Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2019)

To determine the surface charge density near the electrode surface plays an important role in the studies related to biomedical device and bio-related surface reaction. This dissertation presents a technique, Integrated Transient Induced Molecular Electronic Signal (i-TIMES) method, which is an extended technique from our previous system to study surface charge density and biomolecular interaction on the electrode surface.

i-TIMES method is consisted of a microfluidic device with two platinum electrodes embedded in it which are connected to the differential inputs of a transimpedance amplifier (TIA). Based on i-TIMES method and the designed experimental process, we are able to quantify the amount of the surface charge within the electrical double layer at the liquid/solid interface for different buffer strengths, buffer types and pH values. Most uniquely, since i-TIMES signal is generated by the mobile ion or molecule which is not permanently adhered to the electrode surface, the surface molecular coverage can be obtained by comparing the surface charge density on the electrode surface before and after modification. We have measured the surface coverage for thiol-modified single-strand deoxyribonucleic acid (ssDNA) as anchored probe and 6-Mercapto-1-hexanol (MCH) as blocking agent on the platinum surface to prove the concept.

In addition, by introducing the biomolecule into the system, we can further demonstrate the effect on surface charge density with different type of biomolecules. The effect of molecular concentration on the surface charge density has been demonstrated based on various biomolecules including protein (lysozyme and bovine pancreatic ribonuclease A), ligand (N,N’,N″-triacetylchitotriose (TriNAG), p-aminobenzamidine (pABA) and uridine-3'-phosphate(3’-UMP)) and aptamer. Furthermore, the biomolecular interaction can also be determined by analyzing the change of the surface charge density based on our own developed i-TIMES physical model.

Overall, our results indicate that the i-TIMES technique is highly sensitive to the physical and chemical properties of large and small molecules and each type of molecule can produce a unique footprint in its i-TIMES signal. Through these experiments, we have demonstrated that i-TIMES method not only can offer a simple and accurate technique to quantify surface charge density on a metal surface but also can be an enabling tool for studies of biomolecular interaction and surface functionalization for biochemical sensing and reactions. Technologically, i-TIMES provides an accurate and convenient tool for quantitative study of surface charge density and molecular interactions without molecular labeling or immobilization. The technique can be attractive to many applications including drug discovery.

    Cover page: Measuring Electrical Charge and Molecular Interaction at Solid/Liquid Interface from Integrated Transient Induced Molecular Electronic Signal (i-TIMES)
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2019)
    Charge density and molecular coverage on the surface of electrode play major roles in the science and technology of surface chemistry and biochemical sensing. However, there has been no easy and direct method to characterize these quantities. By extending the method of Transient Induced Molecular Electronic Signal (TIMES) which we have used to measure molecular interactions, we are able to quantify the amount of charge in the double layers at the solution/electrode interface for different buffer strengths, buffer types, and pH values. Most uniquely, such capabilities can be applied to study surface coverage of immobilized molecules. As an example, we have measured the surface coverage for thiol-modified single-strand deoxyribonucleic acid (ssDNA) as anchored probe and 6-Mercapto-1-hexanol (MCH) as blocking agent on the platinum surface. Through these experiments, we demonstrate that TIMES offers a simple and accurate method to quantify surface charge and coverage of molecules on a metal surface, as an enabling tool for studies of surface properties and surface functionalization for biochemical sensing and reactions.
      Cover page: Measuring Electric Charge and Molecular Coverage on Electrode Surface from Transient Induced Molecular Electronic Signal (TIMES)
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2015)
      Nucleic acid detection and quantification technologies have made remarkable progress in recent years.  Among existing platforms, hybridization-based assays have the advantages of being amplification free, low instrument cost, and high throughput, but are generally less sensitive compared to sequencing and PCR assays. To bridge this performance gap, we developed a quantitative physical model for the hybridization-based assay to guide the experimental design, which leads to a pico-liter droplet environment for superior performance orders of magnitude above the state of the art in any amplification-free microarray platform. The pico-liter droplet hybridization platform is further coupled with the on-chip enrichment technique to yield ultra high sensitivity both in terms of target concentration and copy number.  Our physical model, taking into account of molecular transport, electrostatic intermolecular interactions, reaction kinetics, suggests that reducing liquid height and optimizing target concentration will maximize the hybridization efficiency, and both conditions can be satisfied in a highly parallel, self-assembled pico-liter droplet microarray that produces a detection limit as low as 570 copies and 50 aM. The pico-liter droplet array device is realized with a micro-patterned super-hydrophobic black silicon surface that allows enrichment of nucleic acid samples by position-defined evaporation.  With on-chip enrichment and oil encapsulated pico-liter droplet arrays, we have demonstrated a record high sensitivity, wide dynamic range (6 orders of magnitude), and marked reduction of hybridization time from >10 hours to less than 5 minutes in a highly repeatable fashion, benefiting from the physics-driven design and nanofeatures of the device. The design principle and technology can contribute to biomedical sensing and point-of-care clinical applications including pathogen detection and cancer diagnosis and prognosis.
        Cover page: Self-Assembled Pico-Liter Droplet Microarray for Ultrasensitive Nucleic Acid Quantification
        Top