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Development of Nanodevices for Bio-detection, Separation, Therapy, and Mechanotransduction

Mahajan, Kalpesh D
http://rave.ohiolink.edu/etdc/view?acc_num=osu1376446892

Abstract Details

, Doctor of Philosophy, Ohio State University, Chemical and Biomolecular Engineering.
Miniaturization of functional devices has been the aim of nanotechnology. Various nanomachines have been devised to perform functions such as assembly, detection, transport, and separation. An ambitious goal is to miniaturize entire bulk manufacturing process with the aforementioned functionalities in an integrated platform. Various technologies have been developed to achieve individual functionalities, including assembly, characterization, separation, and manipulation, but an integrated nanofactory platform combining all these functionalities is lacking. In this dissertation we have demonstrated synthesis and characterization of multifunctional nanodevices along with their applications in biomolecular detection, separation, drug delivery, and mechanotransduction. Inspired by biology, we combined principles of self-assembly and biological transport with engineered nanodevices and magnetic field engineering to yield a nanofactory with both engineering and biological control. A micellar self-assembly approach was used to template the synthesis of nanodevices. We demonstrated synthesis of MultiDots, which encapsulated multiple quantum dots (QDs) with enhanced fluorescence and reduced blinking, MagDots which are fluorescent-magnetic nanohybrids, and PolyDots that have controlled drug release properties. Scale up strategies based on dialysis, sonication, and electrospray were developed for high volume manufacturing at commercial scale. Particles were characterized by conventional techniques such as DLS, TEM, and SMPS. Besides conventional techniques, single particle analysis methods were developed by combining high accuracy, quantitative fluorescence microscopy and image analysis techniques. On the nanofactory platform, nanoassemblies were created using a brick and mortar approach in which micelle templated nanodevices served as nanobricks that were combined to form higher order structures using biomolecular (proteins and DNA) mortar. The assemblies were further templated onto cytoskeletal proteins to form microtubule shuttles. The products of this assembly were captured on a magnetic microchip and were transported along nanoconveyor belts using external magnetic fields. Assemblies were simultaneously visualized and characterized using their fluorescence functionality, which serves as a quality control method. This nanofactory platform was demonstrated as an ultrasensitive medical diagnostic device for detection, separation and quantification of molecular biomarkers. Proteins and ssDNA were detected with a sensitivity of 10-16 M in 5 µl sample volume. Detection and separation of cells with simultaneous receptor expression profiling was shown. Cells were labeled with antibody-conjugated MagDots and were separated on the magnetic microchip. The clinical utility of this technique was illustrated with characterization of HER-2 protein expression on circulating tumor cells isolated from breast cancer patients. This was followed by study on the effect of magnetic force on cells isolated using immunomagnetic separation. The effect of magnetic force exerted through antibodies on the proliferation of endothelial cells was studied. The micelle templated assembly process was also used to synthesize sub-100 nm PLGA nanoparticles (Polydots) with superior drug release kinetics. The particles demonstrated linear drug release profiles that could be tailored by engineering PLGA loading without affecting size and shape of Polydots. Finally, application of MagDots for single molecule characterization was demonstrated by combining image analysis techniques and finite element modeling. Taken together, the findings and the platforms built during this study will have far reaching implications in developing devices for a wide variety of applications.
Jessica Winter (Advisor)
Jeffrey Chalmers (Committee Member)
Ratnasingham Sooryakumar (Committee Member)
Chemical Engineering
Nanotechnology, detection, mechanotransduction, drug delivery

Recommended Citations

Citations

  • Mahajan, K. D. (2013). Development of Nanodevices for Bio-detection, Separation, Therapy, and Mechanotransduction [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1376446892

    APA Style (7th edition)

  • Mahajan, Kalpesh. Development of Nanodevices for Bio-detection, Separation, Therapy, and Mechanotransduction. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1376446892.

    MLA Style (8th edition)

  • Mahajan, Kalpesh. "Development of Nanodevices for Bio-detection, Separation, Therapy, and Mechanotransduction." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1376446892

    Chicago Manual of Style (17th edition)

osu1376446892
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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.