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UW-Madison BME 300 - A Device for Brain Cooling in Mice

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DEPARTMENT OF BIOMEDICAL ENGINEERING A Device for Brain Cooling in Mice Jay Sekhon--Leader Jon Seaton – Communicator David Leinweber – BSAC Mark Reagan – BWIG Client: Giulio Tononi Ph.D./M.D. Ugo Faraguna PhD./M.D. Advisor: Mitch Tyler March 11, 2009MID-SEMESTER REPORT March 11, 2009 2 Table of Contents Background ................................................................ 3 Client Requirements....................................................4 Project Aims .................................................................5 Similar Devices.............................................................6 Product Uniqueness.....................................................7 Design Alternatives......................................................7 Peltier Cell............................................................7 Vortex Tube...........................................................8 Liquid-Cooling......................................................9 Phase-Change Cooling.......................................10 Design Matrix.............................................................11 Thermodynamics .......................................................12 Testing.........................................................................13 Future Work...............................................................14 Appendix A (PDS)......................................................15 Appendix B (Expenses)..............................................18 References...................................................................20MID-SEMESTER REPORT March 11, 2009 3 Background The function of sleep remains one of the greatest unsolved mysteries in modern science. A multitude of theories have been proposed regarding the necessity of sleep, but none have been substantively established. Sleep is known to be an essential process of life, taking up almost 1/3 of the average human’s lifetime. Furthermore, it is such a necessity that deprivation has been known to cause health problems in rats, leading up to death (Everson 1995). Additionally, the effects of sleep have been studied on a variety of life factors. Retaining homeostasis is a commonly accepted view, since studies have shown that lack of sleep hampers healthy metabolic activity and immune system response (Zager 2007). Furthermore, sleep has been linked to proper memory function—lack of sleep has been shown to correlate with cognitive impairment, decreasing by as much as 38% in comparison to a control (Turner 2007). However, these functions all provide effects of sleep; they do not examine the purpose of it. A hypothesis has been proposed by Dr. Giulio Tononi that sleep is used for synaptic downsizing. Specifically, he states that “The synaptic homeostasis hypothesis claims that plastic processes during wakefulness result in a net increase in synaptic strength in many brain circuits; during sleep, synaptic strength is globally downscaled to a baseline level that is energetically sustainable and beneficial for memory and performance” (Tononi 2005). The client has started an experiment to test this hypothesis, using 2-photon microscopy to image synaptic activity in the brain in awake and sleeping mice. The client has proposed an additional experiment based upon the neural activity hypothesis.MID-SEMESTER REPORT March 11, 2009 4 The rationale behind the second experiment lies in the logic assumed by an increase in synaptic strength. If the hypothesis is correct, then wakefulness with a decreased level of synaptic activity will produce a longer time between sleep/wake cycles. Additionally, it has been shown that cooling of brain tissue will reduce synaptic activity (Benita & Conde 1972 ,Waleszcxyk 2005). With this line of reasoning, the client wishes to selectively cool a region of the brain that is responsible for modulating the sleep/wake cycle. By doing so, he believes that he will be able to silence the synaptic activity, affecting the sleep cycle. In order to carry out this new experiment, the client would like a device capable of cooling a 3mm hemispherical region of a mouse’s brain. The device must be able to cool the tissue enough to silence neural activity, but not so much that tissue damage occurs. Furthermore, the device needs to allow the acquisition of an accurate EEG signal in order to confirm that synaptic activity has been suppressed. Client Requirements At the beginning of the semester, our client, Dr. Ugo Faraguna, provided a specific set of requirements. In order to correctly build our prototype, it is imperative that we follow these requirements. Most importantly, we must cool a 3 mm region in the brain to approximately 20°C. As the device reaches the desired cooling temperature, it must not harm the brain cells in any way. Although the client believes it is impossible to completely avoid killing a few brain cells, it would be ideal to find a temperature that will not damage the tissue. The device should be able to cool down the area efficiently—MID-SEMESTER REPORT March 11, 2009 5 meaning it should only take about 30 to 60 minutes to reach the ideal temperature. After the device has cooled the brain region to the desired temperature, the client will run various tests. As such, the temperature should be constant during these tests (±0.5°C) and should be able to last for three to six hours. As mentioned previously, it is important that the device does not cause any interference to the EEG signal. If the device does produce interference, it would defeat the purpose of the client’s experiment which is predicated on the suppression of EEG signals. Another important piece of criteria is the mobility and ease of use of the device. Ideally, the device should be able to fit on a cart so it is capable of being taken from room to room if it needs to be used in more than one experiment. It should also be easy to use, so that the temperature can be controlled by the client in order to successfully carry out the desired experiments. Project Aims The main goal of the device is to cool down a 3mm hemispheric region in a mouse’s brain. The area should be cooled to approximately 20°C, which is the first priority of the device. The second priority of the device is to make sure the device does not interfere with obtaining an EEG signal. This is critical because if there is noise in the EEG signal, it


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