Bioanalytical Applications of Digital Imaging: Applications to Organ-on-chip and Point-of-care Analysis Systems

Qualitative and quantitative analysis through digital imaging has significant potential in several scientific applications including bioanalytical applications. In this document, the implication of digital imaging to validate and characterize a novel microfluidic organ-on-chip device and establish a point-of-care method to estimate epinephrine concentrations in expired and degraded autoinjectors have been described in chapter 2 and 3 respectively. Chapter 4 includes description of the principle and methodology of strong cation exchange-based immunoassay for oxytocin and β-endorphin. In chapter 2, fabrication of a novel microfluidic organ-on-chip device capable of culturing rodent SCN slices has been discussed. Characterization of the aCSF media droplets and carbogen gas bubbles have also been discussed. Viability of the cultured rodent brain slices using digital imagery through fluorescence calcium imaging and PI/DAPI staining have been reported. In chapter 3, utilization of quantitative smartphone imaging to estimate the concentration of epinephrine in expired and degraded autoinjectors have been described. Actual concentrations of the samples have been established by UHPLC technique. The estimated concentrations of the samples via quantitative smartphone imaging have been reported to possess a strong correlation (r \u3e 0.7) with the actual concentration. Different lighting conditions, distance and angle of camera variations have been explored in chapter 3. Direct immunoassay of relatively small neurotransmitters (~1-5 KDa) through capillary electrophoresis is prone to poor resolution challenge. The principle of using strong cation exchange-based chromatography to carry out such immunoassays have been described in chapter 4. The possible use of crosslinking agents such as sulfo-GMBS and sulfo-SMPB to improve antigen-antibody binding has also been discussed in this chapter. Chapter 5 explores the future directions of improving the rodent slice culture device to accommodate various size and shape of brain slices by chamber geometry and surface energy optimization

PLISMIP-ANT, an ice-sheet model intercomparison project

In the context of future climate change, understanding the nature and behaviour of ice sheets during warm intervals in Earth history is of fundamental importance. The late Pliocene warm period (also known as the PRISM interval: 3.264 to 3.025 million years before present) can serve as a potential analogue for projected future climates. Although Pliocene ice locations and extents are still poorly constrained, a significant contribution to sea-level rise should be expected from both the Greenland ice sheet and the West and East Antarctic ice sheets based on palaeo sea-level reconstructions. Here, we present results from simulations of the Antarctic ice sheet by means of an international Pliocene Ice Sheet Modeling Intercomparison Project (PLISMIP-ANT). For the experiments, ice-sheet models including the shallow ice and shelf approximations have been used to simulate the complete Antarctic domain (including grounded and floating ice). We compare the performance of six existing numerical ice-sheet models in simulating modern control and Pliocene ice sheets by a suite of five sensitivity experiments. We include an overview of the different ice-sheet models used and how specific model configurations influence the resulting Pliocene Antarctic ice sheet. The six ice-sheet models simulate a comparable present-day ice sheet, considering the models are set up with their own parameter settings. For the Pliocene, the results demonstrate the difficulty of all six models used here to simulate a significant retreat or re-advance of the East Antarctic ice grounding line, which is thought to have happened during the Pliocene for the Wilkes and Aurora basins. The specific sea-level contribution of the Antarctic ice sheet at this point cannot be conclusively determined, whereas improved grounding line physics could be essential for a correct representation of the migration of the grounding-line of the Antarctic ice sheet during the Pliocene

The patterns and drivers of recent outlet glacier change in East Antarctica

West Antarctica and Greenland have made substantial contributions to global sea level rise over the past two decades. In contrast, the East Antarctic Ice Sheet (EAIS) has largely been in balance or slightly gaining mass over the past two decades. This is consistent with the long-standing view that the EAIS is relatively immune to global warming. However, several recent reports have highlighted instabilities in the EAIS in the past, and some numerical models now predict near-future sea level contributions from the ice sheet, albeit with large uncertainties surrounding the rates of mass loss. Using primarily remote sensing methods, this thesis aims to determine spatial and temporal patterns of outlet glacier change in the EAIS and assess the drivers and mechanisms of any changes in their dynamics. In doing so, it will also explore the wider debate surrounding the potential vulnerability of the ice sheet in the coming decades to centuries. Pan-ice sheet terminus mapping in 1974, 1990, 2000 and 2012 reveals significant decadal variability in the behaviour of the EAIS. The majority of outlet glaciers retreated between 1974 and 1990, before switching to a dominant advance phase from 1990-2000. This trend of outlet glacier advance largely continued between 2000 and 2012, with the exception of Wilkes Land, where 74% of glaciers retreated. It is hypothesized that this anomalous retreat is linked to a reduction in sea ice and associated impacts on ocean stratification. A more detailed examination of six glaciers in Porpoise Bay, Wilkes Land, reveals that large simultaneous calving events in January 2007 and March 2016, totalling ~2,900 km2 and 2,200 km2, were driven by the break-up of the multi-year landfast sea ice which usually occupies Porpoise Bay. However, these break-up events were driven by contrasting mechanisms. The 2007 break-up event is linked to an exceptionally warm December 2005 weakening the band of multi-year sea ice prior to its eventual break-up in the following summer. Whereas, the 2016 event is linked to the terminus advance of Holmes (West) Glacier pushing the multi-year sea ice further into the open ocean, making it more vulnerable to break-up. In order to examine how changes at the terminus of glaciers might impact on their inland velocity, this thesis then analyses Cook Glacier, which is a major outlet glacier which drains a large proportion of the Wilkes Subglacial Basin. Analysis of ice-front positon change from 1947-2017, glacier velocity from 1973-2017 and ice shelf thickness from 1994-2012, reveals dynamic instability in the recent past. Cook West Ice Shelf retreated to its grounding line between 1973 and 1989, resulting the doubling of its velocity. Cook East Ice Shelf did not show a similar retreat pattern, but its ice shelf thinned rapidly between 1998 and 2002, which coincided with an increase of its velocity of ~10%. This rapid thinning is linked to periodic intrusions of warm mCDW. If these intrusions become more persistent in the future, Cook Glacier has the potential to contribute to sea level rise in the future. In a wider context the results from this thesis highlight some key issues which need to be considered when predicting the response of the EAIS to future climate warming: i) The sensitivity of the EAIS to decadal variations in climate. ii) The potential for future changes in the location and persistency of landfast sea ice to alter outlet glacier dynamics. iii) The potential for rapid thinning of those ice shelves with a low steady-state basal melt rate

