noc19 ee41 lec05

Summary

In this engaging and informative lecture, we delve into the intricacies of angiogenesis and the innovative uses of microfluidic chips in cancer research and drug efficacy testing. The lecture reveals how sensors can be employed to analyze electrical and mechanical properties of tissues, thereby aiding in drug screening and cancer treatment. Additionally, the speaker explores how microfluidic platforms can help comprehend the role of angiogenesis in tumor growth. The lecture also touches upon designing patient-centric platforms for immunotherapy drug testing, providing an overview of how microfluidic chips can simulate dynamic conditions for more accurate results.

Highlights

• Discover how angiogenesis is the process of blood vessel creation that supports tumor growth. 🩸
• Learn about innovative microfluidic chip designs for dynamic and precise drug testing. 📈
• See how dual sensor technology measures tissue properties to improve drug selection. 🧬
• Explore the potential of patient-centric microfluidic tests to personalize immunotherapy. 👩‍⚕️
• Understand the implications of blocking angiogenesis to starve cancer cells. 🚫

Key Takeaways

• Understanding angiogenesis is crucial for cancer research and therapy development. 🩸
• Microfluidic chips offer dynamic platforms for testing drug efficacy against cancer cells. 🌱
• Sensors can measure both electrical and mechanical properties of tissues for better drug screening. 🔍
• Microfluidic platforms can help identify effective immunotherapy drugs for specific patients. 💊
• Angiogenesis is a key target for stopping the growth of cancer by cutting its energy supply. 🚫

Overview

In this fascinating module, the focus is laid on angiogenesis—the process of new blood vessel formation which plays a critical role in cancer progression by supplying necessary nutrients to tumor cells. This understanding opens a window into developing therapies that can hinder tumor growth by disrupting its blood supply.

The lecture further discusses the design and utility of microfluidic chips. These chips, as revealed, serve as dynamic platforms for experimenting with various drug combinations in a controlled environment. This provides a powerful avenue for assessing drug effectiveness on living cell models, thus personalizing cancer treatment plans.

Adding to the marvels of microfluidic technology, the lecture touches upon its use in patient-specific testing for immunotherapy drugs. By simulating the body's dynamic conditions, these chips can demonstrate which drugs might work best for individual patients, paving the way for tailored cancer therapies.

Chapters

• 00:00 - 01:30: Introduction and Overview of Sensors Introduction and Overview of Sensors: This chapter begins with an introductory musical piece and a welcoming address to the module. It sets the stage for learning about sensors, emphasizing the significance and purpose of understanding them within the context of the course or material being presented.
• 01:30 - 11:30: Microfluidic Chips for Angiogenesis Study In this chapter, the discussion continues from previous modules focusing on sensors. Various types of sensors are highlighted, including heaters and interdigitated electrodes on heaters. The chapter explores using sensors to measure impedance changes in cells and tissues, as well as analyzing changes in mechanical properties such as elasticity of materials. The context is set within the framework of studying angiogenesis using microfluidic chips.
• 11:30 - 20:30: Understanding Cancer and Energy Sources The chapter discusses the intersection of physics and biology, particularly in the context of designing tools for medical purposes.
• 20:30 - 25:30: Microfluidic Platform Design for Drug Testing This chapter delves into the design of microfluidic platforms for drug testing, specifically focusing on their application in studying angiogenesis. Angiogenesis refers to the formation of new blood vessels, which is a critical process in many biological contexts including cancer progression. The chapter emphasizes understanding angiogenesis to explore different therapeutic combinations aimed at inhibiting this process. Microfluidic chips are highlighted as essential tools for examining the properties and mechanisms of angiogenesis, offering insights into effective therapeutic strategies.
• 25:30 - 33:00: Flexible MEMS Sensor for Tissue Property Measurement The chapter discusses the nutrition and energy requirements of cancer cells, highlighting their notorious nature in comparison to normal body cells. It suggests that cancer cells, like notorious elements within our body, require more energy compared to less active cells. Therefore, if the supply of energy is halted to these notorious cells, they would not survive and die.
• 33:00 - 41:00: Immunotherapy and Microfluidic Chips The chapter delves into the role of immunotherapy in cancer treatment, highlighting how notorious cancer cells can be. It emphasizes carbohydrates as the best source of energy for the body, mentioning common sources like wheat and rice. Additionally, the chapter touches on dietary components such as sugar and their relation to energy and possibly cancer treatment.
• 41:00 - 48:00: Designing Patient-Centric Platforms The chapter focuses on designing platforms that prioritize patient needs and engagement, particularly in managing health conditions such as cancer. An example is discussed where the source of carbohydrates, a significant energy source for cancer cells, is restricted to halt their growth. Alternatives to carbohydrates as energy sources are considered, highlighting the need for innovative solutions in patient care platforms.
• 48:00 - 54:30: Dynamic vs Static Platforms in Drug Testing This chapter discusses the differences between dynamic and static platforms in drug testing. It uses the analogy of dietary choices, such as consuming vegetables and fruits, to explain how altering energy sources can impact cells. By reducing carbohydrate intake, the body is forced to consume fat cells for energy, demonstrating a dynamic adaptation. This concept parallels how dynamic platforms might adapt compared to static ones in drug testing methodologies.
• 54:30 - 61:30: Introduction to Electronic Nose Technology The introduction discusses how cells, including cancer cells, require energy and blood flow to function. It explains the necessity of blood vessels, which enable nutrients to diffuse to cells. This sets the stage for understanding how technologies like the electronic nose could play a role in detecting cancer by understanding its metabolic requirements.
• 61:30 - 63:00: Conclusion and Next Steps The chapter focuses on how cancerous tissues develop by forming new blood vessels, a process known as angiogenesis. It includes a description of how cancer tissue appears and the role of the extracellular matrix in vessel formation.

