Modelling Journal

Week 1: May 5th - May 9th

Modelling team formed. The big idea discussed during the week was to digitalize the diagnostic test using Arduino microcontroller or Raspberry pi. The idea was based on glucose meters with the potential for disposable strips with the device to reduce cost per test. We looked into the advantages and disadvantages of Arduino vs raspberry pi and how they operate. At this point of time, arduino seems to be a more suitable choice for our purposes. We looked into how to program Arduino and started writing simple programs to familiarize ourselves with microcontroller. As part of the digital reporter system, we are looking into using a sensor to detect a change from the biological reaction. As part of the research we did this week, we found that there are arduino sensors that for light, current, methane, ethanol, CO2, propane, butane, and H2. We also researched the basics of microfluidics and the potential application this could have with our designs for the project. Additionally, everyone on the team participated in workshops on DNA and cell biology, PCR (Polymerase Chain Reaction) and PCR optimization, DNA extraction, cloning and transformation, bioinformatics, theory of proteins, protein purification, and protein optimization to get everyone familiar with basic lab techniques and biology theory that we potentially require during the project.

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Week 3: May 19th -May 23rd

This week we started looking into what kind of software we can use for modelling purposes. We decided to use Autodesk Maya to visually model the processes that are occurring within the device. We have access to Autodesk software and connections with knowledgeable advisors who would be able to help us we have any issues that arise. There are also plugins for Maya that can be used for modelling biological parts such as proteins or enzymes. This week we also continued exploring and researching arduino’s functions as well as continuing to look into different designs of a device and what we would use to produce a low cost but effective device. Potential ideas have been to have a device that uses disposable strips for individual tests to reduce costs, while other models suggest effective technology such as microfluidics. In coming weeks we plan to continue research and talking to professors about the benefits and drawbacks of these potential prototypes. Using quantitative modelling in the future we will be able to effectively design such a device so that it operates at its greatest potential.

Week 4: May 26th - May 30th

This week was primarily focussing on the use of Autodesk Maya and learning the functions of the program. Initially Maya 2015 was downloaded, however due to compatibility issues 2013 might be downloaded in the coming weeks to work effectively with the various plugins. Tutorials were performed to learn the basic functions of modelling and animation of the program. Using this knowledge we would be able to eventually use this programming to model the proteins of the project. Additionally we continued to look into potential sensors that could be compatible with the arduino boards and what other designs could be used for a device. After all team members are familiar with using Maya for modelling, we are planning on using the animation features to visually illustrate the biological processes that are occurring within the device when in use. This will help to better explain the project through visual aspects and can cause a greater curiosity and interest in the device. Learning all of the skills of Maya will be an ongoing process throughout the summer, however a focus was placed on developing basic skills this week.

Week 5: June 2nd - June 6th

This week we continued using Maya for modelling and animation purposes. We also began to explore and refresh our memories using Autodesk AutoCad and Inventor for design purposes, as well as downloading matlab for quantitative modelling purposes. Although we currently don’t have all of the necessary data for some of the proposed models, we are currently examining the software to see how we would create these models when the data becomes available. We are continuing to gain more knowledge of Maya, Autocad and Matlab we will be prepared to create quantitative and visual models when the data becomes available. This week we also started looking into mathematical modelling for biological systems and gaining background knowledge in the field through literature. In particular, we looking into basic definitions, process of modelling, relation between state variables and description methods, time constants for cellular processes, fundamental of enzyme kinetics, cell division and growth. By studying and learning proper methods of quantitative analysis we will be able to directly perform this aspect of modelling as soon as data becomes available. We began brainstorming what important aspects of the project we can quantitatively model and what would be useful to help us in the initial design phase. As of next week, a proposed sensor will be chosen and then we will resume our process with the Arduino microcontroller and writing programs to control the device. Additionally we seeked resources regarding the potential of using a voltage or current sensor with the device and are continuing our research for this option. Literature References: A. Kremling, Systems biology : mathematical modeling and model analysis, CRC Press, 2014

Week 6: June 9th - June 13th

This week we contacted two microfluidics experts to get insight on microfluidics and to answer some of the questions we have. Dr. Karan Kaler replied to us saying that he is away at the moment, but will be back in July and will be willing to meet up with our team to assist with the project. He said that their research lab is currently utilizing droplet based microfluidics for the detection of human pathogens using chip based real time qPCR technology developed in their laboratory. He thinks it may be relevant to us and suitable for us to explore. This week we also continued working with Maya and Matlab software. Dave submitted a request so we can get SimBiology toolbox for Matlab that will be very useful for quantitative modelling. We also got the 2013 version of Maya instead of 2015 so that we can get ePMV plug-in that can be used for modelling and animation purposes. After installing the software, we watched tutorials to get familiar with how the plug in works. Unfortunately, so far the tutorials we found were not very useful, so we might have to look for more resources. Also, we reviewed the process of transformation and watched existing animations so we can create our own transformation animation in the near future for practicing purposes. We also found an online book-tutorial by Autodesk for Maya which is so far the best teaching resource for Maya. It explores the functions through examples. It also includes the tutorial on Dynamics and a variety of plug-ins such as nParticle which might be relevant for our project. It is a relatively long book so it would take at least a week to go through it, but it is extremely useful for getting advanced with Maya functions. This week we also arranged regular meeting with Dr. Nygren which will take place every Thursday morning so we can discuss the progress of the engineering/modelling team. We also signed up for Matlab workshops which will take place on Wednesday, June 18th. Next week we are also planning on contacting Cesar from Autodesk to further discuss Maya applications and software, and potential skype meetings in the future.

Week 7: June 16th - June 20th

This week consisted of further looking into Matlab applications and data analysis as well as looking further into what materials we will need to purchase to begin modelling with the arduino board. On the 18th we attended a matlab workshop and information session that was focused on proper data analysis and representation. Additionally we have begun weekly engineering meetings focussed on quantitative modelling and the state of our prototyping. We have begun to look into how we can use quantitative analysis for modelling purposes, in particular, to idealize the device, optimize its materials, dimensions and components as well as use this data and analysis to reevaluate and make changes to our prototype device. At our meeting with Dr. Nygren we further discussed the potential add on to the device in which the results could be easily read or documented on a smartphone or computer. Although this aspect of the design would not be designed for rural areas in the developing world, there is potential of the modular device to have a worldwide impact in not only hospitals in the developing world with more resources, but the developed world as well. The proposed chosen reporter is a fluorescent protein such as Red Fluorescent Protein (RFP) or Green Fluorescent Protein (GFP). Another option for the reporter is LacZ. Using a light sensor, and potentially a filter to ensure we are not detecting ambient light we will detect the presence of light and convert it to a voltage that the arduino can detect and display a result. This will most likely be designed as a closed environment in order to eliminate other sources of light that could potentially trigger the sensor. The concept of light dependent resistors was also discussed, however after further research it was discovered that the level of sensitivity of these components may not be at the level necessary for the device. Although we do not yet have specific numbers on how luminescence the reporter is, we are not currently pursuing this proposed option. We are planning on purchasing an arduino and several light sensors to begin testing and quantifying the effectiveness of the different components. In the next week we are hoping that the proposed reporter will be able to test that part of the system and determine which sensor and process will be the most effective to determine if the signal is present. Additionally the modelling team prepared a presentation on light emission and potential it has in our project and how we are planning on designing the higher level device with a light sensor and a digitized device. In parallel to the research regarding the reporters and the light sensors we have been continuing to explore Maya and Matlab ensuring our skills will be ready in time for application of lab data.