Hydrocephalus is a chronic neurological condition affecting an estimated 1 in every 500 infants born. The most common treatment method involves surgical implantation of a shunt system; however these systems have a high failure rate resulting in repeat invasive surgeries. A promising approach being researched to treat hydrocephalus is a miniaturized valve composed of silicon and a hydrogel material. The current chemical cross-linker used in the hydrogel, EGDMA, however is susceptible to hydrolytic cleavage due to the ester groups.

This thesis proposed a novel hydrogel composed of a HEMA backbone and methacrylated Jeffamines as the chemical cross-linker as a possible replacement for the HEMA and EGDMA hydrogel used currently in the hydrocephalus valve. Jeffamine EDR-148 was methacrylated through reaction with methacryloyl chloride and characterized using 1H NMR spectroscopy. Subsequently, hydrogels were synthesized, using both EGDMA and EDR-MA, and the properties were compared through swelling and rotational rheology. Finally, degradation tests were performed to compare the hydrolytic stability of the two cross-linkers.

Results of this work demonstrated that Jeffamine EDR-148 was able to be successfully methacrylated and used to synthesize a hydrogel. The new hydrogel was shown to have comparable mechanical behavior and robustness to the EGDMA hydrogel, with slightly increased swelling capabilities. Degradation tests did not confirm the theory that the EDR-MA gels would exhibit greater hydrolytic stability however. Future work includes perfecting the purification of the EDR-MA, conducting a longer-term degradation study at physiologically relevant conditions, and demonstrating the tunability of the Jeffamine hydrogels.

Proteins play a central role to human body and biological activities. As powerful tools for protein detections, many surface plasmon resonance based techniques have been developed to enhance the sensitivity. However, sensitivity is not the only final goal. As a biosensor, four things really matter: sensitivity, specificity, resolution (temporal/spatial) and throughput.

This dissertation presents several works on developing novel plasmonic based techniques for protein detections on the last two aspects to extend the application field. A fast electrochemically controlled plasmonic detection technique is first developed with the capability of monitoring electrochemical signal with nanosecond response time. The study reveals that the conformational gating of electron transfer in a redox protein (cytochrome c) takes place over a broad range of time scales (sub-µs to ms). The second platform integrates ultra-low volume piezoelectric liquid dispensing and plasmonic imaging detection to monitor different protein binding processes simultaneously with low sample cost. Experiment demonstrates the system can observe binding kinetics in 10×10 microarray of 6 nL droplet, with variations of kinetic rate constants among spots less than ±5%. A focused plasmonic imaging system with bi-cell algorithm is also proposed for spatial resolution enhancement. The two operation modes, scanning mode and focus mode, can be applied for different purposes. Measurement of bacterial aggregation demonstrates the higher spatial resolution. Detections of polystyrene beads binding and 50 nm gold nanoparticles oscillation show a high signal to noise ratio of the system.

The real properties of protein rely on its dynamic personalities. The above works shed light upon fast and high throughput detection of protein kinetics, and enable more applications for plasmonic imaging techniques. It is anticipated that such methods will help to invoke a new surge to unveil the mysteries of biological activities and chemical process.

Measuring molecular interaction with membrane proteins is critical for understanding cellular functions, validating biomarkers and screening drugs. Despite the importance, developing such a capability has been a difficult challenge, especially for small molecules binding to membrane proteins in their native cellular environment. The current mainstream practice is to isolate membrane proteins from the cell membranes, which is difficult and often lead to the loss of their native structures and functions. In this thesis, novel detection methods for in situ quantification of molecular interactions with membrane proteins are described.

First, a label-free surface plasmon resonance imaging (SPRi) platform is developed for the in situ detection of the molecular interactions between membrane protein drug target and its specific antibody drug molecule on cell surface. With this method, the binding kinetics of the drug-target interaction is quantified for drug evaluation and the receptor density on the cell surface is also determined.

