 Here we have discussed about some facets of fluid mechanics over small scales and just to get a little bit deviated from that perspective, we would like to now focus on like when we are thinking about fluid flow through small passages, how are those small passages fabricated. So how do you make micro channels and micro scale passages which are important for microfluidics based applications. So for that purpose we will have a brief introductory lecture on microfabrication, please do keep in mind that microfabrication is subject by itself, micromanufacturing is a subject by itself. Our objective of this course is not to get into the details of microfabrication but give you some idea that what are the traditional perspectives, what are the current outlooks and what are the futuristic perspectives of microfabrication. So microfabrication versus macro fabrication like I mean because many of you are actually with background of mechanical engineering you have ideas of classical macro scale manufacturing processes like casting, welding, forming and all these and now you have to realize that when we are thinking about manufacturing over small scales, you are not directly using those processes but some of the concepts might be closely associated. So when we are talking about a manufacturing process, we are essentially interested about two types of possibilities. One is called as top down approach and another is called as bottom up approach. Top down approach means shaping of features from bulk systems using tools such as milling, forming, lithography techniques and so on. So basically you have a large system I mean system which is of larger size than the final product and then you shape of some parts from the system to get your final product. So the control is determined by the limitations of the fabrication tools but integration into devices and handling is easy but may lead to wastage of costly components. Bottom up approach involves assembling of the systems to form in more complex structures such as lamination techniques like for example rapid prototyping, self assembly. So you have small parts of the system and sometimes you assemble the small parts to make the final product and these small parts may be assembled by sometimes self assembly or self organization. So that is also a possibility that is because of inherent chemical and biological features associated with such systems. I mean there are tendencies that some atoms may tend or some ions may tend to combine with some other types of ions, some entities may tend to combine with other types of entities and that is how a complex shape or topography may be formed. So careful control of chemical reactions which are backgrounds of such systems are necessary for bottom up approach. These are less expensive and these are able to manufacture features that are beyond the capability of top down processes but you cannot really make very large systems using this. So there are plus and minus points associated with this. So when we say micro fabrication our main goal is micro channel fabrication actually because that is where our fluid flow is taking place where the micro fluidics is mainly concerned. So micro channel fabrication typically I mean you are bothered about either the classical paradigm where one is thinking of photolithography, soft lithography we will discuss about this and micromachining, mechanical micromachining I will give you some idea of how mechanical micromachining is done. Then micromachining on CD based microfluidic devices this we have discussed in the previous lecture and paper based microfluidic devices. So photolithography pattern transferred through molten wax and toner printing. So these are some of the possibilities, we will start with photolithography. Photolithography is basically printing by light. So what you are basically doing is a process of transferring an image from a photographic mask to a resultant pattern on a wafer. So basically there is a mask and the mask has a pattern. You transfer the pattern on to a wafer by a suitable method. We will discuss about what is the suitable method and I mean it is basically transferring a shape from the master pattern to the final object that is what it is. It requires several things like photoresist, spin quarter, mask, mask aligner, developer, making ovens etc. These are some common items that are necessary and photoresist are of different types and these are sensitive made sensitive to either ultraviolet these are chemicals basically. Sensitive to ultraviolet light, electron beam, x rays or ion beam. So based on these you call these as UV lithography, e-beam lithography, x-ray lithography and beam lithography depending on what optical source or what energy source you are using. So you can see here that first, so this is an example of photolithography I will go get into a more detailed example but just to give you an idea that is sometimes you know instead of giving theoretical description if we give a diagrammatic description it becomes more clear that what is happening that is what we are trying to do. So let us say you have a silicon substrate, so you can see here that there is a silicon substrate. On the top of that we can have a layer of SiO2, we will see later on that why this oxide layer may be necessary but it is not always a must that you have to use this layer and then you basically independently you prepare a mask. In the mask