Analysis of Antarctic glacigenic sediment provenance through geochemical and petrologic applications

The number of provenance studies of glacigenic sediments in Antarctica has increased dramatically over the past decade, providing an enhanced understanding of ice sheet history and dynamics, along with the broader geologic history. Such data have been used to assess glacial erosion patterns at the catchment scale, flow path reconstructions over a wide range of scales, and ice sheet fluctuations indicated by iceberg rafted debris in circumantarctic glacial marine sediments. It is notable that even though most of the bedrock of the continent is ice covered and inaccessible, provenance data can provide such valuable information about Antarctic ice and can even be used to infer buried rock types along with their geo- and thermochronologic history. Glacigenic sediments provide a broader array of provenance analysis opportunities than any other sediment type because of their wide range of grain sizes, and in this paper we review methods and examples from all size fractions that have been applied to the Antarctic glacigenic sedimentary record. Interpretations of these records must take careful consideration of the choice of analytical methods, uneven patterns of erosion, and spatial variability in sediment transport and rock types, which all may lead to a preferential identification of different elements of sources in the provenance analyses. Because of this, we advocate a multi-proxy approach and highlight studies that demonstrate the value of selecting complementary provenance methods

Pleistocene records of ice sheet processes and glacial history from Antarctica and Greenland

Anthropogenic climate change is transforming Earth’s Polar Regions. Oceanic and atmospheric warming threaten to melt portions of the Antarctic and Greenland ice sheets and raise sea level dramatically by the end of this century. As a guide for the future, we can examine the geologic record to understand the surface processes that govern ice sheet behavior and establish chronologies of past climate change. In this dissertation, I focus on the Pleistocene glacial history of two polar field sites: the presently ice-free region of McMurdo Sound, Antarctica and formerly glaciated continental shelf of Melville Bugt, Greenland. In my research, I use a combination of detailed geologic mapping, geochemical and isotopic analyses of glacial sediments, and several Quaternary geochronologic techniques. I show that several marine-based ice sheets inundated McMurdo Sound and deposited a series of glacial sediments that record former ice sheet configuration and Antarctic surface processes. Mapping results and a robust radiocarbon chronology indicate that grounded marine-based ice in the Ross Sea overflowed into McMurdo Sound and attained maximum thickness after the global Last Glacial Maximum; ice receded in response to rising sea level and changing ocean circulation. Cosmogenic nuclide exposure ages of boulders from these glacial deposits do not record a simple history of ice extent, but instead the integrated effects of multiple surface processes operating below, along, and above the Antarctic ice sheets. I build upon the insights gained from Antarctica to develop a novel approach to analyzing glacial marine diamict, a mixture of grain sizes and lithologies, deposited on the continental shelf by an expanded Greenland Ice Sheet. Using cosmogenic nuclides, low temperature thermochronometry, and lipid biomarkers, I show that the Greenland Ice Sheet during the Early Pleistocene was similar to today. Extremely low cosmogenic nuclide concentrations indicate the ice sheet already eroded pre-glacial soil cover, but thermochronometry data suggest deep fjords had not yet formed. Abundant lipid biomarkers recovered in this diamict indicate that ice-free areas supported vegetation, similar to the modern ice sheet. This dataset demonstrates how the novel application of proven techniques to glacial sediments can unlock new information about ice sheet history and process

Simulating the Antarctic ice sheet in the late-Pliocene warm period: PLISMIP-ANT, an ice-sheet model intercomparison project

In the context of future climate change, understanding the nature and behaviour of ice sheets during warm intervals in Earth history is of fundamental importance. The late Pliocene warm period (also known as the PRISM interval: 3.264 to 3.025 million years before present) can serve as a potential analogue for projected future climates. Although Pliocene ice locations and extents are still poorly constrained, a significant contribution to sea-level rise should be expected from both the Greenland ice sheet and the West and East Antarctic ice sheets based on palaeo sea-level reconstructions. Here, we present results from simulations of the Antarctic ice sheet by means of an international Pliocene Ice Sheet Modeling Intercomparison Project (PLISMIP-ANT). For the experiments, ice-sheet models including the shallow ice and shelf approximations have been used to simulate the complete Antarctic domain (including grounded and floating ice). We compare the performance of six existing numerical ice-sheet models in simulating modern control and Pliocene ice sheets by a suite of five sensitivity experiments. We include an overview of the different ice-sheet models used and how specific model configurations influence the resulting Pliocene Antarctic ice sheet. The six ice-sheet models simulate a comparable present-day ice sheet, considering the models are set up with their own parameter settings. For the Pliocene, the results demonstrate the difficulty of all six models used here to simulate a significant retreat or re-advance of the East Antarctic ice grounding line, which is thought to have happened during the Pliocene for the Wilkes and Aurora basins. The specific sea-level contribution of the Antarctic ice sheet at this point cannot be conclusively determined, whereas improved grounding line physics could be essential for a correct representation of the migration of the grounding-line of the Antarctic ice sheet during the Pliocene