Development of an integrated opto-electric biosensor to dynamically examine cytometric proliferation and cytotoxicity

My doctoral research has focused on the development of microscale optical techniques for examining micro/bio fluidics. Preliminary work measured the velocity field in a microchannel, by optical slicing, using Confocal Laser Scanning Microscopy (CLSM). Next, Optical Serial Sectioning Microscopy (OSSM) was applied to examine thermometry by detecting the free Brownian motion of nano-particles suspended in mediums at different temperatures. An extension of this work used objective-based Total Internal Reflection Fluorescence Microscopy (TIRFM) to examine the hindered Brownian motion of nano-particles that were very close to a solid surface (within 1 mm). An optically transparent and electrically conductive Indium Tin Oxide (ITO) biosensor and an integrated dynamic live cell imaging system were developed to dynamically examine changes in cell coverage area, cell morphology, cell-substrate adhesion, and cell-cell interaction. To our knowledge this is the first sensor capable of conducting simultaneous optical and electrical measurements. This system consists of an incubator, which keeps cells viable by providing the necessary environmental conditions (37 °C temperature and 5 % CO2), and multiple microscopy techniques, including multispectrum Interference Reflection Microscopy (MS-IRM), TIRFM, Epi-fluorescence Microscopy, Phase Contrast Microscopy (PCM), and Differential Interference Contrast Microscopy (DICM). Along with investigations of cytometric proliferation including cellular barrier functions, in vitro cytotoxicity experiments were also conducted to examine the effect of a drug (cytochalasin D, a toxic agent) on cellular motility and cellular morphology. These cytotoxicity results give us a fundamental understanding of the cellular processes induced by the drug, which will be invaluable in the search for methods of preventing metastases. In this research, MS-IRM is used to examine the focal contacts and the gap morphology between cells and substrates, DICM is used to examine the coverage area of cells, and impedance measurements are used to correlate these two parameters. Advances in the understanding of vascular bio-transport in endothelial cells will have an impact on many aspects of cell biology, tissue engineering, and pharmacology. Particularly important will be the ability to test the popular hypothesis that the cell barrier function is regulated by specific cytoskeleton elements controlling intercellular and extracellular coupling

The Impact of Firm Size on Dynamic Incentives and Investment

Recent studies conclude that small firms have higher but more variable growth rates than large firms. To explore how this empirical regularity affects moral hazard and investment, we develop an agency model with a firm size process having two features: the drift is controlled by the agent's effort and the principal's investment decision, and the volatility is proportional to the square root of size. The firm improves on production efficiency as it grows, and wages are back-loaded when size is small but front-loaded when it is large. Furthermore, there is underinvestment in a small firm but overinvestment in a large firm

The Impact of Firm Size on Dynamic Incentives and Investment

Recent studies conclude that small firms have higher but more variable growth rates than large firms. To explore how this empirical regularity affects moral hazard and investment, we develop an agency model with a firm size process having two features: the drift is controlled by the agent's effort and the principal's investment decision, and the volatility is proportional to the square root of size. The firm improves on production efficiency as it grows, and wages are back-loaded when size is small but front-loaded when it is large. Furthermore, there is underinvestment in a small firm but overinvestment in a large firm

Dynamic Changes in Maritime Research Capability in Chinese Universities

This study determines the top fifty authors in China and their university affiliations in the maritime transportation field, compared to their world ranking. We refer to China in the broad sense of the Chinese economies, including not only mainland China and Hong Kong, but also Chinese Taipei (Taiwan) and Singapore. This study analyzes sixty-five SSCI and SCI journals in the field of maritime and transportation between the years 2000 and 2015. In terms of ranking, three indicators are employed: total number of articles, weighted score (indication of author contribution), and the impact score. With the exception of Shanghai Jiao Tong University, no other universities selected in the first phase of Project 985, which received billions of dollars in government support/aid, were listed in the world ranking. Star authors are deemed to have contributed greatly to the rankings of their affiliated universities. The future of China’s rankings is bright in view of the increasing number of papers being published by Chinese authors and universities and their strong grounding in quantitative methodologies. Document type: Articl

