Lecture 47 : Metabolic Heat Conformation

Welcome back to this class. So, we concluded the last class with thermal emission spectroscopy, and I told you that how the field of biosensors especially is going to shape up, and we are talking about integrated suits which will have all these different kind of tons of sensors which will be embedded in the body. Especially, this is the future of warfare, best design, the people in army, navy and air force, the kind of dresses they are making which falls under technical textile, where there will be lot of integration of the sensors in the textile which the soldiers will be putting on. So, that in the real time they are monitoring of individual soldiers while they are taking part in any kind of warfare like situation or any crisis situation. So, today in the same line we will talk about metabolic heat conformation MHC for glucose sensor. So, as the word indicates metabolic heat conformation during any form of metabolic events, when we talk about metabolism it consists of two words, anabolism and catabolism. Catabolism is a process of breaking down bigger molecules and using them for generation of energy or by breaking down the liberate energy which is used by the body. Anabolism is the process where smaller molecules join together to form bigger molecule for storage simple. Now, during the breakdown of these molecules to generate energy, there is a increase in body temperature because body is metabolized. There is a catabolic process which is happening and this catabolic process takes place inside the cell in a small organelle called mitochondria. Mitochondria is called the power house of the cell and in a integrated term one can call mitochondria the power house of the body. There are trillions of mitochondria present in individual cells add together and they are the ones who dictate the energy dynamics of our body. Now, when mitochondria is functioning it utilizes oxygen. So, there is a direct correlation when you are burning the fuel there will be a presence of oxygen. So, the process of metabolism and oxygen level at a particular site would be a direct indicator of the metabolic heat generation or conformation. That is what exactly MHC technology utilizes. So, for example, here is a cell, the nucleus, here you have the mitochondria. So, within the mitochondria you have metabolic activity in the presence of oxygen and these generate enough amount of heat energy. So, MHC technology consists of measuring the glucose concentration level by measuring physiological parameter associated with the generation of metabolic heat and local oxygen supply. Local oxygen supply and the metabolic heat the technique relies on the fact that metabolic oxidation of glucose. That is what I was trying to tell you metabolic oxidation of glucose not only produces most of the necessary energy for all cellular activities, but also generates a certain amount of heat as a byproduct that correlates with the amount of glucose and oxygen level in the body. So, this metabolism of glucose in the presence of oxygen using Krebs cycle generates significant amount of heat when you add together. Now, the amount of heat could be directly correlated with the amount of raw material which is glucose. So, the simplest reaction what they are talking about is glucose plus oxygen in mitochondria is generating heat plus energy. Now, these are the product and these are the reactant. So, the amount of reactant is directly proportional to the heat and the energy which is generated same with the oxygen. So, everything is directly proportional here. So, based on the heat one can back calculate theoretically speaking the amount of glucose which is being consumed in the process. So, that is what it says this technique relies on the fact that metabolic oxidation of glucose not only produces most of the necessary energy for all cellular activities, but also generates certain amount of heat as a byproduct that correlates with the amount of glucose and oxygen level in the body. The heat emitted in the environment can be in the form of radiation, convection and evaporation. The heat emitted as radiation and convection is linked to skin and ambient temperature whereas, the heat dissipated by evaporation represent amount of evaporation from the skin. So, these are the metabolic heat conformation which are happening. The parameters recorded by the sensors include thermal generation, hemoglobin concentration, oxyhemoglobin concentration and blood flow rate. They are all measured in the finger tip by multi wavelength spectroscopy method along with the temperature in the finger tip ambient and background radiation. The data is then analyzed with different statistical tool including regression, multivariate analysis, discriminant analysis. However, this technique is also sensitive to interference from temperature variation and sweat. Now, I will show you the figure before I get to the figure. So, there is one more parameter which got added must have realized. So, I told you that glucose plus oxygen. So, when you talk about oxygen, oxygen carrier is hemoglobin. So, what they are measuring is that hemoglobin and oxyhemoglobin. That means hemoglobin stand alone and the hemoglobin saturated with oxygen. Hemoglobin has multiple sites where the oxygen bites. There are four different sites where oxygen bites. So, fully saturated, partially saturated and so forth and the blood flow rate. Why blood flow rate? Say for example, metabolism is happening. You have taken food. So, automatically