This thesis encompasses a feasibility study of using low-cost materials to manufacture microfluidic chips that can perform the same functions as chips manufactured using traditional methods within an acceptable range of efficiency of chips created with more exotic methods and materials. The major parts of the project are the selection and characterization of the fabrication methods for creating the channels for fluid flow, the methods for sealing the channels to create a usable chip and the electrophoretic separations of carboxylated microspheres of different potentials. In this work we seek to answer the question if laser-etched PMMA microfluidic chips are comparable in functionality to microfluidic chips created with PDMS or glass. In the process of answering this question we will touch on FEA modeling, characterization of the manufacturing process and multiple prototype designs while keeping within the low-cost theme. The purpose of capillary electrophoresis is to separate proteins based on their inherent electric charge. Capillary electrophoresis is a standard chip design used in the microfluidics world to prove a new fabrication method or chip material before branching out to other experiments because it is a fairly simple and robust design. Common problems associated with the manufacturing methods and materials were taken into account such as electroosmotic flow and chip sealing. CZE designs from literature were referenced to create a chip that would separate carboxylated microbeads with reasonable resolution. Wire electrodes were affixed to the chip to induce electric fields for the electrophoresis experiments. The goal of this thesis is to prove the manufacturing methods and attain results within 70% of literature standards.

Merlin.net Patient Care Network is a St. Jude Medical product that is used for remote patient management. The basic concept of Merlin.net is to allow the physician to view patient device follow-up information as well as general patient and device information on a web application. The Merlin.net system also interfaces with the patient and will send them notification if they miss a follow-up. All device information will be collected automatically while the patient is sleeping. This information is sent through a telephone line to a Merlin.net server to process a report package and display the collected information on the Merlin.net web application. The Merlin.net verification team ensures that all reports generated by the Merlin.net servers are processed and outputted correctly. There are currently 296 device parameters supported by Merlin.net, and the manual extraction and comparison of the expected parameter values takes several hours for each patient follow-up session. Currently there are 250 patient follow-up sessions used for verification testing. Each new release will continue to create additional patient follow-up sessions. Merlin.net releases are approximately 6 months apart, and each new release adds approximately 30-50 new patient follow-up records to support the new devices. In order to meet aggressive project deadlines, while ensuring that the Merlin.net system is processing and outputting patient follow-up data correctly, it is necessary to come up with an automated process to verify the contents of the processed data is correct. This will save a tremendous amount of time as well as improve on the quality of the verification process by eliminating human error and rework. It is critical for patient safety that the patient device follow-up information is processed and outputted correctly. In this thesis an automated process was developed to verify the correct content of the Merlin.net server generated reports for each patient follow-up session. This process leveraged different tools and scripting languages to achieve automation. TDE (Test Development Environment) tool was used to extract the device parameters from the patient follow-up sessions. The TDE script was written to extracts the desired parameter values from the patient follow-up session and automatically populates parameters in a device parameters spreadsheet. Once all the device parameter values are extracted in the spreadsheet, they are passed through a set of mapping rules, which form the expected values. The mapping rules were implemented as VBA (Visual Basic for Application) macros, one macro for each report. The VBA macros write the expected values back to the spreadsheet to form an “expected values spreadsheet”. The patient follow-up session is then sent to the Merlin.net server to process, which generates a processed patient follow-up session that contains a reports package in .zip format. A perl script was then written to compare the parameter values in the Merlinet.net generated reports with the corresponding expected values from the expected values spreadsheet. The perl script generates a comparison report displaying the discrepancies between the actual and the expected values.

The production and approval process for the various labels used in clinical trials wastes significant time and resources through the need to outsource label production or rely on large reams of pre-cut label stock for each revision throughout the process. An in-house, on-demand label printing and cutting system is a potential remedy to this waste. Previous work by Cheadle et al. resulted in a functional electomechanical prototype of the label cutting aspect of this research, capable of rudimentary linear cuts. In this continued research, emphasis was placed on improved label cutting capabilities and creating PC control software for label design. Cutting operations were enhanced through the development of an algorithm for circular cuts, proportional motor control, and a prototype graphical user interface (GUI) for simple user control. The changes to cutting methods have improved linear cutting precision to an average of 0.00402-in (s = 0.00602-in, n=26) at minimum. The new method for circular cuts has an average precision of 0.04384-in (s = 0.01471-in, n=26). The target precision for cuts is 0.040-in, suggesting that linear cuts are satisfactory, but circular cuts must still be refined. The prototype user interface developed for this research is capable of driving the label cutting system through RS232 communication and exposes all functionality of the system to date. Overall, this research has enhanced the capabilities of the label cutting system significantly, but further work is required to realize a complete label production solution.

