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                         <h1 style="text-align:center;">Attributions</h1>
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                     <h1>Human practices</h1>
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In HEKcite we create an oscillating HEK-cell, but for what purpose? Therapeutic drug monitoring is our answer. In the treatment of multiple severe diseases, a stable concentration of drugs is crucial. Steady blood levels determine therapeutic outcomes and increase survival rates. Currently, the most common therapeutic drug monitoring technique is blood sampling. For patients who need lifelong observation, the numerous hospital visits and frequent blood samplings can have a negative effect on the quality of life.
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Therefore, we develop a system that allows patients to determine the level of drugs at home. Furthermore, the ease of these measurements allows for daily or even continuous analysis.</p>
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Using this dynamic data collection instead of the static measurements performed in hospitals today, we might increase both therapeutic outcomes and quality of life of patients. In order to investigate the different views on our projects we talked to specialists in several fields where therapeutic drug monitoring is of great importance: transplantations, psychotics and epileptics. Three specialists have provided insights in how they expect our project will influence the lives of their patients and future treatments. We used this information to further shape our project.
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                                <h3>Professor Diethard Monbaliu MD, PhD</h3>
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                                <p>Professor Monbaliu is a reputable abdominal transplant surgeon, at the department of microbiology and immunology at UZ Leuven. He is also responsible for a course on topographical and radiological anatomy and supervises several thesis students.</p>
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                                <p>Professor Monbaliu confirmed our suspicion that there is a need for a more dynamic measurement. In addition, he suspects that it could lead to a better evaluation of patients’ compliance. Together, these advances could result in fewer transplant rejections. He has also brought our attention to a novel and more prevalent immunosuppressant drug, tacrolimus. Finally, he mentioned that patient variability is an issue in his field, and that our device should take this into account. Want to learn more? Press for more details.</p>
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                                Before this meeting, we were investigating the immunosuppressant cyclosporine, as we thought this compound was commonly used after transplantations in order to reduce the chance of rejection. However, professor Monbaliu clarified that this is no longer the case. Instead, he brought our attention to the compound tacrolimus, which has taken cyclosporine’s place in transplantation medicine. Both drugs have the same mode of action, but tacrolimus has a better clinical outcome and less side effects. We were interested in using this novel drug for our research, but unfortunately, the compound is too expensive for us to use. Therefore, considering our financial situation and the input of the professor, we chose to use cyclosporine in our experiments. </p>
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                                <p>Lastly, according to professor Monbaliu, a possible reduction of blood sampling could be a great advantage. However, he mentioned that every patient is different, which means that finding the optimal concentration of immunosuppressant for each patient could a challenge. As a result, our device should be calibrated individually for every patient. Together with professor Monbaliu, we suspect that the individual differences and the problems that go with them could be assessed during clinical studies. As soon as different patients and their different values can be assembled, it can lead to the procedures needed to determine the optimal drug concentration and calibrate our device.
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                                <p style="text-align:justify"><strong>HEKcite!</strong> Inspired by the human heart rhythm, we aim to create an electrophysiological oscillator from eukaryotic cells. Rhythmic contraction of heart cells is coordinated by a small group of cells located in the sinus node, which have an intrinsic frequency of de- and repolarization. This frequency of electrical oscillation is influenced by environmental parameters as well as certain molecular substrates. The oscillator that we aim to create consists of genetically modified excitable Human Embryonic Kidney (HEK) cells, altered to contain the intrinsic pacemaker ability found in sinus cells. As witnessed in heart cells, the rhythm would be dependent on substrate-activated ion channels in the membrane. As there is a great variety of ion channels available in nature, the oscillator could be modified to measure concentrations of many specific substrates. By integrating a certain ion channel into the oscillating system, specificity for a substrate can be chosen.  
