Multi-Disciplinary Engineering Design Conference Kate Gleason College of Engineering Rochester Institute of Technology Rochester, New York 14623 Project Number: 07041 EXPANDABLE ALVEOLAR SAC Christopher Salvato/Project Manager Timothy Brackbill/Manufacturing Lead Nicholas Daniel/Imaging Lead William Dapolito/Pumping Lead Jessica Oakes/Air Sac Model Lead Matthew Waldron/Controls Lead ABSTRACT An expandable alveolar sac was created for research applications. The system will be used to profile alveolar fluid flow using PIV and to explore fluid mixing dynamics during respiration. The system was designed and implemented to be easily modified as necessary for applications using breathing curves for different diseases and different subject age groups. This is a requirement to allow for a variety of other possible research applications. System was consistent with fluid flow properties in the human lung and compatible with Particle Image Velocimetry (PIV) technology. INTRODUCTION The objective of this design is to create an in vitro alveolar sac that creates fluid flow and pressure parameters similar to those parameters that occur in vivo. The main goal of creating these parameters in vitro is to map velocity field profiles using PIV technology. Secondary goals include using the system to map fluid velocity profiles through layering fluids of varying densities as well as analyzing fluid mixing within an alveolar sac. A previous attempt was made at this design and did not succeed. There were several reasons for this failure. Firstly, the pump access into the negative pressure chamber did not allow for adequate fluid flow to create pressure changes quickly enough within the bottom cavity. Secondly, the material that was used was neither optically clear nor was it flexible with elastic properties. Finally, the method of fabrication of various sized sac models was costly as well as ineffective. A triumph of the previous design, however, was the rough creation of the air sac model. This model, constituted of complex geometries, allowed the current group to focus on more practical problems of the design rather than focusing on creating a complicated air sac model. This model was then redesigned and improved during the course of the current project. These improvements allow for a more accurate in vitro representation of in vivo geometries. Overall, the current project was a major success. All primary customer needs were met. Additionally, most secondary and tertiary customer needs were met and exceeded as well. While the project was a great success, it has also been designed to easily facilitate change and improvement for possible future research applications. NOMENCLATURE casting - to form into a particular shape creating a mold in a fluid state and letting it harden elastomer - a polymer having the elastic properties of natural rubber in vivo – within a living organism in vitro – in an artificial environment outside of the living organism molding – creating the mold that will be used to cast alveolar sacs plasticizer – a substances added to plastics or other materials to make or keep them soft or pliable rapid prototyping - an additive manufacturing process that creates a model of an object directly from a CAD model by building it in layers. syringe pump - a device consisting of a glass, metal, or hard rubber tube, narrowed at its outlet, and fitted © 2007 Rochester Institute of Technology Proceedings of the Multi-Disciplinary Engineering Design Conference with either a piston or a rubber bulb for drawing in a quantity of fluid or for ejecting fluid in a stream. velocity field profiling – discerning vector fields of velocity based on fluid flow observations. DESIGN METHODOLOGY Overview The design of the system was broken down into 5 logical subsystems. Each subsystem had a set of needs that they must satisfy. These subsystems include Imaging, Air Sac, Manufacturing, Pumping, and Controls. Imaging One of the highest level needs for this project was that the system be compatible with PIV. This is an optical method used to measure the velocity profile in a given fluid. PIV uses a laser to illuminate fluorescent particles that are immersed in the fluid. Particle settling is undesirable, for the particles need to move with the motion of the fluid, which will allow for accurate fluid velocity measurements using PIV. Three different forces act on a particle suspended in fluid. These include buoyancy force, FB, force due to gravity, Fg, and force due to drag, FD. The buoyancy force, shown in Eq. (1), where ρf is the density of the fluid, g is gravity and Vp is the volume of the particle. To calculate the drag force Eq. (2) was used where dp is the diameter of the particle and urel is the relative velocity of the particle. The force due to gravity can be calculated with Eq. (3), where ρp is the density of the particle. It was assumed that the particle will have reached terminal velocity when the fluid is in motion. This assumption allows for the summation of forces to equal zero as shown in Eq. (4). FB = V p *g * ρ f (1) FD = 3 * π * d p * u rel (2) Fg = V p * g * ρ p (3) ΣFy = 0 = FD + FB − Fg (4) The relative velocity was solved for, which is the difference between the velocity of the particle and the velocity of the fluid, and it was determined to be 8.06E-9m/s. With a time period of twenty seconds the particle will separate from the fluid a distance of 1.6E5m, which was determined to be negligible. To ensure that the PIV will collect data accurately, it was essential that the index of refraction of the sac material and the surrounding fluid be matched as closely as possible. Refraction occurs when light waves travel between mediums of different refractive indexes, causing the light waves to bend at a certain angle. The index of refraction of the sac material was measured with a refractometer to be 1.482, and the Page 2 fluid selected, glycerin, had an index of refraction of 1.473. Using Snell's Law, a relationship which relates the angle of incidence and angle of refraction to the refractive indexes of the mediums, it can be found that any disparities resulting from the slight difference in index of refractions between the sac material and glycerin was be negligible. Aside from this major concern, most other concerns of the imaging subsystem were handled through design and implementation of the other subsystems. As a result, all needs for this subsystem were fulfilled. Air Sac The primary needs addressed by the air sac subsystem involve creating accurate geometries to properly replicate an in vivo alveolar sac. This requires analysis of the fluid flow parameters and how they relate to geometry. Fluid The alveolar sac in the human lung has a volume of 3.7E-11 m3, which was too small to model in a laboratory setting; therefore a larger model had to be designed in order to allow for it to be manufactured. The Navier-Stokes partial differential equation, as shown in Eq (5), describes fluid flow, where ρ is the fluid density, u is the speed of the fluid, t is time, P is the pressure, ∇ is the gradient in the x, y, and z direction, μ is the fluid viscosity, and g is gravity. The Navier-Stokes equation must be non-dimensional in order to properly scale the model. This is shown in Eq. (6), where ω is the frequency, D is the characteristic diameter, and ν is the kinematic viscosity. ⎡ δu ⎤ + u * ∇u ⎥ = −∇P + μ∇ 2 u + ρg ⎣ δt ⎦ ρ⎢ ⎡ p * g * D2 ⎤ ⎡ ρ * D 2 * ω ⎤ δ u ⎡ ρ * D * vo ⎤ ⎡ Ps * D ⎤ 2 +⎢ ⎥ ⎢ ⎥ ⎥u * ∇u = − ⎢ ⎥∇ P + ∇ u + ⎢ μ μ ⎦ ⎣ μ *v ⎦ ⎣ ⎦ δt ⎣ ⎣ μ * vo ⎦ (5) (6) Two dimensionless parameters that describe inertial flow were characterized from Eq. (6): Reynolds (Re) and Womersley (Wo) numbers. These are shown in Eq. (7) and Eq. (8), respectively. ρ * D * vo μ ρ * D2 *ω Wo = μ Re = (7) (8) Both the Reynolds and Womersley numbers were calculated for in vivo conditions. The dimensionless parameters were determined to be much less than one, characterizing the fluid to be lack inertia. This is beneficial since it is necessary for the fluid to lack Paper Number 07041 Proceedings of the KGCOE Multi-Disciplinary Engineering Design Conference Page 3 inertia in order to create a model for the laboratory setting. Data was generated based on the size of the model and the time required to complete a cycle for a model that expands thirty percent in a pure glycerin fluid. Pure glycerin was used to match the index of refraction of the material and thirty percent expansion was determined from literature [4]. The laboratory model controls are able to be modified based on the data determined from the dimensionless parameters. Geometry The previous senior design group had used idealized alveolar sac geometry was used to create the original alveolar sac model. Three different alveolar sac geometries were created. The previous senior design team created the first model, shown in Fig. 1, using 75% Total Lung Capacity (TLC) Model. These geometries were obtained from literature [1,4]. Because the dimensions from the literature were measured from a lung cast that was created at 75% TLC, the alveoli had to be scaled down to breathing volume which is 50% TLC. This value is referred to as the Functional Residual Capacity (FRC). Each one of the alveoli were scaled to FRC using Eq. (5), where dVm is the diameter of the alveoli at the measured volume, dVFRC is the diameter at FRC, Vm is the volume at which the diameter was measured and VFRC is the volume at FRC. ⎛ V d Vm = ⎜⎜ m d VFRC ⎝ VFRC ⎞ ⎟⎟ ⎠ 1 3 (9) The alveolar sac created was compared to geometry dimensions published in literature [2, 3]. Values from literature were produced by measuring the shape of a alveoli by measuring a dimensionless parameter. This parameter is the ratio of alveoli depth and alveoli mouth diameter. The 75% TLC model and the 50% TLC model dimensionless parameter was much smaller than the data measured in literature. In order to create a model that represented dimensions found in literature, a model was created with fewer alveoli. Each of the alveoli were more defined in the model, therefore the dimensionless number was