virusSCOPE - Educational game about COVID-19 Diagnostics

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We at SCOPES Education care about public education on Coronavirus related issues. We wanted to help explain how the diagnosis process is being done in a simple way. The result is an analog game called virusSCOPE that uses 3D printed parts to explain the binding affinity of antibodies in ELISA diagnostics. Testing for viral infections requires precise methods to detect whether the virus is currently in the patient, or was once present in the patient. This can be done using two common techniques in the lab called reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Both methods are currently being used to diagnose patients with COVID-19. This activity is an educational game that can be used to teach kids the basic principles of how these methods work. This game can be played in two ways. The “analog” version demonstrates the principles of an ELISA based diagnostic test, while the “digital” version demonstrates the principles of RT-PCR based diagnostics. Note: The QR-codes are for the digital, boxSCOPE portion of this activity. Bugs are still being ironed out of the RT-PCR boxSCOPE programming and will follow shortly in an update. 3D Printed COVID-19 ELISA Diagnostic Activity 1. For this activity you will need to print the following: a. Antibodies (8 puzzle pieces - Blue and red in the photos). b. Viruses (16 possible viruses - Purple in the photos). c. Patient samples (Currently 9 samples - Green in the photos). d. COVID-19 Laboratory Report to record which antibodies detect which virus (provided in this pdf). 2. Oh no! It appears we lost the antibody lab book! Therefore, the first step is to figure out which antibody Fab fragments bind to which viruses. Luckily we still have samples for a collection of viruses that infect humans. In this step, pick out a virus. Next, find the two Fab fragment arms of the antibody that bind specifically to this virus. Using the same colors as shown in the images is not necessary, but if you are then please combine one red (heavy chain) and one blue (light chain) to make a complete antibody binding domain. 3. Before we can diagnose our patients, it is important to keep careful documentation of which antibody combinations can detect each virus. Therefore, we must keep careful records in our <a href="http://scopeseducation.org/wp-content/uploads/VirusSCOPE - Lab Report and paper pieces.pdf" target="_blank">COVID-19 Laboratory Report</a>. Record the antibody combination for each virus. 4. Now that you know which antibodies bind to each virus, it is time to screen your patients! Time to perform a Sandwich ELISA. In this experiment, the antibody is bound to the test tube and a patient sample is added. Record what virus each patient has in your lab report. a. If the virus is present, this patient sample will stick to the antibody and the patient will test positive for that virus. b. If the patient sample does not bind to the antibody, then they do not have that virus. Make sure to continue testing different combinations until you find out which virus they have. Try printing two copies of this and race a friend to diagnose all 9 patients first! Every second counts and the quicker you diagnose your patients, the faster you can help them. Paper version of this activity along with the COVID-19 Laboratory Report, can be found <a href="http://scopeseducation.org/wp-content/uploads/VirusSCOPE - Lab Report and paper pieces.pdf" target="_blank">here.</a> ELISA diagnostics There are two different versions of ELISA experiments currently being used to diagnose COVID-19. The first is a modified version of a Direct ELISA and the second is a Sandwich ELISA. The direct ELISA can detect if antibodies for COVID-19 are present in the patient. The Sandwich ELISA can detect if there are proteins from COVID-19 present in the patient. ELISA tests can be either qualitative or quantitative. A qualitative test provides a simple “present” or “not present” readout. In a quantitative readout, the optical density of the sample can be compared to a sample curve and determine the relative concentration of the protein or antibody in the sample. What are antibodies and how do they bind? An antibody (also known as an immunoglobulin) is a special Y-shaped protein produced by your immune system. They recognize unique parts of a pathogen or virus called an antigen. They can bind to antigens using the tip of the Y-shaped protein called the fragment antigen-binding (Fab) variable region. You can think of this similar to a lock and key, where the antibody and antigen can bind each other with precision. Using this binding mechanism, an antibody can tell other parts of the immune system to remove the foreign microbe or virus. They are composed of two chains, a light and a heavy chain. In this ELISA game, the Light chain is represented by the blue pieces and the Heavy chain is represented by the red pieces. Direct ELISA In otherwise healthy patients, when you become infected with a virus, your body will undergo an immune response. This means your body will produce antibodies which are specific for the foreign virus. These can bind proteins to the surface of the virus and signal to other immune cells that they should remove these viruses. Long after the viral infection is over, your body will still produce some of these antibodies, protecting you from being reinfected with the same virus. Using a direct ELISA test, these antibodies can then be detected to determine if you had been infected with the virus in the past. The basic principle of a direct ELISA test for COVID-19: 1. The patient sample is added to a test tube that is coated with anti-human IgM specific antibody. This will bind any antibodies that the patient might have produced against COVID-19. 