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                                <h3>Professor Chris Bervoets  MD, PhD</h3>
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                                 Building an electrical oscillator from cells has several advantages. Intra- or extracellular changes that influence the conductance of ion channels in the membrane have an immediate impact on the frequency of oscillation. Once these cells are connected to each other (by for example gap-junctions), they generate an electrical signal that can easily be measured from a distance and non-invasively—similar to the way electrocardiography (ECG) and electroencephalography (EEG) measure electrical activity in the heart and brain. A multi-purpose sensor suitable for this system could be developed for medical and biotechnological applications. One such application is the measurement of drugs that interact with ion channels, such as antipsychotics, anti-epileptics or a certain class of immunosuppressants.</p>
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                                <p>Professor Chris Bervoets is a psychiatrist. He is responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the UPC (University Psychiatric Center) of KU Leuven. Additionally, he conducts research on neuromodulatory treatments for various psychiatric disorders.</p>
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                                 <p>While investigating different branches in medicine that could benefit from improved therapeutic drug monitoring, our attention was drawn to psychiatry. In this field, there are several drugs, for example lithium, that affect ion channels and could therefore be measured directly by our system. These aspects spiked our interest, and to learn more we contacted the specialist professor Chris Bervoets, who gave us some valuable insights in the difficult world of psychiatry.</p>
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                                After explaining our project, professor Bervoets shared his enthusiasm about the possible advantages of our device. He mentioned three ways in which HEKcite could further shape the field of psychiatry.  </p>
 
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                                <p>First of all, he described the current problems concerning treatments using dopamine antagonists. These dopamine antagonist are blockers of the so-called dopamine receptors, and are used for a wide range of psychologic disorders, among which are depression, psychosis, and many more. At present, researches lack detailed information about the correct dosage of these dopamine antagonists: The amount of receptors that have to be occupied to achieve a certain clinical effect is not yet known. In some cases, doctors see a more favourable clinical outcome when patients take dopamine antagonists irregularly, while for other patients, this is not the case. Therefore, a better understanding of how the correct dosage correlates with dopamine receptor occupancy could be extremely valuable.
 
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<p>Nowadays, this occupancy can only be measured using expensive PET scans. If we could find a way to insert the dopamine receptor in our HEKcite cells and genetically design a correlation of the electric rhythm and the occupancy of the receptors, it could generate valuable information concerning different drug concentrations and their corresponding receptor occupancies. Not only would this measurement be less expensive than a PET scan, it would also provide a more dynamic measurement of the receptor occupancy, which could result in additional insights in dopamine antagonist metabolism.</p>
 
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<p>Furthermore, Chris Bervoets told us about a novel way of clinical assessment, called the experience sampling method (ESM). Patients are asked to answer ten or more questions a day regarding their emotional status. The answers to these questions are then used to improve diagnosis or foresee psychotic episodes. Professor Bervoets suggests that our device could complement this method by combining the answers of the patients with the exact drug concentrations at a certain time. This could lead to a better comprehension of the connection between symptoms and drug dosage, and help further treatments. </p>
 
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<p>Finally, professor Bervoets mentioned safety monitoring, which was our original motivation to investigate the field of psychiatry. With our device, we could verify the concentration of certain drugs that only have a small therapeutic range in which they are effective. Furthermore, Professor Bervoets explained to us that lithium may cause side effects even in the right doses. As a result, many patients visit the hospital unnecessarily. Our device could prevent these avoidable hospital visits by reassuring the patient that the experienced symptoms  are due to a benign lithium intoxication. On the other hand, it could also warn the patients when their lithium concentrations are dangerously high and a hospital visit is required.</p>
 
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<p>After discussing these interesting possibilities for our project, we asked professor Bervoets if he thinks whether patients would accept to undergo the implantation of a small device. He suspects that our project would most likely only reach a select group of patients. For instance, patients who experience severe symptoms are often treated by transcranial magnetic stimulation and are used to medical interventions. This group of patients would not mind a minor subcutaneous implantation, if this would decrease their symptoms. Additionally, our device could help determine which drug is most suitable for a patient and optimise doses to reduce side effects.</p>
 
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<p>To conclude, professor Bervoets confirmed our speculations that therapeutic drug monitoring is important in psychiatry. Furthermore, he opened our eyes to other potential applications of HEKcite in this branch of medicine and research. We are very interested in investigating the correlation of ESM and drug concentrations and the possibilities of developing a system to analyse dopamine antagonists. However, due to time and resource constraints, we have to remain focussed on therapeutic drug monitoring. Thanks to professor Bervoets’ enthusiasm about the project and the possible applications, we have become even more motivated to investigate the possibilities of safety monitoring, and believe it could bring science and medicine a substantial step closer towards solving important problems in psychiatry.</p>
 
 
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                        <p style="text-align:justify">Attributions
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                                <h3>Professor Wim Van Paesschen  MD, PhD</h3>
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                            We thank all our collaborators for their help, guidance and supervision.