you have a certain pattern. So by the name mask it implies that if you have an energy source some part of the energy source will be masked by that particular mask where there is a pattern. So that black region will mask the fall of the energy source and then what you do is, so you coat the wafer with oxide layer with a photo resist. So photo resist is a particular chemical which on which you expose the light through a photo mask. So you can see here say you have this is the mask, the black region are the patterns. So the black regions are the patterns, so through this the light energy cannot pass. So you are having the light falling on selective portions of the photo resist. Now when the light is falling on selective portion of the photo resist either the photo resist will be sort of more soluble in the developer when it is developed and go away or it will be less soluble in the developer and it will not go away. So if you now develop it with the developer you will see for example that here we are talking about the photo resist where the photo resist has become more soluble with the developer and it has gone with the developer. So wherever it was exposed, see this part of the photo resist was not exposed, this part of the photo resist is below this black region. So this was not exposed but whatever was exposed when you develop it in a developer that exposed part is gone. That is a special type of photo resist, we will see what are the different types of photo resist, positive photo resist or negative photo resist. So then that means what you have been successful with is you have now transferred the pattern from the mask to the substrate. So that is what you have been able to achieve and then what you can do is you can use an etchant to etch the film. So if you are using an etchant to etch the film, so you can see here that this is the structure that you eventually get. So if you have, so you see that this black SiO2 film, so if you use an etchant then the part which is exposed to the etchant is gone, so this black part is gone. So only the part which is not exposed to the etchant will remain. So you can see a groove like structure has been formed on the silicon substrate. So now we will, so we have a broad idea that what is the process. Now what we will do is we will get into a little bit more descriptive details of the mask. So mask is a template that allows selective exposure of a photosensitive surface to the pertinent radiation. Mask making but so making a mask is very important and mask making consists of 2 steps. One is a layout of the design and then the pattern transfer to the mask. So typically the layout of the design you do it in a CAD software like say for example AutoCAD or some kind of CAD software and then you transfer that pattern to the mask. What are the properties of the mask? The mask must be transparent to optical wavelengths and must have extremely flat defect free surfaces. It is preferable that it has a coefficient of thermal expansion very similar to silicon. So it is just like think of the mold and the pattern in the casting. The pattern is like mask. So I mean if you have an unequal thermal expansion then that can give rise to defects. So basically so if you are transferring from the mask to the silicon substrate and then it is good that if both of them have same coefficient of thermal expansion. So they respond to temperature in a similar way. Commonly used substrates are silicon wafers, sodaline glass and quartz. Quartz mass have very similar coefficient of thermal expansion to silicon but are somewhat more expensive than sodaline masks. Any temperature variation may have significant effect on masks with high coefficient of thermal expansion and a small change in the dimensions of the mask may translate into big change in the position of fine features. Remember we are thinking of micron size features. So even a small change in temperature can create a significant change as compared to micron size dimensions. So mask making, the layout for each layer is drawn using a CAD software. The patterns of microchannels and chambers are printed on 2 different masks with aligned masks. The CAD generated patterns are printed on the appropriate substrates. Silicon wafers, sodaline glass, quartz or even transparency sheets. Transparency sheets are also I mean many of you might not have seen transparency sheets because I mean nowadays we use LCD projector for projecting presentations but if you have seen little bit old day presentations I mean there are transparency sheets which are available for making overhead presentations. So transparency sheets are not very expensive sheets and one can use this for like mask making. Now growing up I mentioned that on the top of the silicon like silicon is just an example because I mean this lithographic technique is actually borrowed from the semiconductor industry. It is not a mechanical fabrication, mechanical manufacturing process. Basically an electronic fabrication, electronic circuit fabrication process from where we have got this particular process borrowed to make microfluidic devices. So silicon is being one of the very common materials there and silicon is also commonly used for many microfluidic applications. So we are giving silicon substrates as an example. So why oxide layer is grown on silicon substrates? There are 2 particular reasons and these reasons if they are not important for your