INDIAN INSTITUTE OF TECHNOLOGY ROORKEE NPTEL NPTEL ONLINE CERTIFICATION COURSE. Biomedical Nanotechnology. Lec-01 Introduction to Nano

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1 INDIAN INSTITUTE OF TECHNOLOGY ROORKEE NPTEL NPTEL ONLINE CERTIFICATION COURSE Biomedical Nanotechnology Lec-01 Introduction to Nano Dr. P. Gopinath Department of Biotechnology Indian Institute of technology Roorkee Hello everyone, I am Dr. Gopinath, associate professor in the department of biotechnology and also a joint faculty in the center for nanotechnology. I welcome you all to this course on biomedical nanotechnology. The first lecture of this course is introduction to nano. In this course we will learn about the basics of nanoparticles and how we can categorize nano materials according to the dimensions. We will also discuss why nano is good or why small particle is good. We will also learn what is surface area to volume ratio and what are the approaches followed to make nano structures like top-down approach and bottom-up approach. We will also talk about the biomedical applications of these nano materials. Let us see what nanoparticles are. Any material having at least one of its dimension in the range of nanometer is called as a nanoparticle. The word nano is a Greek word and it means DWARF or small. The term nanotechnology was coined by a scientist Norio Taniguchi in A nanometer (nm) is one billionth of a meter that is 10-9 m. So to understand the nano scale let us have a comparison between macro, micro and nano scale. An average person of height 180cm is equal to about 2 billion nanometer, and an apple of size 8cm is equal to 80 million nanometer. An ant of size 5cm is equal to 5 million nanometer. If we compare on the micro scale, the approximate size of human hair is 80,000 nanometer and the smallest size that a human eye can see is only 10,000 nanometer. A bacteria of size 2µm is equal to 2000 nm. The diameter of DNA is only 2 nanometer and the cellulose nano fibrils in plant leaf

2 measures only nanometer in diameter. The size of hydrogen atom is 0.1 nanometer approximately. To cite another example to explain this, the population of India is 1 billion. 1 billion is equal to 100 crores that is So every single individual Indian is nano in comparison to the total population of India. Another simple example to explain nano is to compare 1 rupee to 100 crore rupees. Here 1 rupee is nano. 1 rupee in 100 crores is the scale difference that we are discussing to understand how small the nano is. Now we will discuss about how we can categorize nanoparticles into one, two and three dimensional nanoparticles. In case of one dimensional nanomaterial, it has only one parameter either length or breath or height in the range of nm scale. Examples for one dimensional nanomaterials are thin films, layers and coatings. In case of two dimensional nanomaterial, the length and breadth will be in the nm scale. Examples for two dimensional nanomaterials are nano tubes, nano fibers and nano wires. Third type is three dimensional nanoparticles where all the parameters like length breath and height are in nm scale. Examples are nano shells and nano rings. So why do we need nano when we already have macro and micro? what are the advantages of nano scale materials? Consider the simple example of a full shell cluster. Here you are having seven shells that are comprised of 1415 atoms. So the total number of atoms are 1415 but when you count the surface atoms, it has only 35 surface atoms. If the same seven shells are made into a small particle like single shell, the total number of atoms will be only 13, however it will have 92 surface atoms. So when the size goes down the surface area will be increased. When the surface area increases, nano objects can perform faster. It will be also lighter than the bulk material and it can get in to small spaces. For example, nano sized materials can carry anti-cancer drugs into mammalian cells easily because of its smaller size. They can easily enter into tumor location. It is cheaper than the bulk material and also it is more energy efficient. This is because of the change in the properties of materials when the size of the material is reduced.