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                                <p>Professor Wim Van Paesschen is a neurologist specialized in epilepsy. He also is head of the epilepsy research laboratory of the UZ Leuven, and is a lecturer at the faculty of medicine.</p>
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                             Molecular lab work
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                             Professor Johan Swinnen is a professor and head of the Oncology department at KU Leuven. As our PI, he has provided us with advice, support and lab space. We would also like to thank the rest of his team, especially Frank Vanderhoydonck, for showing us around the lab and helping us with everyday tasks.
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                             Electrophysiology
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                                <p>Professor Van Paesschen confirmed that therapeutic drug monitoring is important for anti-epileptic compounds and mentioned the necessity of verifying patient compliance. He was very enthusiastic about the project, and even suggested other possible applications for the HEKcite cells.</p>
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                             Professor Thomas Voets is head of the laboratory of Ion Channel research at KU Leuven. Apart from allowing us to use his electrophysiology tools, he and his team have learned us several techniques valuable for the project, such as patch clamp and calcium imaging. Furthermore, his lab has kindly provided us with HEK cells stably infected with mHCN2 or hERG genes, and several plasmids containing ion channels, such as mHCN, hERG, and α1G. The assistant of professor Voets, Annelies Janssens, trained us to work with the patch clamp machine which is the central piece of machinery in our project. Without this machine, we couldn’t collect our data.
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                            Professor Chris Ulens is head of the laboratory of structural neurobiology, at the department of cellular and molecular medicine at KU Leuven. He has shared his knowledge of the interactions between ion channels and certain drugs.
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                            Dr Mieke Nys is part of the laboratory of structural neurobiology and has supplemented our results with extra measurements of the mHCN gene another patch clamp machine.
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                            Modelling
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                            Professor Alexander Panfilov is a part of the department of mathematical and theoretical physics at the UGent, specializes in cardiac modelling and has given us advice regarding our model. Furthermore, he has given us the contact details of others who might be able to help.
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                              As our group focuses on drug monitoring as an application, anti-epileptic drugs seemed to be interesting to research. Therefore, we set a meeting with doctor and neurologist Wim Van Paesschen, who is a specialist in epilepsy. Our goal was to discuss the importance of drug monitoring for patients being treated from epilepsy, and whether the HEKcite project could be useful in this regard.  
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                            Nina?
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                            Hardware and measurement
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                             <p>During the meeting, professor Van Paesschen showed a great deal of excitement and enthusiasm about the project, and assured us that drug monitoring of anti-epileptics is indeed necessary, especially for patients who suffer from severe forms of epilepsy. There have been various attempts to introduce therapeutic drug monitoring for epilepsy patients, but none have been successful so far.</p>
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                            Professor Jeroen Lammertyn is head of the Division of Mechatronics, Biostatistics and Sensors (MeBioS) at KU Leuven. We have discussed the possibilities for measurement and data collection from our cells.
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                            <p>Since the concept of HEKcite mainly relies on different ion channels, professor Van Paesschen advices us to focus on the anti-epileptic compounds that directly influence ion channels, even though they are not the most commonly used. Some examples are retigabine, which opens potassium channels, and ethosuximide, which influences T-type calcium channels. Additionally, he mentions that some anti-epileptics can bind to the blood protein albumin, which hinders their activity. Laboratory tests can only measure the total concentration of anti-epileptics in the blood, and are unable to detect the amount of free, active compound. Using our system, we would measure the concentration of free drugs that are able to interact with the ion channels in vivo, which would be a great advantage.</p>
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                             Dr. Frederik Ceyssens is a postdoc at MICAS, at the department of electrical engineering at KU Leuven.  We have had a very valuable discussion about the hardware necessary for the measurement of oscillating cells. He helped with the design of the sensor and everything that goes with the sensor, from batteries to the actual sensor itself.
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<p>Furthermore, we asked professor Van Paesschen whether he thinks patients would agree with an inserted monitoring device. He proceeded to say that biosensing is a very interesting and growing field, and that it would be most welcome by patients, due to its simplicity and accuracy. He also mentions that checking patients’ compliance is crucial for epilepsy treatment, and that the HEKcite project could be used to solve that problem. </p>
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                            Dr. Dries Braeken is working for imec’s life science technology group. He has experience measuring cardiomyocytes using micro-electrode arrays (MEAs), and we have discussed the possibilities of measuring our cells in a similar way. Together with his PhD student, Jordi Cools, we tried different sensors and tried to sense the electrical oscillations with the sensor.