This thesis utilizes previously described manufacturing and design techniques for the creation of a PDMS-glass bonded microfluidic device, capable of electrochemical impedance spectroscopy (EIS). EIS has been used across various fields of research for different diagnostic needs. The major aim of this thesis was to capture cancerous and non-cancerous cells between micron sized electrodes within a microfluidic path, and to complete analysis on the measured impedances recorded from the two differing cell types. Two distinct ranges of impedance frequency were analyzed – the α dispersion range, which quantifies the impedance of the membranes of the cells of interest, and the β dispersion range, which quantifies the impedance of the cytosol of the cells of interest. This thesis is unique in the fact that it looks at the cellular impedances of two types of neural cells, which has not been documented previously in literature. The type of cancerous cells analyzed were Neuro-2-A cells, an immortalized line of murine glio/neuroblastoma. The type of non-cancerous cells analyzed were murine primary astrocytes, a mortal line of neurological support cells found throughout the nervous system, and with great abundance in the brain. By using a LabView program coded by a previous Cal Poly student, a sweep scan across a wide frequency range was completed on both cell types, and statistical analysis was completed on target frequencies of interest. A significant difference was found between the two cell lines’ membrane impedances, however no difference was found between the cytoplasm impedances. In total, this thesis aimed to fabricate a reusable microfluidic device capable of EIS for future Cal Poly students, create a protocol suitable for cell culturing and device operation, and to lay a foundation of knowledge for impedance comparisons regarding neural cancerous and non-cancerous cells.

Design of Controlled Environment for Tissue Engineering Malcolm Lapera Tissue engineering aims at relieving the need for donor tissue and organs by developing a process of creating viable tissues in the laboratory setting. With over 120,000 people awaiting a transplant, the need for generating tissue engineered organs is very large [3]. In order for organs to be engineered, a few issues need to be overcome. A work space that both creates an environment which maintains cell viability over an extended period of time as well as accommodates the necessary fabrication equipment will be needed to further tissue engineering research. Therefore, a design for a “Tissue Engineering Hood,” will be developed and evaluated. The goal of this design will provide an environment capable of providing 37°C, 95% humidity, and 5% CO2, actively deter contamination, and provide the necessary support hardware for a 3D printer designed for tissue engineering. The design detailed in this paper was implemented successfully and evaluated. The current design has issues creating the proper environmental conditions, however does actively prevent contamination, and provides the necessary support hardware for a 3D printer. The current design was capable of reaching a temperature of 32°C, had issues increasing the humidity while incorporating the laminar air flow aspect of the design, and design flaws in the door allowed CO2 to leak too rapidly. After remedying these and a few other minor issues described in the report, the tissue engineering hood will be a beneficial tool for use in tissue engineering.

Although highly underutilized by the medical device industry, Finite Element Analysis (FEA) in the development of new technologies is gaining popularity as regulatory bodies such as the Food and Drug Administration (FDA) begin to require additional proof of safety through scientific methods. Non-linear FEA allows engineers to realistically simulate the mechanical behavior of implants as seen in the in-vitro, or in some cases, the in-vivo configurations. The work presented in this report investigates how computational methods can be used to simulate the interaction of a St. Jude Medical silicone soft-tip as it passes through a Peel-Away Sheath (i.e. introducer). In this analysis the soft-tips were modeled as axisymmetric with hyperelastic material properties assigned to the soft-tips. An Ogden, second order hyperelastic material model was used to describe the non-linear stress-strain behavior of silicone soft-tips. The finite element program, ABAQUS/Standard was used to simulate the soft-tip/introducer interactions. The reaction forces obtained through these simulations represent the force required to push a lead through an introducer, and were then compared to experimental data.

