Alzheimer's disease (AD) and Alzheimer's Related Dementias (ADRD) is projected to affect 50 million people globally in the coming decades. Clinical research suggests that Mild Cognitive Impairment (MCI), a precursor to dementia, offers a critical window for lifestyle interventions to delay or prevent the progression of AD/ADRD. Previous research indicates that lifestyle changes, including increased physical exercise, reduced caloric intake, and mentally stimulating exercises, can reduce the risk of MCI. Early detection of MCI is challenging due to subtle and often unnoticed cognitive decline, traditionally monitored through infrequent clinical tests. As part of this research, the Smart Driving System was proposed, a novel, unobtrusive, and economical technology to detect early stages of neurodegenerative diseases. This system, leveraging a multi-modal biosensing array (MMS) and AI algorithms, assesses daily driving behavior, offering insights into a driver's cognitive function. The ultimate goal is to develop the Smart Driving Device and App, integrating it into vehicles, and validating its effectiveness in detecting MCI through comprehensive pilot studies. The Smart Driving System represents a breakthrough in AD/ADRD management, promising significant improvements in early detection and offering a scalable, cost-effective solution for monitoring cognitive health in real-world settings.

Obesity has consistently presented a significant challenge, with excess body fat contributing to the development of numerous severe conditions such as diabetes, cardiovascular disease, cancer, and various musculoskeletal disorders. In this study, different methods are proposed to study substrate utilization (carbohydrates, proteins, and fats) in the human body and validate the biomarkers enabling to investigation of weight management and monitor metabolic health. The first technique to study was Indirect calorimetry, which assessed Resting Energy Expenditure (REE) and measured parameters like oxygen consumption (VO2) and carbon dioxide production (VCO2). A validation study was conducted to study the effectiveness of the medical device Breezing Med determining REE, VO2, and VCO2. The results were compared with correlation slopes and regression coefficients close to 1. Indirect Calorimetry can be used to determine carbohydrate and fat utilization but it requires additional correction for protein utilization. Protein utilization can be studied by analyzing urinary nitrogen. Therefore, a secondary technique was studied for identifying urea and ammonia concentration in human urine samples. Along this line two methods for detecting urea were explored, a colorimetric technique and it was validated against the Ion-Selective method. The results were then compared by correlation analysis of urine samples measured with both methods simultaneously curves. The equations for fat, carb, and protein oxidation, involving VO2, VCO2 consumption, and urinary nitrogen were implemented and validated, using the above-described methods in a human subject study with 16 subjects. The measurements included diverse diets (normal vs. high fat/protein) in normal energy balance and pre-/post interventions of exercise, fasting, and a high-fat meal. It can be concluded that the indirect calorimetry portable method in conjunction with urine urea methods are important to help the understanding of substrate utilization in human subjects, and therefore, excellent tools to contribute to the treatments and interventions of obesity and overweighted populations.

Pervaporation is a membrane process suited to complex and highly contaminated wastewaters. Pervaporation desalination is an emerging area of study where the development of high-performance membranes is necessary to propel the field forward. This research demonstrated that sulfonated block polymer membranes (Nexar™)show excellent permeance (water passage normalized by driving force) of as much as 135.5 ± 29 kg m-2 hr-1 bar-1, with salt removal values consistently equal to or greater than 99.5%. Another challenging water management scenario is in spaceflight situations, such as on the International Space Station (ISS). Spaceflight wastewaters are highly complex, with low pH values, and high levels of contaminants. Current processes produce 70% wastewater recovery, necessitating the handling and processing of concentrated brines. Since recoveries of 85% are desired moving forward, further efforts in water recovery are desirable. An area of concern in these ISS water treatment systems is scalant deposition, especially of divalent ions such as calcium species. Zwitterions are molecules with localized positive and negative charges, but an overall neutral charge. Zwitterions have been used to modify the surface of membranes have shown to decrease fouling. Building a copolymer between zwitterions and other polymers, creates zwitterion layer on top of previously studied Nexar™ membranes. This coating demonstrates great promise to combat scaling, as it increases the hydrophilicity of the membrane surface measured via contact angle. The zwitterion membranes experienced reduced scaling, with the greatest difference being between 1617 ± 241 wt% on control membranes, to 317 ± 87 wt% on zwitterion coated membranes in the presence of CaCl2. In treating spaceflight wastewater, these zwitterion membranes are effective at retaining the acid in the feed, going from a pH value of 2 to 7 and reducing the contamination level of the feed, with a removal value of 99.3 ± 0.4%, measured through conductivity. These membranes also perform well in separation processes that do not require extreme vacuum and can be operated passively. By optimizing both membrane material properties and process conditions, achieving increased high levels of water recovery from spaceflight wastewaters is attainable.

