Indiana University-Purdue University Indianapolis (IUPUI) / A new process for fabricating a nano fluidic device that can be used in medical application is developed and demonstrated. Nano channels are fabricated using a nano tip in indentation mode on AFM (Atomic Force Microscopy). The nano channels are integrated between the micro channels and act as a filter to separate biomolecules. Nano channels of 4 to7 m in length, 80nm in width, and at varying depths from 100nm to 850 nm allow the resulting device to separate selected groups of lysosomes and other viruses. Sharply developed vertical micro channels are produced from a deep reaction ion etching followed by deposition of different materials, such as gold and polymers, on the top surface, allowing the study of alternative ways of manufacturing a nano fluidic device. PDMS (Polydimethylsiloxane) bonding is performed to close the top surface of the device. An experimental setup is used to test and validate the device by pouring fluid through the channels. A detailed cost evaluation is conducted to compare the economical merits of the proposed process. It is shown that there is a 47:7% manufacturing time savings and a 60:6% manufacturing cost savings.

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In spite of the stablility (lack of reactivity) of diamond powder, I have developed a method for tethering alkyl chains and polymers to deuterium/hydrogen-terminated diamond. One method is through ether linkages via thermolysis of di-tert-amyl peroxide (DTAP). This reaction with DTAP has also been applied to grow polymers on the diamond surface. The other method is atom transfer radical polymerization (ATRP), which was applied to grow polystyrene at the surface of diamond. Both polystyrene-modified diamond and sulfonated polystyrene-modified diamond can be prepared by either method, and can be used for solid phase extraction. Diamond stationary phases are stable under basic conditions, which is not the case for silica-based stationary phases. Surface characterization was performed by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS) and diffuse reflectance Fourier transform infrared spectroscopy (DRIFT). While the main focus of my graduate research has been the surface modification of diamond, I also describe other projects on which I have worked. The use of radical-based processes for modifying diamond is related to a different radical-based synthesis of monolayers or polymers I performed by scribing silicon (Siscr). After preparation of homogeneous olefin-terminated monolayers on scribed silicon made from 1,9-decadiene and chemisorption of Grubbs' catalyst, ring-opening metathesis polymerization (ROMP) of norbornene was demonstrated. These surfaces were characterized by XPS and ToF-SIMS. I also investigated the extent of PDMS oligomers transfer onto different surfaces with a wide range of hydrophobicities, using an uninked, unpatterned PDMS stamp. The effect of surface free energy on PDMS transfer in microcontact printing was investigated and the relationship between the amount of PDMS in ToF-SIMS spectra and the surface tensions of initial surfaces was revealed. Therefore, PDMS transfer can be applied as a probe of surface free energies using ToF-SIMS, where PDMS preferentially transfers onto more hydrophilic surface features during stamping, with little transfer onto very hydrophobic surface features. In much of my thesis work, I performed multivariate analysis of my data, especially of my ToF-SIMS data. Such chemometrics methods include principle components analysis (PCA), partial least squares (PLS) cluster analysis, and multivariate curve resolution (MCR). I also applied these tools to analyze electrospray ionization (ESI) mass spectrometry data from a lipidomics study.

Diseases are often diagnosed by detection of disease-specific biomarkers in fluid samples. However, many state-of-the-art detection methods require a lab with complex machinery, trained operators, and/or lengthy analysis time. In contrast, point-of-care (POC) devices are brought to the patient's location, they are easy to use, and results are obtained almost immediately. Many current POC devices are too difficult to be used without a skilled assistant, and although many are able to detect analytes above a threshold value, they give little or no quantitative information. This work presents the development of polymer-based microfluidic devices capable of sensing and quantifying biomarkers in fluid samples in a straightforward manner using a novel biomarker assay termed "flow valve diagnostics". In this assay, an antibody-modified polydimethylsiloxane (PDMS) microchannel constricts due to the binding force between antibodies and antigens, stopping fluid flow. The flow distance is measured and correlated to antigen concentration. This detection method is an improvement over other methods because it is an innovative, non-instrumented, label-free, easy-to-use approach. These devices are small, portable, disposable, inexpensive, and thus ideal for use in POC testing. I have successfully fabricated flow valve devices with standard micromachining techniques, including photolithography, replica molding with PDMS, and plasma oxidation. Following fabrication, I compared two methods for attaching receptor biomolecules (e.g., antibodies) to the microchannel surfaces: non-specific adsorption and silanization with 3-glycidoxytrimethoxypropylsilane (GOPS). I used laser-induced fluorescence to determine that silanization with GOPS was the better method for biomolecule attachment. Finally, I tested antibody-modified flow valve devices with target antigens to determine if the antibody/antigen binding force was strong enough to cause channel pinching and flow stoppage. By modifying the device design and using higher antigen concentrations, I was able to show that flow valve devices can detect antigens in a concentration-dependent manner. Future work to improve the device design and to modify and test these devices with different receptor/target pairs will bring flow valve diagnostics closer to becoming a valuable asset in biomarker detection and POC testing.

The capability of manipulating microparticle in small volumes is fundamental to many biological and medical applications, including separation and detection of cells. The development of microtools for effective sample handling and separation in such volumes is still a challenge. DEP (dielectrophoresis) is one of the most widely used methods in handling the microparticles. In this thesis we show that forces generated by nonuniform electric field (DEP) can be used for trapping and separating the microparticles (latex beads). This work further explores the DEP force based on different electrode geometries and medium conductivity. A micromanipulator for latex bead separation was designed, fabricated and characterized. For the development of DEP manipulator, the fabrication and packaging of microfluidic structure with the microelectrode is crucial for reliable analysis. A combination of SU-8 photoresist and polydimethylsiloxane polymer was used for this purpose. Besides, the DEP manipulator, preliminary study on a Coulter counter was conducted. The Coulter counter works on the principle of resistive pulse sensing. This counter is used for counting the beads as they pass through the microfluidic channel. Its possible integration with the manipulator was also explored.