3 Now, let us see the concept of surface area to volume ratio. Take a simple example of a cube of 2mm size. The surface area is calculated by the formula given below. Surface area= height x width x number of sides x number of cubes. Hence the surface area of a cube of size 2mm will be 24 (2x2x6x1). However, when the same cube is cut into small cubes each of size 1mm, then the total surface area will be 48 (1x1x6x8). The volume of a cube is calculated by the formula given below Volume= height x width x length x number of cubes. The volume of the cube of size 2mm and of the cube of size 1mm will be same ie., 8. The ratio of surface area to volume for both cubes are calculated as follows Surface area/volume for cube of size 2mm= 24/8= 3. Surface area/volume for cube of size 1mm= 48/8= 6. Hence the ratio of the surface area to volume is increased when the size of cube is decreased. So when the surface area is getting increased, we can see some properties which are different from the normal properties. When the surface area to volume ratio increases a greater amount of substance comes into contact with the surrounding material. The hidden surfaces of the materials will be exposed. When the hidden surface are exposed to the surrounding material or environment it will show some novel properties. It can interact very efficiently with the surrounding material and it can have a good catalytic activity. This results in a better catalyst since a greater proportion of the material is exposed for the potential reaction. Let us see a simple experiment to demonstrate the usefulness of surface area to volume ratio by using a disprin tablet. We will try to dissolve the tablet in the water. First we will dissolve the tablet in its intact form, next we will crush the tablet into fine powder and then dissolve in water. You can see that it took 45 to 50 seconds for dissolving the complete tablet. But in the powdered form, it took only 10 to 15 seconds to dissolve the complete tablet. By this experiment, we can easily understand the surface area to volume ratio concept. When the size goes down it will have more reactivity and interact more with the surface.

4 The properties of materials can be different at the nanoscale because of two main reasons. The first reason is that it will have a relatively large surface area to volume ratio when compared to the bulk material and it will be chemically more reactive. This affect their strength or electrical properties. The second reason is that at the nanoscale the quantum effects will begin to dominate the behavior of matter which is why nanoscale materials show different kind of properties. Usually the bulk materials follow constant physical properties regardless of size but nanoscale materials show size dependent properties. For example quantum confinement in semiconductor particles or super paramagnetism in magnetic particles appears only when the material goes to the nanoscale. So let us see the origin of these properties. Here you can see that in bulk metal the conduction band and valence band are very close and so the unbound electrons have motion that is not confined. In case of nanomaterials, there will be a separation between the valence band and conduction band. This confines the electron motion and quantization sets in. So let us have an example to understand how material properties vary with size of the material. Gold is a shiny yellow metal and is used for making ornaments and jewelries. When gold exists as a bulk material, it is inert. But the properties of gold changes when it goes to the nano scale. For example, gold particles of size between 30 to 500 nm shows metallic property and it will have a turbid crimson to blue color. When the size goes down to 3-30 nm it becomes red and it still retains its metallic property. When the size goes down equal to one nm or less then, it will be in orange color and it will exhibit non-metallic properties. So from metallic, it became non-metallic and from red color it became orange color in the gold cluster. When the size goes down to atom level of one Armstrong, it became colorless. This is an example of same material showing different properties in different size and different shapes. The reason for the difference in color is the surface plasma resonance which will be explained in the next lecture or subsequent lecture. We can also see other physical and chemical properties changing with the size of the material. Electrical properties also changes such that at nano scale

5 non-conducting materials display conducting property. Nanomaterials also get high strength and efficiency. Nanomaterials have optical properties that are different from the bulk material. Materials at the nano scale emit different color. For example silver spheres of 40 nm shows blue color and gold sphere of 50 nm shows green color. Hence depending on the size and shape, nanomaterials show different kind of optical properties. Also when the size of magnetic nanoparticles goes down, it will have very good magnetic properties. Nano technology is not new. You can see here, this beautiful paintings are not made by any color. These paintings are made using different kind of metal nano particles of various size and various shapes. Thousands of years ago, the Chinese have used gold nano particles to introduce red color in their ceramic porcelains. To cite another example, in 1857 Faraday prepared gold colloids so that was stable almost for a century before being destroyed during the world war II. You can consider the example of gold nanoparticles of different size and different shapes. Under the transmitted light you can see it is showing a different color and again the same nano particles when visualised under the reflected light it shows a different color. A Roman Lycurgus cup belonging to fourth century, made of dichroic glass appears red in color when light comes from behind. It appears green when light is from the front. It appears red in transmitted light and green in the scattered light. This dichroic effect of this cup or glass is made by adding tiny proportions of nano particles of gold and silver in the colloidal form and coating the glass cup with the colloid. Nano is not new to India also. We had an ancient ayurvedic medicine like bhasmas that have a lot of metal nano particles and a lot of research is going on to explore the applications of nano particles and bhasmas for various therapeutic applications. So what are the different types of nano particles? The first one is naturally occurring nano particles which can be formed due to forest fires or volcanic ash or viruses. These are naturally occurring nano materials in the range of nano size. The next is man-made nanoparticles. It may be incidental or engineered. Examples for incidental nanoparticles are nanomaterials generated from cooking smoke and diesel exhaust. These processes emit some kind of carbon nano