there will be faster metabolism. So, the blood flow rate will increase. So, depending on the blood flow rate, you will have an idea how much oxygen is being transported at the site and what rate. What is the rate of transfer of oxygen by the hemoglobin molecule? That means you need to first of all know the baseline of the person who has hemoglobin. Say for example, somebody has 16, somebody has 13, somebody has 9. They all will have a different oxygen carrying capacity. If you know the rate of blood flow, then you can back calculate and see how much hemoglobin is reaching and how much hemoglobin is saturated with oxygen and how much hemoglobin is non-saturated with oxygen. So, depending on that, you know how much oxygen is reaching at the site and oxygen is reacting with glucose. That is generating your energy plus as in the last slide I showed, lost it, plus energy. All these are being done. They are all measured in the finger tips by multi wavelength spectroscopy method along with temperature in the finger tips. Temperature is important because that will tell you the generation, how much temperature is rising, ambient and the background radiation. Data is then analyzed with different statistical tool including regression, multivariate analysis, discriminant analysis. Now, if you look at the figure, so this is what it is. So, here you have the sensor and we talk about this sensor is multi wavelength spectroscopic sensor. Now, you are recording the ambient humidity, skin humidity. So, this is the surrounding humidity and the skin humidity. So, it means how much water is present on your fingernail because there are people who generate more sweat versus others. So, you have to understand what is the amount of sweat which is being generated by the individual from whom you are collecting the data. That is the skin humidity. Then comes the ambient temperature that means the surrounding. So, I am standing in this room. It has a temperature probably of 24 degree centigrade versus am I sitting at 42 degree centigrade. So, the ambient temperature skin surface temperature means you have to have a thermometer telling you what is the temperature of your body with respect to the surrounding because that will also determine how much metabolism the body has to do to maintain its homeostasis means the balance of all the parameters. Then the temperature near end metabolic conductor and temperature far end of the metabolic conductor and optical sensor. These are the parameters which has to be figured out. Now, this will help you to calculate the heat dissipated by evaporation. These two parameters will help you to see the heat dissipated by convection and the heat dissipated by radiation. I am telling you this. Now, you go back and check this part. When we talked about the heat emitted as radiation convection and link to the skin and ambient temperature whereas, the heat dissipated by evaporation represent amount of evaporation from the skin. So, you have to know all these three different kind of heat which are being generated by your body. This is what exactly you are doing here heat dissipated by evaporation, heat dissipated by convection, heat dissipated by radiation. Next comes the blood flow rate and then the blood oxygen saturation that is essentially how many molecules hemoglobin is carrying. With this you have to use series of mathematical tools. Now, comes the role of mathematics into the modern day sensing where you have to use what we are mentioning about regression analysis, multivariate analysis and discriminant analysis. These three tools primarily, but there are many other tools regression multivariate and discriminant analysis. These are those three tools multivariate regression and discriminant analysis. Based on that you get the glucose and this technology is one of the big future where people are integrating these kind of technologies with lot of devices which are using MRI. Mostly, they are using them, they are integrating it with MRI devices, they are integrating them with tomography devices. They are using them for all the different kind of diagnostic tools which are used in biomedical world in the strategic applications. This is another technology and not only that in order to increase the sensitivity, we will talk little bit more. There are gels which are being used on the skin surface in order to get a better recording from the body itself. Earlier, in the last class I told you there are lot of development happening in technical textile to develop vest embedded with sensors. Lot of vest which are embedded with sensors are being currently being designed specifically for all the strategic applications. Not only that, in the area of sports they are using further for those workers who have to work in contagious environment or during epidemic where they have to work in a very tricky or extremely susceptible environment. These things are fairly common. Now, that brings us to our next technology which is photo acoustics spectroscopy. Whenever we talk about acoustics, we talk about something to do with sound acoustics, photo acoustics. When we talk about the photo, we are talking about something to do with light and acoustics we are talking about something to do with sound. Mind it, here we are talking about two different kind of radiation. We talk about light, we are talking about a different radiation, different form of wave, radioactive wave and we are talking about acoustic sound waves, we are talking about mechanical waves. So, they are very different