Background: Over 700,000 patients per year undergo open-heart surgery. Healing complication rates can be up to 5% of patients who undergo this procedure, with a morbidity rate of 50% if mediastinitis supervenes. A secure and rigid fixation of surgically divided sternum is critical to avoid healing complications. The purpose of this study was to compare the yield load, construct stiffness, ultimate load, displacement at ultimate load, and post-yield behavior of three sternotomy closure methods (Peristernal wires or Sternalock titanium plates) when stressed in each of three directions: lateral distraction, rostro-caudal (longitudinal) shear distraction, and anterior-posterior (transverse) shear in a cadaveric model. Methods: Forty-two fresh cadaver models were divided into three test groups: group A, B, and C. A cardiothoracic surgeon divided each cadaveric sternum longitudinally and repaired peristernal wires or one of two Sternalock configurations. Tests were performed using a materials testing system that applied force at a constant displacement rate in a uniaxial direction until the construct catastrophically failed. Mechanical behavior was monitored using a 3D texture correlation system to create a real-time three-dimensional representation of strain directions. The resulting displacement pattern is analogous to a finite element contour plot of displacements, Lagrange Strain, or velocity. Statistical analysis was used to show the different mechanical properties of each closure method. Results: When loaded in lateral distraction, both Sternalock configurations surpassed the rigidity of peristernal wires by 600%. Some evidence was also found linking Sternalock with stiffer behavior in the rostro-caudal direction. Though not statistically significant, a trend was observed showing that constructs using the Sternalock also had higher yield loads, as well as, less post-yield displacement when compared to peristernal wires. Conclusions: Data gathered showed the superior performance of the Sternalock system in stiffness in both longitudinal distraction and rostro-caudal shear. Implications for use of the Sternalock system are faster healing times, lower complication rates, and success of the procedure.

The goal of this study is to design and manufacture a microfluidic device capable of measuring changes in impedance valuesof microfluidic cell cultures. Tocharacterize this, an interdigitated array of electrodes was patterned over glass, where it was then bonded to a series of fluidic networks created in PDMS via soft lithography. The device measured ethanol impedance initially to show that values remain consistent over time. Impedance values of water and 1% wt. saltwater were compared to show that the device is able to detect changes in impedance, with up to a 60% reduction in electrical impedance in saltwater. Cells were introduced into the device, where changes in impedance were seen across multiple frequencies, indicating that the device is capable of detecting the presence of biologic elements within a system. Cell measurements were performed using NIH-3T3 fibroblasts.

Fluorescence microscopy has revolutionized medicine and biological science with its ability to study the behavior and chemical expressions of living cells. Fluorescent probes can label cell components or cells of a particular type. Clinically the impact of fluorescence imaging can be seen in the diagnosis of cancers, AIDS, and other blood related disorders. Although fluorescence imaging devices have been established as a vital tool in medicine, the size, cost, and complexity of fluorescence microscopes limits their use to central laboratories. The work described in this thesis overcomes these limitations by developing a low cost integrated fluorescence microscope so single use fluorescence microscopy assays can be developed. These assays will enable at-home testing, diagnostics in resource limited settings, and improved emergency medicine.

Heart disease is one of the most prevalent diseases in the world. The survival chances for patients with ventricular fibrillation/ventricular tachycardia reduces significantly as time passes without treatment and even after getting timely treatment recurring episode are common. These patients can benefit from an Implantable Cardioverter Defibrillator (ICD) which can monitor heart rhythm and provide immediate treatment. Due to the ever changing physical conditions and disease progression, the ICD needs to collect diagnostic data as well as support programming by the physician. The ICD uses inductive telemetry and radio-frequency telemetry for the communication with the external devices such as a programmer or a monitor. Inductive telemetry uses less energy than RF telemetry but has a very short range of communication. In addition to inductive telemetry, the St. Jude Medical ICD supports 2.45 GHz band based asynchronized wakeup and 400 MHz MICS band based synchronized wakeup. The 2.45 GHz band based wakeup has limited wakeup range and the 400 MHz MICS based synchronized wakeup has limited availability for connection because it requires synchronization with the base station. The enhanced Medical Implant Communications Service (eMICS) algorithm is a firmware based algorithm which addresses the issues with other two wakeup schemes and provides fast, robust, and seamless wakeup. This thesis describes the design, implementation, and initial testing of eMICS algorithm on the Unity device platform in Technology Project Management (TPM) phase. The eMICS automated test tool developed at St. Jude Medical was used to test the eMICS algorithm under a controlled lab environment, typical home environment, typical hospital/clinic environment, and in the field. The project was successfully completed and transferred to Product Project Management (PPM) phase. However, the suggested duration of 60-90 seconds for sniff interval which will cause the least effect on the battery life was found unacceptable, and there is also a strong need for energy efficient hardware which draws minimal amount of current during each sniff. Therefore, St. Jude Medical is collaborating with the hardware vender to implement eMICS algorithm in the next version of hardware.