noc19 ee41 lec05 Transcription

• 00:00 - 00:30 [Music] hi welcome to this module so this is a
• 00:30 - 01:00 continuation of our previous few modules on sensors right so we have seen several type of sensors still now including our heater and then you have inter digitated towards on the heater then you have seen that how the sensor can be used to measure the impedance change of these cells right all of the tissues then you are seen how we can measure the change in the mechanical properties the elasticity of a material with the help
• 01:00 - 01:30 of a physicist to micro cantilever right and then we also looked at how we can design a drug screening tool to identify a drug for particular patients or in other way a patient-centric platform we have also seen the other sensors can be used to understand the antibiotic susceptibility testing which antibiotics
• 01:30 - 02:00 will be effective to that particular bacteria now let us see microfluidic chip that can be used to understand NGO Genesis and entire Genesis properties so now what exactly NGO Genesis means and what are the different combination of therapies that one can use to understand that how we can stop the NGO Genesis okay so angiogenesis is a growing of blood vessels and in a way that when
• 02:00 - 02:30 there is a cancer right then the nutrition since cancer is what it's a similar cell of our body just notorious one know so if you if you know if you are more notorious you require more energy if you're less moodily has come sitting on the same place you require less energy so no tertius cells requires more energy if we stop energy to the note of yourselves what will happen cells will die right
• 02:30 - 03:00 so cancer are notorious cells and the best source of energy for our body is carbohydrates carbohydrates where does carburetor come from wheat rise right all the kind of burgers it's a right put it oh then sugar after
• 03:00 - 03:30 carbohydrates sugar right carburetors also comes from milk right so if I cut the source of carbohydrates then the source of the energy that the cancer cells or the cells require has been stopped so what can be the other sources how about I use all the
• 03:30 - 04:00 vegetables instead all right all the fruits instead of course this vegetables has some amount of carbs fruits s amount of carbs but a lot of fibers right so cutting the carburetor is a source of energy can be one way of not providing enough energy to the cells right then the cells start consuming their fat cells so fat cells would be dissolved and that's a way if you understand
• 04:00 - 04:30 ketosis how it works but coming to cancer if I so the point is it requires energy like any other cell right so along with energy what else it requires it requires blood flow and energy to the cell will come from the blood right so the blood blood should flow and the nutrients will diffuse to the blood to that cell isn't it so for flowing the blood there will be there should be a creation of vessels
• 04:30 - 05:00 towards the cancerous tissue this creation of vessels is called angiogenesis right now let me show you on the screen how the cancer tissue looks like and how they discovered with the extracellular matrix and how the vessels form all right if you see the slide so assume that this is
• 05:00 - 05:30 a cell this is a tissue okay tissue is composition of lot of cells this tissue is covered with lot of what I call is called with extracellular matrix this is a cancer tissue all right now what will happen is to provide the energy to the tissue there is formation of vessels formation of vessels right we
• 05:30 - 06:00 won we took through which the nutrition will flow and then these vessels will be further divided into capillaries like that right so through which the nutrition will flow say I just remove the excess of the matrix so so not to confuse you with the other things okay all right just let me let me quickly draw it again these are cell and then
• 06:00 - 06:30 formation of vessels right and then from vessel there are a lot of capillaries right same thing happens on whether the vessel to and then vessel 3 and so on this vessels will carry the blood right this vessels is carrying the blood
• 06:30 - 07:00 through this this will diffuse in the capillaries and it will reach to the each cell within the cancerous tissue itself within the cancerous tissue the nutrition's through this vessels will reach to the cell in the cancerous tissue and thus helping the cells to grow further developing the tissues to go to grow further all right what we
• 07:00 - 07:30 want to know is can we use a drug or a combination of two drugs to stop formation of this vessels if I stop the formation of this vessel what will happen if I stop the formation of this vessel what will happen that the nutrition reaching to the tumor will reduce isn't it how can I design a microfluidic platform Micro fluidic to
• 07:30 - 08:00 study such an effect hmm so for that if you see this particular schematic you can see that this is a representative of a vessel the red one this is cancer this ECM matrix all right now what will happen that the blood will flow through