purpose you need not use the oxide layer. So one is to make the surface of the silicon hydrophilic and the second is to protect specific zones of the surface where etching is not possible. So there are different thicknesses of oxide layers that are formed and typically protocol is that silicon substrate is kept in oxygen furnace at around 1200 degree centigrade and dry oxygen is passed through around 2 hours. So these figures are not important for you, I mean it is important for practicing engineers and when you practice in the lab this may be important but I mean I can assure you that these numbers 1200 degree centigrade and 2 hours and all those things will not be important so far as your exam related issues are concerned. Depending upon the thickness of SiO2 being obtained duration of the heating varies. So that is like these are sort of sometimes these are done through simulations the optimization and all but most of the times these are actually trial and error based figures. To obtain thickness above 500 nanometers oxygen with water vapor is passed in addition to dry oxygen for different time interval depending upon the thickness of SiO2 required. So an important note is that development of oxide layer is not a must for making microchannels, it may be required for specific applications like making of electronic device, protecting specific zones for fabrication etc so not a must. Now on the SiO2 layer combination we coat with a photo resist that is the next level of coating before we shine the entire system with a light source which is masked by the mask with certain patterns. So when we do that so photo resist how the photo resist is deposited it is basically deposited by a process called a spin coating. So there is a device called a spin quarter which basically deposits a thin layer thin film of the photo resist on the substrate. The photo resist may be either positive or negative. Negative photo resist becomes less soluble in the developer solution when they are exposed to radiation. So when they are exposed so this is an example of a negative photo resist. So negative photo resist when it is exposed it is less soluble to the developer solution so it is remaining. On the other hand positive photo resist becomes more soluble after exposure. So here the photo resist is gone after development. So basically you can see that so far as this groove is concerned you depending on the positive or the negative photo resist you get either the positive replica or the negative replica but the pattern is transferred. Positive photo resist can give higher resolution typically they are aqueous based solvents and they are less sensitive. Negative photo resist is more sensitive relatively tolerant to developing conditions they are having better chemical resistance and one of the very important points that they are less expensive and that is why I mean a very common negative photo resist is used in many labs which is called as SU-8 very common negative photo resist but it gives lower resolution and typically organic based solvents are used. So here I would like to give you a demonstration of fabricating micro channel grooves and these micro channel grooves I mean these dimensions and everything are based on experiments which have been done in our lab to fabricate micro heat pipes. So in one of our initial lectures I discussed about that what is a micro heat pipe and how can it help in electronic cooling. So I will show you that what are the steps which you do to achieve it. So you have a wafer so typical dimensions like this is 275 micron on the top of that SiO2 which is the blue which is 1 micron photo resist 0.5 micron then exposure under UV through mask plate. So this is the mask. So you can see the mask is masking the UV light and this is allowing the UV light. So when this UV light is coming so now you have the cross link photo resist after you develop with the developer. So typical developer is HNR120 this is just an example of a developer. So you have the cross link photo resist then etching of the exposed SiO2 using buffer HF. So you see that whatever is the exposed blue colored region that is the SiO2 that is now gone with etching with a buffer HF. Then the photo resist itself is removed photo resist the pink colored material which was there the cross link photo resist that photo resist is removed by immersing inside a solution called as Pirhana solution. So that is removed then the silicon which is there see SiO2 is protecting the silicon at certain places. So wherever the silicon is there the silicon is aced by KOH solution which is a 44% solution in deionized water to obtain V group channels and because of the orientation of the natural flip planes and all you will not get a rectangular shape but the etching will give rise to this V group. And typical etching is done at 70 degree centigrade for 1 hour 30 minutes these are again like experience based numbers. Then you remove the remaining SiO2 by dipping in buffer HF. So you can see that nice micro groups are formed these are like group shaped microfluidic channels you can use these as heat pipes. So this is a summary of the process and I did not get into the details because we have already discussed about the photolithography process. A process which is sort of related to the lithography technique but uses soft materials is known as soft lithography. So soft lithography refers to a family of techniques for