Second, a label-free mechanically amplification detection method coupled with a microfluidic device is developed for the detection of both large and small molecules on single cells. Using this method, four major types of transmembrane proteins, including glycoproteins, ion channels, G-protein coupled receptors (GPCRs) and tyrosine kinase receptors on single whole cells are studied with their specific drug molecules. The basic principle of this method is established by developing a thermodynamic model to express the binding-induced nanometer-scale cellular deformation in terms of membrane protein density and cellular mechanical properties. Experiments are carried out to validate the model.

Last, by tracking the cell membrane edge deformation, molecular binding induced downstream event – granule exocytosis is measured with a dual-optical imaging system. Using this method, the single granule exocytosis events in single cells are monitored and the temporal-spatial distribution of the granule fusion-induced cell membrane deformation are mapped. Different patterns of granule release are resolved, including multiple release events occurring close in time and position. The label-free cell membrane deformation tracking method was validated with the simultaneous fluorescence recording. And the simultaneous cell membrane deformation detection and fluorescence recording allow the study of the propagation of the granule release-induced membrane deformation along cell surfaces.

This paper introduces a wireless reconfigurable “button-type” pressure sensor system, via machine learning, for gait analysis application. The pressure sensor system consists of an array of independent button-type pressure sensing units interfaced with a remote computer. The pressure sensing unit contains pressure-sensitive resistors, readout electronics, and a wireless Bluetooth module, which are assembled within footprint of 40 × 25 × 6mm3. The small-footprint, low-profile sensors are populated onto a shoe insole, like buttons, to collect temporal pressure data. The pressure sensing unit measures pressures up to 2,000 kPa while maintaining an error under 10%. The reconfigurable pressure sensor array reduces the total power consumption of the system by 50%, allowing extended period of operation, up to 82.5 hrs. A robust machine learning program identifies the optimal pressure sensing units in any given configuration at an accuracy of up to 98%.

Early detection and treatment of disease is paramount for improving human health and wellness. Micro-scale devices promote new opportunities for the rapid, cost-effective, and accurate identification of altered biological states indicative of disease early-onset; these devices function at a scale more sensitive to numerous biological processes. The application of Micro-Electro-Mechanical Systems (MEMS) in biomedical settings has recently emerged and flourished over course of the last two decades, requiring a deep understanding of material biocompatibility, biosensing sensitively/selectively, biological constraints for artificial tissue/organ replacement, and the regulations in place to ensure device safety. Capitalizing on the inherent physical differences between cancerous and healthy cells, our ultra-thin silicone membrane enables earlier identification of bladder cancer—with a 70% recurrence rate. Building on this breakthrough, we have devised an array to multiplex this sample-analysis in real-time as well as expanding beyond bladder cancer. The introduction of new materials—with novel properties—to augment current and create innovative medical implants requires the careful analysis of material impact on cellular toxicity, mutagenicity, reactivity, and stability. Finally, the achievement of replacing defective biological systems with implanted artificial equivalents that must function within the same biological constraints, have consistent reliability, and ultimately show the promise of improving human health as demonstrated by our hydrogel check valve. The ongoing proliferation, expanding prevalence, and persistent improvement in MEMS devices through greater sensitivity, specificity, and integration with biological processes will undoubtedly bolster medical science with novel MEMS-based diagnostics and therapeutics.

Hydrocephalus is a chronic medical condition characterized by the excessive accumulation of cerebrospinal fluid in the brain. It is estimated that 1-2 of every 1000 babies in the United States is born with congenital hydrocephalus, with many individuals acquiring hydrocephalus later in life through brain injury. Despite these alarming statistics, current shunts for the treatment of hydrocephalus display operational failure rates as high as 40-50% within two years following implantation. Failure of current shunts is attributed to complexity of design, external implantation, and the requirement of multiple catheters. The presented hydrogel wafer check valve avoids all the debilitating features of current shunts, relying only on the swelling of hydrogel for operation, and is designed to directly replace failed arachnoid granulations- the brain’s natural cerebrospinal fluid drainage valves. The valve was validated via bench-top (1) hydrodynamic pressure-flow response characterizations, (2) transient response analysis, and (3) overtime performance response in brain-analogous conditions. In-vitro measurements display operation in range of natural CSF draining (cracking pressure, PT ~ 1–110 mmH2O and outflow hydraulic resistance, Rh ~ 24 – 152 mmH2O/mL/min), negligible reverse flow leakages (flow, QO > -10 µL/min), and demonstrate the valve’s operational reproducibility of this new valve as an implantable treatment.