• 08:00 - 08:30 this and it will diffuse into the tumor right that's what we have discussed so how this microphone ik platform will help us to understand which drug is called NT angiogenesis drug which anti-angiogenesis drugs our combination of it will stop the formation of vessels right to study that we will be using a
• 08:30 - 09:00 microphone a platform such that it has two channels here a channel one here there is channel 2 channel 1 channel - in between there is a material there is a material you see here also this is channel 1 this is channel 2 and in between this region there is a material
• 09:00 - 09:30 ok so now what what will happen that in channel 1 will load cancer cells in channel 2 will load endothelial cells endothelial cells what our endothelial cells endothelial cells are the cells which helps the form the vessels - from the vessels that will carry the blood this this cells alright
• 09:30 - 10:00 so now I will and then I will flow thee I will flow the media on these endothelial cells and I will just lower the cancer cells with media I'll not flow it right because the flow of the blood occurs in the vessels not the there is excess air matrix we provides the nutrition this media will provide the nutrition but it is in a stable condition we are not flowing it it's stagnant
• 10:00 - 10:30 alright so what I said is that in the channel one there will be media there will be media but not flowing media but not flowing channel two there is a flow of media media is a solution to keep the cells alive media is solution which are
• 10:30 - 11:00 not the nutritions to keep the cells intact okay in between what is there is material is that now I will see how there is a formation of channels because the release of cytokines there is a formation of blood vessels from channel to towards channel one like this when I flow it for 48 hours that I will see that there is a channel formation from
• 11:00 - 11:30 channel 2 towards channel 1 okay I want to stop the formation of this vessels I want to stop the formation of this vessels for that what can I do I will treat my cancer cells in channel 1 with drug one and again see how each this vessels are forming from channel 2 to
• 11:30 - 12:00 channel 1 then I will treat the cells in the channel in the cancer cells which with drug 2 again I study the formation of the channels then I treat the cancer cell with one plus drug two and I will again check the formation of Chen and channels from Chen and from channel number two to number one formation of vessels from channel number two the channel number one what I will find is then a drug
• 12:00 - 12:30 which is effective combination of the drug which is effective with star formation of channels or the phenols would be broken like this you know channels are broken or channels are not forming then the nutrition from the blood cannot reach to the cancer because there is no channel carrying the nutrients got it so the idea is how to design this microphone X system and this
• 12:30 - 13:00 microphone system would be a platform to understand combination of different drugs all right so we will study how to fabricate this in the class I'll go to the next platform now this is a flexible MEMS sensor and this is to understand the electrical and mechanical electrical
• 13:00 - 13:30 and mechanical properties of tissue all right how you see what is that here if I see there's this ohm shape sensors are there eight one two three four five six seven
• 13:30 - 14:00 and eight eight sensors are there right and if i zoom one of that it looks like oh but in other way it also looks like a resistor it looks like a resistor right so what is it it is a strain gauge it's a strain gauge that means if I apply a pressure on this particular platform then there will be change in the strain and it's a pathologist to strain gauge
• 14:00 - 14:30 so there will be change in the resistance in the strain gauge resistance of the strain gauge food chain so if I apply if I put a tissue in the centre of this particular chip and if I apply of force then there will be change in the resistance of the strain gauges right depending on the elasticity of the tissue okay
• 14:30 - 15:00 second thing on this strain gauge on the area of this two engages we have an insulating material over which there are gold pads these are the gold pads one two three four five six seven eight and I assume one gold pad what do I find I find that the gold pen looks like why because vino gold pad there is an insulating material what is that
• 15:00 - 15:30 insulating what they are insulating whatever it is my silicon dioxide right so silicon dioxide is used as an insulating material and we have a strain gauge on the bottom so it's like stresses to engage insulating material on that you have the gold pads this guy all right now on this gold pad I will fabricate it some pillars like this pillars okay