fabricating or replicating structures using elastomeric stamps, molds and conformable photo masks. It is called as soft because it uses elastomeric materials most notably PDMS. Soft lithography is generally used to construct features measured on micrometer to nanometer scale. So there are many techniques of soft lithography like micro contact printing, replica molding, micro transfer molding, micro molding and soft assisted micro molding. So these are all soft lithography techniques. I will show you one or two typical examples of how the soft lithography is done. But by this time you have heard from me about PDMS several times that PDMS is a material commonly made for microfluidic channels and for many biological applications and the question is why PDMS? Why do you use PDMS as a very common material? It is a flexible elastomer. It can be used to replicate topography from a master. It can be used as a conformable stamp for patterning onto other substrates. It is good for sealing microfluidic devices. It can be sealed to many materials. It can be spin coated. It is possible to dry edge. It is very well suited for applications in biotechnology. It is well suited for applications in plastic electronics. It is suited for applications involving large or non-planar surfaces and it is a low cost pattern replication process. So the whole idea is that if you have a good mask then that is a master pattern that may be obtained by a sort of expensive process. Then to make structure on PDMS you do not have to use that expensive process. You do not have to do the standard photolithography which requires a very controlled environment called as clean room. We will come to the concept of clean room later. So you can make the soft lithography process in a clean room free environment. Literally it is not clean room free because the mask that you have made requires a clean room. But once you make a mask you can replicate it to make many several structures by using the PDMS. So you can have low cost pattern replication. So you can see, so this is the pictorial demonstration. So let us say that your mask is SU 8 base structure. So pour PDMS onto the SU 8 structure form, heat it, then peel off the PDMS layer. So it is just like casting if you see. So you see the PDMS that is being poured in the figure. Then heat it, then peel off the PDMS layer and bond the PDMS mold with a glass and then you make plasma treatment and heat again. So simple schematic representation, the previous was a diagram to represent the generic process but how do we make microchannels using that? So that is what is demonstrated in this figure which is of particular importance to us for microfluidics based applications. So let us say that this is the mask and this is the SI structure on which you have photoresist. So you have developed a master. So this is the master pattern. You have kept the master pattern and then you cast PDMS on the top of that. Then you remove the elastomer from the master. See this is the shape that the PDMS has assumed. Why this is the shape? Because this yellow colored region is, I mean there the PDMS is not filled. So just imagine that this white colored region is lifted again. So if the white colored, it is peeled off. So if this is peeled off, you will get this group shape and then you seal it against glass after a plasma treatment and insert tubing. So you seal it against glass. So you make a bonding between the PDMS and glass and the group region will make microfluidic channel. So this is how we commonly, this is our day to day activity of like our labs. That is what we commonly do. Very simple process. I mean once you are familiar with it, it is a very simple process of making microfluidic channels for biological applications. Clean room concept. Now as I told you that many microfluidic channels are made by the lithography technique, the standard lithography technique and which requires a very clean environment to be maintained. So this type of environment control is just like the kinds of controls that are necessary for the ventilation or the intensive care units of hospitals. So you require very sophisticated dust free environment so that you know your intricate dimensions which you intend they are not disturbed by deposition of dust particles. So a clean room has controlled level of contamination that is specified by number of particles per cubic meter at a specified particle size. So typically ambient air outside in a typical urban environment might contain as many as 35 into how many? 10 to the power 6 particles per cubic meter. And I mean typically like in the busy urban places that are there in India it might be even more I do not know per cubic meter 0.5 micron and larger in diameter corresponding to an ISO 9 clean room. So clean rooms are classified according to the number and size of particles permitted per volume of air. So size numbers like class 100 or class 1000 denote the number of particles of size 0.5 micron or larger permitted per cubic foot of air okay. So typically so if you are told that it is a class 100 clean room so that is what it will mean that you will have maximum number of 100 number of particles of size 0.5 micron or larger permitted per cubic foot of air in that room that is the definition. So there are several standards like ISO standards and all those things for specifying clean rooms I have put this in the slides which you will be available to