things. The technology uses the same idea of ultrasound waves, but it employs short laser pulses with a wavelength that is absorbed by specific molecule in the fluid to produce microscopic localized heating dependent on the specific heat capacity of the tissue under examination. Absorbed heat causes a volumetric expansion of the medium generating an ultrasound wave that can be detected by an acoustics or pressure sensor. By tracking the peak to peak variation of the detected signal, it is possible to correlate them with the variations in glucose level in the blood. So, you see this kind of interrogation uses two different kind of waves. On one hand, it uses light form of laser and it uses other form of vibration which is mechanical vibration. That is why it is called photo acoustic spectroscopy. For non-invasive detection of glucose, pulse and continuous waveform C W are the two main forms of excitation. In pulse mode, the pulses have duration in the range of nanosecond and a pulse repetition rate of few kilohertz leading to a fast and adiabatic thermal expansion of the sample and generating a wide spectrum of acoustics frequencies. Basically, what you are doing? You are giving a pulse and within the fluid, there are lot of vibrations which are being generated. These vibrations leads to a pressure wave and what you are measuring is the pressure wave. So, depending on the type of particles within that liquid, the pressure waves nature changes. So, now I am generating a wide spectrum of acoustic frequencies along with the jitter and the acoustic noises in the wide bandwidth of detector or transducers. On the other hand, when we are using continuous pulse excitation implies a modulated continuous wave generating a single acoustic frequency in the detected spectrum as well as in the higher signal to noise ratio used in a lock in detection configuration. So, these are different configurations, but what is most important for you to understand how one can integrate two different kind of waves, radiation and a mechanical wave in order to detect a molecule. So, these kind of things is pretty interesting if you look at the pulse sensing. So, here it is. So, you have the piezoelectric transducer here, you have the ultrasound waves which are being generated, here you have the laser. So, you are throwing the laser here. So, this is your photo part of this whole process and here you have the acoustic part and here you have the acoustic resonator. So, now depending on the variation, depending on the wave which is generated because of the photons which are hitting the ultrasound acoustic resonator creates a specific signal and what you are doing is measuring that acoustic signal. If you look at this figure, it shows the basic configuration of pass sensing, the light emitted by a laser impact the sample to generate a ultrasound waves by process previously discussed. We have already discussed this, the generated ultrasonic wave propagates through the acoustic resonator also known as a cell and reaches the detector. We generally consist of piezoelectric transducers such as microphones, the electrical signal at the output of the sensor is subsequently amplified, digitized and sent to the computer for analysis. This configuration however has main drawbacks of poor sensitivity and in vivo detection of glucose. So, as to suggested by Kotman et al an alternative to this method is to use two laser sources, one covering the wave length of the strong glucose absorption, other covering the regions of insensitive to glucose oxidation. So, essentially you are trying to deduct from a lesser sensitive to a greater sensitive laser in order to obtain a larger ratio between the two measurements improving the overall SNR of the system, signal to noise ratio of the system SNR is that. Currently the configuration has provided a good stability, but the sensitivity is still low although it can be improved by increasing the power of the laser. This is the overall pass based technology what we have been talking about. In addition pass can be used a wide range of wave length from ultraviolet to NIR. However, it has not been until recently that test had shown that pass can even be used for MIR bands. This development allows us to take advantage of the strong absorption characteristic of glucose molecule in the range of 800 to 1200 centimeter to the power 1. Despite its low penetration depth into the human skin which is around 8.33 to 12.5 micrometer and thanks to particular vibration mode of the stretching and bending of CHO band as a result current efforts are focusing on using QCL. We talked about the QCL laser to improve the SNR signal to noise ratio of the body in which it is feasible to reach an interstitial fluid 10 to 15 micrometer. This is in nutshell the basic of the pass and the recent development which are happening in photo acoustic spectroscopy. You realize that slowly this whole field is now at the phase of integration of multiple sensors integrating them into a textile integrating them to your body via textile. Flexible electronics, technical textile, sensor technology, algorithms, management of the data, optimization algorithms. These all are getting integrated for the next generation of integrated sensor technology. With this I will close the class. In the next class we will move on to electromagnetic sensing and that process will gradually close the glucose sensing and we will move on to the evolution of different kind of electrodes and the electrochemical sensor development. Thank you.