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.

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.

From previous research, it has been observed that neural summation can be observed from reaction time tasks. This is observed through race models, as proposed by J.O. Miller. These models are referred to as “race models” as different stimuli “race” to extract a response during tasks. The race model is augmented by the Race Model Inequality, which claims the probability that two simultaneous signals will have a faster reaction time than the summation of the probabilities of two individual signals. When this inequality expression is violated, it indicates neural summation is occurring. In another study, researchers studied how the location of visual stimuli influences neural summation with tactile information, observing the visual stimuli from different distances and a mirrored reflection condition. However, results of the mirror condition did not follow the other visual conditions, offering unique properties. The mirrored case is examined more closely in this project, attempting to answer if the presence of a mirrored representation of the hand will affect reaction time during timed tasks, suggesting the occurrence of neural summation, and suggesting that a mirrored reflection of self is interpreted as an independent channel of information. This was measured by evaluating participants’ response time while manipulating the presence of a reflection and checking if they violate the race model. However, the results of this study indicated that the presence of a mirror does not have an effect in reaction time and therefore did not present the occurrence of neural summation

Alginate microspheres have recently become increasingly popular in the realm of drug delivery for their biocompatibility, nontoxicity, inexpensiveness, among other factors. Recent strict regulations on microsphere size have drastically increased manufacturing cost and waste, even though the effect of size variance on drug delivery and subsequent performance is unclear. If sphere size variance does not significantly affect drug release profiles, it is possible that future ordinances may loosen tolerances in manufacturing to limit waste produced and expenditures. We use a mathematical model developed by Nickel et al. [12], to theoretically predict drug delivery profiles based on sphere size, and correlate the expected release with experimental data. This model considers diffusion as the key component for drug delivery, which is defined by Fick’s Laws of Diffusion. Alginate, chosen for its simple fabrication method and biocompatibility, was formed into microspheres with a modified extrusion technique and characterized by size. Size variance was introduced in batches and delivery patterns were compared to control groups of identical size. Release patterns for brilliant blue dye, the mock drug chosen, were examined for both groups via UV spectrometry. The absorbance values were then converted to concentration value using a calibration curve done prior to experimentation. The concentration values were then converted to mass values. These values then produced curves representing the mass of the drug released over time. Although the control and experimental values were statistically significantly different, the curves were rather similar to each other. However, when compared to the predicted release pattern, the curves were not the same. Unexpected degradation caused this dissimilarity between the curves. The predictive model was then adjusted to account for degradation by changing the diffusion coefficient in the code to a reciprocal first order exponent. The similarity between the control and experimental curves can insinuate the notion that size tolerances for microsphere production can be somewhat lenient, as a batch containing fifteen beads of the same size and one with three different sizes yields similar release patterns.