you as notes and so you might read them and if you are becoming a practicing engineer in this particular field this will be essentially important. Now we will discuss something about clean room free fabrication. See clean room maintenance of clean room is quite expensive. So until and unless you have very large number of products then it may not be cost effective like clean rooms can still give rise to cost effective products in for the semiconductor industry because the large number of consumers that are there but when you are thinking of microfluidic channels currently microfluidic channels are not consumed by so many large number of consumers. So maintaining a clean room for making microfluidic devices has been a bottleneck of many research institutes and many educational institutes which may not be able to afford such things even if they are able to afford it is not possible. So I mean many people are trying to I mean simultaneously get jobs done by the same facility. So you may have to wait for long before you get a chance for your channel to fabricate but you cannot stop your research there. So you must be having an alternative low cost paradigm where you might not be getting that kind of sophistication but whatever you will be getting will be good enough to sustain your research in the area of microfluidics. So one of the possibilities is like going for mechanical micromanufacturing. So for example micro milling when in our lab we started work with micro channels this is the method that we first used to make microfluidic channels. So it is an inexpensive fabrication procedure the width of the micro channel is determined by the width of the milling cutter. So if you have a small width milling cutter you can have and these are available you can make small width micro channels. Conventional micro milling cutter specifications I mean these are typical to what we have used in our lab so do not generalize it. Number of teeth 64 outer diameter 30 millimeter width can vary from 100 to 500 microns. Nowadays we are getting width even less than that. So 100 to 500 microns channel very easily we can make using this and feed rates can be varied as 12, 15 and 20 millimeter per minute using this particular system that we are having in our lab. Can you say why the feed rate is important? Your surface roughness characteristics is dependent on the feed rate. So feed rate is very important and both up and down milling processes can be performed. So you can see that like this is the rotation of the cutter and this is the feed direction. If they are opposing each other then that is up milling and if they are in the same direction that is called as down milling. So both up milling and down milling facilities are possible in micro channel. So typically when we are using micro milling we are using a material which in loose name is called as perspex or some people call it plexiglass and it is actually polymer PMMA polymethyl methacrylite PMMA. Just like PDMA it is also a very common material in making microfluidic channels. It has a density lower than that of glass and is not brittle. It is softer and hence can be scratched more easily than glass. It can be easily formed just by heating to the normal boiling point of water. It transmits more light than glass and unlike glass it does not filter UV light and it is less expensive. So it has so many great advantages and you can have because of its transparency you can visualize the flow. So when you are doing fluid mechanics or fluid dynamic studies so you have a say PIV system by which you are visualizing the flow. So it is very nice it is very convenient to visualize the flow because of its transparent system but it is not as brittle as glass. So typical like how the things will look this is a integrated micro channel setup with pressure tapings and tubings for pressure driven flow. So you can see that basically there are 2 blocks of PDMS and sorry PMMA 2 blocks of PMMA on one block one groove is made by micro milling on another block block another groove is made by micro milling and they are just screwed together. So the 2 groups U shaped groups together form a micro channel. Fabrication of CD based microfluidic devices I will not go into the details of this because we have already discussed it in the previous lecture. So these might be in your mind already. So these are usually fabricated by stacking and pressure bonding of CNC machine polycarbonate disks. Various diameters of milling bits and drill bits are utilized for CNC machining in the microfluidic network. So the CNC machine CD system typically 5 layer structure has 3 polycarbonate disks and 2 pressure sensitive adhesive layers. So these are the 5 layers and I have shown you in the last class that how these layers are made and how these layers are bonded together. Now paper based microfluidics. So why are we interested about paper based microfluidics? In CD based microfluidics you require I mean there are several advantages that you can make many micro channels active simultaneously by rotating the disk. If there are many channels all the channels will become active. So you can have multiple tasks being executed by that system of channels. However it is always important for like for the developing world that to go for microfluidic substrates which are even less expensive and the least expensive substrate that we can think of is a paper. So can we make micro channels