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Open Access Publications from the University of California

Scholarly Works (15 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2010)

The conventional projection-type photolithography approach to nanoscale manufacturing is facing possibly insurmountable challenges, especially to invent novel technical solutions that remain economical for the next generation of semi-conductor integrated circuits. Although extreme ultra violet (EUV) lithography with the next generation photo-masks and 193-nm immersion lithography with double patterning are expected to deliver 22 nm and smaller nodes, it still cannot effectively address the reliability and cost issues required for mass production. Maskless nanolithography is a potentially agile and cost effective approach, but most of the current solutions have throughputs that are too low for manufacturing purposes.

This dissertation reports a new low-cost high-throughput approach to maskless nanolithography that uses an array of plasmonic lenses (PL) that "fly" above the rotating surface to be patterned, concentrating short wavelength surface plasmons into sub-100 nm spots. However, these nanoscale spots are only formed in the near field (within a few nanometers of the surface), which makes it very difficult to scan the array above the surface at high speeds. To overcome this problem a self-spacing air-bearing surface was designed and fabricated that can fly the array just nanometers above a disk that is spinning at speeds on the order of 10 meter/second, and patterning with feature sizes far smaller than the far-field diffraction limit have been experimentally demonstrated . Using this plasmonic nanolithography (PNL) approach, a 22-nm half-pitch direct pattern writing was successfully demonstrated using ultra-fast laser assisted nanoscale heat management and advanced PL designs.

This nano-fabrication scheme has the potential of a few orders of magnitude higher throughput than current maskless techniques, and it opens the way for a new cost effective approach towards the next generation lithography for nano-manufacturing.

    Cover page: High-Throughput Plasmonic Nanolithography
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2017)
    Dendritic cells (DCs) are the most potent antigen-presenting cells, and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes (CTLs) in lymphatic tissues. DC vaccination is a newly emerging and potent form of cancer immunotherapy and has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC-vaccines is strongly influenced by various techniques for the priming antigen loading onto DCs and their ability to migrate to the draining lymph nodes (LNs). Therefore, it is critical to improve DC-vaccines homing to draining LNs after administration in order to optimize DC-based therapy for individual patients. This review underlines 1) appropriate strategy to load tumor antigens onto DCs and 2) to optimize vaccine administration methods to ensure loaded DCs can migrate to LNs, in particular, Intraperitoneal (IP) injection. IP injection of DC-based vaccine may be a potential regimen for gastrointestinal tumors including hepatocellular carcinoma (HCC) and pancreatic adenocarcinoma (PDAC) since huge populations of LNs are present throughout the gastrointestinal track. Which might improve the subsequent migration to LNs.
      Cover page: Dendritic cells based immunotherapy.Creative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2018)

      Background

      Previous studies have shown the poor prognosis of metastatic breast cancer including bone metastasis. The early prediction and intervention of invasive breast carcinoma with bone metastasis are crucial to the outcomes of patients. The purpose of our study is to test the hypothesis that the collagen deposition of primary breast cancer can be used as a quantitative biomarker for the early prediction of bone metastasis.

      Methods

      A total of sixty breast cancer patients were included in our study, and the surgical specimens of these patients were divided into three groups: patients with no metastasis (group 1), lymph node metastasis (group 2), and bone metastasis (group 3). Masson's trichrome staining and hematoxylin and eosin staining were applied to all primary breast cancers. Collagen area percentage and tumor cell measurement of each sample were measured by HistoQuest software.

      Results

      Measurement results of collagen area percentage (%) in primary breast tumors were 32.39 ± 13.30, 25.37 ± 11.10, and 22.71 ± 8.91 for groups 1, 2, and 3, respectively. The corresponding P values were 0.0779 (group 1 vs. group 2), 0.4086 (group 2 vs. group 3), and 0.0102 (group 1 vs. group 3). The correlation between collagen area percentage and tumor cell measurement were group 1 (P = 0.5927, r = -0.1273), group 2 (P = 0.5711, r = -0.1348), and group 3 (P = 0.0003, r = -0.7253).