2. A small amount of COVID-19 protein (not infectious) is added to the same test tube and incubated with the bound patients’ antibodies. 3. All unbound COVID-19 protein is then washed away, leaving only the proteins that were bound by the patients’ antibodies in the test tube. 4. A second antibody that recognizes COVID-19 protein is added to the test tube. It has a special substrate bound to it. 5. An enzyme is then added that reacts with the substrate, resulting in a detectable signal. 6. If there is no COVID-19 protein in the patient, this new antibody will not bind anything. If there is COVID-19 protein in the patient, it will bind and be detectable by reading the absorbance in a microplate reader. Sandwich ELISA for testing of COVID-19 Alternatively, some ELISAs can detect the presence of proteins from the virus. The basic principle of a sandwich ELISA test for COVID-19: 1. The wells of a test tube are coated with antibodies that can bind COVID-19 proteins. 2. A sample from the patient is added to the same test tube. If they are currently infected with COVID-19, some of the proteins will bind to the antibodies in the test tube. 3. A second antibody that recognizes COVID-19 protein is added to the test tube. It has a special substrate bound to it. 4. An enzyme is then added that reacts with the substrate, resulting in a detectable signal. 5. If there is no COVID-19 protein in the patient, this new antibody will not bind anything. If there is COVID-19 protein in the patient, it will bind and be detectable by reading the absorbance in a microplate reader. What is SCOPES? SCOPES (Sparking Curiosity through Open-source Platforms in Education and Science) is an open-source STEM didactic tool that is self-contained, independent of local resources and cost-effective. SCOPES can be adapted to communicate complex subjects from genetics to neurobiology, perform real-world biological experiments and explore digitized scientific samples. Our design philosophy: We have developed SCOPES as a cost-effective platform to bring life science labs to the classroom. SCOPES is designed to be a modular platform that can be easily adapted for the specific needs of the educator, even without any computer or programming skills. During the design of SCOPES, we considered resource limitations that some classrooms might face. While dedicated computer classrooms in schools are becoming standard in developed countries, buying new hardware is both time consuming and expensive. Sometimes a stable source of electricity might also not be available in some areas. Therefore, we chose the Raspberry Pi Zero W (Pi for short) which is a tiny, power-efficient computer, to be the brains of our project. The Pi is powered via a 5V USB port that is commonly used for charging smartphones and tablets and can be run remotely from a battery or small solar panel. We also do not want you to have to run out and buy a new screen or adapter. Therefore, we chose to make use of your mobile devices to display the visual output of SCOPES. The Pi acts as a wireless access point that mobile devices can connect to and display information provided by the Pi. Several devices can connect to SCOPES in parallel, allowing for multiple young scientists to interact with an individual SCOPES. Thus, SCOPES is self-contained and can be operated in the complete absence of any infrastructure with just a mobile device and a battery. SCOPES 3.0 The <a href="https://www.prusaprinters.org/prints/27938-boxscope-run-your-own-biological-experiments" target="_blank">boxSCOPE case</a> is the latest revision of our original SCOPEScase. The original version can be made from laser-cut plywood, and if you are interested in learning more about this, we recommend visiting our website to find all the files (http://scopeseducation.org). We have also made a 3D printed version that uses a 2 L pop bottle instead of a box. For more information and all the files, please see this <a href="https://www.prusaprinters.org/prints/27346-popscope-pop-bottle-digital-microscope-to-run-your" target="_blank">post</a> on Prusa Printers. Thank you for checking out virusSCOPE! If you like this project please leave a comment or review, and share with your friends. For more information about how you can use <a href="https://www.prusaprinters.org/prints/27938-boxscope-run-your-own-biological-experiments" target="_blank">boxSCOPE</a> to do a number of other exciting STEM education activities, please visit my other prints. More information about SCOPES Education: https://scopeseducation.org/

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virusSCOPE - Educational game about COVID-19 Diagnostics

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