on paper? So this concept was first introduced by Professor George Whitesides in the Harvard University that like how do you think of making paper based microfluidic channels. I will talk about some innovations today that what we have made in our lab concerning this and maybe in a later lecture when we talk about the biological applications of this I will talk about one or two more innovations. So what kind of paper you can use filter paper, nitrocellulose paper these are commonly used but you can use any sort of paper just try it out. I mean it is just a matter of your effort. These are cost effective, miniaturized, one can use this for multiple tasks and operational technical expertise is not necessary. So even a very unsophisticated or little bit trained person with not very sophisticated level of training can work with this. So basically what you are interested to do an ideal for point of care diagnostics. So what essentially you try to do in the paper based microfluidics. See paper has a large number of pores. So if you put a fluid in a paper it will flood the entire paper by diffusing through the pores and paper based diagnostic devices without having micro channels are very are available in the market. Like if you see for example the pregnancy test kits I mean you will see that I mean those are like paper based devices. So any paper based device is not a paper based microfluidic device. Paper based microfluidic device is a device where you make micro channels on paper. How do you make micro channels on paper? You basically block the pores in certain transverse direction. So that fluid will flow only along the longitudinal direction that is the direction of your micro channel. So for that we usually are interested for low cost way of making micro fluidic channels on paper typically where no sophisticated infrastructure or clean room facilities is necessary. But you can do paper you can make micro channels on paper by lithography. For example we will begin with that you can for example soak the chromatography paper with a photoresist and then you have a mask which is the design prepared in AutoCAD and printed on transparency sheet using a normal 600 dpi printer with this you can have a minimum feature size of around 200 microns. So for this you do not require actually a clean room based process but it is just lithography process. So it is pre-baked at 110 degree centigrade for around 10 minutes and exposed to UV light. So you can see that this structure which is there in the transparency it is transferred to the paper and then it is post-baked at 110 degree centigrade for around 10 minutes and reinstated acetone. So you have the cross link photoresist which is this violet color that you see and the white color region is the paper channel. So it is just like the lithography process but you can make even paper based microfluidic channels in a simple way. So this is the recent innovation that we had made in our lab. So when we have a paper based device in the next chapter that we will study we will study electrokinetics that is how by exploiting electrostatics with hydrodynamics we can actuate fluid flow. So if you can now apply electric field you can make the fluid flowing through the paper based device at a very fast rate and if the paper based device is handling blood that means you can diagnose blood very fast. So to do that you know you have to apply electric fields and depositing electrodes on microfluidic systems are usually considered to be expensive processes. So what we did is instead of using any standard electrode deposition technique we scratched the paper with pencil and this is what is shown in this black region and this graphite in the pencil acted as electrodes and then you connect it with copper wire leads. So this is now a paper and pencil device. So if you have a low cost micro channel fabrication system on a paper couple that with the pencil based electrode scratching then you can have a very low cost diagnostic platform which is ready for use of blood use for blood testing. So there are fabrication now how do you fabricate microstructures on paper. So you can have physical blocking of pores that is what one possibility that I had told or physical deposition of reagent on a paper, chemical modification of the paper or 2 dimensional shaping or cutting. Accordingly there are several techniques which are available like photolithography, PDMS printing, laser treatment, inkjet etching, wax printing, wax screen printing, plexographic printing, plasma treatment, inkjet printing and so on so forth. So depending on so either you block pores or you make new structures on paper. So basically your objective is to direct the liquid flow in a certain direction on the paper. So this is a different way in which you can do it as compared to what we showed in the previous slides. So pattern transfer through molten wax on a paper. So how it is possible? So you have a autocad design that is printed on this PMMA sheet then you wax it and heat at around 70 degree centigrade. So at this temperature molten wax solidifies within the groove, the groove which is made. So molten wax solidifies when it cools down to room temperature. So this basically melts the wax at 70 degree centigrade and when you bring it to the room temperature it will solidify and it will solidify in the groove. But there will be some excess wax. So the excess wax is removed that is spread