      Conclusions

      The collagen deposition of primary breast cancer can be used as a quantitative biomarker for the early prediction of bone metastasis.
        Cover page: Quantitative measurement of breast carcinoma fibrosis for the prediction in the risk of bone metastasis.Creative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2019)
        As the major thermogenic tissue in body, the brown adipose tissue (BAT) was recently identified as an important factor to induce the rapid weight loss and malnutrition in malignancy. Current methods for detecting and quantifying brown adipose tissue (BAT) are in limited use. The aim of this study was to evaluate the changes of BAT tissue and its function in the development of pancreatic ductal adenocarcinoma (PDAC) by using magnetic resonance imaging (MRI). Ten-week-old female C57BL/6 mice were inoculated orthotopically with Pan02 tumor cells. R2* maps and two-point Dixon MRI were performed weekly for evaluation of BAT function and volume, respectively. The T2-weighted MRI was applied weekly for monitoring tumor growth. Meanwhile, the body weight was measured daily as another indication of malnutrition. The UCP1 levels in BAT and white adipose tissue (WAT) were assessed. The serum IL-6 was also measured as the biomarker of cancer-associated cachexia. T2-weighted MRI indicated the rapid tumor growth from week 3 to week 5 after tumor cell inoculation. The water-fat separated MRI could clearly identify and quantify the BAT. The function and volume of BAT could be monitored by weekly MRI measurement in tumor-bearing mice. The total body weights of PDAC tumor-bearing mice were relatively stable, however, was significantly lower than that of control C57BL/6 mice. The results of this study demonstrated the feasibility of detection and quantification of BAT in vivo by MRI during the development of pancreatic cancer.
          Cover page: MRI Assessment of Associations between Brown Adipose Tissue and Cachexia in Murine Pancreatic Ductal Adenocarcinoma
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2018)
          Dendritic cell (DC) based immunotherapy is a promising approach for cancer treatment and has been approved in clinical settings for decades. Clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC immunotherapy is strongly influenced by their ability to migrate to the draining lymph nodes (LNs). Therefore, it is critical to deliver DCs and monitor the in vivo biodistributions of DCs after administration. The purpose of this study is to determine whether a novel injection route of DCs improves DC migration to LNs, tissues, organs and lymphatics. In the present study, a modified method was investigated to acquire DCs from mouse bone marrow. Cultured antibody labeled DCs were analyzed by flow cytometry. India ink was used to visualize mouse abdominal LNs and PKH26 was utilized to label DCs for intraperitoneal (IP) injection, results were evaluated by histology. Our results showed that large amounts of DCs with a relatively high purity were acquired. IP injection of india ink marked the abdominal LNs and PKH26 labeled DCs showed IP was an effective administration route to increase the absorption of viable DCs, and different time points after IP inject showed no significant difference of the migrated DCs. The findings indicated that large amounts of high purity DCs can be acquired through our method and IP injection accelerates DCs migration to abdominal LNs, which can be directly translated to clinical settings, especially for abdominal cancers. This study makes a foundation for future researches of DC-based immunotherapy as a treatment modality against cancer.
            Cover page: Mouse dendritic cell migration in abdominal lymph nodes by intraperitoneal administration.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2011)
            Optical imaging and photolithography promise broad applications in nano-electronics, metrologies, and single-molecule biology. Light diffraction however sets a fundamental limit on optical resolution, and it poses a critical challenge to the down-scaling of nano-scale manufacturing. Surface plasmons have been used to circumvent the diffraction limit as they have shorter wavelengths. However, this approach has a trade-off between resolution and energy efficiency that arises from the substantial momentum mismatch. Here we report a novel multi-stage scheme that is capable of efficiently compressing the optical energy at deep sub-wavelength scales through the progressive coupling of propagating surface plasmons (PSPs) and localized surface plasmons (LSPs). Combining this with airbearing surface technology, we demonstrate a plasmonic lithography with 22 nm half-pitch resolution at scanning speeds up to 10 m/s. This low-cost scheme has the potential of higher throughput than current photolithography, and it opens a new approach towards the next generation semiconductor manufacturing.
              Cover page: Maskless Plasmonic Lithography at 22 nm Resolution
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2019)
              The purpose of our study was to investigate the hypothesis that DWI-MRI and DCE-MRI cab be used to distinguish between IRE and RE zones of IRE treatment in a rabbit liver model. 6 rabbits underwent baseline and post-procedure MR imaging with DWI and DCE-MRI as well as IRE (10 pulses, 2000 V, 10 µs/pulse, 10 ms between pulses). Rabbits were euthanized immediately after post-procedure MRI to acquire liver tissue for histology. Liver tissues were fixed and then stained with HE and TUNEL. T1w and T2w intensities in different treatment zones were calculated and normalized to paraspinal muscle signal. ADC maps were generated from DWI. AUC, PE, TTP, WIS, Ktrans, Kep, and VE were calculated from DCE-MRI. Apoptosis index was calculated from TUNEL stained tissues. P<0.05 was considered statistically significant. Entire IRE treated region was hyperintense compared with untreated tissues on T1w, with the RE zone having a higher signal intensity. On DWI, IRE treated tissue had decreased ΔADC. The IRE zone has a lower ΔADC than the RE zone within the treated region. On DCE-MRI, IRE zone demonstrated the highest TTP and the lowest PE, WIS, Ktrans, Kep, and VE, followed by the RE zone then the untreated tissue. TUNEL staining of liver tissues showed that the IRE zone had the highest apoptosis index, followed by the RE zone and then untreated tissue. In conclusion, DCE-MRI and DWI parameters allow differentiation between RE and IRE zones in a rabbit liver model.
