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Dr. Mangilal Agarwal
Dr. Yogesh Joglekar
Dr. Likun Zhu
Dr. Jian Xie
Dr. Rajesh Sardar
Dr. Ruihua Cheng
Dr. Frédérique Deiss
Dr. Maher Rizkalla
Dr. Horia Petrache
Dr. Hazim El-Mounayri
Development of Advanced Plasmonic Nanobiosensors for Cancer Diagnosis
Dr. Rajesh Sardar, Chemistry and Chemical Biology, NSF Award 1604617.

Changes in the expression or degradation levels of microRNAs, which are classified as (15-25 nucleotides) short non-coding RNAs, modulate various biological processes in cells including tumorgenesis (tumor progression, invasion, and metatasis). Thus, microRNAs can be considered as oncogenic/tumor suppression molecules. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays and various forms of gel electrophoresis are routinely used to assay microRNAs. However, these methods are semi-quantitative, may require amplification and radioactive labeling steps, and suffer from imprecise internal controls. Dr.Sardar's group is the first one to develop optical-based, label-free microRNA sensor without extraction and/or labeling of nucleic acid for detection of miR-21 and miR-10b at attomolar (aM) concentrations in human plasma from pancreatic cancer patients [37,38]. They accomplished this by utilizing the unique localized surface plasmon resonance (LSPR) properties of chemically synthesized gold nanoprisms (GNPs) (Figure 3), which undergo a large optical shift in wavelength, thus behaving as a "nanoantenna." Dr. Sardar selected GNPs as nanoantennas because their atomically flat surface enables homogeneous packing between receptor molecule-containing long-chain alkylthiols and molecular spacers. The spacer plays an important role by inhibiting steric repulsion between analytes (e.g., microRNAs). His long-term research goal is to investigate the nanoscale structural parameters (chemical structure of molecular spacer, edge-length and thickness of the GNPs, electronic properties of the solid substrates) in order to achieve unprecedentedly high sensitivity with the possibility of detecting and quantifying microRNAs from a single cancer cell.

Undergraduate students will: (1) Design new we-chemical methods based on our existing approach to synthesize various edge-length and thickness of GNPs; (2) Establish a relationship between LSPR properties and edge-length and thickness; (3) Determine substrate (e.g., doped silicon, indium tin oxide, and conducting polymer-modified class) effects on LSPR properties; and (4) Construct best microRNA sensor based on the above-mentioned structural analysis. Finally, the REU students will gain expertise on discrete dipole approximation (DDA) simulation to correlate the experimental LSPR properties with the theory. The LSPR responses will be measured via traditionally used UV-visible spectrometry by monitoring changes in the dipole peak of GNPs. Students will characterize the structure of GNPs using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In our two recent publications [37,38] on microRNA sensing, a high school student in my laboratory was involved in collecting and analyzing data. Moreover, my group has published total 7 undergraduate-authored peer-reviewed articles over the last six years on nanoparticle research [37,39-44].

References:
  1. G.K. Joshi, S. Deitz-McElyea, T. Liyanage, K.N. Lawrence, S. Mali, R. Sardar, and M. Korc, "Label-free Nanoplasmonic-based Short Noncoding RNA Sensing at Attomolar Concentration Allows for Quantitative Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes," ACS Nano, 9, 11075-11089, 2015.
  2. S. Dolai, P. Dutta, B. B. Muhoberac, C. D. Irving, and R. Sardar, "Mechanistic Study of the Formation of Bright White Light-emitting Ultrasmall CdSe Nanocrystals: Role of Phosphine Free Selenium Precursors," Chem. Mater, 27, 1057-1070, 2015.
  3. N. W. Dennis, B. B. Muhoberac, J. C. Newton, A. Kumbhar, and R. Sardar, "Correlated Optical Spectroscopy and Electron Microscopy Studies of the Slow Ostwald-ripening Growth of Silver Nanoparticles Under Controlled Reducing Conditions," Plasmonics, 9, 111-120, 2014.
  4. G. K. Joshi, K. A. Smith, M. A. Johnson, and R. Sardar, "Temperature-Controlled Reversible Localized Surface Plasmon Resonance Response of Polymer-Functionalized Gold Nanoprisms in the Solid State," J. Phys. Chem. C, 117, 26228-26237, 2013.
  5. G. K. Joshi, P. McClory, B. B. Muhoberac, A. Kumbhar, K. A. Smith, and R. Sardar, "Designing Efficient Localized Surface Plasmon Resonance-based Sensing Platforms: Optimization of Sensor Response by Controlling the Edge Length of Gold Nanoprisms," J. Phys. Chem. C, 116, 20990-21000, 2012.
  6. G. K. Joshi, P. McClory, S. Dolai, and R. Sardar, "Improved Localized Surface Plasmon Resonance Biosensing Sensitivity Using Chemically Synthesized Gold Nanoprisms as Plasmonic Transducers," Journal of Materials Chemistry, 22, 923-931, 2012.
  7. J. C. Newton, K. Ramasamy, M. Mandal, G. K. Joshi, A. Kumbhar, and R. Sardar, "Low-Temperature Synthesis of Magic-Sized CdSe Nanoclusters: Influence of Ligands on Nanocluster Growth and Photophysical Properties," Journal of Physical Chemistry C, 116, 4380-4389, 2012.