Microwave tomography (MWT) differs from the current forms of biomedical imaging modalities by measuring the dielectric properties in different tissues in order to create an image of the object under evaluation. This technology could be harnessed for the evaluation of a stroke because the areas of the brain that are not being provided oxygen will have a reduced concentration of blood, leading to a reduced relative permittivity (also referred to as dielectric constant). Strokes themselves require accurate diagnosis for proper treatment to be administered. Microwave tomography offers advantages of stroke diagnosis over imaging methods such as magnetic resonance imaging (MRI) and computerized tomography (CT). Like MRIs, microwave tomography passes only non-ionizing radiation through the patient, allowing for multiple safe scans. Because MWT requires only an array of antennas sending a non-ionizing electromagnetic field, which is on the level of the fields sent in cell phones, a patient undergoing a stroke could be diagnosed inside an ambulance with multiple MWT scans, greatly reducing the time before treatment. The challenge for this thesis is to correctly solve an ill-posed problem presented in a microwave tomography system and output an image of the object's electrical properties. The system itself is an inverse problem because the object to be imaged and its properties are unknown. Rather, the incident field and resulting scattered field due to interaction with the object of interest are known. To achieve a unique solution for this problem, a software implementation of a common microwave inversion method known as Born's Iterative Method is realized through MATLAB.

The team has designed and built a golf swing analyzer that informs the user of his mistakes while putting with a golf club. The team also interfaced a Linux program with the analyzer that allows the user to review the flaws in his golf swing. In addition, the application is more personalized than existing devices and tailored to the individual based on his level of experience. The analyzer consists of an accelerometer, gyroscope, magnetometer, vibration motor, and microcontroller that are connected on a board that attaches to the top of the shaft of a golf club, fitting inside a 3D printed case. The team has assembled all of the necessary hardware, and is able to successfully display critical parameters of a golf putt, as well as send instant feedback to the user. The final budget for this project was $378.24

A Microbial fuel cell (MFC) is a bio-inspired carbon-neutral, renewable electrochemical converter to extract electricity from catabolic reaction of micro-organisms. It is a promising technology capable of directly converting the abundant biomass on the planet into electricity and potentially alleviate the emerging global warming and energy crisis. The current and power density of MFCs are low compared with conventional energy conversion techniques. Since its debut in 2002, many studies have been performed by adopting a variety of new configurations and structures to improve the power density. The reported maximum areal and volumetric power densities range from 19 mW/m2 to 1.57 W/m2 and from 6.3 W/m3 to 392 W/m3, respectively, which are still low compared with conventional energy conversion techniques. In this dissertation, the impact of scaling effect on the performance of MFCs are investigated, and it is found that by scaling down the characteristic length of MFCs, the surface area to volume ratio increases and the current and power density improves. As a result, a miniaturized MFC fabricated by Micro-Electro-Mechanical System(MEMS) technology with gold anode is presented in this dissertation, which demonstrate a high power density of 3300 W/m3. The performance of the MEMS MFC is further improved by adopting anodes with higher surface area to volume ratio, such as carbon nanotube (CNT) and graphene based anodes, and the maximum power density is further improved to a record high power density of 11220 W/m3. A novel supercapacitor by regulating the respiration of the bacteria is also presented, and a high power density of 531.2 A/m2 (1,060,000 A/m3) and 197.5 W/m2 (395,000 W/m3), respectively, are marked, which are one to two orders of magnitude higher than any previously reported microbial electrochemical techniques.