• 15:30 - 16:00 and I will perform a process called liftoff liftoff technique to coat these pillars with a metal now when I place a tissue on the spinners what will happen there d if I place a tissue on these pillars right like this and if I apply a
• 16:00 - 16:30 force so let's say I have equipped I have a tool which looks like this and it has the gold pad gold head right this one is a gold pad and there is some
• 16:30 - 17:00 connection to this gold bed all right so this is a connecting wire connecting wire this is the indenter alright what will happen if I apply a force with this indenter onto the tissue the tissue that amount of force that I am applying here
• 17:00 - 17:30 right the amount of force as a sensor will experience is based on the elasticity of the tissue or stiffness of the dish right if I apply a force through this indenter right this one to apply force to this indenter onto the tissue then the amount of force the sensor will experience will be based on the stiffness of the tissue second point
• 17:30 - 18:00 is if I apply a voltage you see there is a gold pad right apply a voltage let's say v2 this is what voltage between v1 and v2 are paired 1 and pair 2 then depending on the resistance of this tissue depending on the resistance of this tissue I will see different change in current you got it if I apply a voltage between the top pair and the bottom pad that the top one
• 18:00 - 18:30 is on the indenter the bottom one is on the chip right in a fire for a voltage between two pads I would be able to see the change in the distance of the tissue thus you can measure the electrical property which is the resistance and mechanical property which is the stiffness of the tissue with the help of this particular chip so there is a mechanical sensor and then there is an electrical sensor both are integrated on a single chip and this chip can be used
• 18:30 - 19:00 to measure the change in this electro mechanical properties air from onset to the disease progression synth is made up of flexible material that's why we can bend it and then I'll show it to you after you fabricated fabricate this sensor how to use it for your experiments okay let me move to the next part of the sensor and this is on the
• 19:00 - 19:30 immunotherapy a microfluidic microfluidic chip sorry microfluidic chip for understanding understanding the efficacy of my node therapy drugs microphonic
• 19:30 - 20:00 chip for understanding the efficacy of the immuno therapy and drugs alright so the idea here is that if there are three drugs eye-to-eye 81 82 and 83 this Illumina therapy drug one immunotherapy doctor immunotherapy drug three for a given there are patient one patient -
• 20:00 - 20:30 okay there are two patients we have to give which drug out of three two patient one and two patient - how we will design how we will know that patient one out of three which duck would be more effective which dog has more efficacy right same thing with a patient - so you have to
• 20:30 - 21:00 design a patient centric platform that can help the doctor to identify which drug to subscribe or you each dog question one should be given which dog patient two should be given out of given or available drugs in the market we will discuss about you know therapy later on so one way of doing it is using a trance well so in the transfer I'll I will take
• 21:00 - 21:30 these cells from the patient I will take the cells from the patient and then I'll grow the spheroid so I will take the cells I will put in a you bottom plate and after a while I will see that the you bottom plate will have this clumped spheroids is called spheroids all right so this viroids
• 21:30 - 22:00 I will load here in the this is your trans well alright then I will take the T cells and extract T cells from blood of the patient that's a patient 1 and I'll load T cells here now this filters
• 22:00 - 22:30 are such that the T cells cannot go through this filter and this cancer cells or spheroids are covered with material now what we have here we have cancer steroids plus nitrogen here we have T cells right now because of the release
• 22:30 - 23:00 of cytokines there so in T cells consists of pennies are T cells T cells is a white blood cells in a way and the basic thick ossification can be T regulatory cells cd4 cells cd8 cells cd4 cells are also called helper cells cd8 cells are also called killer cells all right so when there is when do we keep the T cells or the
• 23:00 - 23:30 conserve rides which are covered with material then after 48 hours if we take out the T cells and perform flow cytometry analysis flow cytometry flow cytometry analysis what we will find is that the cd4 cd8 ratio is different cd4 cd8 ratio is different
• 23:30 - 24:00 now similarly I take three different transfers three different transfers right and there is this transfer looks like this and I lower the spheroids with
• 24:00 - 24:30 material if there are three we should keep it uniform and then there are cells here which are your T cells T cells T cells these T cells T cells are treated with immunotherapy drug one these T