Ischemia caused by particles becoming dislodged during transcatheter aortic valve replacement (TAVR) is a possible complication of TAVR. The particles that become dislodged can travel out of the aortic valve, into the aortic arch, and then into either the brachiocephalic artery, the left common carotid artery, the left subclavian artery or continue into the descending aorta. If the particles continue into the descending aorta it poses no risk of causing ischemia however if it travels into the other arteries then it increases the possibility of the particle causing an ischemic event. The goal of this study is to determine what parameters cause the particle to enter one artery over another. The parameters analyzed are the particle diameter, the particle density, the blood pressure, and the diameter of the catheter used in the surgery. This was done by creating a finite element model in COMSOL Multiphysics® to track the particles flowing through a scan of an actual aortic arch. It was determined that the particle diameter, particle density, and the blood pressure affect which artery the particles take to exit the aortic arch. However the diameter of the surgical catheter used in a transaortic approach is not statistically significant when determining which artery the particles will exit. The study shows that larger diameter particle would lead to a higher transmissions probability into the brachiocephalic artery, the left common carotid artery, and the left subclavian artery while a smaller diameter particle would have a higher transmission probability for the descending aorta. Averaging all particle diameters, densities and blood pressure found that 54.95 ± 13.66% of the particles released will travel into the cerebral circulatory system.

A Calibrated Cuff Plethysmography device was built, tested for verification, and used to experiment on human subjects to measure the cardiovascular response of consuming a beet supplement, specifically looking at arterial compliance and pressure-area curves. Each subject was tested four times. A baseline was measured under normal conditions and after five-minute hyperemia conditions. 10 subjects were given 6 ounces of water mixed with either purple Kool-Aid (control), a SuperBeets supplement, or a SuperBeets Sport supplement and after 45 minutes, measurements were taken undergoing normal and hyperemia conditions once more. The verification testing demonstrated the calibration of the device was effectively able to measure volume changes using a stationary metal pipe and IV bag, showing an average percent error of 3.11%. Data collected during the patient experiment resulted in the expected arterial compliance curves as well as pressure-area curves, when measurements were taken properly, and the subject didn’t move. These tests were able to validate the use of the device for measuring arterial compliance and seeing distinctions between normal and hyperemic conditions. However, many issues were presented and are thoroughly addressed in this paper for future research using the same device.

Back pain and injury are a global health issue and are a leading cause of work and activity absence. Prevention would not only save those affected from the burden of pain and discomfort, but would also save people from loss of over 290 million workdays annually and save the healthcare system billions of dollars in expenses per year. Successful research and development of a wearable technology capable of comprehensively monitoring spinal postures that are leading causes of back pain and injury can result in prevention of mild to severe back pain and injury for high-risk people. To accomplish this, the Smart Spine Tape is being developed with specific focus on accuracy, usability, and accessibility, all of which are important factors to consider when engineering for a wide array of populations. Accuracy was assessed using three human participants, with spinal angle data of the Smart Spine Tape being compared to established motion analysis technology data. Prototypes of the device showed promise in the ability to accurately measure spinal postures, but inconsistencies between samples and trials indicated that further development is necessary. Usability and accessibility were assessed using ten human participants who completed one workout each and reported on the tape’s comfort, durability, and ease of use, as well as their thoughts on how much they would be willing to pay for a fully functional version of the device. Participants reported high comfort, high durability, and moderate ease of use throughout their experiences, with the average price range that they would be willing to pay being between $25 and $75. Future directions have been identified that address inconsistencies in data collected by the Smart Spine Tape, possibly caused by inconsistent resistive properties of the piezoresistive ink and plastic deformation of the tape during testing. These future directions involve modifying testing, material, and fabrication methods.

A study was performed on a recently developed prototype of the Yong-Geddes surrogate arm design to collect compliance data of the various system components and determine the accuracy of measurements made through the bench top model. The study was performed to perceive the effectiveness of the model as a tool for validating non-invasive blood pressure detection monitors. Three stages of testing were performed to gather pressure and volume data from an artificial artery component, a sphygmomanometer, and the surrogate arm system to produce compliance estimations. Mathematical equations from supported arterial hemodynamics studies and clinical trials were applied to the pressure and volume data. Dr. Drzewiecki’s equation for arterial compliance was capable of predicting the region of the highest compliance of the artificial artery and produced an overall value of 38.81% for the data. A second degree inverse polynomial was developed and modeled the sphygmomanometer compliance measurements with a of 99.09%. Significant error was observed throughout all stages of the compliance testing, which was attributed to factors such as excessive noise due to faulty data collection equipment and irreparable leaks in the fluid flow system.