                Cover page: DWI and DCE-MRI approaches for differentiating reversibly electroporated penumbra from irreversibly electroporated ablation zones in a rabbit liver model.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2019)
                The promise of dendritic cell (DC)-based immunotherapy has been established by two decades of translational research. However, long-term benefits of DC vaccination are reported in only scattered patients with pancreatic ductal adenocarcinoma (PDAC). Here we optimize DC vaccination and evaluate its safety and antitumor efficacy in the genetically engineered PDAC model (KrasLSL-G12D p53LSL-R172H Pdx-1-Cre (KPC mice)). KPC transgenic mice and orthotopic models using KPC cell lines were treated with DC vaccine via an intraperitoneal route. Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Histological analysis and flow cytometry were used to evaluate tumor-directed T cell immunity of these mice. DC vaccine via intraperitoneal injection suppressed tumor progression (P = 0.030) and significantly prolonged survival time (P = 0.028) in KPC mice. Vaccinated KPC mice displayed an increased antitumor T cell response indicated by a higher IFN-γ production (P = 0.016) and tumor-specific cytotoxicity (P = 0.027). Particularly, the mean apparent diffusion coefficient (ADC) values of KPC tumor calculated from diffusion weighted MRI (DW-MRI) were significantly higher in DC vaccine group than that in control group (P < 0.001). More interestingly, we observed that ADC positively correlated with fibrosis in KPC tumor (R2 = 0.463, P = 0.015). Our study demonstrated that the immunization with our improved DC vaccine can elicit a strong tumor-specific immune response and tumor suppression in PDAC.
                  Cover page: Dendritic cell immunotherapy induces anti-tumor effect in a transgenic mouse model of pancreatic ductal adenocarcinoma.
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2018)
                  Brown Adipose Tissue (BAT) has a major role in thermoregulation, producing heat by non-shivering thermogenesis. Primarily found in animals and human infants, the presence of significant brown adipose tissue was identified only recently, and its metabolic role in adults was reconsidered. BAT is believed to have an important role in many metabolic diseases, such as obesity and diabetes, and also to be associated with cancer cachexia. Therefore, it is currently a topic of great interest in the research community, and many groups are investigating the mechanisms underlying BAT metabolism in normal and pathological conditions. However, well established non-invasive methods for assessing BAT distribution and function are still lacking. The purpose of this review is to summarize the current state of the art of these methods, with a particular focus on PET, CT and MRI.
                    Cover page: Non-invasive Imaging Methods for Brown Adipose Tissue Detection and Function Evaluation.
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2022)
                    RATIONALE AND OBJECTIVES: Irreversible electroporation (IRE) is a promising non-thermal ablation technique for the treatment of patients with hepatocellular carcinoma. Early differentiation of the IRE zone from surrounding reversibly electroporated (RE) penumbra is vital for the evaluation of treatment response. In this study, an advanced statistical learning framework was developed by evaluating standard MRI data to differentiate IRE ablation zones, and to correlate with histological tumor biomarkers. MATERIALS AND METHODS: Fourteen rabbits with VX2 liver tumors were scanned following IRE ablation and forty-six features were extracted from T1w and T2w MRI. Following identification of key imaging variables through two-step feature analysis, multivariable classification and regression models were generated for differentiation of IRE ablation zones, and correlation with histological markers reflecting viable tumor cells, microvessel density, and apoptosis rate. The performance of the multivariable models was assessed by measuring accuracy, receiver operating characteristics curve analysis, and Spearman correlation coefficients. RESULTS: The classifiers integrating four radiomics features of T1w, T2w, and T1w+T2w MRI data distinguished IRE from RE zones with an accuracy of 97%, 80%, and 97%, respectively. Also, pixelwise classification models of T1w, T2w, and T1w+T2w MRI labeled each voxel with an accuracy of 82.8%, 66.5%, and 82.9%, respectively. Regression models obtained a strong correlation with behavior of viable tumor cells (0.62 ≤ r2 ≤ 0.85, p < 0.01), apoptosis (0.40 ≤ r2 ≤ 0.82, p < 0.01), and microvessel density (0.48 ≤ r2 ≤ 0.58, p < 0.01). CONCLUSION: MRI radiomics features provide descriptive power for early differentiation of IRE and RE zones while observing strong correlations among multivariable MRI regression models and histological tumor biomarkers.
                      Cover page: Early Differentiation of Irreversible Electroporation Ablation Regions With Radiomics Features of Conventional MRI.
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