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UW-Madison BME 200 - Mass Controller System for Hypoxia and Hyperoxia Testing

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Mass Controller System for Hypoxia and Hyperoxia TestingHuser, A.J., Kreofsky, C.R., Nadler, D.C., Poblocki J.R.BME 201/200Department of Biomedical EngineeringUniversity of Wisconsin – Madison5 May, 2004Client:Brad Hodgeman, Instrument SpecialistDepartment of Comparative BiosciencesAdvisor:John G. Webster, Professor EmeritusDepartment of Biomedical EngineeringAbstract Mass flow controllers are used to regulate the flow of gas through chambers, thus controlling theconcentrations of gas in an enclosed chamber. A system was designed to test the effects of different concentrations of O2 and N2, within mice. The system has three main variables as outlined by the client: software, mass flow controllers, and interface for communication. A plethora of research has been completed on different types of mass flow controllers, mass flow controller manufacturers, and different types of communication interfaces. A LabView softwareprogram has been designed to control hypoxia and hyperoxia testing, and is the alpha stage of testing. Problem StatementThe purpose of this project is to design a system that can create a reproducible and accurate hypoxic/hyperoxic environment with the capability of oscillating between various concentrations of oxygen and nitrogen. Client MotivationOur client, Brad Hodgeman, has the following motivations:1) Determine the physiological mechanism of neural respiratory plasticity. It is widely believed that neural plasticity is dependent on serotonin 5HT, but the whole mechanism isyet to be discovered.2) Purchase new mass flow controllers and develop user-friendly software. The current mass flow controllers are inaccurate and the software is outdated3) Increase the automation of the system. Currently, there are manual aspects of the system that the client would like to eliminate in order to increase efficiency within the system.Hypoxia BackgroundThe neural respiratory control system’s responses to respiratory stresses such as intermittent & continuous hypoxia along with hyperoxia are being associated to clinical disorderssuch as sudden infant death syndrome (SIDS), apnic sleep disorders, and spinal cord injury. 2Links between these (and other) clinical disorders and hypoxia/hyperoxia are being investigated by researchers in hopes of finding the mechanisms behind their correlations. Normal respiration includes ~21% atmospheric O2, ~78% N2, and a very small percentage of all other gases. A lack of inspired O2 (<21%) can cause a condition called hypoxia, where insufficient amounts of O2 reach the tissues of an organism. Induced hypoxic conditions are more extreme but analogous to atmospheric oxygen at high altitudes (Fig. 1). Thephysiological and morphological effects from hypoxia can be detrimental to the organism if the O2 level is down low enough and is induced for long enough periods of time. Figure 1. Phrenic response to Short-term hypoxia. The steady decline in phrenic response following the short-term hypoxic response, exhibits no long term facilitation (LTF) induced from continuous hypoxia. (From Kinkead et al, 1998)Developmental respiratory control in many mammalian species can be heavily influencedby variation in gas concentrations (Johnson and Mitchell, 2003). Hyperoxia is a condition of ambient O2 levels being above the standard (low altitude) atmospheric O2 levels of 21%. Animalmodels support the conclusion that perinatal changes in O2 levels induce developmental plasticity: lasting changes in the respiratory control system that can be drawn out only during 3critical periods of development (Bavis et al., 2003b). Carotid body chemoreceptors bathe in the arterial blood and measure the PO2 levels, adjusting breathing rate and volume as PO2 changes accordingly (Feldman and McCrimmon, 2003). Neonatal hyperoxia-treated rats, when comparedto control rats, had significantly less carotid body volume (Fuller et al., 2002). Smaller volume of carotid bodies and attenuated responses to respiratory stresses of hypoxia later in the rat’s life (>3 months) has researchers believing developmental hyperoxia has detrimental effects to postnatal carotid body morphological and functional maturation (Bavis et al., 2002). Respiratory plasticity is defined as a future change in performance or persistent change inthe neural control system based on prior experience (Mitchell and Johnson, 2003). Intermittent hypoxia and not continuous hypoxia induce long-term facilitation (LTF) the most common and widely studied form of respiratory plasticity (Fig. 2). LTF is defined as the augmented phrenic burst frequency and amplitude lasting minutes to hours after episodes of intermittent hypoxia (Baker and Mitchell, 2000). Intermittent hypoxia is necessary to induce but not maintain LTF, thus there are other mechanisms behind the increased drive to breathe, as seen with the increasedphrenic output. It is widely accepted among researchers that LTF results from serotonin receptoractivation and is maintained with new protein synthesis, enhancing synaptic inputs to phrenic motoneurons (Fuller et al., 2002). Serotonin, or 5-hydroxytryptamine (5Ht), is a neuromodulatorthat aids in increasing respiratory drive. The exact physiological process in which serotonin elicits LTF is uncertain. 4Figure 2. The phrenic and hypoglossal (XII) response to 3 episodes of intermittent hypoxia (H1, H2, H3). LTF is the amplified response above baseline (BL) signified at 60 min post intermittent hypoxia. (From Zabka et al., 2001).MFC backgroundIn an experimental protocol that involves dynamic entities such as gas flow and control, accuracy is of paramount concern. In our client’s situation, this concern is addressed through thetechnology of mass flow controllers. Mass flow controllers (MFCs) accomplish accuracy through automating gas flow rates, and thus gas concentrations, to desired levels, for use in further testing. As a desired gas is fed into the mouth of the MFC, it is divided into two differentpaths. A large fraction flows into the bypass of the device, creating a pressure drop that shunts the smaller, remaining portion (usually 5% of the total mass) of gas up into the thermal sensor (Fig. 3). The shunted gas is subjected to a pair of heating coils which measure the change in temperature from the beginning to the end of the tube. 5Figure 3 (left), About 5% of the gas is shunted through the sensor


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UW-Madison BME 200 - Mass Controller System for Hypoxia and Hyperoxia Testing

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