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Open Access Publications from the University of California

Scholarly Works (9 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2020)

Healthcare has seen a big boon in technological advancement with the last few years with next-generation genome sequencing, robotics, artificial intelligence, and bioinformatics. While the origins of these breakthroughs are deeply rooted in biology, life sciences, and medical science, the new age of technological breakthrough require an interdisciplinary approach. Materials science itself is an interdisciplinary field, with a huge contribution of physics and chemistry, and within the past few decades, advances in nanotechnology has allowed integration into healthcare giving materials science a new emerging role. Such is the case with a vibrational spectroscopy technique called Surface Enhanced Raman Spectroscopy (SERS).

SERS has the ability to measure the molecular bonds of the target analyte at the single molecular level. Yet, SERS is not a recognized spectrometry tool in healthcare. This dissertation examines the fundamental challenges that require a technique like SERS to transition from the academic research laboratories to clinical applications. While there are broad potential clinical applications, this dissertation focuses on the SERS measurement of diseases originating from cellular morphologies. The two main focal topics are cancer and microbiology research, where the proteome identification can provide new diagnostic and therapeutic treatment options.

The first major section is about testing the capabilities of our group’s unique graphene gold nanopyramid hybrid platform in controlled research laboratory environments. Varies cases of cancers are examined: lung, skin, and breast, through their various size, morphology, and proteomic differences. Afterwards, the field of microbiology is explored with bacteria and fungus species.

The second major section involves the SERS’s platform performance with clinical patient data. The first case study looks at the diagnosing meningitis from patients in China. The second case study looks at multidrug resistance detection of tuberculosis in rural Pakistan.

The last major section tries to consolidate the major lessons in this journey of bringing SERS to clinical applications. In particular, this section tackles the main question of why a technique like SERS has not been fully recognized in clinics yet and brings the case to why our SERS hybrid platform is very close to it.

