Nanopores exhibit behaviors not seen in the micro-scale, such as ion current rectification or ion selectivity, which are useful for biotechnology, building of ionic circuits, and other fields. Nanopores in polymer films prepared by the track etched technique are useful due to the ease which one can scale from a single nanopore to 109 pores/cm2. In addition, it is straightforward to control pore diameters, geometry, and pore wall chemistry. In this document, polymer membranes were used for two applications. For the first application, the undulating pore walls of single pores in a polyethylene terephthalate film were exploited to extend the resistive-pulse technique to distinguish between spherical and aspherical particles. In the resistive-pulse technique, particles are driven through the pore by an electrical potential while the ion current is continuously monitored. The particle's presence in the pore is detected as a current decrease, called a resistive-pulse. Particles which pass through pores with undulating diameters has a pulse whose shape reflects the pore topography. The pulses of spherical and aspherical particles are compared in both rough and smooth pores, and it was determined that undulating diameters are crucial to distinguishing between the two types of particles. In the second application, polymer membranes with porosity of 108 pores/cm2 are used for desalination in reverse osmosis experiments. Although the narrow opening of the conical pores are larger than the classical Debye length, it was found that with high surface charge densities, ion rejection still occurs. Ion rejection was found to further increase if the narrow opening was modified to positive charges, forming a bipolar junction on the pore wall. Lastly, single pores with diameters between 10-15 nm were drilled into 30 nm thick silicon nitride membranes to study low aspect ratio systems. While a bare silicon nitride pore exhibited no ion rectification behavior, when a gold layer is deposited at one pore opening, rectification was observed. This is due to the polarization of the gold, which generated regions of enhanced concentrations of ions in the pore, breaking the pore's electrochemical symmetry. The research demonstrates interdisciplinary character and a wide range of applications of nanopores.

The use of membranes with a single pore to measure particles as they pass through is a promising method to allow the rapid determination of properties of individual particles in solution. However, this will involve an understanding and control of the forces that these particles undergo while in the pore. In this work we use single cylindrical pores in PET membranes to test and compare the translocations of deformable hydrogel particles and rigid polystyrene spheres. We find that the hydrogel particles cause a characteristic initial increase in current, pass by electroosmosis, and can also undergo dehydration and deformation in pores of smaller diameter. We also show that the force on a particle by an applied hydrostatic pressure gradient can be sufficiently balanced with a transmembrane voltage that is dynamically triggered when the particle enters the pore, and the subsequent fluctuations in the current from the particle diffusing within the pore can be observed for tens of seconds. Finally, we show that repeated translocations of a single particle can be performed using a set rising edge or falling edge triggered voltage wave, or an even greater number of repetitions can be achieved by subtracting in real time the capacitance effects based on a previous test pulse.

This dissertation is a compilation of the work done during my graduate career and consists of two sections. The first section, comprised of the first three chapters, will discuss the research I conducted in the Siwy lab on selective polymer and nanopore systems. The second section is comprised of chapters four and five which detail the curriculum I have developed for chemical education in the general chemistry laboratory series.Chapters 1 and 2 detail the use of polymers of intrinsic microporosity as porous, large-ion selective membranes. Porous membranes have been used for many applications, including separations in biotechnology, the food industry, water purification, and even energy storage devices. The benefit of polymers of intrinsic microporosity (PIMs) is their consistently sized nanopore channels. Inherent functionalities of the PIM structure not only create these channels but are also available for further modifications that can change the interactions of ions and molecules inside of the pore. Chapter 1 describes solid state nanopores on which are drop-casted two different PIMs, functionalized with either a cyano group or a carboxylic acid. Ionic transport through the membranes is investigated based on pore size and charge-charge interactions, as well as steric and hydrophobic interactions. Chapter 2 describes a chiral carboxylic acid PIM drop casted onto a solid state nanopore and its interactions with chiral small molecules. The ionic transport of the small molecules is investigated based on chiral interactions and hydrogen bonding. Achieving specific ion selectivity with easily processable porous membranes opens new avenues for water purification strategies, energy storage, and pharmaceutical separations. Chapter 3 describes a single nanopore that can be functionalized with a range of enzymes for biomolecule detection. Biosensors are extremely important in a wide variety of disease diagnostics. However, a separate sensor must be made specifically for the disease model it is detecting. Thus, it is desirable to produce a biosensor that can be adapted for many different diseases with simple modification steps. We report a single 20 nm nanopore functionalized with a biotin linker capable of binding to a range of enzymes that detect cancer molecules. Chapters 4 and 5 are devoted to curriculum development for an online course in response to the pandemic and for returning to in-person instruction. The instruction of high enrollment general and organic chemistry laboratories at a large public university always have curricular, administrative, and logistical challenges. Chapter 4 discusses how the instructional teams met these challenges in the transition to remote teaching during the COVID-19 pandemic. Chapter 5 discusses how the general chemistry instructional team transitioned to argument-driven inquiry for reopening back to in-person instruction. Both chapters report the reasoning behind the approaches, the utilization of our existing web-based course content, the additions and alterations to our curriculum, replacement of original experimental work with videos or theme-based inquiries, the results of both student and TA surveys, and lessons learned for iterations of these courses in the near future.

