For the last two decades, a consistent statistic in the United States is that one out of every six people report experiencing at least one migraine every three months. The Neural Microsystems Laboratory at Arizona State University has developed a wireless implantable neurostimulator (WINS), which they believe can be used to treat these widespread, episodic attacks. This device is about the size of a grain of rice and contains micro circuitry that generates an electric current when exposed to ultrasound. One problem facing the lab is that there is no process to place the WINS inside of the human body. For this Honors Thesis/Creative Project, I invented a tool that can be used to inject the WINS into the body, while addressing key issues of positioning, repositioning, and orientation. After testing was conducted on an artificial skin model and imaged with an optical microscope, the implantation tool proved to be successful. The tool made it easy to inject the WINS perpendicular to an artificial occipital nerve for every trial of the testing, also maintaining a proper alignment of the device so that it could receive maximum exposure to external ultrasound. Successful testing of this prototype shows that it is ready to be redesigned for mass production so that it can deliver the WINS to as many victims of migraine attacks as possible.

Advancing the understanding and treatment of many neurological disorders can be achieved by improving methods of neuronal detection at increased depth in the mammalian brain. Different cell subtypes cannot be detected using non-invasive techniques beyond 1 mm from cortical surface, in the context of targeting particular cell types in vivo (Wang, 2012). These limitations in the depth of imaging and targeting are due to optical scattering (Ntziachristos, 2010). In order to overcome these restrictions, longer wavelength fluorescent proteins have been utilized by researchers to see tagged cells at depth. Optical techniques such as two-photon and confocal microscopy have been used in combination with fluorescent proteins to expand depth, but are still limited by the penetration depth of light due to optical scattering (Lee, 2015). This research aims to build on other detection methods, such as the photoacoustic effect and automated fluorescence-guided electrophysiology, to overcome this limitation.

Polymeric nanoparticles (NP) consisting of Poly Lactic-co-lactic acid - methyl polyethylene glycol (PLLA-mPEG) or Poly Lactic-co-Glycolic Acid (PLGA) are an emerging field of study for therapeutic and diagnostic applications. NPs have a variety of tunable physical characteristics like size, morphology, and surface topography. They can be loaded with therapeutic and/or diagnostic agents, either on the surface or within the core. NP size is an important characteristic as it directly impacts clearance and where the particles can travel and bind in the body. To that end, the typical target size for NPs is 30-200 nm for the majority of applications. Fabricating NPs using the typical techniques such as drop emulsion, microfluidics, or traditional nanoprecipitation can be expensive and may not yield the appropriate particle size. Therefore, a need has emerged for low-cost fabrication methods that allow customization of NP physical characteristics with high reproducibility. In this study we manufactured a low-cost (<$210), open-source syringe pump that can be used in nanoprecipitation. A design of experiments was utilized to find the relationship between the independent variables: polymer concentration (mg/mL), agitation rate of aqueous solution (rpm), and injection rate of the polymer solution (mL/min) and the dependent variables: size (nm), zeta potential, and polydispersity index (PDI). The quarter factorial design consisted of 4 experiments, each of which was manufactured in batches of three. Each sample of each batch was measured three times via dynamic light scattering. The particles were made with PLLA-mPEG dissolved in a 50% dichloromethane and 50% acetone solution. The polymer solution was dispensed into the aqueous solution containing 0.3% polyvinyl alcohol (PVA). Data suggests that none of the factors had a statistically significant effect on NP size. However, all interactions and relationships showed that there was a negative correlation between the above defined input parameters and the NP size. The NP sizes ranged from 276.144 ± 14.710 nm at the largest to 185.611 ± 15.634 nm at the smallest. In conclusion, the low-cost syringe pump nanoprecipitation method can achieve small sizes like the ones reported with drop emulsion or microfluidics. While there are trends suggesting predictable tuning of physical characteristics, significant control over the customization has not yet been achieved.

SUMMARY: A failed attempt to conduct a systematic review of disparities in racial inclusivity in stroke rehabilitation research: A call to action Group Members: Adeline Beeler & Mikayla McNally Faculty Mentor(s): Dr. Sydney Schaefer & Dr. Keith Lohse Topic Overview: Stroke is responsible for the death of an individual every four minutes in the United States. While all Americans are gravely affected by this statistic, Black Americans are at a significantly increased risk of first stroke incidence when compared to their white counterparts, majorly due to heightened prevalence of stroke risk factors. Not only does race contribute as a factor in stroke incidence, but it also has a considerable impact in the physical impairment of Black Americans following stroke occurrence. While it still remains unclear as to whether or not stroke plays a significant role in stroke rehabilitation efforts, there is a clearly demonstrated need for increased reporting or participation of Black Americans in stroke rehabilitation clinical trials to have the ability to conduct a systematic review of these racial disparities in the near future. In the analysis of 36 stroke rehabilitation-related clinical research studies, 80% of selected trials failed to report any participant racial demographics, with 77.3% of the NIH-funded trials not reporting, as well. Out of the 7 trials that did provide some sort of participant racial information, only 5 successfully provided statistically significant racial data compared to the remainder that simply categorized participants’ race as “white” or “other.” In order to fully investigate the effects of race on stroke rehabilitation, it is imperative that researchers collect and report equally distributed and diverse participant racial data when publishing clinical research. Potential methods of improvement for researchers to include more racially diverse subject populations include more comprehensive and in-depth advertising and recruitment strategies for their studies. Research Methods: In order to produce accurate analyses of the current state of the relationship between race and stroke rehabilitation efforts, 36 stroke rehabilitation clinical research trials from various locations across the United States were identified using the Centralized Open-Access Rehabilitation Database for Stroke (SCOAR). These trials were evaluated in order to extract relevant data, such as number of trial participants, average age of participants, if the research trial was funded by the National Institute of Health (NIH) or not, and any reported participant racial demographic details. Trends across these categories were compared between all trials to determine if any disparities existed in providing data sufficient to support the relationship between varying racial populations and stroke rehabilitation efforts. Future Project Efforts: Future efforts will include the completion of submitting a Point of View/Directions for Research article for publication to offer an opportunity for clinical and basic researchers to examine the discrepancies surrounding racial inclusivity in stroke rehabilitation clinical research. The aim is to improve the ability of clinicians to interpret the literature, translate research studies into practices, and better direct future experiments. Further identification of stroke rehabilitation clinical research trials will be necessary, as well as modifications to current written work content.