comparable to that found in the literature [2, 3]. Manufacturing The primary concerns that the manufacturing subsystem had to address involved creating a physical model of the alveolar sac. The process had to be efficient and easily repeated so that many different models of various sizes could be used in the system. Also, the sac model had several material requirements. The material had to be optically clear to satisfy the Fig. 1. Original alveolar sac model with measurement locations corresponding to duct diameter, sac diameter and sac length labeled. requirements for PIV. Also, elastic properties had to exist that were similar to the elastic properties of alveolar sacs in vivo. Material In order to satisfy the material requirements several different materials were researched. Samples were obtained and their properties were analyzed. At this point, the chosen method of fabrication involved dipping a mold into the molten material and letting the resulting model cure. This meant that the material had to have a reasonable melting point, must meet the requirements of PIV, maintain its physical and optical properties after being melted and would cure quickly. An elastomer material called UltraFlex was found through a supplier. After testing, this material was shown to have all desired material properties, including an index of refraction that matched that of glycerin. A process was then developed to create alveolar sac models from this material. Molding The first attempt was to dip a rapid prototyped male mold of our alveolar sac coated with epoxy. These attempts had shown that most organic chemicals, such as epoxy and rapid prototyping material, reacted with the elastomer. These reactions caused changes to the optical and physical properties of the material. This method, therefore, ruined the cast. We found however that when metals or glass were used to create the cast no reactions occurred. This process also yielded adequate surface finishes. From this realization it was decided to pursue options in creating aluminum molds. The RIT School for American Crafts had provided a means of creating aluminum molds in an efficient and cost effective manner. The process of creating aluminum molds started with an 8 piece, rapid prototyped female mold of the Copyright © 2007 by Rochester Institute of Technology Proceedings of the Multi-Disciplinary Engineering Design Conference alveolar sac. The mold was filled with molten wax and set to cool to create a male model from the mold. Next, this male wax model was removed and cleaned of any unintended effects. From here, male ducts were attached to the wax mold to allow aluminum to enter. This created a sand cast of the wax model. When a sand cast was made, it was taken to the kiln and the aluminum is melted. Molten aluminum was then skimmed to remove defects from the metal that float to the surface. The molten aluminum was then poured into the sand cast and allowed to cool. When the aluminum had thoroughly cooled, the sand cast was opened and the metal casting was then removed. The additional ducting was sawed off of the top of the completed aluminum casts so that only the alveolar sac remains. The top duct of the aluminum cast was then lathed to the desired diameter and the cast of the mold was sanded to a smooth surface finish. Casting The procedure to cast the alveolar sac molds was devised iteratively until a process that produced desired results consistently was produced. The main element of the process involved the dipping of the aluminum mold into molten material and then curing. After nine different processes were developed and tested a final process was decided upon based on the results of the testing. First, scissors were used to dice the required amount of elastomer into cubes that were approximately 0.2” per side. Next, a beaker was placed on a hot plate in a fume hood and the hot plate was turned to the maximum setting. At this point, approximately ten to twelve cubes of the elastomer were placed into the beaker and heated from the top with a heat gun. When the elastomer started to melt, it was stirred while still applying heat from the hot plate and heat gun. When the elastomer in the beaker had mostly melted, more elastomer was added until the necessary amount of elastomer was melted to dip the mold. When the required amount of elastomer was melted, heat was continually applied with both the hot plate and heat gun while stirring until the elastomer lost most of its viscous properties. The molten material was then left idle under the heat until all bubbles evacuated from the fluid. The top duct of the metal mold was then placed into vice grips and heated under the heat gun until the mold achieved a temperature between 120 ºC and 175ºC. This was done to prevent the elastomer from rapidly cooling and solidifying when dipped. At this point, the heated aluminum mold was slowly dipped into the beaker of molten elastomer. This was done extremely slowly so that no bubbles formed in the sharp corners of the mold. When the mold had been