6 materials. Engineered nanoparticles are also of human origin but we make them in the lab. So when you compare to the incidental nanoparticles which are more variable and forms in different size and different shapes, engineered nanoparticles which are made in the lab, have a controlled and well defined size and shape. Also you can have the core and shell, we can have the organic coating and we can modify and engineer the nanoparticles according to our need. Examples are metal nanoparticles, quantum dots and nano capsules. So how to make these nano structures? There are two main approaches. One is top down approach and next one is bottom up approach. First we will see what top down approach is. Top down approach is building something by starting with the larger component and carving away the material. It is similar to making a sculpture from the rock. So here your rock is a bulk material. You are carving out smaller particles from the rock and making the statue. Similarly nanomaterials are made from bulk material by carving out. This is called as top down approach. From the bigger sized bulk material, you are making the nano sized materials. Next one is bottom up approach. For example, here you are building something by assembling smaller components. We are assembling the smaller components and making a building or a car engine. Here we will be having atoms and molecules. We will assemble the atoms and form the nanoparticles. It is called as bottom up approach because from atomic scale it becomes nano scale. When you make these nanoparticles, so we can make them from inorganic or organic materials or it can be of hybrid ie., from both inorganic as well as organic materials. The size could be between 1 to 100 nanometer and the shape can be tuned to rod or sphere or any other shape. The surface can be functionalized with the polyethylene glycol, that is the PEGylation or can be coated with other materials. We can have the surface charge as either plus or minus. When you have the positively charged nanoparticles, it has high affinity for binding to the cell surface because cells and DNA have negative charge. We can also have a targeting ligand attached to the nanoparticle by adding an antibody or a peptide so that it can specifically go and bind only to the diseased cell and not to the normal cell.

7 Now let us see the difference between the nanoscience and nanotechnology. Nanoscience is the study of nano materials, their properties and other related phenomena. As a simple example, consider quantum dots. Quantum dots are semi-conductor nano crystals and it exhibits different fluorescence properties with respect to changes in size. So if we are using the quantum dots and studying the physical and chemical properties, then it is nanoscience. And if we are using the quantum dots and making a slim LED TV, then it is called nanotechnology. Nanotechnology employs the application of nanoscience to produce devices and products. Now let us see the difference between nanotechnology, nano-biotechnology and bionanotechnology. There is a minor difference between nano- biotechnology and bionanotechnology. In nano-biotechnology, will be using nanomaterials as tools for biological applications. We will be using nanoparticles for diagnosing a disease or imaging the disease. This will help in rapid diagnosis of cancer and other diseases. So that means, when you are using the nanomaterials or nano tools for biological application, then it is nano- biotechnology or nano biology. Bio-nanotechnology is related to understanding the biological nano structures and its potential applications. For example, we can use the DNA like a construction material instead of genetic material. We can make nano cages and protein based inks. This can be useful for making nano devices and nano machines. We can make small size nano robots by mimicking the bacterial flagella. Hence, this means you are taking the idea from the biology to understand the biological nano structures and we are using it for various applications. This is called as bio-nanotechnology. Nanoparticles have wide applications in almost all the fields. In this course, we will mainly focus on bio medical and health care applications. So why are we using these nanoparticles for bio medical applications? Nanoparticles, because of its small size, can interact very well with the bio molecules. Also, it can easily enter in to many areas of the body and it can detect the diseases while in the early stage. Nanoparticles can also be made to deliver therapeutic drugs and molecules.