over the sheet and the PMMA sheet is clamped with paper and heated at 70 degree centigrade for 10 to 30 seconds. So then this wherever this wax is there that is now when it is clamped with paper then there is a transfer of molten wax on paper by fixing the paper with the PMMA sheet. So from the PMMA sheet the wax will be transferred, the wax pattern will be transferred to the paper sheet if you clamp them tightly. So this is basically pattern transfer. There is another very low cost fabrication of paper based devices. I mean this typical low cost fabrication processes we follow in our lab. So that is why I am discussing about this. So you make toner printing through inkjet printer. So what you do is that printing is done on each side of the paper using inkjet printer. A typical commercial inkjet printer name is given but it is not a mass that you use it. Once the print was done the paper was heated on a hot plate at 200 degree centigrade for 4 to 5 minutes. So that toner particles can properly embed within the pores of the matrix. So this is how? So basically you block the pores by embedding toner particles. So this black region is the toner particle. So although you have pores but what you do is that by embedding toner particles in the transverse direction you do not allow the fluid to flow. So fluid will flow only in the longitudinal direction but you have to do it on both sides of the paper because the pores are 3 dimensional structures. So if you do it in one side then you can see fluid is leaking. So that you cannot do. So using this you can make fabricate complex structures on paper. So like you can use paper as a mixing device to make microfluidic mixing study reactions and so on. Now what next? See we have discussed about microfluidic platforms starting from microfluidic channel fabrication platforms starting from high cost paradigm to low cost paradigm, ultra low cost paradigm whatever but what are the new research issues. So you have to think of that when we are making micro channels many times our objective is to study the biological phenomena inside human bodies. For example how blood is transmitted through a complex topographically complex arrangement of network channels. So that is one thing. Sometimes we are interested to study drug delivery. For example in some cancer treatments it is necessary that you basically do a trans arterial chemo embolization that means what you do is that you pass a particular medicine, you load a particular type of bead with a particular medicine and pass that medicine through small passages of arterial and venal networks and then what you basically do is that this medicine will be targeted to the tumour cells. So what they will do? They will serve two purposes. One purpose is that they will block the supply of oxygen to the tumour cells. So that will give rise to ischemia and cell death but that does not mean that the cell cannot do DNA replication. So for that you have to destroy the cell chemically. So what for that? You basically supply drugs on the tumour cells. So you actually achieve two purposes. One is you block the oxygen supply by going through the small vessels and by blocking the small vessels the capillary networks which are commonly created around cancer cells. So that cancer cells are supplied with nutrients. So you block those that is number one. Number two is that you supply the medicine which is loaded with small beads to the target tumour cells. So now this entire process of course can be trialled with a human being and then you can see that whether it is becoming successful or unsuccessful or it can be trialled with an animal. You know that many times drugs are trialled first with animals and then with humans and then drugs come to the market. Can we make a in vitro microfluidic device or an artificial microfluidic device which will mimic this network and instead of making a trial with animals or human beings we can make a lab based trial of whether this cancer treatment is working or not. So in reality how this drug works I will try to run a movie. Just I would like to let you know that this movie is obtained from a commercial source but we have no commercial interest in showing this particular movie. This movie I have obtained from one of my collaborators Dr. Zumli Zhang from the University of Southampton and we work on projects related to this and we have authored the papers related to this but having no commercial interest or conflict of interest with what I am showing. So just have a look into it as purely from academic or scientific point of view and don't be bothered about any particular brand name or any particular company which is related to this. Hepatosellular carcinoma or HCC is one of the most common cancers worldwide and the third highest cause of cancer related deaths. Less than a third of HCC patients are eligible for the curative treatments of resection, ablation or transplantation. For these patients the only treatment option with a proven survival benefit is transarterial chemoembolization or TACE. DCB is a drug delivery embolization system that brings a new level of accuracy and tolerability to the TACE procedure, precision TACE. DCB is composed of a sulfonate modified hydrogel macroma containing negatively charged sites. This allows DCB to bind with positively charged drugs such as doxorubicin. Using a septic technique, doxorubicin is loaded into DCB. The positively