fully immersed in the molten elastomer it was removed from the beaker. Immediately upon removal from the beaker, the mold was rotated along the axis Page 4 Fig. 2. Original concept art of system design. The top cavity holds fluid to flow into the sac. The bottom cavity creates a negative pressure system driven by a syringe pump. of the vice grips while the elastomer was still molten in order to even out any discontinuities from dipping. Immediately after the outside of the elastomer had hardened, the mold was placed with elastomer film under slow-running cold water tap for approximately five minutes. This was to prevent plasticizers from evaporating and to decrease the cooling time. Once the mold had completely cooled, the elastomer film was rolled off of the mold. This was done while ensuring that the film did not rip on the way off. The molds were then sealed in a container for storage to assure that no dirt or dust from the environment would adhere to them. Pumping The pumping subsystems had to meet primary needs that were associated with creating the negative pressure environment that would drive the expansion of the alveolar sac. This consisted of two main parts; the system housing and pump design. Housing There were many designs for the housing that the team produced in the first few weeks of the project. Some ideas included a rigid-bottomed container, a piston-bottomed container, and a diaphragm flexible bottom. There were many different methodologies that were assessed to change the volume with each of these ideas. Some of these included using one or more syringe pumps, an eccentric crank, and a magnetic actuator. It was decided that the final design was to be a rigid-bottomed container with a single syringe pump that would evacuate fluid from a bottom cavity. This bottom cavity would house the alveolar sac. The alveolar sac would be attached to the bottom of a lid that would also create a top cavity. The top cavity would hold fluid that would flow into the alveolar sac and be used to measure volume within the sac. This original concept design is shown in Fig. 2. Paper Number 07041 Proceedings of the KGCOE Multi-Disciplinary Engineering Design Conference A 3D model was then created based on concept art using the design software SolidWorks. Many inherent problems with the first design iteration were apparent. Firstly, the upper portion of the housing was too large to adequately monitor volume change. To alleviate this problem, the upper cavity was replaced with a graduated cylinder that allowed for fluid access into the alveolar sac model. Secondly, the through-wall fitting in the first design was much too small. Since it was assumed that the fluid within the cavities would be glycerin, the head loss on such a small through wall fitting would have been much too great unnecessarily using a small through wall fitting. Hence, the second design iteration implemented a larger through wall fitting. The first design included a looking glass in order to assure PIV compatibility. This looking glass was to provide the PIV laser and camera optical access to the inside of the bottom cavity. Lastly, the second design iteration eliminated this looking glass and used lexan for the housing walls so that the entire housing was optically clear. A review of the housing design yielded another design iteration resulting in more refinements. The graduated cylinder on the upper portion was made to have a smaller diameter thereby giving volume measurements more resolution. An even larger through-wall fitting was also added to allow for an easier accommodation of pressure changes in the bottom cavity. Washers and bolts were added to the detail of the housing model. Lastly, a pressure sensor was added to the assembly. A final review of the housing design was done creating the final iteration of the housing design. Due to leaks around the seal between the housing lid and the bottom cavity an aluminum collar was made. This collar more evenly distributed the pressure across the sealing gasket. Threaded holes were also added for a bleed valve and a mechanical pressure gauge. This final design is shown in Fig 2. Pumping A syringe pump system was chosen to create the negative pressure system. By attaching the syringe pump to the housing’s through wall fitting it was possible to have a syringe pump evacuate fluid from the bottom cavity causing negative pressure. To meet all of the required needs associated with pumping a pump had to be decided upon without knowing the operating pressures and the volumetric flow rate ranges. This is due to the amount of unknown parameters that existed when the design process began. To find a starting point for the pump selection, many assumptions were made. First, it was assumed that the maximum alveolar sac size would be the same as the previously attempted Senior Design Project. With this information it was possible to find the maximum flow rate. Secondly, it was assumed that the working fluid would be glycerin. From this Page 5 Fig. 3. Final system design. The top