Browsing by Author "Srinivasaraghavan, Vaishnavi"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Bioimpedance spectroscopy of breast cancer cells: A microsystems approach
    Srinivasaraghavan, Vaishnavi (Virginia Tech, 2015-11-04)
    Bioimpedance presents a versatile, label-free means of monitoring biological cells and their responses to physical, chemical and biological stimuli. Breast cancer is the second most common type of cancer among women in the United States. Although significant progress has been made in diagnosis and treatment of this disease, there is a need for robust, easy-to-use technologies that can be used for the identification and discrimination of critical subtypes of breast cancer in biopsies obtained from patients. This dissertation makes contributions in three major areas towards addressing the goal. First, we developed miniaturized bioimpedance sensors using MEMS and microfluidics technology that have the requisite traits for clinical use including reliability, ease-of-use, low-cost and disposability. Here, we designed and fabricated two types of bioimpedance sensors. One was based on electric cell-substrate impedance sensing (ECIS) to monitor cell adhesion based events and the other was a microfluidic device with integrated microelectrodes to examine the biophysical properties of single cells. Second, we examined a panel of triple negative breast cancer (TNBC) cell lines and a hormone therapy resistant model of breast cancer in order to improve our understanding of the bioimpedance spectra of breast cancer subtypes. Third, we explored strategies to improve the sensitivity of the microelectrodes to bioimpedance measurements from breast cancer cells. We investigated nano-scale coatings on the surface of the electrode and geometrical variations in a branched electrode design to accomplish this. This work demonstrates the promise of bioimpedance technologies in monitoring diseased cells and their responses to pharmaceutical agents, and motivates further research in customization of this technique for use in personalized medicine.
  • Thumbnail Image
    The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells
    Babahosseini, Hesam; Srinivasaraghavan, Vaishnavi; Zhao, Zongmin; Gillam, Francis; Childress, Elizabeth; Strobl, Jeannine S.; Santos, Webster L.; Zhang, Chenming; Agah, Masoud (The Royal Society of Chemistry, 2015-11-19)
    Cancer progression and physiological changes within the cells are accompanied by alterations in the biophysical properties. Therefore, the cell biophysical properties can serve as promising markers for cancer detection and physiological activities. To aid in the investigation of the biophysical markers of cells, a microfluidic chip has been developed which consists of a constriction channel and embedded microelectrodes. Single-cell impedance magnitudes at four frequencies and entry and travel times are measured simultaneously during their transit through the constriction channel. This microchip provides a high-throughput, label-free, automated assay to identify biophysical signatures of malignant cells and monitor the therapeutic efficacy of drugs. Here, we monitored the dynamic cellular biophysical properties in response to sphingosine kinase inhibitors (SphKIs), and compared the effectiveness of drug delivery using poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with SphKIs versus conventional delivery. Cells treated with SphKIs showed significantly higher impedance magnitudes at all four frequencies. The bioelectrical parameters extracted using a model also revealed that the highly aggressive breast cells treated with SphKIs shifted electrically towards that of a less malignant phenotype; SphKI-treated cells exhibited an increase in cell-channel interface resistance and a significant decrease in specific membrane capacitance. Furthermore, SphKI-treated cells became slightly more deformable as measured by a decrease in their channel entry and travel times. We observed no significant difference in the bioelectrical changes produced by SphKI delivered conventionally or with NPs. However, NPs-packaged delivery of SphKI decreased the cell deformability. In summary, this study showed that while the bioelectrical properties of the cells were dominantly affected by SphKIs, the biomechanical properties were mainly changed by the NPs.
  • Thumbnail Image
    A Microfabricated Bioimpedance Sensor with Enhanced Sensitivity for Early Breast Cancer Detection
    Srinivasaraghavan, Vaishnavi (Virginia Tech, 2011-12-01)
    Bioimpedance is the term given to the complex impedance value that is characteristic of the resistance that biological cells offer to the flow of electric current. The objective of this study is to analyze the differences in the bioimpedance of highly metastatic MDA-MB-231 and normal MCF 10A breast epithelial cells and use this information to detect a very small number of breast cancer cells present in a background of normal breast cells and other cells that are typically present in a human biopsy sample.To accomplish this, a bioimpedance sensor with flat gold microelectrodes on a silicon substrate was designed and fabricated. Suberoylanilide hydroxamic acid (SAHA), an FDA-approved anti-cancer agent was used to improve the sensitivity of the bioimpedance sensor towards cancer cells by selectively modifying their cytoarchitecture.