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                             <p>Last but not least, he gave a few suggestions for other useful applications of the HEKcite project. First of all, he suggested using our system as a form of personalized medicine. By using ion channels that contain the exact mutation present in the patient, we could use our system to verify which drug is most effective for his or her exact condition. Additionally, he mentioned that epilepsy is often the result of multiple mutations in several channels. Our system could study the interactions between the different ion channels and their mutations to further improve the understanding of the mechanisms that can lead to epilepsy. </p>
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                            Professor Bernard Schneider a senior scientist in the neurodegenerative studies laboratory in the École polytechnique fédérale de Lausanne (EFPL). He has provided us with a sample of an implantable macrocapsule, and has confirmed the possibilities of integrating chips in this device.
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<p>These examples further illustrate that the project could be used for multiple applications. All in all, the meeting was extremely helpful to us, as he was able to confirm our suspicions that HEKcite could be useful for patients of epilepsy, and shed some more light on the further possibilities within this field.  
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                            Professor Adrian Ranga is specialised in tissue engineering. We discussed biomaterials and the immune implications of implantable devices.
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                            Professor Jennifer Patterson is a specialist in hydrogel structures for tissue engineering. She has given us some ideas about the possibilities of integrating a MEA in a hydrogel structure.
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                             Professor Monbaliu is a transplant surgeon at the department of microbiology and immunology at UZ Leuven. He has provided us with insights on how the project could influence the field of transplantation medicine.
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                             Transplantoux is a patient organisation for people that have undergone a transplantation. We would like to thank them for bringing us into contact with patients whose insights were extremely valuable for our project.
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                             Professor Wim Van Paesschen is a neurosurgeon and head of the epilepsy research laboratory of UZ Leuven. He has shed light on the importance of therapeutic drug monitoring in the field of epileptics.
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                            Professor Chris Bervoets is a psychiatrist responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the University Psychiatric Center of KU Leuven. He has helped us by discussing the several possibilities of our project within the field of psychiatry.
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                            Hier moet nog over die van het laatste gesprek geschreven worden.
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                            Education
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                            We would like to thank some middle schools: Sint-Romboutscollege (Mechelen), Go Shill (Mechelen) and Via Tienen (Tienen). We were able to teach amazing kids more about DNA, genetics and the basics of synthetic biology.
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                            Card and Mobile Game
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                                <h3>Filip Bouckaert MD, PhD</h3>
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                            Mindbytes produces serious games and e-learning applications, and has provided us with advice about our games. They gave us advice on how we can incorporate education in a game because we didn’t want to develop a random game. We wanted to create a game that explains to the broad public what synthetic biology is and what genetic manipulation is all about.
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                                <p>Filip Bouckaert is a geriatric psychiatrist and member of the University Psychiatric Center (UPC) at KU Leuven. He is specialised in geriatric psychiatry, anxiety, mood disorders, psychosis and electroconvulsive therapy (ECT). </p>
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                            Cartamundi is a world-leading producer of playing cards and card games. They have printed our card game, as well as guide the final steps in the card designing process. For this we have to thank Tom Van Den Berghen and Marco Van Haaften.
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                            Dries Deryckere is a teacher in Kortrijk, at Howest College. He works for the department of Digital Art & Entertainment, he looked at the possibilities to help us with the development of the computer game. He tried to recruit some of his students, so they could finish the game as part of their education.
