about 1 to 2 microns. So, the reason why I am illustrating all this is that these some of these features and structures rhyme very well size wise with this biological entities. For example, this is again another very interesting example. It is a polysilicon gate with nitride spacing and the minimum feature size of a MOS transistor which has been declared by the ITRS roadmap in the year 2004 is less than 100 nanometers. For such a 100 nanometer device, the gate insulator region which may be this region is as low as a few nanometers about 2, 3 nanometers or so. You can see that even at the molecular level, there are these features and structures which are created which rhyme very well size wise with these molecules. So, it gives you an opportunity to sort of interact with the biological world more appropriately by building micro size features and objects. Therefore, the MEMS changed its direction mostly into biomedical MEMS and it had immense utility on some of the very interesting projects developed by the human civilization like the human genome project so on so forth. So, there was a huge class of materials called integrated biochips which got formulated and this one of the major areas of MEMS where some of these components could be microfluidics or could be with molecular specific sensors could be MEMS and MEMS systems and molecular devices and memory structures etcetera. They got integrated into these 2D CMOS platforms and they could do integrated sensing detection diagnostics very rapidly. Therefore, I have kind of illustrated or walked you through the history of these micro systems technology so called you know started in 1970s as a fallout of the micro electronic revolution and then basically went to realize some of the physical micro devices which could sense physical velocity acceleration pressure so on so forth some physical parameters and then finally, emerged into this biological micro systems or bio medical micro devices which could do sensing diagnostics very rapidly. So, it has been a very useful area of research and work so far and what we will learn in this course really is how to make some of these micro systems devices using conventional or most of the time advanced machining processes or machining technologies. Let us look at some of the examples of physical MEMS as I told you before and these are some of the commercially available MEMS structures and devices as on date in the industry. So, this mostly is an area which is realized using silicon and let us see example one here it is a bulk micro machined accelerometer and this comes from a company called silicon microstructures and typically this accelerometer is having a basic principle as illustrated here the concept of a proof mass. So, if you look at this top left corner we have schematically shown how this accelerometer works. So, this proof mass here is essentially a very small feature which can be about 20s of microns by 50s of microns and this is pivoted typically. So, if you look at this domain cut. So, if you look at this proof mass and the way it is pivoted it is illustrated here by this small cartoon which I am making for you in the screen. So, essentially this mass is pivoted like this on a surface and the surface here is actually is inside cavity or it is etched inside cavity inside is etched and the remaining part of the wafer is placed like this. So, you have a pivoted proof mass here by this shaded region which is nothing as but this illustrated here and you have a cavity here around and typically what happens is that there are metal structures which are coming out from this proof mass on both sides. So, these are some of the metal structures which are coming out on both sides and can be illustrated here as one, this one, this one, two and this is again three, this four and similarly there are other four indicated by these arrows here on the right side. So, these metal structures are coming out as you can see by the vertical shaded lines on both sides and then there are certain other metal structures which are actually present on the top of this surface which has been micro machined and out of which the cavity has been made and these structures are present in an inter-digitated manner as you can see. So, you have one structure, this one present between component three and component four. So, it is sort of inter-digitated and it is placed in that manner. So, whenever there is a movement of this particular MEMS housing there is a change in the angle of this proof mass here. So, the proof mass may actually become something like this as you can illustrate and can be illustrated in this diagram by the dotted line and so therefore, there is always a change in the interfacial area between these wings which are there on the proof mass and the metal structures which are printed on to the otherwise plane surface and because of the change in the interfacial area there is always a change in interfacial capacitance and because of this capacitance change there is a signal there is an electronic signal. So, if I can really calibrate this, this capacitance change with respect to the acceleration, roll, pitch, yaw, different physical parameters that is really what an accelerometer measures. These accelerometers are increasingly used nowadays in automobile sector for airbag based actuation and in fact very small accelerations or decelerations can be recorded very easily using some of these structures. The advantage is that this kind of an accelerometer would have a very miniscule least count or the accuracy of measurement would be higher because this proof mass may only be a few may be about nanograms or so in weight. So, it is a very small amount of mass that you are really carving out so that you can check physical parameters with great accuracy. Example two is this very interesting tool which is also the cornerstone of nanotechnology it is called an atomic force microscope or AFM. You can see here is a silicon structure coming out it is like cantilever and the tip of this cantilever is atomically sharp. So, you can see this tip here it is sharp to the size of a few atoms and this again is used extensively for topological measurements of surfaces where this cantilever tip is moved over a rough surface and whatever crests and troughs are present on the surface are being monitored by means of the deflection by monitoring the deflection in the z direction of this particular cantilever. So, therefore, if suppose I were to monitor these small