SUMMARY: A failed attempt to conduct a systematic review of disparities in racial inclusivity in stroke rehabilitation research: A call to action Group Members: Adeline Beeler & Mikayla McNally Faculty Mentor(s): Dr. Sydney Schaefer & Dr. Keith Lohse Topic Overview: Stroke is responsible for the death of an individual every four minutes in the United States. While all Americans are gravely affected by this statistic, Black Americans are at a significantly increased risk of first stroke incidence when compared to their white counterparts, majorly due to heightened prevalence of stroke risk factors. Not only does race contribute as a factor in stroke incidence, but it also has a considerable impact in the physical impairment of Black Americans following stroke occurrence. While it still remains unclear as to whether or not stroke plays a significant role in stroke rehabilitation efforts, there is a clearly demonstrated need for increased reporting or participation of Black Americans in stroke rehabilitation clinical trials to have the ability to conduct a systematic review of these racial disparities in the near future. In the analysis of 36 stroke rehabilitation-related clinical research studies, 80% of selected trials failed to report any participant racial demographics, with 77.3% of the NIH-funded trials not reporting, as well. Out of the 7 trials that did provide some sort of participant racial information, only 5 successfully provided statistically significant racial data compared to the remainder that simply categorized participants’ race as “white” or “other.” In order to fully investigate the effects of race on stroke rehabilitation, it is imperative that researchers collect and report equally distributed and diverse participant racial data when publishing clinical research. Potential methods of improvement for researchers to include more racially diverse subject populations include more comprehensive and in-depth advertising and recruitment strategies for their studies. Research Methods: In order to produce accurate analyses of the current state of the relationship between race and stroke rehabilitation efforts, 36 stroke rehabilitation clinical research trials from various locations across the United States were identified using the Centralized Open-Access Rehabilitation Database for Stroke (SCOAR). These trials were evaluated in order to extract relevant data, such as number of trial participants, average age of participants, if the research trial was funded by the National Institute of Health (NIH) or not, and any reported participant racial demographic details. Trends across these categories were compared between all trials to determine if any disparities existed in providing data sufficient to support the relationship between varying racial populations and stroke rehabilitation efforts. Future Project Efforts: Future efforts will include the completion of submitting a Point of View/Directions for Research article for publication to offer an opportunity for clinical and basic researchers to examine the discrepancies surrounding racial inclusivity in stroke rehabilitation clinical research. The aim is to improve the ability of clinicians to interpret the literature, translate research studies into practices, and better direct future experiments. Further identification of stroke rehabilitation clinical research trials will be necessary, as well as modifications to current written work content.

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection. Light-activated tissue sealing, particularly the use of near-infrared light, is an attractive alternative, as it localizes heat, thereby preventing thermal damage to the surrounding healthy tissue. Previous work identified a glutaraldehyde-crosslinked chitosan film as a lead sealant for gastrointestinal incision sealing, but in vivo testing resulted in tissue degradation in and around the wound. The suggested causes for this degradation were excess acetic acid, endotoxins in the chitosan, and thermal damage. A basic buffer wash protocol was developed to remove excess acid from the films following fabrication. UV-Vis spectroscopy demonstrated that following the wash, films had the same concentration of Indocyanine green as unwashed films, allowing them to absorb light at the same wavelength, therefore showing the wash did not affect the film’s function. However subsequent washes led to degradation of film mass of nearly 20%. Standard chitosan films had significantly greater mass gain (p = 0.028) and significantly less subsequent loss (p= 0.012) than endotoxin free chitosan-films after soaking in phosphate buffered saline for varying durations , while soaking duration had no effect (p = 0.332). Leak pressure testing of films prepared with varying numbers of buffer washes, laser temperature, and lasering time revealed no significant interaction between any of the 3 variables. As such, it was confirmed that proceeding with in vivo testing with the buffer wash, various lasering temperatures, and laser times would not affect the sealing performance of the films. Future investigation will involve characterization of additional materials that may be effective for sealing of internal wounds, as well as drug loading of agents that may hasten the healing process.