8 Now, one by one let us see the bio medical applications of these nano materials. The first application is that we can use these nano materials for diagnosing various diseases and we can make some fluorescence nanoparticles which can easily reach the tumor location. The fluorescence signals from these nanoparticles can be easily monitored. The next application is the targeted drug delivery. The main drawback of the traditional cancer therapy is that we are not able to specifically target only the cancer cells. The traditional drugs kill the healthy cells also. But by using nanoparticles, we can specifically make them go only to the cancer cell and kill the cancer cell. So we can make a targeted drug delivery system. We can also go for tissue engineering by using nanoparticles. In tissue engineering, if you have damaged skin or damaged organ, we can grow that damage organ or skin in the lab and we can replace it in the body. Another upcoming area is organ printing by which we can print any organ and we can go for the organ transplantation. So these recent advancements are under clinical trials. A lot of research is going on about this organ printing. We can also make artificial cells in some cases when we dont need the complete organ. Here, we can replace only the damaged cells or dysfunctional cells. For example if we want to make an artificial RBC, it is possible by this artificial cell technology. DNA nanotechnology and protein nanotechnology also come under bio-nanotechnology. So here we can use DNA and protein as a construction material and also like a nano tool to make nano machines or nano devices. These are useful for making bio degradable therapeutics and for understanding various diseases. So bio-medical nanotechnology is the combination of nanobiotechnology as well as bio-nanotechnology. In the present course, we will be learning the bio material applications of nano materials. Before I conclude the lecture, I will also show you another upcoming area called nano robots. It may look like a science fiction but a lot of research is going on to make it a reality. The idea for nano robot came from the bacteria. You know bacteria move from one location to other location using the flagella. So based on that they made a small nano robot that has a tail like structure. It also has a micro camera by which we can monitor whether it is going to the proper location or

9 not. The nano robots can be engineered to have a payload. Payload is a therapeutic molecule. By means of a capacitor, the nanorobot will have the energy to move from one location to another location. So it will move from one location to another location, like to the arteries and veins using the tail like appendages and it can read the location and it can deliver the drug. Nano robots are called in short as nanobots. Nano robots for cancer therapy can swim in the blood stream and reach the tumor location. Once it reaches the tumor location, it can destroy the tumor cell and the cancer cells. So this is the conceptual idea of nano robots for cancer therapy. A lot of research is still going on in developing this kind of nano robots. Not only for the cancer therapy, the nano robots can also be used for breaking the kidney stones. Nano robots can carry a small ultra-sonic signal generators and it will deliver the frequencies directly to the kidney stones. You can see here, simple stones are very large to pass through. So what happens is, these nano robots can generate shock waves, which can break the stones. Once broken, the smaller stones can easily pass through in the urine. Nano robots can also be used for removing the fatty layer deposits on the arteries or blood veins. Apart from bio-medical applications, nano robots can also be used for the day to day applications. One simple example is a mouth wash full of smart nanobots. So we can have nanobots for cleaning the teeth. So nano is getting applications in all our day to day life also and not confined only to bio-medical applications. However, in this course we will be learning the bio-medical applications of nanomaterials. We will be emphasizing only on the bio medical applications of these nanomaterials and how we can use it for various therapeutic applications and diagnostic applications in the subsequent lectures. As the summary of the first lecture, we have learned what the size of nano particle is and how we can categorized them in dimensions of 1D and 2D and 3D. And we have also learnt why small is good. We learnt about why nano particle is good or better than the bulk material and how the properties of the material getting changed with respect to the size. We also learnt what the surface area to volume ratio is and about the top-down and bottom-up approaches. Finally, we also got an idea about how we can use these nanomaterials for various bio-medical applications.

10 I will end my lecture here, thank you all for listening to this lecture. I will see you in another interesting lecture. For Further Details Contact Coordinator, Educational Technology Cell Indian Institute of Technology Roorkee Roorkee E Mail: etcell.iitrke@gmail.com, etcell@iitr.ernet.in Website: Production Team Sarath. K. V Jithin. K Pankaj Saini Arun. S Mohan Raj. S Camera, Graphics, Online Editing & Post Production Binoy. V. P NPTEL Coordinator Prof. B. K. Gandhi An Eductaional Technology Cell IIT Roorkee Production Copyright All Rights Reserved