valleys which are present over the surface I would simply scan this cantilever on the top of these valleys and wherever there is a valley and if we have some positive pressure on to the stop of the cantilever it would go and go into the valley and there would be a z direction displacement in the negative z direction and if we can record that we can really take all such data points and reconstruct the image of the surface based on some of these points. So, an AFM can really be used in the in the touching mode or the tap tapping mode and again silicon micro machining or micro manufacturing using some of these advanced manufacturing techniques are used for building some of these systems. So, along the course we might have example problem where we might see how to develop or device these AFM tips using non-conventional or advanced manufacturing. Example 3 here is a very interesting example is one of the commercially available devices which are available in the power point in the multimedia projectors and this is something called digital micro mirror device chip from Texas instruments. So, let us look at the basic principle of how this system works. So, you can see here in this particular figure an array of plates which are shiny and they are probably made up of metal and they are very teeny tiny. So, therefore, it is actually a blown up image and each of these plates may be something like about a 6 micron into 6 micron. So, here this dimension may be about 6 micrometers and similarly this dimension may also be another 6 micrometers and each of these plates are arranged in an array format in a very complex manner as can be illustrated in this figure. So, these plates are really pivoted on both ends and they are like a simply supported beam configuration and these plates also are electrically actuated from the bottom structure which is indicated in blue here and they have these electrodes. So, if there is an electric field applied between this blue base and the bottom of this plate which is hanging the plate deflects and because of the deflection if this plate was shiny on the surface and if suppose light was falling on to this plate light would go out of focus. So, here for example, is the DMD chip which actually is carved out of this array of different plates. And here for instance, if suppose this light beam falls in a certain direction from the focus the optical focus and there is some preprocessing done like passing it through RGB filters and then optical choppers etcetera. And let us say it were supposed to go in a direction towards the focus or the focusing lens. So, typically if the plate gets deflected the beam would go out of focus and so typically the pixel which was being represented by the plate which got deflected would close. So, you have a pixel close because of movement of the small mirror. So, you may be able to realize that image which is projected is really a function of such pixels it is an array of pixels. So, a pixel illustrated by a certain color or brightness or intensity would be representative of creating some impression on the surface which is corresponding to the image. Simultaneously a pixel which is closed or a pixel which is switched off would represent a dark region of the particular image. So, it is really an array of these pixels which would be able to demonstrate an image and you can do suitable amount of optical magnification etcetera to this particular image to transmit it. So, if you have a signal in form of a 0 or a 1 you can drive the angular defection of several of these mirrors in unison thus closing several pixels and opening several pixels and that can be used to translate the digital information of an image that is recorded in a computer on to the projector. So, it is one of very fantastic examples of what MEMS structures can do in terms of image projection. Let us look at some of the other examples of MEMS these are two very interesting examples of silicon MEMS. Again an accelerometer device from analog devices which is used typically for the deployment of air bags as I was mentioning and this is again a single chip microphone which is again the principle is based on this vibrating membrane which is highly perforated as you can see on the bottom and you have a layer of piezoelectric material coated on the top. So, whatever you are speaking into this small microphone basically resonates and vibrates this perforated membrane and it creates an electrical signal which can be processed or magnified and that is how you can hear sound transmitted electronically over distances. So, typically all speaker based systems like telephones, cell phones, microphones etcetera are based on some of this miniaturized or super miniaturized principles at work. So, that is some of the examples of silicon MEMS. I would now like to also illustrate some other examples. So, let us now see some more illustrations on applications of MEMS or micro systems in biology and here I have for you about six different illustrations of how micro systems can be really used in biology and as you can see here the first example is very widely referred to in red is basically this set of micro electrodes which were developed at the University of Michigan by Dr. Weiss's team actually. So, essentially this was used for monitoring the electrical activity of brain tissue and these electrodes here as you can see are printed and they are in plane and this needle here needle like structure here may be only a few tens of microns in width and a few hundreds of microns in length and they are all printed with these so called electronically placed or for electrical identification of signals. They are all coated metal prints or imprints placed on the top of these electrodes. This again another very fascinating example from research group at Stanford and this is a neuro probe and it is used for providing deep electrical stimulation to patients suffering from Parkinson's disease where these stimulations are medically advised sometimes for proper operations or for you know the sort of routinizing of functionalities of any human being suffering from these diseases. So, again very fantastic example of micro systems at work slender like tall needles which may be about 20 to 30 microns in width wise and few hundred microns tall and these are quite excellent examples of micro systems in biology. This is another example of what micro systems can do for monitoring the crosstalk between neurons these are some neuron cells growing over an