This thesis successfully integrates laminate microfluidic devices with an analytic Surface Plasmon Resonance (SPR) instrument. Integration was accomplished at low-cost using materials such as polydimethylsiloxane (PDMS), Poly(methyl methacrylate) (PMMA), Tygon tubing, and a 3-way stopcock. The main components of this thesis are the design and fabrication of the low-cost, in-house fluidics that can integrate with upstream microfluidics and the validation of the in-house fluidics using the Biosensing Instruments BI-2000 SPR instrument. The low-cost fluidics was designed and fabricated “in-house” using a novel investment casting technique that required the use of laser cutting technology to make a master cast, and candle wax to make the fluidic flow gasket. Integration of upstream microfluidic devices is the next step towards fully integrated point-of-care (POC) diagnostics. Development of low-cost POC diagnostics will enable physicians to diagnosis patients outside of clinical settings, granting treatment access to a much wider population. Surface Plasmon Resonance is used for its detection abilities combined with its ability to perform real-time sample analysis. Validation of the in-house fluidics was accomplished by conducting (2) experiments: (1) to compare the angular shift elicited by ethanol solutions between in-house fluidics, factory fluidics, and the literature, and (2) to compare the angular shift between in-house fluidics and factory fluidics caused by the cleaving of fibroblasts from the SPR sensor chip. Successful comparisons made in both experiments proved successful development of low-cost fluidics that could integrate upstream microfluidic devices.

<p dir="ltr">Scientists across many disciplines have observed a striking phenomenon: chemical reactions that do not appreciably occur in large volumes often proceed readily in microdroplets. At the core of suggested mechanisms is the influence of interfacial chemistry on the overall reaction; when the interfacial area dominates the reactor volume, the measured reaction rate is often accelerated. For instance, microdroplets with a high surface area-to-volume ratio (generally with radii smaller than 10 µm) provide a unique reaction environment and have been observed to accelerate a wide variety of chemical reactions. This is likely surprising to most readers, as much of our chemical intuition comes from experiments performed on benchtops in beakers (large, single-phase systems). However, microdroplets are regularly exploited by nature, from multiphase atmospheric aerosols to biomolecular condensates in cells. Thus, it is vital to have measurement tools capable of studying multiphase, nanoscale reactors. An electrochemical perspective on measuring multiphase chemistry under nanoconfinement is given in Chapters 2-4. To my knowledge, there were no reports of accelerated reactivity in microdroplets from electrochemical studies until the 2021 observation that enzyme turnover rates are inversely-related to the size of the containing nanodroplet (given in Chapter 6). In this dissertation work, we developed new electroanalytical tools to probe chemical transformations/reactions at micro- and nano-interfaces and made use of new reaction schemes that capitalize on multiphase microenvironments.</p><p dir="ltr">Much of the method development was built on the foundation of stochastic nanoelectrochemistry, a technique that is reviewed thoroughly in Chapters 2, 4, and 5. Briefly, stochastic nanoelectrochemistry is the measurement of single nano-entities, one-at-a-time, as the collide with a micron-sized electrode. The nano-entities studied in this dissertation were aqueous droplets, either suspended in an immiscible oil continuous phase or propelled through air. We dove deeply into these studies, from using correlated microscopy to watch how these micro- and nanodroplets collide with other interfaces to building simulations to quantify changes to the chemistry inside. We showed how the surface environment directs water nanodroplet collisions (Chapter 10) and measured the sub-diffraction-limited nanometer contact area that forms between a microdroplet and a metal surface (Chapter 11). Using the nanodroplets as tiny reactors, we measured accelerated rate constants and promoted unfavorable nucleation events in attoliter-femtoliter aqueous droplets (see Chapter 6-7 and Chapter 12, respectively) and in microliter aqueous droplets (see Chapter 8 and Chapter 9, respectively).</p><p dir="ltr">As mentioned above, microdroplets are ubiquitous in air (<i>e.g.,</i> aerosols). However, electrochemistry is not an obvious choice for the measurement of intact aerosols because electrochemistry is traditionally performed in a conductive solution, and electrochemistry in air is difficult. In this dissertation we laid the groundwork for a path forward that allows electrochemical access the air|microdroplet interface. We designed and characterized a novel electrochemical cell, where the working electrode is a microwire traversing a suspended liquid film (Chapters 13-15). The early results were born from pure curiosity: Can we do electrochemistry in a soap bubble wall? Chapter 13 shows that the answer is “Yes!”, and that electrochemistry can report on aerosol contents that are collected from the air into this thin film. However, the soap bubble wall was severely limited by the lifetime of the bubble wall (bubbles pop), so in Chapters 14 and 15, we introduce a suspended ionic liquid film that does not pop from evaporation. With the more robust system, we realized the ability to probe intact single microdroplets, one-at-a-time (Chapter 14), giving electrochemical access to the air|water interface.</p><p dir="ltr">As detection of illicit substances from aerosols has the potential for immediate impact on first responder, user, and bystander safety, we employed the new technology to electroanalyze aerosolized methamphetamine (Chapter 13) and fentanyl (Chapter 15). Electrochemistry is small, simple, and affordable, making it a realistic candidate for an in-field sensor. We overcame selectivity challenges by using our understanding of interfacial microenvironments to leverage local pH changes, as demonstrated by the reliable detection of low purity cocaine in mixed powders (Chapter 16). This patented method provides a highly selective technique for cocaine identification in the presence of adulterants without the need to bring any chemicals to the scene (water is our only reagent!).</p><p dir="ltr">In sum, this body of work contributes to the electrochemical studies in nano- and microdroplets, extending the reach to account for droplet size on measured rates and to include microdroplets with a water|air boundary. Applications of the work were focused on in-field detection of illicit substances.</p>