charged doxorubicin binds preferentially to negatively charged sulfonate groups displacing water from the bead during the loading period. TACE is a minimally invasive catheter based procedure. The drug loaded beads are drawn up into a syringe and mixed with non-ionic contrast medium to aid delivery and visualization. Following angiography the catheter is inserted into the common femoral artery and then carefully positioned in the feeding vessel of the tumor. DCB is slowly injected into the catheter. The DCB drug delivery embolization system has been specifically developed to contain the chemotherapeutic drug until it reaches the tumor, maximizing tumor delivery and minimizing systemic exposure. The calibrated nature of the beads ensures targeted vessel occlusion, stopping intratumoral blood flow and causing ischemia and tumor cell destruction. Once at the tumor site DCB starts a controlled release of the drug. Doxorubicin enters the ischemic cells preventing DNA replication and destroying membrane proteins. This results in apoptosis and cell death. The controlled drug delivery from DCB is sustained over an extended period of up to 14 days with peak drug delivery three days after the precision taste procedure. Tumor necrosis can be seen two to three weeks after delivery resulting in reduced viable tumor burden. Due to the targeted nature of the drug release virtually no drug related toxicities have been reported in published clinical trials and pharmacokinetic data show a two log reduction in systemic levels of doxorubicin compared to conventional taste. The high tolerability of precision taste should support patient acceptance and encourage adoption of this new and highly effective treatment option. DCB delivering precision taste is the new standard in safe and effective treatment of unresectable hepatomas. Microsylic channels which mimic this complex structures so microchannel network design. So you can make microchannel network design on the basis of micro vascular geometries and bifurcation structures and blood flow conditions of selected vascular regions a range of bifurcation shapes can be designed using CAD software and then devices are fabricated on two PMMA sheets using micro milling protocol alternatively PDMS based microchannel can be fabricated by soft lithography but the question is are these channels and it is a million dollar question are these channels which we are trying to fabricate as flexible as that of blood vessels in human bodies. So that so the idea is not just make complex networks of channels but complex networks of channels which are biomimetic microfluidic devices. So one can cast typical materials for example collagen into a PDMS gasket with a needle held across the casting chamber. On collagen polymerization the needle is extracted to create a hollow cylindrical channel with a collagen material collagen is related to tissue engineering. So it is a soft material which is a tissue material and that kind of material if you use for making this biological this microfluidic channels and then as the next step if you could possibly line this with endothelial cell lines that is if you have endothelial cell deposition on this collagen based networks then you could possibly make God gifted God made channels by making microfluidic by using microfluidic techniques. So if that is what is common that is what is possible then many mysteries in human body can actually be unveiled by microfluidic experiments done in laboratories and that is where the futuristic direction in microfabrication research should go to. The job is very challenging because the flexibility of the microfluidic channels in human bodies that depends sensitively on many things one is that it varies sensitively with local blood pressure in a very unknown and in a very complex manner and that is it is very difficult to mimic that in a paradigm of microfabrication. So how do we make microfluidic channels which are as flexible as that of micro channels in human bodies. So if we can make that and if we can mimic that then there are many mysteries in medical science and technology which can actually be resolved which can actually be solved and then one can make I mean one can then mimic small I mean collection of cells which is tissues on a microfluidic chip one can then go for a collection of tissues to make organs on a chip and there are concepts of organs on a chip but the organs on a chip the concept from concept to the real realization of organ on a chip where it will behave functionally exactly like organs is something which is which is a matter of great great importance. So and then if you go further ahead with that one can go ahead with a collection of organs on a chip where the where the microfluidic networks mimic microfluidic networks connecting the organs mimic the flexible networks flexible micro flexible channel networks within human bodies and then that is that is going to give rise to the paradigm of human body on a chip. So one can see that starting from the very basics of microfabrication how can we go ahead and these are not just fancy stories or fairy tales research is currently going on in many laboratories in the world towards these directions and if these these are the real possibilities and then one can really revolutionize the medical engineering and medical advancements in medical science using microfabrication. Thank you very much we will stop here today.