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                                <p>As psychiatry seemed a very interesting target for therapeutic drug monitoring, we contacted Filip Bouckaert for a second opinion. He suspects that only a small amount of psychiatric patients, people severely affected by bipolar disorder, would benefit from our project. However, he expects that their quality of life would be hugely improved.</p>
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                            Business Plan
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                            Professor Jos Vander Sloten en Wim Fyen gave us some advice on how to write a complete business plan, we listened to their opinions and tried to implement it. Thanks to them we could create a complete business model.</p>
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                            <p>During our discussion with Filip Bouckaert, he was very enthusiastic about the project. Additionally, he has provided us with some new ideas and possibilities regarding HEKcite in the field of psychiatry.</p>
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<p>First, he mentioned that only a limited number of antipsychotic drugs are available, of which clozapin, depacin, notrilin and lithium-based medicine are the most common examples. As a result of the limited treatment options, side effects are prevalent and often unavoidable. These effects may be severe and even lethal, especially when multiple drugs are taken by a patient. For example, cardiac arrhythmias can occur. Therefore, the psychiatrist suspects that the system developed in our project could provide a peace of mind for these patients, as these arrhythmias may result in sudden death.</p>
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<p>When further discussing the possibilities of HEKcite in the field of psychiatry, Filip Bouckaert declared that, despite his enthusiasm for our project, he suspects that only a limited number of psychiatric patients, people suffering from severe bipolar disorder, could benefit from the therapeutic drug monitoring we propose. However, he thinks it would greatly increase their quality of life, specifically as drug compliance is a well-known problem for bipolar patients. During symptomatic episodes, the disease affects the patients’ life severely, and might result in manic episodes, depression, et cetera. However, during asymptomatic periods, the patients often lose the motivation to take the drugs, which results in more frequent relapses. As a result, they may end in a vicious circle of relapse after relapse. Using the HEKcite therapeutic drug monitoring device, a dynamic measurement of the blood levels would be possible. This way, the doctors will notice when an alarming change in the rhythm appears and they can intervene before it is too late. The device can thus work as modern ‘gate keepers’.  
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<p>Another small group of patients that could be helped with our project are those suffering from aichmophobia, the fear of needles and sharp objects, as fewer blood samplings are needed after the device is implanted. </p>
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<p>Filip Bouckaert also noted the importance of monitoring drugs with a small therapeutic window, e.g. lithium-carbonate. When the blood levels of these drugs are too high, the drugs are very toxic for the patients. We suggested that the HEKcite monitoring device could be helpful in monitoring these risk-bearing drugs, especially in the psychiatric world, where patients show mainly subjective clinical symptoms. Currently, doctors look for certain side effects, such as tremor, to determine whether patients have a toxic amount of drugs in the blood. Therefore, measuring the concentration of lithium-carbonate before clinical symptoms as tremor appear, using for example the HEKcite device, could be helpful. However, he suggests that when we look into this application further, we must make sure to take the metabolization of the drugs, and the interindividual differences thereof, into account. This is important as these differences may influence the precision of our device.  
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<p>Furthermore, it is important to consider the fact that some drugs influence other drugs as well. For example: lithium is metabolized by the kidneys, but other therapeutics, such as angiotensine, ACE-inhibitors, NSAIDs and lis-diuretics affect the kidneys. Moreover, the outside temperature and the amount of hydration can also influence the blood levels: The more dehydrated a person is, the higher the drug blood levels are, and vice versa. This could affect the frequency of our device and could give a distorted image of the actual drug level in the body.  
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Revision as of 23:27, 12 October 2017

Attributions

HEKcite! Inspired by the human heart rhythm, we aim to create an electrophysiological oscillator from eukaryotic cells. Rhythmic contraction of heart cells is coordinated by a small group of cells located in the sinus node, which have an intrinsic frequency of de- and repolarization. This frequency of electrical oscillation is influenced by environmental parameters as well as certain molecular substrates. The oscillator that we aim to create consists of genetically modified excitable Human Embryonic Kidney (HEK) cells, altered to contain the intrinsic pacemaker ability found in sinus cells. As witnessed in heart cells, the rhythm would be dependent on substrate-activated ion channels in the membrane. As there is a great variety of ion channels available in nature, the oscillator could be modified to measure concentrations of many specific substrates. By integrating a certain ion channel into the oscillating system, specificity for a substrate can be chosen. Building an electrical oscillator from cells has several advantages. Intra- or extracellular changes that influence the conductance of ion channels in the membrane have an immediate impact on the frequency of oscillation. Once these cells are connected to each other (by for example gap-junctions), they generate an electrical signal that can easily be measured from a distance and non-invasively—similar to the way electrocardiography (ECG) and electroencephalography (EEG) measure electrical activity in the heart and brain. A multi-purpose sensor suitable for this system could be developed for medical and biotechnological applications. One such application is the measurement of drugs that interact with ion channels, such as antipsychotics, anti-epileptics or a certain class of immunosuppressants.