Potential redox-sensitive Akt activation by dopamine activates Bad and promotes cell death in melanocytes

Dopamine (DA) is a well known oxidative neurotoxin. In addition, Akt has been reported to deliver a survival signal that inhibits apoptosis. However, it has also been reported that chronic Akt activation leads to apoptosis in response to oxidative stress. The objective of the present study was to investigate the possible role of the Akt pathway in vitiligo and its possible relationship with DA-induced cell death using Mel-Ab cells. Cultured Mel-Ab cells were treated with DA with and without N-Acetyl-L-cysteine (NAC), which is known to have antioxidative properties. Cell viability was then assessed by a crystal violet assay and Annexin staining was performed. The changes in the expression of Akt were analyzed by western blot analysis. The cell viability was reduced by approximately 60% in response to treatment with 500 µM DA, and NAC effectively prevented this cytotoxic effect. Likewise, treatment with DA produced numerous Annexin positive cells, while treatment with NAC prevented this apoptotic cell death. Akt was slowly phosphorylated after treatment with DA, while NAC clearly inhibited the DA-induced Akt activation. Western blot analysis also showed that treatment with DA induced the activation of Bad. Finally, LY294002 exerted a protective effect against DA-induced apoptotic cell death. DA may induce redox-sensitive Akt activation and increase the level of Bad, which can promote cell death by heterodimerization with survival proteins. Moreover, NAC effectively protects against DA-induced melanocyte death via inhibition of DA-induced Akt activation

Solid–liquid interface temperature measurement of evaporating droplet using thermoresponsive polymer aqueous solution

The present study aims to measure the solid–liquid interface temperature of an evaporating droplet on a heated surface using a thermoresponsive polymer. Poly(N-isopropylacrylamide) (pNIPAM) was used owing to its sensitive optical and mechanical properties to the temperature. We also measured the refractive index variation of the pNIPAM solution by using the surface plasmon resonance imaging (SPRi). In particular, the present study proposed a new method to measure the solid–liquid interface temperature using the correlation among reflectance, refractive index, and temperature. It was found that the reflectance of a pNIPAM solution decreased after the droplet deposition. The solid–liquid interface temperature, estimated from the reflectance, showed a lower value at the center of the droplet, and it gradually increased along the radial direction. The lowest temperature at the contact line region is present because of the maximum evaporative cooling. Moreover, the solid–liquid interface temperature deviation increased with the surface temperature, which means solid–liquid interface temperature should be considered at high temperature to predict the evaporation flux of the droplet accurately

The effect of adsorbed volatile organic compounds on an ultrathin water film measurement

Using surface plasmon resonance imaging (SPRi), we have recently shown for the first time the existence of a monolayer water film between droplets during dropwise condensation. This study examines the effect of adsorbed volatile organic compounds (VOCs) on the ultrathin film measurement using SPRi. Further, the work presents the proper surface-treatment process that enables measurements of the ultrathin water layer during high-speed imaging of dropwise condensation at 3000 frame per second. In this study, two methods were applied for cleaning the surface (gold-coated glass)-(1) standard cleaning procedure (SCP) using acetone, isopropyl alcohol, and deionized water and (2) SCP followed by air plasma cleaning. This work discusses the effect of the cleaning procedures on surface roughness, contact angle, and surface chemistry using atomic force microscopy, optical microscopy, and an X-ray photoelectron spectroscope meter. The results showed that SCP before the SPRi is a proper surface-treatment method. The effect of adsorbed VOCs during dropwise condensation on a surface treated with SCP was measured to be 0.0025 (reflectivity unit), which was 70% smaller than the reflectance associated with a monolayer water film. The results of this work confirm a monolayer water film observation during the dropwise condensation, which has been reported before