cavity had been reduced to a single graduated cylinder. The bottom cavity creates a negative pressure system driven by a syringe pump with access for multiple sensors and is sealed by a gasket and aluminum collars. assumption, viscous losses were calculated. Then, the necessary additional pressure due to viscous losses alone was calculated. Lastly, the pressure to expand the alveolar sac was grossly over estimated to ensure that the chosen pump would work. The operating pressure for the pump was then calculated by adding the pressure due to viscous losses to the estimated pressure required to expand the alveolar sac model. The previous Senior Design group had purchased an expensive pump that they had attempted to use. This pump, a NE-500 Syringe Pump System from New Era Pump Systems, allowed for a syringe pump to interface with a motor that is controlled by a microcontroller. This would allow for control with a computer, as desired by the customer as well as possibly providing the required specifications that had been calculated. Testing and analysis had shown that simple modifications could be made to yield the necessary output parameters from the motor. The first and most simplistic modification was to change the syringe size. More specifically, the diameter of the syringe was greatly increased. By increasing the syringe diameter and keeping the linear velocity constant, the volumetric flow rate increases. The original syringe had a 60 ml capacity. This was replaced with a 140 ml syringe. The larger syringe also had a 50% increase in diameter over the original. Secondly, the gear ratio between the stepper motor and the driving lead screw was modified. The original syringe pump had a gear reducer setup. This means that the stepper motor’s shaft speed was greater than the lead screw’s shaft speed. This setup was changed to a speed multiplier, which. This means that the stepper motor’s shaft speed was less than the lead screw’s shaft speed. This was accomplished by replacing the belt and pulley system with a chain and sprocket system. With this modified system many gearing ratios were possible. This makes power transmission within the system very flexible for different volumetric flow rates. Since this Copyright © 2007 by Rochester Institute of Technology Proceedings of the Multi-Disciplinary Engineering Design Conference made the lead screw rotate much faster, the flow rate increased. The trade-off associated with this modification was between speed and torque. In this instance, torque was sacrificed where a speed increase occurred. To compensate for this, the stepper motor was upgraded to a more powerful model with higher overall torque and speed. In order to perform this upgrade, the circuitry of the microcontroller board had to be modified by changing several resistors as well as other electronics. Other various enhancements to the pump were made in order to improve overall functionality. When the base that holds the lead screw sprocket was modified, it structurally weakened the pump’s base. To correct this, a new base was constructed out of aluminum. Other improvements include two thrust bearings and a shaft collar that were added to the lead screw for better stability. The summation of all of these modifications allowed the syringe pump meets all customer specifications. Controls The two primary needs that were met by the controls subsystem include driving the model alveolar sac to expand and contract similar to in vivo breathing patterns and to monitor model volume and pressure. The latter need had to be done such that the experimental model data can be compared with in vivo data. The sac expansion and contraction was controlled by the negative pressure system created by the pumping subsystem. The rate of fluid fluid flow was controlled by a LabVIEWTM program that continually changed the pumping rate to match a desired transient breathing curve. An example of the in vivo tidal volume curve that the LabVIEWTM program matched is shown in Fig. 4. After this curve was converted to a digital and discrete waveform, the volume and time scales were normalized to match the shape of the desired breathing curve. Within LabVIEWTM, the volume and time scales were denormalized to the model and experiment parameters put in by the user. These parameters included the unexpanded model volume, peak percent expansion, and breath period. The NE-500 syringe pump was capable of receiving commands that dictate the rate of either withdrawing or infusing fluid. To make the pump action match the breathing curve, the LabVIEWTM program sampled the curve every several milliseconds, and calculated the desired change in volume to compute the flow rate. The command to change the rate to the calculated value was sent to the pump, and this process was repeated approximately 20 times per second to generate a smooth change in volume that very closely matches the desired curve. To accommodate different activity levels and breathing pathologies, the LabVIEWTM program was designed to be flexible enough so that