Given the surmounting disagreement amongst researchers in the area of liquid flow behavior at the microscale for the past thirty years, this work presents a fundamental approach to analyzing the pressure losses experienced by the laminar flow of water (Re = 7 to Re = 130) through both rectangular straight duct microchannels (of widths ranging from 50 to 130 micrometers), and microchannels with sudden expansions and contractions (with area ratios ranging from 0.4 to 1.0) all with a constant depth of 104 micrometers. The simplified Bernoulli equations for uniform, steady, incompressible, internal duct flow were used to compare flow through these microchannels to macroscale theory predictions for pressure drop. One major advantage of the channel design (and subsequent experimental set-up) was that pressure measurements could be taken locally, directly before and after the test section of interest, instead of globally which requires extensive corrections to the pressure measurements before an accurate result can be obtained. Bernoulli's equation adjusted for major head loses (using Darcy friction factors) and minor head losses (using appropriate K values) was found to predict the flow behavior within the calculated theoretical uncertainty (~12%) for all 150+ microchannels tested, except for sizes that pushed the aspect ratio limits of the manufacturing process capabilities (microchannels fabricated via soft lithography using PDMS). The analysis produced conclusive evidence that liquid flow through microchannels at these relative channel sizes and Reynolds numbers follow macroscale predictions without experiencing any of the reported anomalies expressed in other microfluidics research. This work also perfected the delicate technique required to pierce through the PDMS material and into the microchannel inlets, exit and pressure ports without damaging the microchannel. Finally, two verified explanations for why prior researchers have obtained poor agreement between macroscale theory predictions and tests at the microscale were due to the presence of bubbles in the microchannel test section (producing higher than expected pressure drops), and the occurrence of localized separation between the PDMS slabs and thus, the microchannel itself (producing lower than expected pressure drops).

Aortic aneurysms are the 14th leading cause of death in the United States. Annually, abdominal aortic aneurysm (AAA) ruptures are responsible for 4500 deaths. There are another 45,000 repair procedures performed to prevent rupture, and of these approximately 1400 lead to deaths. With proper detection, the aneurysm may be treated using endovascular aneurysm repair (EVAR). Understanding how the flow of the blood within the artery is affected by the aneurysm is important in determining the growth of the aneurysm, as well as how to properly treat the aneurysm. The goal of this project was to develop a physical construct of the AAA, and use this construct to validate a computational model of the same aneurysm through flow visualization. The hypothesis was that the fluid velocities within the physical construct would accurately mimic the fluid velocities used in the computational model. The physical model was created from a CT scan of an AAA using 3D printing and polymer casting. The result was a translucent box containing a region in the shape of the aneurysm. Fluid was pumped through the construct to visualize and quantify the velocity of the fluid within the aneurysm. COMSOL Multiphysics® was used to create a computational model of the same aneurysm, as well as obtain velocity measurements to statistically compare to those from the physical construct. There was no significant difference between the velocity values for the physical construct and the COMSOL Multiphysics® model, confirming the hypothesis. This study used a CT scan to create an anatomically accurate model of an AAA that was used to validate a computational model using a novel technique of flow visualization. As EVAR technologies continue to progress, it will become increasingly important to understand how the blood flow within the aneurysm affects the growth and treatment of AAAs.

The goal of this project is to eliminate electroosmotic flow (EOF) in a microfluidic chip. EOF is a naturally occurring phenomenon at the fluid-surface interface in microfluidic chips when an electric field is applied across the fluid. When isoelectric focusing (IEF) is carried out to separate proteins based on their surface charge, the analytes must remain in the separation chamber, and not migrate to adjacent features in the microfluidic chip, which happens with EOF. For this project, a microfluidic chip was designed and commissioned to be photolithographically transferred onto a Si wafer. A PDMS component was then casted on the Si wafer and plasma bonded to a glass substrate. This chip was initially designed to carry out continuous IEF, and the focus of the project was shifted to the analysis of eliminating EOF in a microfluidic chamber. Per previous research test methods, methylcellulose will be used to analyze the phenomenon of electroosmotic flow in the chamber. A COMSOL model is used a theoretical basis of comparison when analyzing the flow velocities of the treated versus untreated microfluidic chips. The purpose of this project is to use the research performed in on this chip as a precursor to future analyses of continuous IEF on microfluidic chips in the Cal Poly Microfluidics group.

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.

Research to increase the efficiency of conventional solar cells is constantly underway. The goal of this work is to increase the efficiency of conventional solar cells by incorporating quantum dot (QD) nanoparticles in the absorption mechanism. The strategy is to have the QDs absorb UV and fluoresce photons in the visible region that are more readily absorbed by the cells. The outcome is that the cells have more visible photons to absorb and have increased power output. The QDs, having a CdSe core and a ZnS shell, were applied to the solar cells as follows. First, the QDs were synthesized in an octadecene solution, then they were removed from the solution and finally they were dried and deposited into polydimethylsiloxane (PDMS) and the PDMS/QD composite is allowed to cure. The cured sample is applied to a silicon solar panel. The panel with the PDMS/QD application outputs 2.5% more power than the one without, under identical illumination by a tungsten halogen lamp, using QDs that fluoresce in the orange region. This work demonstrates the feasibility of incorporating QDs to increase the efficiency of conventional solar cells. Because the solar cells absorb better in the red region, future effort will be to use QDs that fluoresce in that region to further boost cell output.