Research

This is a collaborative project lead by Professor Alexander Revzin at the Mayo Clinic in Rochester MN. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the United States. NAFLD is a conglomerate of the relatively nonprogressive non-alcoholic fatty liver (NAFL) and progressive non-alcoholic steatohepatitis (NASH). While hepatic steatosis is a conserved feature of both NAFL and NASH, the latter is characterized by liver injury, inflammation, fibrosis, and the risk of liver cancer and cirrhosis. At the present time, there are no effective noninvasive and scalable screening strategies to distinguish between NAFL and NASH nor monitor NASH progression. Thus, there is a significant unmet need for biomarkers which are relatively easy to obtain, can be tested repeatedly over time, can distinguish NAFL from NASH, are pathophysiologically informed, and help risk stratify patients with NASH. Extracellular vesicles (EVs) carry signals from diseased cells and organs and therefore represent ideal biomarkers for NAFL and NASH. However, the development of EV based biomarkers has been confounded by several challenges. In this project, we will address the aforementioned challenges by developing novel technologies: 1) nanoprojectile (NP) secondary ion mass spectrometry (SIMS) that will enable analysis of EVs using microliters of sample and 2) microfluidic organotypic liver cultures that will allow us to harvest undiluted liver EVs from healthy or diseased tissue. 

This collaborative research project is lead by Prof. Chang-Yong Nam at Brookhaven National Laboratory. We recognize three critical gaps that currently impede the timely development, optimization, and deployment of improved EUV photoresists. These gaps are as follows: (1) the slow and complex nature of conventional chemical synthesis, (2) limited industry access to advanced material characterization techniques required for accelerated material discovery, and (3) the untapped research potential available in academia due to the lack of access for academic researchers––and even commercial EUV resist developers and suppliers––to expensive industrial EUV patterning systems needed for evaluating the ultimate EUV patterning performance of newly developed materials. To improve semiconductor device yield and enhance the performance of EUV photoresists, precise measurements of resist composition and uniformity at nanoscale are crucial. Nano-projectile secondary ion mass spectrometry (NP-SIMS) is an analytical technique that offers molecular and elemental analysis from thin film samples with high lateral resolution. Using NP-SIMS, our primary goal is to assess the molecular and elemental homogeneity of organic-inorganic hybrid EUV photoresist systems synthesized through VPI and MLD methods. 

Professor Eller is developing a new analytical methods for nanoscale molecular analysis based on secondary ion mass spectrometry (SIMS). The research will investigate the use of massive gold clusters as SIMS projectiles to examine nanoparticles and molecular assemblies, with the goal of elucidating molecular organization at a scale approaching 5 nm. The results of the project will provide new insights into nanoparticle-surface interactions with low-dimensional materials and nanostructured surfaces. Professor Eller will develop an interconnected research and educational program which will work in concert with CSUN's institutional goal of encouraging students from underrepresented groups to actively participate and succeed in STEM research fields.

The approach is based on nano-projectile secondary ion mass spectrometry, NP-SIMS. NP-SIMS has three innovative features (1) the nature of the projectile (2) the mode of data acquisition (3) the method of data analysis. Briefly, surfaces are probed with a suite of individual gold nanoparticles (e.g. Au4004+) separated in time and space. These projectiles generate abundant emission of analyte-specific ions. The ions emitted in each impact are mass analyzed and stored as an individual mass spectrum (single ion counting mode). The homogeneity of a component(s) can be evaluated by examining these individual mass spectra for the co-emission of analyte-specific species. Since the emission volume of a single nano-projectile defines the volume addressed with each measurement, nano-scale analysis is feasible. To dramatically expand the capabilities of the method two approaches will be pursued (a) identifying “rare” sites, i.e. reveal and characterize instances of molecular aggregation or segregation (b) decreasing the probing volume of each projectile to increase the sensitivity of the method. Fundamental advances in NP-SIMS methodologies achieved by this work will have broad impacts. A) Identification of rare molecular defects will be achieved using our approach of stochastically probing a large area (100-500µm) with 10^6-7 individual impacts (<0.5% of the analyzed area). In our concept of storing the ionized ejecta from each impact separately, nano-scale aggregations or segregations can be identified via detection of multiple analyte-specific ions. Enabling domains at least three standard deviations from the mean to be investigated for molecular/compositional information. B) The second objective seeks to relate the volume probed with the amount and accuracy of the molecular/compositional information obtained. The investigators are experienced with producing a range of nano-projectiles from Au3 to Au2800, which generate impact craters ranging from ~3-20 nm.