• 24:30 - 25:00 cells are treated with immunotherapy drug - these T cells are treated with immunotherapy drug three okay now after 48 hours when I take out T cells from here and I measure cd4 cd8 concentration
• 25:00 - 25:30 or and then plot it in a ratio same thing I will do four here and same thing I will do it for here what will happen that the drug which is more effective there will be more number of keener sense the drug which is more effective will have more number of cd8 cells so from this platform we can select which immunotherapy drug will work for our
• 25:30 - 26:00 patient one right so this can be used as a patient's and take that form what is the difficulty and if the difficulty that you can see here is that each of this is a static platform all three of this is a static platform what we require we require dynamic platform why we require a
• 26:00 - 26:30 template form because our body is dynamic and that's why you require a microphone a chip for understanding the immunotherapy drugs efficacy of the immanent have been drugs right and in a way that we can run in the dynamic platform which is your micro fluidic chip right so we will see how you can design this macro fredrik chip as a part of the course and I'll stop here
• 26:30 - 27:00 [Music] discussion about this two different sensors because I feel that you know you you have a smaller modules it will be easier for you to understand a lot of new terms that came to you so that certainly you have learned in this particular module like angiogenesis at vessel formation endothelial cells cancer cells material extracellular
• 27:00 - 27:30 matrix like efficacy of a drug screening of the drug flow cytometry a cathodic chip so so many things that you have learned in this last few minutes so the first digest those stuff understand google it that what exactly each meaning means efficacy what does it mean right flow cytometry how does it work so a lot of things that I say you have to catch up the words and go and see in detail each experiment because I cannot cover
• 27:30 - 28:00 everything in the in this particular code because that itself is a part of a different course alright so I'll stop here and the only idea that I wanted to show is that you can design a microphone a platform to study how to use this immunotherapy drug so I'll let me just show it to you this platform and then we will stop the lecture if you can see the screen this makeup filter from that we can see over here right there are two channels channel one and to channel 1 and channel 2 we can flow
• 28:00 - 28:30 so this both the channels are merging at a point like here right both channels are merging so what we can do is we can first take the spheroids and load spheroid is in the central region all right now there are some spacers here and then we will flow the T cells and this and this and then with the help of the pair static pump we can do this flow
• 28:30 - 29:00 for 48 hours all right there is an inlet and there is a outlet so if you connect the inlet with outlet after flow it will come back and again it will flow so when you allow it for 48 hours after 48 hours you can check the cd4 cd8 concentration all right and then you treat the drug T cells with results with immunotherapy drug one and again flow it
• 29:00 - 29:30 for 48 hours understand the change in the cd4 cd8 2 again 48 hours see the change in cd4 cd8 duct 3 again 48 hours see the change in cd4 cd8 and the one with the cd8 is higher you use that drug as a patient-centric platform this is just an idea of using a microphone a chip as a dynamic system or a dynamic platform compared to the existing transfer all right and then we will talk about what is PD 1 what is PDL
• 29:30 - 30:00 1 right when we actually see how we can fabricate this particular chip in our process all right so it's a immuno checkpoints I will discuss in detail what is PD one PDL one how the cancer cell looks like that's a part of our study but since we are understanding the immunotherapy drug and the test immunotherapy drug we need to understand how the what are different terminologies that are used in this particular
• 30:00 - 30:30 research area alright so here I will stop my class in the next class we will see a very interesting problem called electronic are not actually a problem a technology that people are working which is an electronic nose to identify a very important problem which is a non-invasive way of detecting a disease can weed is the new design a system that can help us to identify the disease just from understanding the breath signature
• 30:30 - 31:00 whatever I am exhaling from that my Excel breath can I identify particular disease right we will see how the sensors for that particular application can be fabricated we will see in this class but how what why it is important to do that analysis we will see in the next module all right till then you take care any questions free to ask in a in the forum and I'll
• 31:00 - 31:30 see you in the next module that you take care bye