    Cover page: Exploring the Challenges of Advancing Surface Enhanced Raman Spectroscopy-Based Biosensing From Research Laboratory to Clinics
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2013)
    A graphene-Au nano-pyramid hybrid system that enables label-free single molecule detection is demonstrated. The bio-compatible graphene-based SERS platform boosts a high density of hot spots with local SERS enhancement factor over 10(10) . We demonstrate that graphene can play a key role in quantitative study of SERS mechanisms, and can also serve as a promising building block in SERS active structures especially for biosensor applications.
      Cover page: Ultra‐Sensitive Graphene‐Plasmonic Hybrid Platform for Label‐Free Detection
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2016)
      Manipulation of biomolecules in aqueous solution has been a critical issue for the development of many biosensing techniques and biomedical devices. Electrostatic force is an effective method for increasing both sensitivity and selectivity of various biosensing techniques. In this study, we employed surface-enhanced Raman spectroscopy (SERS) as an in situ label-free method to monitor the motion of biomolecules driven by this manipulation technique. We present the results of a combined experimental and simulation study to demonstrate that electrostatic force could enhance SERS detection of molecules in aqueous solutions with respect to sensitivity and selectivity. In regards to sensitivity, we successfully observed the signature of single molecule addition to individual SERS hot spots, in the form of the stepwise increase of Raman signal with time. With regard to selectivity, we obtained discernible SERS signature of selected families of molecules from a mixture of other molecular families of higher concentration by driving the specifically charged or polarized molecules toward or away from the electrodes/SERS surface based on their charge state, polarizability, mass, and environment pH value. We further report the experimental results on how the key factors affect the selective attraction and repulsion motion of biomolecules.
        Cover page: Selective Manipulation of Molecules by Electrostatic Force and Detection of Single Molecules in Aqueous Solution
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2020)
        Large-scale close-packed two-dimensional (2D) colloidal crystal with high coverage is indispensable for various promising applications. The Langmuir-Blodgett (LB) method is a powerful technique to prepare 2D colloidal crystals. However, the self-assembly and movement of microspheres during the whole LB process are less analyzed. In this study, we clarify the crucial impact of hydrophilicity of the microspheres on their self-assembly in the LB process and on the properties of the prepared 2D colloidal crystals. The characteristic surface pressure-area isotherms of the microspheres have been analyzed and adjusted by only counting the quantity of the microspheres on the water surface, which leads to more accurate results. The critical surface pressures for hydrophilic and hydrophobic microspheres are about 61 and 46 mN/m, respectively. The decrease of the surface hydrophilicity of microspheres facilitates their self-assembly on the water surface, which further leads to higher coverage and less defects of the 2D colloidal crystals. A coverage of as high as 97% was obtained using hydrophobic microspheres. Entropy and intersphere capillary forces drive the self-assembly and transportation of the microspheres, respectively. Caused by the diffraction of visible light, opposite contrasts at local adjacent regions on the surface of the 2D colloidal crystals have been observed. The understanding of self-assembly of the microspheres during the LB process paves the way to fabricate the high-quality 2D colloidal crystals for various applications such as photonic papers and inks, stealth materials, biomimetic coatings, and related nanostructures.
          Cover page: Crucial Impact of Hydrophilicity on the Self-Assembled 2D Colloidal Crystals Using Langmuir–Blodgett Method
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2020)
          Surface enhanced Raman spectroscopy (SERS) holds great promise in biosensing because of its single-molecule, label-free sensitivity. We describe here the use of a graphene-gold hybrid plasmonic platform that enables quantitative SERS measurement. Quantification is enabled by normalizing analyte peak intensities to that of the graphene G peak. We show that two complementary quantification modes are intrinsic features of the platform, and that through their combined use, the platform enables accurate determination of analyte concentration over a concentration range spanning seven orders of magnitude. We demonstrate, using a biologically relevant test analyte, the amyloid β-protein (Aβ), a seminal pathologic agent of Alzheimer's disease (AD), that linear relationships exist between (a) peak intensity and concentration at a single plasmonic hot spot smaller than 100 nm, and (b) frequency of hot spots with observable protein signals, i.e. the co-location of an Aβ protein and a hot spot. We demonstrate the detection of Aβ at a concentration as low as 10-18 M after a single 20 μl aliquot of the analyte onto the hybrid platform. This detection sensitivity can be improved further through multiple applications of analyte to the platform and by rastering the laser beam with smaller step sizes.
            Cover page: Ultrasensitive amyloid β-protein quantification with high dynamic range using a hybrid graphene-gold surface-enhanced Raman spectroscopy platform.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            Ultrasensitive detection and spatially resolved mapping of neurotransmitters, dopamine and serotonin, are critical to facilitate understanding brain functions and investigate the information processing in neural networks. In this work, we demonstrated single molecule detection of dopamine and serotonin using a graphene-Au nanopyramid heterostructure platform. The quasi-periodic Au structure boosts high-density and high-homogeneity hotspots resulting in ultrahigh sensitivity with a surface enhanced Raman spectroscopic (SERS) enhancement factor ∼10(10). A single layer graphene superimposed on a Au structure not only can locate SERS hot spots but also modify the surface chemistry to realize selective enhancement Raman yield. Dopamine and serotonin could be detected and distinguished from each other at 10(-10) M level in 1 s data acquisition time without any pretreatment and labeling process. Moreover, the heterostructure realized nanomolar detection of neurotransmitters in the presence of simulated body fluids. These findings represent a step forward in enabling in-depth studies of neurological processes including those closely related to brain activity mapping (BAM).
              Cover page: Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2018)
              Amyloid β-protein (Aβ) self-association is one process linked to the development of Alzheimer's disease (AD). Aβ peptides, including its most abundant forms, Aβ40 and Aβ42, are associated with the two predominant neuropathologic findings in AD, vascular and parenchymal amyloidosis, respectively. Efforts to develop therapies for AD often have focused on understanding and controlling the assembly of these two peptides. An obligate step in these efforts is the monitoring of assembly state. We show here that surface-enhanced Raman spectroscopy (SERS) coupled with principal component analysis (PCA) readily distinguishes Aβ40 and Aβ42. We show further, through comparison of assembly dependent changes in secondary structure and morphology, that the SERS/PCA approach unambiguously differentiates closely related assembly stages not readily differentiable by circular dichroism spectroscopy, electron microscopy, or other techniques. The high discriminating power of SERS/PCA is based on the rich structural information present in its spectra, which comprises not only on interatomic resonances between covalently associated atoms and hydrogen bond interactions important in controlling secondary structure, but effects of protein orientation relative to the substrate surface. Coupled with the label-free, single molecule sensitivity of SERS, the approach should prove useful for determining structure activity relationships, suggesting target sites for drug development, and for testing the effects of such drugs on the assembly process. The approach also could be of value in other systems in which assembly dependent changes in protein structure correlate with the formation of toxic peptide assemblies.
                Cover page: Surface enhanced Raman spectroscopy distinguishes amyloid Β‐protein isoforms and conformational states
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2016)
                We report systematic transient characterization of a graphene ribbon (GR) used as an interconnect for electrostatic discharge (ESD) protection of future integrated circuits. A large set of GR wires (around 6000) with varying and practical dimensions were fabricated using the chemical vapor deposition method and characterized by transmission line pulsing (TLP) and very fast TLP (VFTLP) measurements. Comprehensive TLP and VFTLP testing with varying pulse rise time (tr) and duration (td) was performed across a wide temperature range ( T = -30/+110°C). Measurement-based statistics reveal the relationship between ESD capability of GR wires and the wire length (L), width (W), and number of graphene layers, as well as ESD pulse shapes and operation temperature.
                  Cover page: Systematic Characterization of Graphene ESD Interconnects for On-Chip ESD Protection
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2017)
                  Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.
                    Cover page: Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification
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