Atrial fibrillation (AF) is the disordered activation of the atrial myocardium, which is a major cause of stroke. Currently, the most effective, minimally traumatic treatment for AF is percutaneous catheter ablation to isolate arrhythmogenic areas from the rest of the atrium. The standard in vitro evaluation of ablation catheters through lesion studies is a resource intensive effort due to tissue variability and visual measurement methods, necessitating large sample sizes and multiple prototype builds. A computational test bed for ablation catheter evaluation was built in SolidWorks® using the morphology and dimensions of the left atrium adjacent structures. From this geometry, the physical model was built in COMSOL Multiphysics®, where a combination of the laminar fluid flow, electrical currents, and bioheat transfer was used to simulate radiofrequency (RF) tissue ablation. Simulations in simplified 3D geometries led to lesions sizes within the reported ranges from an in-vivo ablation study. However, though the ellipsoid lesion morphologies in the full atrial model were consistent with past lesion studies, perpendicularly oriented catheter tips were associated with decreases of -91.3% and -70.0% in lesion depth and maximum diameter. On the other hand, tangentially oriented catheter tips produced lesions that were only off by -28.4% and +7.9% for max depth and max diameter. Preliminary investigation into the causes of the discrepancy were performed for fluid velocities, contact area, and other factors. Finally, suggestions for further investigation are provided to aid in determining the root cause of the discrepancy, such that the test bed may be used for other ablation catheter evaluations.

During development and testing of the functionality of the pacemaker and defibrillator device, engineers in the St. Jude Medical Cardiac Rhythm Management Division use an in-house development tool called Universal Engineering Programmer (UEP) to ensure the device functions as expected, before it can be used to test on an animal or a human during the implantation process. In addition, some applications of UEP are incorporated into the official releases of the device product. UEP has been developed and used by engineers across departments in the St. Jude Medical Cardiac Rhythm Management Division (CRMD). This thesis covers the flexible and reusable design and implementation of UEP features, to allow engineers to easily and effectively develop and test the devices.

This Master’s Thesis project consists of the research, design, and fabrication of a system that could perform broadband impedance measurements (1kHz-20Mhz) of single cells using National Instruments Labview data acquisition and programming in coordination with a single cell capture device. Presented first is the background information on cells and their electrical properties, along with background in micro-total-analysis systems as well as impedance spectroscopy. Experimental Methods are then discussed for the electrode design, cellular modeling in COMSOL, fabrication methods, and Labview 8.0 Set-up and programming. Measurements were performed using the single-cell capture device on saline, yeast cells, and a polysterene bead. Analysis of the impedance data showed a clear visual and statistically significant difference between live yeast, the bead, and saline. A comparison of live yeast cells to nutrient-starved yeast cells was also performed and a distinct difference in spectra was observed.

Melanoma skin cancer is the abnormal growth of the melanocytes – the pigmented cells located in the epidermis. The current gold standard diagnostic technique for determining whether a lesion is cancerous involves subjectively examining suspicious lesions and performing an invasive biopsy to confirm melanoma. This method may neglect some lesions or cause scarring from biopsies that turn out to be benign. Thus, impedance-based detection using a multi-electrode device was investigated as a noninvasive technique to diagnose melanoma skin cancer. The multi-electrode device was designed with 8 equally spaced Ag/AgCl electrodes surrounding one central electrode at a 5 mm radius. The electrodes were held in place by a vice-like mechanism using three circular Delrin sections. The electrodes were interfaced to an 8:1 multiplexer and National Instruments Educational Laboratory Virtual Instrumentation Suite (ELVIS) for measurement control and impedance analysis. The ELVIS system, multiplexer, and electrode device were validated for accuracy with various values of resistors and capacitors. Raw and cooked chicken thigh meat and skin were tested to evaluate the capabilities of the electrode device to discern different tissue types and tissue moisture contents by impedance measurements. EpidermTM and Melanoma tissue-engineered skin analogues, provided by MatTek Corporation, were tested to mimic the in situ disease state. The electrode device was found to produce reliable measurements for known electrical components with resistances between 10 ohms and 100 k-ohms and capacitances between 10 nF and 10 uF. The measurements from the chicken tissues and tissue-engineered skin constructs – excluding cooked chicken skin data – fell within the reliable range of the electrode device and were thus considered reliable as well. All analyses concluded that a statistical difference between the impedances of raw meat and raw skin, cooked meat and raw meat, and EpidermTM and Melanoma existed. Therefore, the hypothesis that a multi-electrode device could differentiate between melanoma and healthy skin tissues based on impedance measurements was satisfied.