Biological nanopores are an essential element to the success of the lipid bilayer that makes life possible on the cellular level. Protein based pores are responsible for the transport of specific ions and molecules across the bilayer and can accomplish their jobs with incredible variety. Some pores, such as those from bacteria have relatively simple structures and allow for many types of transport. Others, like those found in neurons have very high specificity as well as the ability to respond to different cues in the surrounding environment. The vast number of biological ion channels and their complex structures make it difficult to study and understand the nanofluidic phenomena they exhibit. Inspired by the pores seen in nature, scientists have begun to create their own synthetic versions which are usually simpler in structure. These man made pores have been fabricated through a variety of techniques and materials and provide well controlled systems capable of isolating and testing specific transport phenomena. Additionally, these pores provide the building blocks with which more complicated and truly biomimetic pores can be made.

In this thesis, three very different types of nanopores will be examined. First, an alpha hemolysin pore will be isolated and the physics governing transport time will be studied. The diameter and charge of single stranded DNA molecule is modified before being electrophoretically driven through the pores inner constriction. These translocation events are monitored via current measurements across the pore and a biological model is formulated to explain the behavior. This work has the potential to improve DNA sequencing technologies which are dependent on slowing down DNA translocation speed for accurate reads. Next, a synthetic conical nanopore etched in a polymer film will be used as the foundation for a biomimetic nanopore gate. Through the attachment of ssDNA to the pore walls, a pH and voltage responsive nanochannel is created. This is done through the careful selection of the DNA sequence to contain protonatable nucleotides which enable the formation of a transport blocking mesh. Synthetic gated channels that can respond to multiple stimuli as well as have a robust and reversible closing mechanism have been historically difficult to design and are essential to advancing the nanopore field. Finally, a different type of synthetic nanochannel is made from the inner volume of a carbon nanotube. We present a platform that allows for the isolation and study of a single nanotube and use it to examine the underlying transport properties. Carbon nanotube based nanochannels show several unique behaviors which the current literature has not been able to completely explain. Several questions such as the magnitude and origin of enhanced flow and even what carries the current remain open, motivating additional studies, such as ours, which aim to help provide much needed answers.