Chimeric antigen receptor (CAR)-T cell therapy is a type of cancer immunotherapy has shown promising results in engineering the T cells which targets a specific antigen. Despite their success rate, there are certain limitations to the use of CAR-T therapies that includes cytokine release syndrome (CRS), neurologic toxicity, lack of response in approximately 50% of treated patients, monitoring of patients treated with CAR-T therapy. However, rapid point- of- care testing helps in quantifying the circulating CAR T cells and can enhance the safety of patients, minimize the cost of CAR-T cell therapy, and ease the management process. Currently, the standard method to quantify CAR-T cell in patient blood samples are flow cytometry and quantitative polymerase chain reaction (qPCR). But these techniques are expensive and are not easily accessible and suitable for point- of- care testing to assist real- time clinical decisions. To overcome these hurdles, here I propose a solution to these problems by rapid optical imaging (ROI)- based principle to monitor and detect CAR-T cells. In this project, a microfluidic device is developed and integrated with two functions: (1) Centrifuge free, filter- based separation of white blood cells and plasma; (2) Optical imaging- based technique for digital counting of CAR T- cells. Here, I carried out proof- of- concept test on the laser cut prototype microfluidic chips as well as the surface chemistry for specific capture of CAR-T cells. These data show that the microfluidic chip can specifically capture CAR-T positive cells with concentration dependent counts of captured cells. Further development of the technology could lead to a new tool to monitor the CAR-T cells and help the clinicians to effectively measure the efficacy of CAR-T therapy treatment in a faster and safer manner.

Freshwater as the resource for the survival of humans and all lives on earth is very precious but scarce. The shortage of the original freshwater resources and the interfering activities by human and other natural factors form this issue together. To reduce the water supply pressure and deterioration of freshwater systems (for example, river, wetland, and groundwater), the quantity-increase and the quality-increase strategies should be implemented at the same time. Therefore, corresponding membrane technologies have been developed to achieve water purification with high efficiency and low cost. For desalinating seawater and other types of saline water, pervaporation has been proved that has the potential to complete desalination with salt rejection rate over 99 % when dealing with high salinity water that reverse osmosis (RO) cannot handle. In this dissertation, except the discussion of commonly used materials to synthesize pervaporation membranes, two types of novel pervaporation desalination membranes (nanophotonic-enhanced membrane and free-standing sulfonated membrane) have been presented and discussed. The novel membranes were tested to see the potential of pervaporation to desalinate seawater and saline water with more complex ionic composition, and the possibility of achieving zero liquid discharge in the desalination field when having pervaporation as the assistance. For mitigating polluted water that is caused by human activities, especially agricultural activities, electrodialysis is an effective method to remove specific ions from water, and it does not require extra chemical cost or regeneration. A type of anion exchange membranes inspired by ion exchange resins was synthesized and tested, and the performance on nitrate removal has been evaluated in this dissertation.

Non-invasive biosensors enable rapid, real-time measurement and quantification of biological processes, such as metabolic state. Currently, the most accurate metabolic sensors are invasive, and significant cost is required, with few exceptions, to achieve similar accuracy using non-invasive methods. This research, conducted within the Biodesign Institute Center for Bioelectronics and Biosensors, leverages the selective reactivity of a chemical sensing solution to develop a sensor which measures acetone in the breath for ketosis and ketoacidosis diagnostics, which is relevant to body weight management and type I diabetes. The sensor displays a gradient of color changes, and the absorbance change is proportional to the acetone concentration in the part- per-million range, making applicable for detection ketosis and ketoacidosis in human breath samples. The colorimetric sensor response can be fitted to a Langmuir-like model for sensor calibration. The sensors best performance comes with turbulent, continuous exposure to the samples, rather than batch sample exposure. With that configuration, these novel sensors offer significant improvements to clinical and at- home measurement of ketosis and ketoacidosis.

Cardiovascular disease is affecting millions of people worldwide and is the leading cause of death in the United States. This disease is closely related to the abnormal creatinine levels in blood. For this reason, there is a need for a low-cost point-of-care device that could measure the creatinine level in blood with the goal of managing and preventing cardiovascular disease. This project introduces a Molecular Reactive Lateral Flow Assay (MoReLFA) device that is aimed toward creatinine detection based on an optimized chemical reaction of creatinine and alkaline picrate. The device consists of different membranes that accommodate 50 microliters of fluid sample and carry out a colorimetric reaction, in which deposited-colored region is analyzed for Red, Green, and Blue (RGB) components via an image processing software. The color intensity from the RGB outputs was then studied and compared with a gold standard spectrophotometry-based technique. The results show that the MoReLFA sensor could successfully detect creatinine levels in standard solutions. The plot of the sensor color intensity against the absorbance from spectrophotometry shows a good correlation between the two methods (R2 = 0.96). Furthermore, the paper introduces the development of a RGB reader box that is portable and for easy assessment of RGB values. The color intensity from the box shows an increasing trend with increasing creatinine concentrations; and the coefficient of determination of this relationship is 0.85.