The prevalence and devastating nature of cardiovascular diseases has led to many advancements in the therapies used to treat the millions of patients that suffer as a result of these conditions. As coronary artery disease (CAD) is the most common of these cardiovascular conditions, it is a major focus of research among the medical industry. Although lifestyle changes and drug therapies can treat early CAD, more advanced cases often require more definitive interventions. In conjunction with angioplasty, stenting of an occluded vessel has shown significant success in preventing restenosis. However, as with nearly every therapeutic process in the medical field, several complications have arisen in stented patients that pose a need for further improvement of the devices. As a result, the stent industry is constantly striving towards improving the characteristics and outcome of their product and with these efforts comes the need for extensive testing and research. Continuous improvement and innovation in the field of tissue engineering has brought about the possibility of creating laboratory grown tissue engineered vascular grafts (TEVGs) for the purpose of replacing and/or bypassing damaged or occluded regions of the vasculature. By employing the techniques used to produce TEVGs, a blood vessel mimic (BVM) bioreactor system has been developed with the intent of using the resulting construct as a model for testing the cellular response of a human blood vessel to an intravascular device such as a stent. This would allow gathering of more significant data in the early stages of device development and may reduce the overall costs and time required to refine a design. Although the BVM system has previously been used to cultivate viable constructs that were subsequently used to observe the response to a deployed stent, the flow conditions within the original design are not representative of the physiologic conditions in a native vessel. This aspect of the original system presented a need for development in order to be considered by researchers as an accurate in vitro representation of the target vessels in which the stents are used. One of the primary concerns of this environment is creating and maintaining physiologic flow conditions that will represent those present in native vessels in order to facilitate cells sodded on the construct to grow as they would under native conditions. The two key aspects of flow are pulsatility and wall shear stress. Studies in this thesis were carried out to determine the best and most feasible methods for implementing appropriate levels of pulsation and wall shear stress in the previously established BVM bioreactor system with the intention of maintaining the original system’s simplicity and high throughput potential. Pulsatile flow was created by elevating backpressure in the BVM chamber while using a different pump head and pump tubing. Wall shear stress was adjusted by altering the viscosity of the perfusate and flow rate through the system. Both pulsatile flow and shear stress were established without any major changes to the overall configuration of the system. Pulsatile pressures of ~80 mmHg and wall shear stress forces of ~6.4 dyn/cm2 were established with minimal alteration to the original system. Pulsatility was created by using a 3-roller peristaltic pump head in place of the originally specified 8-roller head to create pulses that were then regulated with backpressure created by restricting down stream flow. Increasing the viscosity and corresponding flow rate allowed for instigation and control of wall shear stress at the inner wall of the BVM graft. Although the resulting protocols presented here require refinement for ultimately successful implementation, they are important underpinnings that will facilitate the eventual development of an ideal BVM system that is highly suitable for use as a high-throughput intravascular device testing model.

California Polytechnic State University, San Luis Obispo is a university that encourages students to approach learning hands-on. As such, there is cutting-edge technology being developed by students in all departments on campus. Being that the university possesses an outstanding biomedical engineering department, there are groundbreaking medical devices that students are creating at Cal Poly SLO. These are devices that can better the lives of individuals suffering from ailments or fulfill needs in the medical industry. Subsequently, it is vital that these devices make it out of campus laboratories and into the hands of consumers. In order to move a product from ideation to the market, numerous steps must be completed and often times, especially with the challenges of commercializing medical devices, these efforts can result in failed product launches. As such, there is demand for a commercialization process to be created at Cal Poly SLO that will aid student created medical devices in reaching the market. This paper documents the progress made thus far on such a process at Cal Poly SLO.