Ionic current transport and nanopores go hand in hand. Ionic current has been used to investigate properties of nanopores and vice versa for many years. Nanopores are simply holes which contain dimensions on the nanoscale and ionic current is produced through them by placing the pores in a solvent containing an electrolyte. Ionic transport is investigated typically using current-voltage or current-time measurements. In this thesis ionic transport is studied and manipulated through three separate projects. We begin using cylindrical polymer pores ~700 nm in diameter and 11 μm in length to investigate the effect of organic solvents on ionic transport and thus electrochemical properties of polymer/liquid interfaces. Current-voltage measurements were taken in solutions with varying solvent type and varying concentration of LiClO4. These measurements probed electroosmotic flow and allowed us to deduce surface charge properties of the pores. It was found that the carboxlyated surface of PET can flip charge polarity dependent on solvent type and concentration of LiClO4. This work helped overall understanding of the origin of the effective xii surface charge in organic solvents and its impact on ionic transport. Another method of ionic transport manipulation which was investigated utilized an ionic bipolar junction transistor. Nanopores in silicon nitride were sandwiched together with a thin film of Nafion which also contained a gate electrode. Current-voltage measurements were taken across the device while varying voltage at the gate. It was successfully demonstrated through this system that an ionic transistor with fully ionic inputs and outputs can easily be rearranged into amplifying units providing amplifications up to 300 times. Finally, this document goes on to investigate interpore effects by using arrays of nanopores with a gate electrode placed near one of the pores within the array. Ionic transport is investigated through modeling currentvoltage characteristics both with and without application of voltage at the gate electrode. In this system complex interactions were revealed which allow for different pores to exhibit different ionic transport properties though subject to the same bulk solution concentration and voltage configuration. Findings from these projects could be useful in a variety of applications including preparation of artificial biocircuits or spatially controllable drug delivery devices.

The thesis describes development of membranes containing nanopores with charged pore walls, which could be used for desalination of brackish water. Semipermeable membranes composed of high density conical nanopores have been proposed for desalination by reverse osmosis. These nanopores feature a bipolar surface charge pattern so that the pore walls contain a junction between a zone with positive surface charges and a zone with negative surface charges. In this work we seek to show that polyimide (PI) membranes containing conical nanopores with such surface charge pattern may be produced by the process of track-etching of commercially available Kapton 50HN foils. The membranes prepared had a nanopore density of ~108 per cm^2. Salt rejection of the membranes was probed using 100 mM KCl as the feed solution and pressure differences up to several atmospheres. Maximum rejection of ~55% was achieved in a single-step desalination process. Modeling of salt rejection was also performed using the coupled Poisson-Nernst- Planck and Navier-Stokes equations. Our results demonstrated that conically shaped nanopores with bipolar surface charge pattern could be used for desalination of brackish water.

In this dissertation, methods for characterizing cells based on their mechanical phenotypes are described. A novel microfluidic channel design is presented and data are gathered as cells pass through undulations in the channel. Deep learning methods are applied to the data in a new approach for classifying cells solely based on their mechanical properties. First, in a supervised deep learning approach, a highly interpretable random forest was created and trained to extract the most influential features for cell classification. Feature attributions of the random forest were uncovered using Shapley values. Analysis of the most influential features revealed by the Shapley values highlighted the importance of temporal features, such as the change in aspect ratio over time, in classifying cells. This led to the development of a powerful convolutional recurrent neural network, which dramatically improved classification accuracy to more than 90% when using five-fold cross-validation. Next, an unsupervised deep learning approach for cell classification was explored for problems where classes of cells are unknown a priori. Unsupervised clustering was first tested using manually extracted features and traditional clustering algorithms. However, performance was significantly improved with the development of a variational autoencoder (VAE), which extracted higher-dimensional features. The encoder for the VAE was turned into a classifier using a clustering loss function. This trained network exhibited an accuracy of up to 80% when thresholding the top ~10% of the predictions.

Polymer nanopores offer themselves as excellent test beds for study of phenomena that occur on the nano - scale, such as Debye layer formation, surface charge modulation, current saturation, and rectification. Studying ions interactions within the Debye layer, for example, is not possible on the micro - scale, where the pore diameter can be 100 times the size of the zone where interactions of interest occur. However, in our nanopores with an opening diameter less than 10 nm, a slight change of the Debye length can lead to drastic changes of the recorded ion current.

Here we present our nanopores' use as a tool to study geometrical and electrochemical properties of porous manganese oxide. There is great value in studying nano - scale properties of this material because of its importance in lithium ion batteries and newly developed nano - architectures within supercapacitors. We electrodeposited manganese oxide wires into our cylindrical nanopores, filling them completely. In this use, nanopores became a template to probe properties of the embedded material such as surface charge, ion selectivity, and porosity. This information was then reported to the Energy Frontier Research Center (EFRC) collaboration, so that other groups can incorporate these recently discovered characteristics into future their nano - architecture design.