any shape curve can be loaded into the system. This allowed for Page 6 Fig. 4. Sample Tidal Volume vs. Time Breathing Curve. The Labview program must change the pumping rate to make the model volume displacement match in vivo patterns. Image adapted from Slonim, N. B., Hamilton, L. H. Respiratory Physiology. C.V. Mosby 1971 operation over a range of breath periods and expansion volumes. So long as the desired operation did not exceed the limits of the pump, the system performed well and matched the true change in volume closely to the desired change. In order to monitor how well the model activity actually followed the desired operation, two pressure sensors were used: one was located in the wall of the housing to measure the pressure produced by the pump to displace the sac volume, the other was located at the duct of the model to measure the model volume change via the hydrostatic pressure of the fluid outside of the model. Since the hydrostatic pressure of the fluid outside of the model would always be positive (with respect to atmospheric pressure) the sensor was chosen to be sensitive enough so that there was a large change in output voltage over the expected range of fluid heights. The pressure caused by the pump was expected to be both positive and negative, depending on either exhalation or inhalation of the model. Since the sensor will only read pressure positive with respect to atmospheric pressure, the sensor is placed at the very bottom of the housing enclosure. This way, the hydrostatic pressure of the fluid had positively offset pressure fluctuations created by the pump. This allowed the measured pressure to always be within the range of the sensor. The output of the two sensors was continuously measured with LabVIEWTM. The changes in sensor output voltage were correlated to the sac volume and pressure outside of the sac. The results were recorded. To measure the flow rate of fluid into and out of the sac, the derivative of the sac volume was be computed within LabVIEWTM. After an experiment was run, transient plots of volume, flow rate, and pressure can be obtained, which provided a good indication of how well the true model behavior matched the desired behavior. Literature from experiments on in vivo human respiration often present graphical relationships between pressure vs. volume, and flow vs. volume, so these plots can also generated from the recorded sensor readings. After testing the LabVIEWTM program with the optimum model size and with various percent expansions and breath periods, the actual model moved very similarly to the model behavior desired by the input waveform. It was evident that there is a maximum and a minimum pumping rate at which the Paper Number 07041 Proceedings of the KGCOE Multi-Disciplinary Engineering Design Conference pump could operate. This problem emerges due to the nature of the stepper motor driving the pump. These minimum and maximum boundaries can be overcome by modifications to the pump as explained in the pumping subsystem. Also, another method of alleviating this problem was to change speed and sampling constants within the LabVIEWTM source code. This improvement, however, comes at the expense of accuracy matching the desired breathing curve. For ideal specifications however, the LabVIEWTM control system meets all the necessary needs. ACKNOWLEDGMENTS The team would like to acknowledge and thank Dr. Risa Robinson who was the team's guide, sponsor and customer. Secondly, the team acknowledges the Provost Learning Initiative Grant provided by the office of the Provost at RIT. Additionally, the team would like to thank all consultants who provided prompt and relevant assistance as well as consultative advice when necessary. These consultants include Dr. Steven Day, Dr. Steve Weinstein, Dr. Elizabeth DeBartolo, Dr. David Borkholder, Dr. Daniel Phillips, Dr. Kathleen Lamkin-Kennard and Ms. Jackie Russo. Page 7 The team thanks the School for American Crafts (SAC) at RIT that has contributed both their time and effort in creating the aluminum alveolar sac molds. Also, the team thanks Mr. Jeffrey G. Lonneville of the Surface Mount Technology Lab at RIT for his assistance in replacing surface mount resistors. Finally, the team thanks William Leonard of the Mechanical Engineering Technology department at RIT for his assistance in creating the rapid prototypes of the molds. REFERENCES [1] Haefeli-Bleuer B and Weibel ER, 1988, Morphometry of the human pulmonary acinus. Anat.Rec. 220: 4: pp.401-414. [2] Klingele, T G Staub,N C, 1970, Alveolar shape changes with volume in isolated, air-filled lobes of cat lung. 28: pp.411. [3] Mercer, R R Laco, J M Crapo,J D,1987, Threedimensional reconstruction of alveoli in the rat lung for pressure-volume relationships. 62: 1480 [4] Weibel ER, 1964, Morphometrics of the lung. Handbook of applied physiology. Respiration. [5] Slonim, N. B., Hamilton, L. H. Respiratory Physiology. C.V. Mosby 1971 Copyright © 2007 by Rochester Institute of Technology
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