array of MOSFETs and this area is also known as nanobiology and it has recently come out very well sometimes physiological monitoring of cells using this signals this electronic signals becomes very critical to understanding the crosstalks. So, essentially the idea is that these neurons are growing over the gate region of these MOS transistor arrays and if there is a change in the surface protein expression of these cells it is recorded in terms of change of surface potential and so if you can keep on monitoring the current based on the change in surface potential it can give you an idea of what crosstalk is going on a single cell level between many cells growing together on the top of this array. Example 4 here is again a very interesting and very fascinating example of MEMS in biology this is a micro needle and this is based on the sting or the needle of a mosquito. So, when a mosquito bites you hardly feel the pain because the needle is not able to really damage or deflect the pain receptors which are placed underneath the human skin. So, of course, there is a swelling which comes, but that swelling is more because of an enzyme that it releases so that it can thin out the blood samples that it is taking, but otherwise this needles are about 20 microns and again about 180 or 200 microns in length 20 microns in diameter. So, it is a high aspect ratio slender structure and such structures if we can fabricate as arrays or groups and fabricated over let us say pads which can be mounted on the fingers or different regions of the body you can think of or envision the system of painless drug delivery to the human body. So, in fact this slide has been borrowed or this picture has been borrowed from this company called Cometrix which commercialized some of these micro needles technologies for drug delivery applications. This again is an example of very fascinating area of micro systems called integrated biochips and sensors. Now, this area also got into picture because of the need dictated by the human genome project again where analysis of samples became very critical at a very rapid pace or fast pace. So, typically these biochips integrated biochips are made up of some channels and chambers and architectures which can handle minuscule amount of volumes of fluids of a certain target and they can be mixed in proportions, different proportions with their analytes of interest so that they can be recognized. So, there is some kind of a transduction of signal which changes the chemical information on to the analyte of interest into electrical signal or an optical signal and the whole integration of how to change the signal or how to process the signal or how to infer from the signal is done together on this integrated biochip. So, these technologies or these group of technologies are also known as lab on chip kind of technologies and they are very useful for the diagnostics, the clinical diagnostics world. Again a very fascinating application of MEMS. Again, this example 6 here illustrates a bunch of different cantilevers and I have already mentioned about these cantilevers extensively while talking about AFM and the technology of AFM. So, these cantilevers can be very easily used for recognizing DNA molecules. In fact, this work done for the first time at IBM Zurich Research indicated that deflection on these cantilevers can be synergistic with some of the binding events that may happen on to the top of these cantilevers between capture probes which are very intelligently placed on the top of each cantilever and the target molecule which may come and bind. So, this deflection can be recorded with certainty to indicate whether there is a binding action which has happened and this can be used typically for applications like DNA microarrays etcetera. So, this is again another very fantastic example of micro systems in biology and its applications. So, if we really look at a bunch of these different technologies sort of micro and nano systems and the way that they apply to the biological world. So, I would try to classify these technologies as once which have a biological impact or a bio inspired and it is synergistic learning process where on the left side these three boxes are representative of learning experiences from micro nano systems which would result in some novel solutions for frontiers in medicine and biology and these can use examples like diagnostics we have discussed about biochips. There can be nano micro structures like quantum dots, silicon nanowires, carbon nanotubes so on and so forth. There can be some therapeutic applications like targeted drug delivery, painless drug delivery or drug release systems again where micro nano systems can be used for some developing some solutions or frontiers in medicine and biology and then you have these hybrid bio devices where you can develop through tissue engineering a complete organ, but again keeping the principles of micro nano fabrication or advanced manufacturing of such processes as applied to biology and medicine. The boxes on the right here are illustrative of a reverse learning experience which you get through what biology and medicine has to offer and how you can apply on to some systems which would be useful for developing micro nanotechnology. For example, let us consider self assembly which can be DNA protein mediated or mediated with SAMs or self assembled monolayers again something which is naturally available and you can directly apply this to do some very novel work of maybe nano scale interconnects or micro scale interconnects which can be a part also of molecular electronics or single molecules or DNA can be used as a basis of conducting wires nanowires between more than two posts. There is another very fantastic example of developing these bio inspired materials like for example, the human skin. So, if you look at the skin it is such a wonderful instrument it can self heal, it can respond, it can repair, it can sense and learning from what mother nature has to offer in terms of the scheme and trying to enumerate the fabrication technology so that you can develop these advanced machining processes is another way of looking to develop these novel solutions or frontiers in materials or information processing. So, therefore, it is a synergistic learning experience. On the left you have learning from micro nano systems as applied to the biological world and on the right you have learning from biological world as applied to micro nanotechnology systems.