<p>As of 2021, 38.4 million people worldwide are living with Human Immunodeficiency virus (HIV), with eastern and southern Africa having the highest prevalence. The efficacy of treatment is determined by identifying acute HIV infections (AHI) and prompting early antiretroviral therapy (ART) initiation to achieve viral suppression and reduce the risk of transmission. Existing rapid tests that detect host antibodies are affected by long seroconversions which allow the viruses to remain undetected until long after infection. On the contrary, highly sensitive nucleic acid amplification test (NAAT) based assays, serving as the gold standard for detection are restricted by their long turnaround time and high cost of implementation thus, restricting their use in low resource settings. Further, drug resistance cases and patient non-compliance to treatment may lead to HIV progression to aids; therefore, effective viral load monitoring is a critical component in the HIV care continuum. To address the gaps in viral load monitoring and early HIV detection, I propose to develop assays for handheld self-test platforms to detect low concentrations of HIV via two different approaches: 1) I will optimize an existing NAAT - based assay to semi-quantitatively detect HIV particles that were spiked in clinical samples and 2) I will Investigate the binding kinetics between HIV p24 antigen and Anti-HIV-1 p24 Antibody using the principle of Bio-layer Interferometry. Thus, I will lay the foundation for the development of a novel and highly sensitive p24 detection assay. Overall, this work will enable detection of ahi detection as well as support people living with HIV (PLHIV) management, all while remaining connected to healthcare and provider support. </p> <p><br></p>

Bioelectronics effectively bridges the gap between the biochemical and the electrical domains, integrating aspects of biology, electronics, physics, and material science to foster innovative solutions and impact the trajectory of human health and environmental science, by translating biological responses into electrical signals for advanced analysis. Despite its transformative potential, current bioelectronic systems face limitations in terms of scalability, sensitivity, and ease of integration. This thesis claims that co-designing Complementary Metal-Oxide-Semiconductor (CMOS) integrated circuits with highly specific and sensitive genetically engineered biosensors is pivotal in bioelectronics evolution, offering high accuracy, reliability, miniaturization, and multiplexed sensing capabilities essential for addressing challenges in healthcare, environmental monitoring, sustainable manufacturing, and beyond. To support this claim, this dissertation highlights two key contributions: a low-power ingestible sensor for gastrointestinal tract monitoring and a hybrid platform technology combining droplet microfluidics and CMOS electronics for impedance spectroscopy and luminescence sensing for rapid screening and optimization of biosensors under different environmental conditions. The first contribution details an ingestible capsule that could transform healthcare diagnostics through a novel threshold-crossing-based detector and CMOS-integrated photodiodes. This innovation exemplifies how hybrid bioelectronic systems can significantly improve the precision and non-invasiveness of real-time health monitoring. Moving beyond the traditional scope of bioelectronics and the sole purpose of health monitoring, the second contribution extends its application by integrating droplet microfluidics with CMOS chips, facilitating high-throughput droplet screening to optimize biosensor performance for application deployment. To achieve this goal, this platform is equipped with a low-noise, high-resolution CMOS impedance spectroscopy chip and a high-resolution CMOS luminescence detector chip. In highlighting these contributions, the thesis reinforces the assertion that hybrid bioelectronic systems are key to addressing a wide range of societal challenges. Moreover, the integration of synthetic biology and microfluidics with CMOS technology, as demonstrated in this work, not only overcomes existing barriers, such as achieving miniaturization, high sensitivity, rapid data processing, and energy efficiency, but also paves the way for future innovations with extensive potential in personalized medicine and environmental sustainability. / 2026-01-17T00:00:00Z

Nucleic acid sequence based amplification (NASBA) is a primer based isothermal method of RNA/DNA amplification. Currently, primer design for NASBA has been restricted to hand creating sequences of oligonucleotides that must follow a set of rules to be compatible for the amplification process. This process of hand-creating primers is prone to error and time intensive. The detection of mutants, post amplification, also offers a benefit in point of care scenarios and the design of hybridization probes for sequences in the region of amplification is also an erroneous and time intensive process. By creating a program to design primers and hybridization probes based on the set of rules provided for a sequence of user input DNA or RNA, one can avoid costly errors in primers design and save time. Utilizing Python (a high-level object-oriented programming language), along with a series of bioinformatic libraries such as Biopython and UNAfold one can definitively choose the best primer sequences for a given sample of DNA.

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