Additionally, we constructed conical nanopores to study interactions between the surface charges found on the walls and alkali metal ions. In particular we looked at lithium, as it is the electrochemically active ion during charge cycling in EFRC energy storage devices. We attempted to reveal lithium ion's affinity to bind to surface charges. We found this binding led to lowering of the effective surface charge of the pore walls, while also decreasing lithium's ability to move through channels or voids that have charged walls. In connection to manganese oxide, a porous, charged material with voids, information on lithium's interaction with these charges is paramount.

Lithium ion battery technology has flourished since its introduction into the consumer market. Not only has it helped revolutionize consumer electronics, it also compliments R&D into clean forms of energy harvest e.g. solar, wind, and hydro-electric. As demand for the technology grows, innovative approaches have been taken to improve capacity, output, and lifetime in Li-ion batteries. The approach studied in this research involves the inclusion of nanostructures, which have the potential to significantly increase capacity. While several techniques to fabricate nanostructures are understood, underlying phenomena governing ion transport in and around these nanostructures is only partially understood, which could directly impact design principles for such devices.

This thesis examines a variety of model systems which could serve to simulate environments found in proposed devices and answer questions regarding ion transport phenomena. The main components we studied from such battery systems were electrolyte and cathode materials. The electrolyte experiences different ion transport phenomena arising from the nanoconfinement of the cathode structures both around and inside the electrode material. Thus, having model systems to examine electrolyte and cathode material separately and in tandem is useful for elucidating phenomena without the challenge of deconvolution resulting from other current-carrying mechanisms.

Our main tools for carrying out our research were synthetic nanopores. The nanopore structures afforded means to access nanoscale, control environment, and even fabricate components for study. By studying the current-voltage curves in these systems, we were able to draw meaningful conclusions about mechanisms of ion transport in these model systems. The main findings of this research include the inducement of positive surface charge on nanopore structures by organic solvent-based electrolytes by means of dipole and/or ion adsorption, positive evidence of gel electrolyte fitting current models of ion current rectification, and the impact of oxidation state and cycling in cathode material on ion transport through its porous media. Each of these findings is directly related to the thrust of the research and potentially provide insights for future battery design.

This thesis describes research conducted on the physics and applications of micro- and

nanoscale ion-conducting channels. Making use of the nanoscale physics that takes place

in the vicinity of charged surfaces, there is the possibility that nanopores, holes on the order

of 1 nm in size, could be used to make complex integrated ionic circuits. For inspiration on

what such circuits could achieve we only need to look to biology systems, immensely com-

plex machines that at their most basic level require precise control of ions and intercellular

electric potentials to function. In order to contribute to the ever expanding field of nanopore

research, we engineered novel hybrid insulator-conductor nanopores that behave analagously

to ionic diodes, which allow passage of current flow in one direction but severely limit the

current in the opposite direction. The experiments revealed that surface polarization of the

conducting material can induce the formation of an electrical double layer in the same way

static surface charges can. Furthermore, we showed that the hybrid device behaved similar to

an ionic diode, and could see potential use as a standard rectifying element in ionic circuits.

Another application based on ion conducting channels is resistive pulse sensing, a single par-

ticle detection and characterization method. We present three main experiments that expand

the capacity of resistive pulse sensing for particle characterization. First, we demonstrate

how resistive pulse sensing in pores with longitudinal irregularities can be used to measure

the lengths of individual nanoparticles. Then, we describe an entirely new hybrid approach

to resistive pulse sensing, whereby the electrical measurements are combined with simulta-

neous optical imaging. The hybrid method allows for validation of the resistive pulse signals

and will greatly contribute to their interpretability. We present experiments that explore

some of the possibilities of the hybrid method. Then, building off the hybrid method we

present experiments performed to measure single particle deformability with resistive pulse

sensing. Using a novel microfluidic channel design, we were able to reproducibily induce

bidirectional deformation of cells. We describe how these deformations could be detected

with the resistive pulse signal alone, paving the way for resistive pulse sensing based cell

deformability cytometers.