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The monitoring of electrolytes and charged biomolecules in body fluids is a crucial step in both the diagnosis and management of many diseases, including chronic kidney disease and cardiovascular disease. Ion-selective electrodes (ISEs) are considered the gold standard in analyzing these analytes in clinical settings due to their high selectivity, near instant response time, and linear response. These ISEs are generally incorporated into a mainframe clinical blood analyzer which, due to the high cost, fragility, and need for trained staff to operate, are in centralized hospitals or laboratories. As a result, patients living in remote, or resource-limited areas often do not have access to such clinical diagnostics. There is, therefore, a need for point-of-care based ISEs, characterized by low-cost, high ease of use, and portability. Despite recent interest in the development of point-of-care based ISEs, there remain fundamental issues in the design and performance of these sensors, which I address in my research. This thesis presents work that supports the advancement of point-of-care based ISEs in several key areas.While paper has been proposed as a substrate for point-of-care sensors, it has impurities from manufacturing and being natural in origin. Moreover, its structure and surface composition are highly heterogeneous, which are disadvantageous when designing sensors for high reproducibility. In this work, I propose the use of a novel synthetic textile with higher purity and a more controlled structure to serve as a supporting substrate for miniaturized, membrane-free ISEs. To expand the versatility of these devices, I embedded both ion-sensing and reference membranes into the polyester fabric and successfully measured the activity of chloride (a highly relevant clinical biomarker) in aqueous solutions and 100% blood serum. This is the first example of an ISE that both embeds membranes into a fabric and uses the fabric to wick samples into contact with those membranes. I also determined the effect of pore structure on device performance, a finding applicable not only to textile-based ISEs, but also to other porous materials such as paper. I showed that devices fabricated on the textile had an order of magnitude improvement in the lower limit of detection (LOD) of chloride as compared to analogous paper-based devices. I also further the understanding of the sources of non-ideal performance in paper based ISEs through a systematic study of both sensor materials and interactions between materials and aqueous samples. While it has been suggested by many that these limitations are due to interactions of paper with sample or sensing components, to date this has not been thoroughly investigated. To this end, I studied interactions of target ions with paper by using a range of analytical techniques. My data shows two main reasons that explain the sub-optimal performance of paper-based devices for chloride sensing, which I explain and propose novel fabrication techniques to overcome. A key performance parameter in ISEs designed to be used outside of central laboratories is that of reproducibility, with the goal of calibration-free devices. Our group has previously improved sensor-to-sensor reproducibility with the use of redox buffers, which buffer redox-active impurities in the system. I propose the use of a novel cobalt(III/II)bis(terpyridine) as a hydrophilic redox buffer to be incorporated into the inner filling solution of ISEs for anion sensing. Conventional ISEs with a plasticized poly(vinyl)chloride ion-exchange membrane for Cl– and the redox buffer incorporated into the inner filling solution resulted in a E0 SD of 0.3 mV–one of the lowest reported SD thus far in the literature. The redox buffer was also found to be compatible with reference membranes as well as textile-based sensing setups. As the purpose for these devices is to be used in clinical diagnostics, it is also crucial to increase the number of analytes measured to include clinically relevant ions such as K+, Ca2+, and pH. I therefore also show the use of textile-based devices with ionophorecontaining membranes that selectively complex target ions. While a textile-based Ca2+ ISE was fabricated and successfully detected Ca2+ in aqueous samples, performance limitations arose in the detection of K+, H+, Ag+, and CO32-. A study of the effects of textile coating techniques and considerations of material-membrane interactions seek to address these shortcomings.