Attributions We thank all our collaborators for their help, guidance and supervision. Molecular lab work Professor Johan Swinnen is a professor and head of the Oncology department at KU Leuven. As our PI, he has provided us with advice, support and lab space. We would also like to thank the rest of his team, especially Frank Vanderhoydonck, for showing us around the lab and helping us with everyday tasks. Electrophysiology Professor Thomas Voets is head of the laboratory of Ion Channel research at KU Leuven. Apart from allowing us to use his electrophysiology tools, he and his team have learned us several techniques valuable for the project, such as patch clamp and calcium imaging. Furthermore, his lab has kindly provided us with HEK cells stably infected with mHCN2 or hERG genes, and several plasmids containing ion channels, such as mHCN, hERG, and α1G. The assistant of professor Voets, Annelies Janssens, trained us to work with the patch clamp machine which is the central piece of machinery in our project. Without this machine, we couldn’t collect our data. Professor Chris Ulens is head of the laboratory of structural neurobiology, at the department of cellular and molecular medicine at KU Leuven. He has shared his knowledge of the interactions between ion channels and certain drugs. Dr Mieke Nys is part of the laboratory of structural neurobiology and has supplemented our results with extra measurements of the mHCN gene another patch clamp machine. Modelling Professor Alexander Panfilov is a part of the department of mathematical and theoretical physics at the UGent, specializes in cardiac modelling and has given us advice regarding our model. Furthermore, he has given us the contact details of others who might be able to help. Nina? Hardware and measurement Professor Jeroen Lammertyn is head of the Division of Mechatronics, Biostatistics and Sensors (MeBioS) at KU Leuven. We have discussed the possibilities for measurement and data collection from our cells. Dr. Frederik Ceyssens is a postdoc at MICAS, at the department of electrical engineering at KU Leuven. We have had a very valuable discussion about the hardware necessary for the measurement of oscillating cells. He helped with the design of the sensor and everything that goes with the sensor, from batteries to the actual sensor itself. Dr. Dries Braeken is working for imec’s life science technology group. He has experience measuring cardiomyocytes using micro-electrode arrays (MEAs), and we have discussed the possibilities of measuring our cells in a similar way. Together with his PhD student, Jordi Cools, we tried different sensors and tried to sense the electrical oscillations with the sensor. Professor Bernard Schneider a senior scientist in the neurodegenerative studies laboratory in the École polytechnique fédérale de Lausanne (EFPL). He has provided us with a sample of an implantable macrocapsule, and has confirmed the possibilities of integrating chips in this device. Professor Adrian Ranga is specialised in tissue engineering. We discussed biomaterials and the immune implications of implantable devices. Professor Jennifer Patterson is a specialist in hydrogel structures for tissue engineering. She has given us some ideas about the possibilities of integrating a MEA in a hydrogel structure. Human practices Professor Monbaliu is a transplant surgeon at the department of microbiology and immunology at UZ Leuven. He has provided us with insights on how the project could influence the field of transplantation medicine. Transplantoux is a patient organisation for people that have undergone a transplantation. We would like to thank them for bringing us into contact with patients whose insights were extremely valuable for our project. Professor Wim Van Paesschen is a neurosurgeon and head of the epilepsy research laboratory of UZ Leuven. He has shed light on the importance of therapeutic drug monitoring in the field of epileptics. Professor Chris Bervoets is a psychiatrist responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the University Psychiatric Center of KU Leuven. He has helped us by discussing the several possibilities of our project within the field of psychiatry. Hier moet nog over die van het laatste gesprek geschreven worden. Education We would like to thank some middle schools: Sint-Romboutscollege (Mechelen), Go Shill (Mechelen) and Via Tienen (Tienen). We were able to teach amazing kids more about DNA, genetics and the basics of synthetic biology. Card and Mobile Game Mindbytes produces serious games and e-learning applications, and has provided us with advice about our games. They gave us advice on how we can incorporate education in a game because we didn’t want to develop a random game. We wanted to create a game that explains to the broad public what synthetic biology is and what genetic manipulation is all about. Cartamundi is a world-leading producer of playing cards and card games. They have printed our card game, as well as guide the final steps in the card designing process. For this we have to thank Tom Van Den Berghen and Marco Van Haaften. Dries Deryckere is a teacher in Kortrijk, at Howest College. He works for the department of Digital Art & Entertainment, he looked at the possibilities to help us with the development of the computer game. He tried to recruit some of his students, so they could finish the game as part of their education. Business Plan Professor Jos Vander Sloten en Wim Fyen gave us some advice on how to write a complete business plan, we listened to their opinions and tried to implement it. Thanks to them we could create a complete business model.